Antibiotics doi: 10.3390/antibiotics13030274
Authors: Jorge Alberto Cortés Claudia Rocío Sierra Ricardo Sánchez
The aim of this study was to evaluate the effect of inappropriate therapy in adult patients with community-acquired pyelonephritis caused by Escherichia coli receiving empirical treatment with cefuroxime during hospital stay and readmission. A retrospective cohort study was performed. Inappropriate treatment was considered treatment for a nonsusceptible isolate according to the results of the urine culture. Adjustment for confounding factors was performed with propensity score-derived inverse probability of treatment weighting. Between 2013 and 2020, 747 patients were included, 102 (13.7%) of whom received inappropriate therapy. Compared to appropriate therapy, inappropriate therapy was associated with a shorter length of stay in the adjusted analysis (Hazard Ratio = 0.34; 95% CI = 0.23–0.49). After 735 patients were discharged from the hospital, 66 were readmitted in the following 30 days. In comparison with appropriate therapy, inappropriate antimicrobial therapy was not related to readmission (OR 1.47; 95% CI = 0.35–2.79). Inappropriate therapy was not related to a longer hospital stay or readmission due to pyelonephritis after adjusting for confounders and covariates.
]]>Antibiotics doi: 10.3390/antibiotics13030273
Authors: Adriana Barbosa Ribeiro Pillar Gonçalves Pizziolo Lorena Mosconi Clemente Helena Cristina Aguiar Beatriz de Camargo Poker Arthur Augusto Martins e Silva Laís Ranieri Makrakis Marco Aurelio Fifolato Giulia Cristina Souza Viviane de Cássia Oliveira Evandro Watanabe Cláudia Helena Lovato da Silva
Oral infections occur due to contact between biofilm rich in Candida albicans formed on the inner surface of complete dentures and the mucosa. This study investigated historical advances in the prevention and treatment of oral mucosal infection and identified gaps in the literature. Bibliographic research was conducted, looking at PubMed, Embase, Web of Science, and Scopus, where 935 articles were found. After removing duplicates and excluding articles by reading the title and abstract, 131 articles were selected for full reading and 104 articles were included. Another 38 articles were added from the gray literature. This review followed the PRISMA-ScR guidelines. The historical period described ranges from 1969 to 2023, in which, during the 21st century, in vitro and in vivo studies became more common and, from 2010 to 2023, the number of randomized controlled trials increased. Among the various approaches tested are the incorporation of antimicrobial products into prosthetic materials, the improvement of oral and denture hygiene protocols, the development of synthetic and natural products for the chemical control of microorganisms, and intervention with local or systemic antimicrobial agents. Studies report good results with brushing combined with sodium hypochlorite, and new disinfectant solutions and products incorporated into prosthetic materials are promising.
]]>Antibiotics doi: 10.3390/antibiotics13030272
Authors: Nathan D. Nielsen James T. Dean Elizabeth A. Shald Andrew Conway Morris Pedro Povoa Jeroen Schouten Nicholas Parchim
Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost. Short term risks—hepatic/renal dysfunction, intermediate effects—concomitant superinfections, and long-term risks—potentiating antimicrobial resistance (AMR), are all possible consequences of antimicrobial administration. These risks are increased by longer periods of treatment and unnecessarily broad treatment courses. Recently, the literature has focused on multiple strategies to determine the appropriate duration of antimicrobial therapy. Further, there is a clinical shift to multi-modal approaches to determine the most suitable timepoint at which to end an antibiotic course. An approach utilising biomarker assays and an inter-disciplinary team of pharmacists, nurses, physicians, and microbiologists appears to be the way forward to develop sound clinical decision-making surrounding antibiotic treatment.
]]>Antibiotics doi: 10.3390/antibiotics13030271
Authors: Farkhod Eshboev Nilufar Mamadalieva Pavel A. Nazarov Hidayat Hussain Vladimir Katanaev Dilfuza Egamberdieva Shakhnoz Azimova
Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites.
]]>Antibiotics doi: 10.3390/antibiotics13030270
Authors: Maria K. Armillei Ivan B. Lomakin James Q. Del Rosso Ayman Grada Christopher G. Bunick
Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin’s anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology.
]]>Antibiotics doi: 10.3390/antibiotics13030269
Authors: Ioana Ilyes Marius Boariu Darian Rusu Vincenzo Iorio-Siciliano Octavia Vela Simina Boia Georgios Kardaras Petra Șurlin Horia Calniceanu Holger Jentsch Alexandru Lodin Stefan-Ioan Stratul
Objectives: This randomized, placebo-controlled, double-masked clinical trial aimed to evaluate the clinical and microbiological efficacy of professional mechanical plaque removal (PMPR) with or without adjunctive application of piperacillin plus tazobactam gel in the treatment of peri-implant mucositis (PiM) for up to 6 months. Materials and Methods: The study included 31 patients with peri-implant mucositis (bleeding on probing (BoP) > 1 at at least one site at baseline, absence of peri-implant bone loss compared with a previous radiograph). After randomized assignment to test and control groups, patients received full-mouth supragingival scaling with or without piperacillin plus tazobactam gel. Clinical examination was performed at baseline and after 3 and 6 months, and a microbiological examination was performed at baseline and after 3 months. Results: After six months, both treatment modalities resulted in significant reductions and improvements in clinical parameters at the implant sites. Neither study group achieved a complete resolution of PiM (i.e., BoP ≤ 1 per implant). The number of implants with BoP decreased statistically significantly between subsequent time points (p < 0.001) in both the test and the control group. Significant BoP differences (p = 0.039) were observed between groups at 6 months (difference to baseline) following therapy. Conclusions: Within the limitations of the present study, the single use of a slow-release, locally applied antibiotic combination of piperacillin and tazobactam gel, adjunctive to PMPR, showed an improvement in clinical variable of implants diagnosed with PiM. The adjunctive treatment resulted in higher BoP reduction when compared to the control, but no significant differences were observed regarding the changes in other clinical and microbiological parameters.
]]>Antibiotics doi: 10.3390/antibiotics13030268
Authors: Faith D. Huynh Giovanni Damiani Christopher G. Bunick
Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, perineal, and inframammary regions, and can develop fistulas and sinus tracts over time. Its pathogenesis remains elusive and is best characterized at the moment as multi-factorial. Additionally, questions remain about the role of cutaneous dysbiosis as a primary HS trigger or as a secondary perturbation due to HS inflammation. This article features works in relation to HS and its interplay with bacterial microflora. We address current treatment approaches and their impact on HS-related bacteria, as well as areas of therapeutic innovation. In the future, disease-modifying or remittive therapy will likely combine an advanced/targeted anti-inflammatory approach with one that effectively modulates cutaneous and deep tissue dysbiosis.
]]>Antibiotics doi: 10.3390/antibiotics13030267
Authors: Elisabetta Bretto Simone Frara Angelo Armandi Gian Paolo Caviglia Giorgio Maria Saracco Elisabetta Bugianesi Demis Pitoni Davide Giuseppe Ribaldone
Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to the pathogenesis of autoimmune diseases. While the specific etiopathogenesis of inflammatory bowel diseases (IBDs) is still unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. Various bacterial and viral pathogens have been implicated in the pathogenesis of IBDs. Numerous studies suggest a correlation between H. pylori infection and IBDs. While subject to debate, this link suggests that the bacterium’s presence somehow impacts the progression of IBDs by modifying the diversity of the gut microbiota, consequently altering local chemical profiles and disrupting the pattern of gut immune response. However, epidemiological evidence indicates a protective role of H. pylori infection against the onset of autoimmune diseases. Additionally, laboratory findings demonstrate H. pylori’s capacity to promote immune tolerance and restrict inflammatory reactions. The aim of this review is to elucidate the proposed mechanisms and confounding factors that underlie the potential association between H. pylori infection and IBDs.
]]>Antibiotics doi: 10.3390/antibiotics13030266
Authors: Wilmer Silva-Caso Giancarlo Pérez-Lazo Miguel Angel Aguilar-Luis Adriana Morales-Moreno José Ballena-López Fernando Soto-Febres Johanna Martins-Luna Luis J. Del Valle Sungmin Kym Deysi Aguilar-Luis Dayana Denegri-Hinostroza Juana del Valle-Mendoza
Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced pneumonia confirmed via real-time RT-PCR. Patients aged > 18 years who were admitted to a specialized COVID-19 treatment center in Peru were selected for enrollment. A. baumannii was detected via the PCR amplification of the blaOXA-51 gene obtained from nasopharyngeal swabs within 48 h of hospitalization. A total of 295 patients with COVID-19 who met the study inclusion criteria were enrolled. A. baumannii was simultaneously identified in 40/295 (13.5%) of COVID-19-hospitalized patients. Demographic data and comorbidities were comparable in both Acinetobacter-positive and -negative subgroups. However, patients identified as being infected with Acinetobacter were more likely to have received outpatient antibiotics prior to hospitalization, had a higher requirement for high-flow nasal cannula and a higher subjective incidence of fatigue, and were more likely to develop Acinetobacter-induced pneumonia during hospitalization. Conclusions: The group in which SARS-CoV-2 and A. baumannii were simultaneously identified had a higher proportion of fatigue, a higher frequency of requiring a high-flow cannula, and a higher proportion of superinfection with the same microorganism during hospitalization.
]]>Antibiotics doi: 10.3390/antibiotics13030265
Authors: Al Maamon R. Abu Jaber Bilgen Basgut Ali Abdullah Hawan Ali Amer Al Shehri Sultan Ahmad AlKahtani Nehad J. Ahmed Abdikarim Abdi
Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients’ baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI’s clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients’ 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI’s clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI’s microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients’ characteristics.
]]>Antibiotics doi: 10.3390/antibiotics13030264
Authors: Dalida Bivona Carmelo Bonomo Lorenzo Colombini Paolo G. Bonacci Grete F. Privitera Giuseppe Caruso Filippo Caraci Francesco Santoro Nicolò Musso Dafne Bongiorno Francesco Iannelli Stefania Stefani
Intracellular survival and immune evasion are typical features of staphylococcal infections. USA300 is a major clone of methicillin-resistant S. aureus (MRSA), a community- and hospital-acquired pathogen capable of disseminating throughout the body and evading the immune system. Carnosine is an endogenous dipeptide characterized by antioxidant and anti-inflammatory properties acting on the peripheral (macrophages) and tissue-resident (microglia) immune system. In this work, RAW 264.7 murine macrophages were infected with the USA300 ATCC BAA-1556 S. aureus strain and treated with 20 mM carnosine and/or 32 mg/L erythromycin. Stable small colony variant (SCV) formation on blood agar medium was obtained after 48 h of combined treatment. Whole genome sequencing of the BAA-1556 strain and its stable derivative SCVs when combining Illumina and nanopore technologies revealed three single nucleotide differences, including a nonsense mutation in the shikimate kinase gene aroK. Gene expression analysis showed a significant up-regulation of the uhpt and sdrE genes in the stable SCVs compared with the wild-type, likely involved in adaptation to the intracellular milieu.
]]>Antibiotics doi: 10.3390/antibiotics13030263
Authors: Arij Akir Abrar Senhaji-Kacha Maria Carmen Muñoz-Egea Jaime Esteban John Jairo Aguilera-Correa
Background: The Mycobacterium avium complex includes the commonest non-tuberculous mycobacteria associated with human infections. These infections have been associated with the production of biofilms in many cases, but there are only a few studies about biofilms produced by the species included in this group. Methods: Three collection strains (M. avium ATCC25291, M. intracellulare ATCC13950, and M. chimaera DSM756), three clinically significant strains (647, 657, and 655), and three clinically non-significant ones (717, 505, and 575) of each species were included. The clinical significance of the clinical isolates was established according to the internationally accepted criteria. The biofilm ultrastructure was studied by Confocal-Laser Scanning Microscopy by using BacLight Live–Dead and Nile Red stains. The viability, covered surface, height, and relative autofluorescence were measured in several images/strain. The effect of clarithromycin was studied by using the technique described by Muñoz-Egea et al. with modifications regarding incubation time. The study included clarithromycin in the culture medium at a concentration achievable in the lungs (11.3 mg/L), using one row of wells as the control without antibiotics. The bacterial viability inside the biofilm is expressed as a percentage of viable cells. The differences between the different parameters of the biofilm ultrastructure were analyzed by using the Kruskal–Wallis test. The correlation between bacterial viability in the biofilm and treatment time was evaluated by using Spearman’s rank correlation coefficient (ρ). Results: The strains showed differences between them with all the studied parameters, but neither a species-specific pattern nor a clinical-significance-specific pattern were detected. For the effect of clarithromycin, the viability of the bacteria contained in the biofilm was inversely proportional to the exposure time of the biofilm (ρ > −0.3; p-value < 0.05), excluding two M. chimaera strains (M. chimaera DSM756 and 575), which showed a weak positive correlation with treatment time (0.2 < ρ < 0.39; p-value < 0.05). Curiously, despite a clarithromycin treatment of 216 h, the percentage of the biofilm viability of the strains evaluated here was not less than 40% at best (M. avium 717). Conclusions: All the M. avium complex strains studied can form biofilm in vitro, but the ultrastructural characteristics between them suggest that these are strain-specific characteristics unrelated to the species or the clinical significance. The clarithromycin effect on MAC species is biofilm-age/time-of-treatment-dependent and appears to be strain-specific while being independent of the clinical significance of the strain.
]]>Antibiotics doi: 10.3390/antibiotics13030262
Authors: Fan-Fan Xing Kelvin Hei-Yeung Chiu Chao-Wen Deng Hai-Yan Ye Lin-Lin Sun Yong-Xian Su Hui-Jun Cai Simon Kam-Fai Lo Lei Rong Jian-Liang Chen Vincent Chi-Chung Cheng David Christopher Lung Siddharth Sridhar Jasper Fuk-Woo Chan Ivan Fan-Ngai Hung Kwok-Yung Yuen
The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.
]]>Antibiotics doi: 10.3390/antibiotics13030261
Authors: Petros Rafailidis Periklis Panagopoulos Christos Koutserimpas George Samonis
The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections.
]]>Antibiotics doi: 10.3390/antibiotics13030260
Authors: Song Zhang Xinyu Liao Tian Ding Juhee Ahn
Since the discovery of penicillin, β-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing β-lactamases. Therefore, a combination of β-lactam antibiotics with β-lactamase inhibitors has been a promising approach to controlling β-lactam-resistant bacteria. The discovery of novel β-lactamase inhibitors (BLIs) is essential for effectively treating antibiotic-resistant bacterial infections. Therefore, this review discusses the development of innovative inhibitors meant to enhance the activity of β-lactam antibiotics. Specifically, this review describes the classification and characteristics of different classes of β-lactamases and the synergistic mechanisms of β-lactams and BLIs. In addition, we introduce potential sources of compounds for use as novel BLIs. This provides insights into overcoming current challenges in β-lactamase-producing bacteria and designing effective treatment options in combination with BLIs.
]]>Antibiotics doi: 10.3390/antibiotics13030259
Authors: Chikwanda Chileshe Misheck Shawa Nelson Phiri Joseph Ndebe Cynthia Sipho Khumalo Chie Nakajima Kajihara Masahiro Hideaki Higashi Hirofumi Sawa Yasuhiko Suzuki Walter Muleya Bernard Mudenda Hang’ombe
Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has resulted in non-prudent antimicrobial use on farms, intending to prevent and treat poultry diseases for growth optimisation and maximising profits. This cross-sectional study aimed to identify the different types of bacteria causing diseases in chickens in Lusaka and to detect the extended-spectrum lactamase (ESBL)-encoding genes. We collected 215 samples from 91 diseased chickens at three post-mortem facilities and screened them for Gram-negative bacteria. Of these samples, 103 tested positive for various clinically relevant Enterobacteriaceae, including Enterobacter (43/103, 41.7%), Escherichia coli (20/103, 19.4%), Salmonella (10/103, 9.7%), and Shigella (8/103, 7.8%). Other isolated bacteria included Yersinia, Morganella, Proteus, and Klebsiella, which accounted for 21.4%. E. coli, Enterobacter, Salmonella, and Shigella were subjected to antimicrobial susceptibility testing. The results revealed that E. coli, Enterobacter, and Shigella were highly resistant to tetracycline, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole, while Salmonella showed complete susceptibility to all tested antibiotics. The observed resistance patterns correlated with antimicrobial usage estimated from sales data from a large-scale wholesale and retail company. Six (6/14, 42.9%) E. coli isolates tested positive for blaCTX-M, whilst eight (8/14, 57.1%) Enterobacter samples tested positive for blaTEM. Interestingly, four (4/6, 66.7%) of the E. coli isolates carrying blaCTX-M-positive strains were also positive for blaTEM. Sanger sequencing of the PCR products revealed that five (5/6, 83.3%) of the abovementioned isolates possessed the blaCTX-M-15 allele. The results suggest the presence of potentially pathogenic ESBL-producing Enterobacteriaceae in poultry, threatening public health.
]]>Antibiotics doi: 10.3390/antibiotics13030258
Authors: Dong-Hwan Lee Shin-Young Kim Yong-Kyun Kim So-Young Jung Ji-Hoon Jang Hang-Jea Jang Jae-Ha Lee
Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.
]]>Antibiotics doi: 10.3390/antibiotics13030257
Authors: Theodoros Karampatakis Katerina Tsergouli Payam Behzadi
Acinetobacter baumannii is a Gram-negative pathogen responsible for a variety of community- and hospital-acquired infections. It is recognized as a life-threatening pathogen among hospitalized individuals and, in particular, immunocompromised patients in many countries. A. baumannii, as a member of the ESKAPE group, encompasses high genomic plasticity and simultaneously is predisposed to receive and exchange the mobile genetic elements (MGEs) through horizontal genetic transfer (HGT). Indeed, A. baumannii is a treasure trove that contains a high number of virulence factors. In accordance with these unique pathogenic characteristics of A. baumannii, the authors aim to discuss the natural treasure trove of pan-genome and virulence factors pertaining to this bacterial monster and try to highlight the reasons why this bacterium is a great concern in the global public health system.
]]>Antibiotics doi: 10.3390/antibiotics13030256
Authors: Jessica da Silva Guedes David Velilla-Rodriguez Elena González-Fandos
The purpose of this investigation was to evaluate the microbial quality and safety of rabbit meat. A total of 49 rabbit meat samples were taken at the retail level. The mesophiles, staphylococci, Enterobacterales, and Pseudomonas spp. counts were 4.94 ± 1.08, 2.59 ± 0.70, 2.82 ± 0.67, and 3.23 ± 0.76 log CFU/g, respectively. Campylobacter spp. were not detected in any sample. Listeria monocytogenes was isolated from one sample (2.04%) at levels below 1.00 log CFU/g. Multi-resistant S aureus was found in seven samples (14.9%). Methicillin-resistant S. aureus, S. epidermidis, S. haemolyticus, M. caseolyticus, and M. sciuri were found in a sample each (10.20%), and all of them were multi-resistant. Multi-resistant ESBL-producing E. coli were detected in two samples from the same retailer (4.08%). The high resistance found in methicillin-resistant staphylococci and ESBL-producing E. coli is of particular concern, and suggests that special measures should be taken in rabbit meat.
]]>Antibiotics doi: 10.3390/antibiotics13030255
Authors: Regina Koloh Viktória L. Balázs Lilla Nagy-Radványi Béla Kocsis Erika Beáta Kerekes Marianna Kocsis Ágnes Farkas
The irresponsible overuse of antibiotics has increased the occurrence of resistant bacterial strains, which represents one of the biggest patient safety risks today. Due to antibiotic resistance and biofilm formation in bacteria, it is becoming increasingly difficult to suppress the bacterial strains responsible for various chronic infections. Honey was proven to inhibit bacterial growth and biofilm development, offering an alternative solution in the treatment of resistant infections and chronic wounds. Our studies included chestnut honey, valued for its high antibacterial activity, and the bacteria Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and S. epidermidis, known to form multi-species biofilm communities. Minimum inhibitory concentrations (MIC) of chestnut honey were determined for each bacterial strain. Afterwards, the mixed bacterial biofilms were treated with chestnut honey at different stages of maturity (incubation times: 2, 4, 6, 12, 24 h). The extent of biofilm inhibition was measured with a crystal violet assay and demonstrated by scanning electron microscopy (SEM). As the incubation time increased and the biofilm became more mature, inhibition rates decreased gradually. The most sensitive biofilm was the combination MRSA-S. epidermidis, with a 93.5% inhibition rate after 2 h of incubation. Our results revealed that chestnut honey is suitable for suppressing the initial and moderately mature stages of mixed biofilms.
]]>Antibiotics doi: 10.3390/antibiotics13030254
Authors: Eleni Papachatzi Despoina Gkentzi Sotiris Tzifas Theodore Dassios Gabriel Dimitriou
During the last two decades, the incidence of late-onset sepsis (LOS) has increased due to improved survival of premature neonates. Persistent bacteremia (PB) in LOS is defined as more than two positive blood cultures obtained on different calendar days during the same infectious episode. Although rare, PB should be treated aggressively to prevent adverse outcomes. Daptomycin, a lipopeptide antibiotic, has been used in neonates with persistent coagulase-negative staphylococci (CoNS) bacteremia with promising results, but studies reporting on the efficacy and safety of the agent are scarce. The purpose of this study was to evaluate the efficacy and safety of daptomycin use for persistent CoNS bacteremia in a neonatal cohort. This is a retrospective, observational, single-center study of neonates treated with daptomycin during 2011–2022 in the Tertiary Neonatal Intensive Care Unit (NICU) of the University General Hospital of Patras, Greece. For the years 2011–2022, there were 3.413 admissions to the NICU. During the last 3 years (2020–2022)—the active epidemiological surveillance period—123 infants (out of 851 admissions, 14.4%) developed CoNS bacteremia (LOS). During the study period, twelve infants with PB were treated with daptomycin. They had a median gestational age of 32 weeks (IQR 31–34) and mean (SD) birth weight of 1.840 (867) grams. CoNS bacteremia isolates were s. epidermidis (50%), s. haemolyticus (20%), s. hominis (20%) and s. warneri (10%). The decision to start daptomycin (6 mg/kg/dose twice daily) was taken on median day 10 (ΙQR 7–15) of infection. None of the infants had focal complications or meningitis. Daptomycin therapy caused no renal, hepatic, muscular or gastrointestinal adverse events. One neonate developed seizures, and one death occurred due to multiple complications of prematurity. Most infants (11/12) were successfully treated and eventually had negative blood culture. Daptomycin monotherapy showed an adequate cure rate in premature neonates with persistent CoNS bacteremia in a tertiary NICU. In our study, daptomycin was effective and well tolerated; the safety profile, however, needs to be confirmed in larger studies and randomized controlled trials.
]]>Antibiotics doi: 10.3390/antibiotics13030253
Authors: Hamad Abdel Hadi Faiha Eltayeb Sara Al Balushi Joanne Daghfal Faraz Ahmed Ceu Mateus
Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.
]]>Antibiotics doi: 10.3390/antibiotics13030252
Authors: Vid Kuralt Rok Frlan
Antimicrobial resistance is a global health threat that requires innovative strategies against drug-resistant bacteria. Our study focuses on enoyl-acyl carrier protein reductases (ENRs), in particular FabI, FabK, FabV, and InhA, as potential antimicrobial agents. Despite their promising potential, the lack of clinical approvals for inhibitors such as triclosan and isoniazid underscores the challenges in achieving preclinical success. In our study, we curated and analyzed a dataset of 1412 small molecules recognized as ENR inhibitors, investigating different structural variants. Using advanced cheminformatic tools, we mapped the physicochemical landscape and identified specific structural features as key determinants of bioactivity. Furthermore, we investigated whether the compounds conform to Lipinski rules, PAINS, and Brenk filters, which are crucial for the advancement of compounds in development pipelines. Furthermore, we investigated structural diversity using four different representations: Chemotype diversity, molecular similarity, t-SNE visualization, molecular complexity, and cluster analysis. By using advanced bioinformatics tools such as matched molecular pairs (MMP) analysis, machine learning, and SHAP analysis, we were able to improve our understanding of the activity cliques and the precise effects of the functional groups. In summary, this chemoinformatic investigation has unraveled the FAB inhibitors and provided insights into rational antimicrobial design, seamlessly integrating computation into the discovery of new antimicrobial agents.
]]>Antibiotics doi: 10.3390/antibiotics13030251
Authors: Furkan Eker Emir Akdaşçi Hatice Duman Yalçın Mert Yalçıntaş Ahmet Alperen Canbolat Arda Erkan Kalkan Sercan Karav Dunja Šamec
The growing number of antibiotic resistance genes is putting a strain on the ecosystem and harming human health. In addition, consumers have developed a cautious attitude towards chemical preservatives. Colostrum and milk are excellent sources of antibacterial components that help to strengthen the immunity of the offspring and accelerate the maturation of the immune system. It is possible to study these important defenses of milk and colostrum, such as lactoferrin, lysozyme, immunoglobulins, oligosaccharides, etc., as biotherapeutic agents for the prevention and treatment of numerous infections caused by microbes. Each of these components has different mechanisms and interactions in various places. The compound’s mechanisms of action determine where the antibacterial activity appears. The activation of the antibacterial activity of milk and colostrum compounds can start in the infant’s mouth during lactation and continue in the gastrointestinal regions. These antibacterial properties possess potential for therapeutic uses. In order to discover new perspectives and methods for the treatment of bacterial infections, additional investigations of the mechanisms of action and potential complexes are required.
]]>Antibiotics doi: 10.3390/antibiotics13030250
Authors: Giovanni Boscarino Rossana Romano Carlotta Iotti Francesca Tegoni Serafina Perrone Susanna Esposito
Neonatal sepsis is a clinical syndrome mainly associated with a bacterial infection leading to severe clinical manifestations that could be associated with fatal sequalae. According to the time of onset, neonatal sepsis is categorized as early- (EOS) or late-onset sepsis (LOS). Despite blood culture being the gold standard for diagnosis, it has several limitations, and early diagnosis is not immediate. Consequently, most infants who start empirical antimicrobial therapy do not have an underlying infection. Despite stewardship programs partially reduced this negative trend, in neonatology, antibiotic overuse still persists, and it is associated with several relevant problems, the first of which is the increase in antimicrobial resistance (AMR). Starting with these considerations, we performed a narrative review to summarize the main findings and the future prospects regarding antibiotics use to treat neonatal sepsis. Because of the impact on morbidity and mortality that EOS and LOS entail, it is essential to start an effective and prompt treatment as soon as possible. The use of targeted antibiotics is peremptory as soon as the pathogen in the culture is detected. Although prompt therapy is essential, it should be better assessed whether, when and how to treat neonates with antibiotics, even those at higher risk. Considering that we are certainly in the worrying era defined as the “post-antibiotic era”, it is still essential and urgent to define novel strategies for the development of antibacterial compounds with new targets or mechanisms of action. A future strategy could also be to perform well-designed studies to develop innovative algorithms for improving the etiological diagnosis of infection, allowing for more personalized use of the antibiotics to treat EOS and LOS.
]]>Antibiotics doi: 10.3390/antibiotics13030249
Authors: Ji Young Park Hyun Mi Kang
This study aimed to investigate national data for a quantitative evaluation of antibiotic usage in Korean children during the pre- and early COVID-19 period. This was a cross-sectional study from 2016 to 2021 of children <18 years, grouped by age (0, 1, 2–4, 5–11, and 12–17 years) and city/province. Systemic antibiotic prescriptions, days of administration, and population by age and region were collected. Days of therapy (DOT)/1000 pediatric inhabitant per day (PID) was used for antibiotic quantitative monitoring. A total of 257,088,265 antibiotic doses were prescribed to 170,309,944 children during the 6-year period. The highest DOT during the entire study period was observed in the 1-year age group, followed by the 2–4- and 0-year age groups. The highest DOT was observed in 2019, with 72.8 DOT/1000 PID in the 1-year age group, which fell to 34.7 DOT/1000 PID in 2020, however, DOT soon increased at similar rates to that in the pre-COVID-19 period. A higher DOT/1000 PID was observed for third-generation cephalosporins in 58.8% of the regions compared to beta-lactam/beta-lactamase inhibitors. To conclude, reductions in antibiotic use during the early COVID-19 pandemic period were not maintained. Further interventions are needed to decrease antibiotic overuse and misuse.
]]>Antibiotics doi: 10.3390/antibiotics13030248
Authors: Ana Paula Gonçalves Coelho Vieira Amanda Neves de Souza William Gustavo Lima Julio Cesar Moreira Brito Daniela Carolina Simião Lucas Vinícius Ribeiro Gonçalves Lídia Pereira Barbosa Cordeiro Denise de Oliveira Scoaris Simone Odília Antunes Fernandes Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly Maria Elena de Lima
The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8–16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.
]]>Antibiotics doi: 10.3390/antibiotics13030247
Authors: Ádám Kerek Bence Török Levente Laczkó Zoltán Somogyi Gábor Kardos Krisztián Bányai Eszter Kaszab Krisztina Bali Ákos Jerzsele
The global spread of antimicrobial resistance has become a prominent issue in both veterinary and public health in the 21st century. The extensive use of amoxicillin, a beta-lactam antibiotic, and consequent resistance development are particularly alarming in food-producing animals, with a focus on the swine and poultry sectors. Another beta-lactam, cefotaxime, is widely utilized in human medicine, where the escalating resistance to third- and fourth-generation cephalosporins is a major concern. The aim of this study was to simulate the development of phenotypic and genotypic resistance to beta-lactam antibiotics, focusing on amoxicillin and cefotaxime. The investigation of the minimal inhibitory concentrations (MIC) of antibiotics was performed at 1×, 10×, 100×, and 1000× concentrations using the modified microbial evolution and growth arena (MEGA-plate) method. Our results indicate that amoxicillin significantly increased the MIC values of several tested antibiotics, except for oxytetracycline and florfenicol. In the case of cefotaxime, this increase was observed in all classes. A total of 44 antimicrobial resistance genes were identified in all samples. Chromosomal point mutations, particularly concerning cefotaxime, revealed numerous complex mutations, deletions, insertions, and single nucleotide polymorphisms (SNPs) that were not experienced in the case of amoxicillin. The findings suggest that, regarding amoxicillin, the point mutation of the acrB gene could explain the observed MIC value increases due to the heightened activity of the acrAB-tolC efflux pump system. However, under the influence of cefotaxime, more intricate processes occurred, including complex amino acid substitutions in the ampC gene promoter region, increased enzyme production induced by amino acid substitutions and SNPs, as well as mutations in the acrR and robA repressor genes that heightened the activity of the acrAB-tolC efflux pump system. These changes may contribute to the significant MIC increases observed for all tested antibiotics. The results underscore the importance of understanding cross-resistance development between individual drugs when choosing clinical alternative drugs. The point mutations in the mdtB and emrR genes may also contribute to the increased activity of the mdtABC-tolC and emrAB-tolC pump systems against all tested antibiotics. The exceptionally high mutation rate induced by cephalosporins justifies further investigations to clarify the exact mechanism behind.
]]>Antibiotics doi: 10.3390/antibiotics13030246
Authors: Emma C. L. Marrs Olivia Milburn Gary J. Eltringham Danielle J. C. Fenwick Sylvain Orenga Gulsen Hazırolan Pinar Zarakolu John D. Perry
The aim of this study was to assess the utility of CHROMID® Colistin R for direct detection of colistin-resistant Gram-negative bacteria from positive blood cultures. A total of 390 blood cultures from hospitalised patients containing Gram-negative bacteria were included in this study. These blood cultures were referred to clinical laboratories in the United Kingdom and Türkiye. A further 16 simulated positive blood culture bottles were included that contained a range of colistin-resistant strains as well as susceptible control strains. Fluid from each positive blood culture was diluted 1/200 in saline and 10 µL aliquots cultured onto cystine-lactose-electrolyte-deficient agar and CHROMID® Colistin R. All recovered bacteria were identified, and for Gram-negative bacteria, their minimum inhibitory concentration of colistin was measured using the broth microdilution method. From a total of 443 Gram-negative isolates, 57 colistin-resistant isolates were recovered, of which 53 (93%) grew on CHROMID® Colistin R within 18 h. Of the 377 isolates determined to be colistin-susceptible, only 9 isolates were able to grow, including 6 isolates of Pseudomonas aeruginosa. For positive blood cultures that are shown to contain Gram-negative bacteria, culture on CHROMID® Colistin R is a useful diagnostic tool to detect susceptibility or resistance to colistin within 18 h.
]]>Antibiotics doi: 10.3390/antibiotics13030245
Authors: Phornphan Sornchuer Kritsakorn Saninjuk Sumet Amonyingcharoen Jittiporn Ruangtong Nattaya Thongsepee Pongsakorn Martviset Pathanin Chantree Kant Sangpairoj
Members of the Bacillus cereus group are spore-forming Gram-positive bacilli that are commonly associated with diarrheal or emetic food poisoning. They are widespread in nature and frequently present in both raw and processed food products. Here, we genetically characterized 24 B. cereus group isolates from foodstuffs. Whole-genome sequencing (WGS) revealed that most of the isolates were closely related to B. cereus sensu stricto (12 isolates), followed by B. pacificus (5 isolates), B. paranthracis (5 isolates), B. tropicus (1 isolate), and “B. bingmayongensis” (1 isolate). The most detected virulence genes were BAS_RS06430, followed by bacillibactin biosynthesis genes (dhbA, dhbB, dhbC, dhbE, and dhbF), genes encoding the three-component non-hemolytic enterotoxin (nheA, nheB, and nheC), a gene encoding an iron-regulated leucine-rich surface protein (ilsA), and a gene encoding a metalloprotease (inhA). Various biofilm-associated genes were found, with high prevalences of tasA and sipW genes (matrix protein-encoding genes); purA, purC, and purL genes (eDNA synthesis genes); lytR and ugd genes (matrix polysaccharide synthesis genes); and abrB, codY, nprR, plcR, sinR, and spo0A genes (biofilm transcription regulator genes). Genes related to fosfomycin and beta-lactam resistance were identified in most of the isolates. We therefore demonstrated that WGS analysis represents a useful tool for rapidly identifying and characterizing B. cereus group strains. Determining the genetic epidemiology, the presence of virulence and antimicrobial resistance genes, and the pathogenic potential of each strain is crucial for improving the risk assessment of foodborne B. cereus group strains.
]]>Antibiotics doi: 10.3390/antibiotics13030244
Authors: Nayoung Han Ock Hee Oh John Oh Yoomi Kim Younghee Lee Won Chul Cha Yun Mi Yu
Prevention of drug allergies is important for patient safety. The objective of this study was to evaluate the outcomes of antibiotic allergy-checking clinical decision support system (CDSS), K-CDSTM. A retrospective chart review study was performed in 29 hospitals and antibiotic allergy alerts data were collected from May to August 2022. A total of 15,535 allergy alert cases from 1586 patients were reviewed. The most frequently prescribed antibiotics were cephalosporins (48.5%), and there were more alerts of potential cross-reactivity between beta-lactam antibiotics than between antibiotics with the same ingredients or of the same class. Regarding allergy symptoms, dermatological disorders were the most common (38.8%), followed by gastrointestinal disorders (28.4%). The 714 cases (4.5%) of immune system disorders included 222 cases of anaphylaxis and 61 cases of severe cutaneous adverse reactions. Alerts for severe symptoms were reported in 6.4% of all cases. This study confirmed that K-CDS can effectively detect antibiotic allergies and prevent the prescription of potentially allergy-causing antibiotics among patients with a history of antibiotic allergies. If K-CDS is expanded to medical institutions nationwide in the future, it can prevent an increase in allergy recurrence related to drug prescriptions through cloud-based allergy detection CDSSs.
]]>Antibiotics doi: 10.3390/antibiotics13030243
Authors: Andreas Iffland Maria Zechel Jan-Christoph Lewejohann Birgit Edel Stefan Hagel Michael Hartmann Bettina Löffler Jürgen Rödel
Early identification of acute gastroenteritis (AGE) pathogens via PCR may improve the management of patients presenting to the emergency department (ED). In this study, we evaluated the implementation of a testing algorithm for ED patients with AGE using the BD MAX automated PCR system. Data from 133 patients were analyzed. A total of 56 patients (42%) tested positive via PCR for at least one bacterial or viral pathogen. The median time to report PCR results was 6.17 h compared to 57.28 h for culture results for bacterial pathogens. The most common pathogen was Clostridioides difficile (n = 20, 15%). In total, 14 of the 20 C. difficile-positive patients were aged >65 years and 17 of the 20 patients (85%) were diagnosed with a clinically relevant infection based on typical symptoms and laboratory values. They received antibiotics, mostly oral vancomycin, starting a median of 11.37 h after ED admission. The introduction of PCR for the diagnosis of AGE infection in patients presenting to the ED may have the greatest impact on the rapid identification of C. difficile and the timely administration of antibiotics if necessary.
]]>Antibiotics doi: 10.3390/antibiotics13030242
Authors: Daniella Tosta Link Gustavo Guimarães Fernandes Viana Lívia Pasolini Siqueira Carolina Magri Ferraz Romário Alves Rodrigues Luis Antonio Mathias Marita Vedovelli Cardozo Gabriel Augusto Marques Rossi
The consumption of seafood is crucial for food security, but poor hygiene along the food production chain can result in low microbiological quality, posing significant risks for public health and seafood quality. Thus, this study aimed to assess the microbiological quality and antimicrobial sensitivity of E. coli from 69 samples of illegally marketed shrimp and mussels in the Vitória Region, Brazil. These foods exhibited poor microbiological quality due to high counts of mesophilic, psychrotrophic, and enterobacteria microorganisms. While this issue is widespread in this area, shrimp samples displayed higher microbial counts compared to mussels, and fresh mussels had elevated counts of enterobacteria compared to frozen ones. Among the 10 E. coli isolates, none carried the genes blaCTX-M-1, blaCTX-M-2, blaCTX-M-3, blaCTX-M-15, mcr-1, mcr-2, mcr-3, mcr-4, and tet, associated with antibiotic resistance. Phenotypical resistance to tetracycline and fosfomycin was not observed in any isolate, while only 20% demonstrated resistance to ciprofloxacin. Regarding ampicillin and amoxicillin with clavulanic acid, 60% of isolates were resistant, 10% showed intermediate susceptibility, and 30% were sensitive. One isolate was considered simultaneously resistant to β-lactams and quinolones, and none were conserved as ESBL producers. These findings highlight the inherent risks to local public health that arise from consuming improperly prepared seafood in this area.
]]>Antibiotics doi: 10.3390/antibiotics13030241
Authors: Martina Penati Laura Musa Laura Filippone Pavesi Alessandro Guaraglia Fernando Ulloa Paolo Moroni Renata Piccinini Maria Filippa Addis
This study investigated the presence, distribution, and antimicrobial resistance profiles of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in a dairy herd located in Northern Italy. The feces of clinically healthy calves, their mothers, and the cows treated for mastitis, as well as water, environmental samples, and waste milk were collected and subjected to bacteriological culture on CHROMagarTM ESBL plates. A questionnaire was administered to identify risk factors. The isolates were identified as E. coli by MALDI-TOF MS and subjected to the double-disk synergy test (DDST) and minimal inhibitory concentration (MIC) assay. As a result, ESBL E. coli was isolated from the feces of 28 of 37 (75.67%) calves, the feces of 2 of 3 (66.67%) treated cows, 8 of 14 (57.15%) environmental samples, and waste milk. All ESBL isolates showed multiple resistances and were categorized as multidrug-resistant (MDR). Several risk factors for ESBL E. coli selection and diffusion were identified, including lack of routine cleaning of calf feeding and housing equipment, administration of waste milk to male calves, and blanket dry cow therapy. In conclusion, this study highlighted the presence of MDR, ESBL E. coli in the feces of most dairy calves, and their association with different sample sources. Accordingly, adding to the prudent use of antibiotics, the adoption of adequate farm hygiene and biosecurity measures might also help prevent the spread and transmission of ESBL E. coli within the herd.
]]>Antibiotics doi: 10.3390/antibiotics13030240
Authors: Daniela Teodora Marti Felix Bratosin Ovidiu Rosca Roxana Folescu Cosmin Citu Adrian Ratiu Zoran Laurentiu Popa
This study investigates the complex interplay among genital infections, antibiotic usage, and preterm birth. This study aims to identify common genital pathogens associated with preterm births, assess the impact of various antibiotic treatments on pregnancy outcomes, and understand antibiotic resistance patterns among these pathogens. This study included 71 pregnant women who experienced preterm birth and 94 women with genital infections who delivered at term. Various maternal characteristics, medical history, signs and symptoms, gestational weight, gestational age, type of birth, vaginal pH, Nugent scores, and vaginal flora were analyzed. Antibiotic resistance patterns of isolated microorganisms were also examined. The prevalence of sexually transmitted diseases (STDs) and genital herpes was significantly higher in the preterm group. Preterm births were associated with fever, pelvic pain, vaginal spotting, and fatigue. Vaginal pH levels and Nugent scores were significantly higher in the preterm group, indicating disturbed vaginal flora. The presence of Extended-Spectrum Beta-Lactamases (ESBLs) was a particularly strong risk factor, increasing by more than four times the odds of preterm birth (OR = 4.45, p = 0.001). Vancomycin-Resistant Enterococci (VRE) presence was another critical factor, with a four-fold increase in the odds of preterm birth (OR = 4.01, p = 0.034). The overall presence of Multidrug-Resistant (MDR) organisms significantly increased the odds of preterm birth (OR = 3.73, p = 0.001). Specific pathogens like Chlamydia trachomatis (OR = 3.12, p = 0.020) and Mycoplasma hominis (OR = 3.64, p = 0.006) were also identified as significant risk factors. Ureaplasma urealyticum also showed a significantly higher risk of preterm birth (OR = 2.76, p = 0.009). This study highlights the importance of screening for and treating genital infections during pregnancy, especially STDs and genital herpes, as they can significantly increase the risk of preterm birth. Additionally, the presence of specific microorganisms and antibiotic resistance patterns plays an essential role in preterm birth risk. Early detection and targeted antibiotic treatment may help mitigate this risk and improve pregnancy outcomes.
]]>Antibiotics doi: 10.3390/antibiotics13030239
Authors: Dong Yun Kim You Bin Oh Je Seon Park Yu-Hong Min Min Chul Park
Many anti-microbial peptides (AMPs) and pro-apoptotic peptides are considered as novel anti-microbial agents, distinguished by their different characteristics. Nevertheless, AMPs exhibit certain limitations, including poor stability and potential toxicity, which hinder their suitability for applications in pharmaceutics and medical devices. In this study, we used recombinant mussel adhesive protein (MAP) as a robust scaffold to overcome these limitations associated with AMPs. Mussel adhesive protein fused with functional peptides (MAP-FPs) was used to evaluate anti-microbial activities, minimal inhibitory concentration (MIC), and time-kill kinetics (TKK) assays against six of bacteria strains. MAP and MAP-FPs were proved to have an anti-microbial effect with MIC of 4 or 8 µM against only Gram-negative bacteria strains. All tested MAP-FPs killed four different Gram-negative bacteria strains within 180 min. Especially, MAP-FP-2 and -5 killed three Gram-negative bacteria strain, including E. coli, S. typhimurium, and K. pneumoniae, within 10 min. A cytotoxicity study using Vero and HEK293T cells indicated the safety of MAP and MAP-FP-2 and -3. Thermal stability of MAP-FP-2 was also validated by HPLC analysis at an accelerated condition for 4 weeks. This study identified that MAP-FPs have novel anti-microbial activity, inhibiting the growth and rapidly killing Gram-negative bacteria strains with high thermal stability and safety.
]]>Antibiotics doi: 10.3390/antibiotics13030238
Authors: Maddalena Calvo Stefania Stefani Giuseppe Migliorisi
Intensive care units constitute a critical setting for the management of infections. The patients’ fragilities and spread of multidrug-resistant microorganisms lead to relevant difficulties in the patients’ care. Recent epidemiological surveys documented the Gram-negative bacteria supremacy among intensive care unit (ICU) infection aetiologies, accounting for numerous multidrug-resistant isolates. Regarding this specific setting, clinical microbiology support holds a crucial role in the definition of diagnostic algorithms. Eventually, the complete patient evaluation requires integrating local epidemiological knowledge into the best practice and the standardization of antimicrobial stewardship programs. Clinical laboratories usually receive respiratory tract and blood samples from ICU patients, which express a significant predisposition to severe infections. Therefore, conventional or rapid diagnostic workflows should be modified depending on patients’ urgency and preliminary colonization data. Additionally, it is essential to complete each microbiological report with rapid phenotypic minimum inhibitory concentration (MIC) values and information about resistance markers. Microbiologists also help in the eventual integration of ultimate genome analysis techniques into complicated diagnostic workflows. Herein, we want to emphasize the role of the microbiologist in the decisional process of critical patient management.
]]>Antibiotics doi: 10.3390/antibiotics13030237
Authors: Chedia Aouadhi Ahlem Jouini Karima Maaroufi Abderrazak Maaroufi
During the current investigation, eight essential oils (EOs) were tested for their antimicrobial activity against six species, belonging to the genus of staphylococcus, multi-resistant to antibiotics (S. epidermidis, S. cohni, S. wareneri, S. scuiri, S. chromogenes, S. pasteuri), three methicillin-resistant Staphylococcus aureus strains (MRSA) and two strains of Escherichia coli, producing extended-spectrum β-lactamase (ESBL) responsible for bovine mastitis. Our results indicated that the antimicrobial activities of eight EOs varied significantly among the types of EOs and bacterial species. Thymus capitatus and Trachyspermum ammi EOs display important antibacterial activity against all tested strains, with the inhibition zone diameters situated between 20 and 45 mm, while EOs of Artemisia absinthium, Eucalyptus globulus, Eucalyptus camaldulensis, Myrtus communis and Mentha pulegium exerted an intermediate activity. For Cymbopogon citratus, this effect depends on bacteria species. In fact, an important effect was observed against S. warneri, S. epidermidis, S. cohenii, S. pasteuri and MRSA (EC 39+) strains. In addition, the important lytic effect was observed against MRSA strains, showing that Gram-positive bacteria were more sensitive to T. capitatus EO than Gram-negative ones. Concerning the characterization of the mode action of T. capitatus, experiments of kill-time, bacteriolytic, loss of salt tolerance and loss of cytoplasmic material showed that the used EO was able to destroy cell walls and membranes followed by the loss of vital intracellular materials. In addition, it inhibits the normal synthesis of DNA, causing the bacterial death of E. coli and MRSA strains. This study shows the potential of using of EOs, particularly T. capitaus, to inhibit the growth of Gram-positive and Gram-negative bacteria multi-resistant to antibiotics causing bovine mastitis.
]]>Antibiotics doi: 10.3390/antibiotics13030236
Authors: Loïc Fonkoue Elizabeth K. Tissingh Michelle Tognia Ngouateu Kennedy Olivier Muluem Olivier Ngongang Pretty Mbouyap Perrin Ngougni Pokem Kuetche Fotsing Jean Bahebeck Martin McNally Olivier Cornu
Fracture-related infection (FRI) is a common and devastating complication of orthopedic trauma in all settings. Data on the microbiological profile and susceptibility of FRI to antibiotics in low-income countries are scarce. Therefore, this study aimed to investigate the microbial patterns and antimicrobial susceptibility of FRI in a sub-Saharan African setting in order to provide guidance for the formulation of evidence-based empirical antimicrobial regimens. We conducted a retrospective analysis of patients treated for FRI with deep tissue sampling for microbiological culture from January 2016 to August 2023 in four tertiary-level hospitals in Yaoundé, Cameroon. There were 246 infection episodes in 217 patients. Cultures were positive in 209 (84.9%) cases and polymicrobial in 109 (44.3%) cases. A total of 363 microorganisms from 71 different species were identified, of which 239 (65.8%) were Gram-negative. The most commonly isolated pathogens were Staphylococcus aureus (n = 69; 19%), Enterobacter cloacae (n = 43; 11.8%), Klebsiella pneumoniae (n = 35; 9.6%), Escherichia coli (n = 35; 9.6%), and Pseudomonas aeruginosa (n = 27; 7.4%). Coagulase-negative staphylococci (CoNS) were isolated in only 21 (5.9%) cases. Gram-negative bacteria accounted for the majority of the infections in early (70.9%) and delayed (73.2%) FRI, but Gram-positive bacteria were prevalent in late FRI (51.7%) (p < 0.001). Polymicrobial infections were more frequent in the early (55.9%) and delayed (41.9%) groups than in the late group (27.6%) (p < 0.001). Apart from Staphylococcus aureus, there was no significant difference in the proportions of causative pathogens between early, delayed, and late FRI. This study found striking resistance rates of bacteria to commonly used antibiotics. MRSA accounted for 63% of cases. The most effective antibiotics for all Gram-positive bacteria were linezolid (96.4%), vancomycin (92.5%), clindamycin (85.3%), and fucidic acid (89.4%). For Gram-negative bacteria, only three antibiotics displayed a sensitivity >50%: amikacin (80.4%), imipenem (74.4%), and piperacillin + tazobactam (57%). The most effective empirical antibiotic therapy (with local availability) was the combination of vancomycin and amikacin or vancomycin and imipenem. In contrast to the literature from high-resource settings, this study revealed that in a sub-Saharan African context, Gram-negative bacteria are the most common causative microorganisms of FRI. This study revealed striking resistance rates to commonly used antibiotics, which will require urgent action to prevent antimicrobial resistance in low and middle-income countries.
]]>Antibiotics doi: 10.3390/antibiotics13030235
Authors: Marco Catarci Stefano Guadagni Francesco Masedu Massimo Sartelli Leonardo Antonio Montemurro Gian Luca Baiocchi Giovanni Domenico Tebala Felice Borghi Pierluigi Marini Marco Scatizzi the Italian ColoRectal Anastomotic Leakage (iCral) Study Group the Italian ColoRectal Anastomotic Leakage (iCral) Study Group
The evidence regarding the role of oral antibiotics alone (oA) or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8359 colorectal resections gathered over a 32-month period from 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA) and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infection (SSI) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs. 6 (2.5%) events; OR: 3.77; 95%CI: 1.22–11.67; p = 0.021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.
]]>Antibiotics doi: 10.3390/antibiotics13030234
Authors: Valeria Gargano Delia Gambino Adriana Maria Oddo Mariangela Pizzo Arianna Sucato Gaetano Cammilleri Francesco La Russa Maria Liliana Di Pasquale Maria Giovanna Parisi Giovanni Cassata Giuseppe Giangrosso
The Eurasian woodcock (Scolopax rusticola) belongs to those bird species that make systematic migratory flights in spring and autumn in search of favorable breeding and wintering areas. These specimens arrive in the Mediterranean Area from northeastern European countries during the autumn season. The purpose of this study was to assess whether woodcocks can carry antibiotic resistance genes (ARGs) along their migratory routes. Although the role of migratory birds in the spread of some zoonotic diseases (of viral and bacterial etiology) has been elucidated, the role of these animals in the spread of antibiotic resistance has not yet been clarified. In this study, we analyzed the presence of beta-lactam antibiotic resistance genes. The study was conducted on 69 strains from 60 cloacal swabs belonging to an equal number of animals shot during the 2022–2023 hunting season in Sicily, Italy. An antibiogram was performed on all strains using the microdilution method (MIC) and beta-lactam resistance genes were investigated. The strains tested showed no phenotypic resistance to any of the 13 antibiotics tested; however, four isolates of Enterobacter cloacae and three of Klebsiella oxytoca were found to carry the blaIMP-70, blaVIM-35, blaNDM-5 and blaOXA-1 genes. Our results confirm the importance of monitoring antimicrobial resistance among migratory animals capable of long-distance bacteria spread.
]]>Antibiotics doi: 10.3390/antibiotics13030233
Authors: Lucia Boccabella Elena Gialluca Palma Ludovico Abenavoli Giuseppe Guido Maria Scarlata Mariavirginia Boni Gianluca Ianiro Pierangelo Santori Jan F. Tack Emidio Scarpellini
Background and aim: Antimicrobial resistance (AMR) is a chronic issue of our Westernized society, mainly because of the uncontrolled and improper use of antimicrobials. The coronavirus disease 2019 (COVID-19) pandemic has triggered and expanded AMR diffusion all over the world, and its clinical and therapeutic features have changed. Thus, we aimed to review evidence from the literature on the definition and causative agents of AMR in the frame of the COVID-19 post-pandemic era. Methods: We conducted a search on PubMed and Medline for original articles, reviews, meta-analyses, and case series using the following keywords, their acronyms, and their associations: antibiotics, antimicrobial resistance, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), COVID-19 pandemic, personal protective equipment. Results: AMR had a significant rise in incidence both in in-hospital and outpatient populations (ranging from 5 up to 50%) worldwide, but with a variegated profile according to the germ and microorganism considered. Not only bacteria but also fungi have developed more frequent and diffuse AMR. These findings are explained by the increased use and misuse of antibiotics and preventive measures during the first waves of the SARS-CoV2 pandemic, especially in hospitalized patients. Subsequently, the reduction in and end of the lockdown and the use of personal protective equipment have allowed for the indiscriminate circulation of resistant microorganisms from low-income countries to the rest of the world with the emergence of new multi- and polyresistant organisms. However, there is not a clear association between COVID-19 and AMR changes in the post-pandemic period. Conclusions: AMR in some microorganisms has significantly increased and changed its characteristics during and after the end of the pandemic phase of COVID-19. An integrated supranational monitoring approach to this challenge is warranted in the years to come. In detail, a rational, personalized, and regulated use of antibiotics and antimicrobials is needed.
]]>Antibiotics doi: 10.3390/antibiotics13030232
Authors: Ognjen Ožegić Branka Bedenić Sunčanica Ljubin Sternak Mario Sviben Jasminka Talapko Iva Pažur Ivana Škrlec Ivan Segedi Tomislav Meštrović
Antimicrobial resistance (AMR) poses a global threat, leading to increased mortality and necessitating urgent action—however, its impact on athletes and the world of sports has hitherto been neglected. Sports environments (including athletic and aquatic) exhibit high levels of microbial contamination, potentially contributing to the spread of resistant microorganisms during physical activities. Moreover, the literature suggests that travel for sports events may lead to changes in athletes’ gut microbiomes and potentially impact their antibiotic resistance profiles, raising questions about the broader implications for individual and public/global health. The prevalence of Staphylococcus aureus (S. aureus) among athletes (particularly those engaged in contact or collision sports) ranges between 22.4% and 68.6%, with MRSA strains being isolated in up to 34.9% of tested individuals. Factors such as training frequency, equipment sharing, delayed post-training showers, and a history of certain medical conditions are linked to higher colonization rates. Moreover, MRSA outbreaks have been documented in sports teams previously, highlighting the importance of implementing preventive measures and hygiene protocols in athletic settings. In light of the growing threat of AMR, there is a critical need for evidence-based treatment guidelines tailored to athletes’ unique physiological demands to ensure responsible antibiotic use and mitigate potential health risks. While various initiatives—such as incorporating AMR awareness into major sporting events—aim to leverage the broad audience of sports to communicate the importance of addressing AMR, proactive measures (including improved AMR surveillance during large sporting events) will be indispensable for enhancing preparedness and safeguarding both athletes’ and the general public’s health. This narrative review thoroughly assesses the existing literature on AMR and antibiotic usage in the context of sports, aiming to illuminate areas where information may be lacking and underscoring the significance of promoting global awareness about AMR through sports.
]]>Antibiotics doi: 10.3390/antibiotics13030231
Authors: Idan Hefetz Rita Bardenstein Shahar Rotem Galia Zaide Gal Bilinsky Ohad Shifman Oren Zimhony Ronit Aloni-Grinstein
Bloodstream infections (BSI) are defined by the presence of viable bacteria or fungi, accompanied by systemic signs of infection. Choosing empirical therapy based solely on patient risk factors and prior antibiotic susceptibility test (AST) may lead to either ineffective treatment or unnecessarily broad-spectrum antibiotic exposure. In general, Clinical & Laboratory Standards Institute guideline-approved ASTs have a turnaround time of 48–72 h from sample to answer, a period that may result in a critical delay in the appropriate selection of therapy. Therefore, reducing the time required for AST is highly advantageous. We have previously shown that our novel rapid AST method, MAPt (Micro-Agar-PCR-test), accurately identifies susceptibility profiles for spiked bioterrorism agents like Bacillus anthracis, Yersinia pestis and Francisella tularensis directly from whole-blood and blood culture samples, even at low bacterial levels (500 CFU/mL). This study evaluated the performance of MAPt on routine bloodstream infection (BSI), focusing on Escherichia coli and Klebsiella pneumoniae isolates from clinical cultures, including resistant strains to some of the six tested antibiotics. Notably, MAPt yielded results exceeding 95% agreement with the standard hospital method within a significantly shorter timeframe of 6 h. These findings suggest significant potential for MAPt as a rapid and reliable BSI management tool.
]]>Antibiotics doi: 10.3390/antibiotics13030230
Authors: Oumaima Boutoub Soukaina El-Guendouz Isabel Matos Lahsen El Ghadraoui Maria Clara Costa Jorge Dias Carlier Maria Leonor Faleiro Ana Cristina Figueiredo Letícia M. Estevinho Maria Graça Miguel
Although the plants of the genus Euphorbia are largely exploited by therapists in Morocco, the composition and antibacterial activities of propolis from these plants are still unknown. To address this gap, this study aimed to characterize the pollen type, the volatile compounds, and the phenolic and mineral profiles of three Euphorbia propolis samples collected in Morocco and evaluate their antimicrobial activities. The minimum inhibitory concentration of the propolis samples was determined by the microdilution method, and the anti-adherence activity was evaluated by the crystal violet assay. The examination of anti-quorum-sensing proprieties was performed using the biosensor Chromobacterium violaceum CV026. Pollen analysis revealed that Euphorbia resinifera pollen dominated in the P1 sample (58%), while E. officinarum pollen dominated in the P2 and P3 samples (44%). The volatile compounds were primarily composed of monoterpene hydrocarbons, constituting 35% in P1 and 31% in P2, with α-pinene being the major component in both cases, at 16% in P1 and 15% in P2. Calcium (Ca) was the predominant mineral element in both E. resinifera (P1) and E. officinarum (P2 and P3) propolis samples. Higher levels of phenols, flavonoids and dihydroflavonoids were detected in the E. officinarum P2 sample. The minimum inhibitory concentration (MIC) value ranged from 50 to 450 µL/mL against Gram-positive and Gram-negative bacteria. Euphorbia propolis displayed the ability to inhibit quorum sensing in the biosensor C. violaceum CV026 and disrupted bacterial biofilm formation, including that of resistant bacterial pathogens. In summary, the current study evidences the potential use of E. officinarum propolis (P2 and P3) to combat important features of resistant pathogenic bacteria, such as quorum sensing and biofilm formation.
]]>Antibiotics doi: 10.3390/antibiotics13030229
Authors: Carlos Arturo Álvarez-Moreno Laura Cristina Nocua-Báez Guillermo Ortiz Juan Carlos Torres Gabriel Montenegro Williams Cervera Luis Fernando Zuluaga Alonso Gómez
Introduction: The objective of this study was to compare the continuous infusion of cefepime with the intermittent infusion in patients with sepsis caused by Gram-negative bacilli (GNB). Methods: Randomized 1:1 multicenter double-blinded placebo-controlled study with allocation concealment; multicenter study in the intensive care units of Colombia. Patients with sepsis, severe sepsis or septic shock, and GNB-suspected bacteremia. Cefepime was administered for 7 to 14 days over 30 m intermittently every 8 h over 24 h plus continuous saline solution (0.9%) (G1) or 3 g administered continuously plus saline solution every 8 h (0.9%) (G2). The percentage of clinical response at 3, 7, and 14 days, relapse at 28 days, and mortality at discharge were measured. Results: The recruitment was stopped at the suggestion of the Institutional Review Board (IRB) following an FDA alert about cefepime. Thirty-two patients were randomized; 25 received the intervention, and GNB bacteremia was confirmed in 16 (9 G1 and 7 G2). Favorable clinical response in days 3, 7, and 14 was 88.8%, 88.8%, and 77.8% (G1) and was similar for G2 (85.7%). There were no relapses or deaths in G2, while in G1, one relapse and two deaths were observed. Conclusions: The results of this study support the use of cefepime for the treatment of Gram-negative infections in critically ill patients, but we could not demonstrate differences between continuous or intermittent administration because of the small sample size, given the early suspension of the study.
]]>Antibiotics doi: 10.3390/antibiotics13030228
Authors: Xuanxuan Ma Na Yang Ruoyu Mao Ya Hao Da Teng Yinhua Huang Jianhua Wang
Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid–glycolic acid (PLGA)–polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion–solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity against Staphylococcus epidermidis (S. epidermidis) (4–8 μg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population of S. epidermidis G4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused by S. epidermidis.
]]>Antibiotics doi: 10.3390/antibiotics13030227
Authors: Akela Ghazawi Nikolaos Strepis Febin Anes Dana Yaaqeib Amal Ahmed Aysha AlHosani Mirah AlShehhi Ashrat Manzoor Ihab Habib Nisar A. Wani John P. Hays Mushtaq Khan
Addressing the emergence of antimicrobial resistance (AMR) poses a significant challenge in veterinary and public health. In this study, we focused on determining the presence, phenotypic background, and genetic epidemiology of plasmid-mediated colistin resistance (mcr) in Escherichia coli bacteria isolated from camels farmed in the United Arab Emirates (UAE). Fecal samples were collected from 50 camels at a Dubai-based farm in the UAE and colistin-resistant Gram-negative bacilli were isolated using selective culture. Subsequently, a multiplex PCR targeting a range of mcr-genes, plasmid profiling, and whole-genome sequencing (WGS) were conducted. Eleven of fifty camel fecal samples (22%) yielded colonies positive for E. coli isolates carrying the mcr-1 gene on mobile genetic elements. No other mcr-gene variants and no chromosomally located colistin resistance genes were detected. Following plasmid profiling and WGS, nine E. coli isolates from eight camels were selected for in-depth analysis. E. coli sequence types (STs) identified included ST7, ST21, ST24, ST399, ST649, ST999, and STdaa2. Seven IncI2(delta) and two IncX4 plasmids were found to be associated with mcr-1 carriage in these isolates. These findings represent the first identification of mcr-1-carrying plasmids associated with camels in the Gulf region. The presence of mcr-1 in camels from this region was previously unreported and serves as a novel finding in the field of AMR surveillance.
]]>Antibiotics doi: 10.3390/antibiotics13030226
Authors: Diego Garcia Miranda Florence Carrouel Tatiane Cristina Alberti Silva Mariana Cafalchio Rozzatto Amjad Abu Hasna Carlos Eduardo Rocha Santos Flavia Villaça Morais Luciane Dias de Oliveira Lucas de Paula Ramos
(1) Background: In hospitals, medical and dental clinics, antiseptics or disinfectants play an essential role in the control of nosocomial infections. This study aimed to evaluate R. officinalis and P. paniculata glycolic extracts regarding: (I) their antimicrobial action on planktonic and biofilm (monotypic and cutaneous biofilm model—S. aureus, S. epidermidis and C. acnes); and (II) their cytotoxicity on human keratinocytes (HaCaT). (2) Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were performed (CLSI protocol M7-A6 and M11-A8). MTT analysis was used to evaluate the antibiofilm activity of the extracts on biofilms and their cytotoxicity on human keratinocytes. (3) Results: The combined glycolic extracts MIX A (75% P. paniculata + 25% R. officinalis); MIX B (50% P. paniculata + 50% R. officinalis); and MIX C (25% P. paniculata + 75% R. officinalis) promoted MBC values by 50 mg/mL on S. aureus, absent on S. epidermidis, and ranged 6.25–50 mg/mL for C. acnes. The cutaneous biofilm model was reduced more than 90%. In addition, it showed biocompatibility with human keratinocytes, resulting in percentages of viability greater than 50%. (4) Conclusions: The combination of extracts promoted antimicrobial action on planktonic cultures, and monotypic and heterotypic biofilms of skin pathogens. Additionally, these extracts are biocompatible against human keratinocytes.
]]>Antibiotics doi: 10.3390/antibiotics13030225
Authors: Dhary Alewy Almashhadany Abdulwahed Ahmed Hassan Rzgar Farooq Rashid Amir Abdulmawjood Izhar U. H. Khan
The excessive and uncontrolled application of antibiotics in the fish farming industry, coupled with a lack of health monitoring and medication practices, is a driving force behind the escalating development of antimicrobial resistance. The present study assessed and compared qualitative field diffusion (QFD) and disk diffusion (DD) assays for the detection of antimicrobial residues (ARs) in diverse freshwater aquaculture fish. A total of 380 freshwater aquaculture fish (160 fresh and 180 frozen) samples were systematically collected between January and June 2021 from various retail stores located in Erbil Governorate, Iraq. Based on QFDA results, overall, ARs were detected (52; 15.3%) at a relatively lower frequency with comparatively higher frequency (21; 31.1%) in fresh than (31; 17.2%) frozen fish samples. On the other hand, DDA also revealed a comparable (45; 13.2%) prevalence rate of ARs. However, a low detection was observed more in fresh (17; 10.6%) than frozen (28; 15.6%) fish samples. Moreover, no statistically significant disparity (χ2 = 0.069; p = 0.79) between two assays and types of fish was recorded. In conclusion, the results of the present study showed that detecting a considerable frequency of ARs in these fish samples raises concerns about potential threats to public health. This underscores the necessity for understanding antibiotic application in aquaculture and its potential connection to antibiotic resistance in bacterial pathogens. Such comprehension is pivotal for formulating and implementing effective control and farm management strategies to address this pressing issue.
]]>Antibiotics doi: 10.3390/antibiotics13030224
Authors: Md. Kaisar Rahman Ryan B. Williams Samuel Ajulo Gizem Levent Guy H. Loneragan Babafela Awosile
The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34–3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81–0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06–5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39–67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae.
]]>Antibiotics doi: 10.3390/antibiotics13030223
Authors: Chyer Kim Allissa Riley Shobha Sriharan Theresa Nartea Eunice Ndegwa Ramesh Dhakal Guolu Zheng Claire Baffaut
While environmental factors may contribute to antimicrobial resistance (AMR) in bacteria, many aspects of environmental antibiotic pollution and resistance remain unknown. Furthermore, the level of AMR in Escherichia coli is considered a reliable indicator of the selection pressure exerted by antimicrobial use in the environment. This study aimed to assess AMR variance in E. coli isolated from diverse environmental samples, such as animal feces and water from wastewater treatment plants (WWTPs) and drainage areas of different land use systems in Central Virginia. In total, 450 E. coli isolates obtained between August 2020 and February 2021 were subjected to susceptibility testing against 12 antimicrobial agents approved for clinical use by the U.S. Food and Drug Administration. Approximately 87.8% of the tested isolates were resistant to at least one antimicrobial agent, with 3.1% showing multi-drug resistance. Streptomycin resistance was the most common (73.1%), while susceptibility to chloramphenicol was the highest (97.6%). One isolate obtained from WWTPs exhibited resistance to seven antimicrobials. AMR prevalence was the highest in WWTP isolates, followed by isolates from drainage areas, wild avians, and livestock. Among livestock, horses had the highest AMR prevalence, while cattle had the lowest. No significant AMR difference was found across land use systems. This study identifies potential AMR hotspots, emphasizing the environmental risk for antimicrobial resistant E. coli. The findings will aid policymakers and researchers, highlighting knowledge gaps in AMR–environment links. This nationally relevant research offers a scalable AMR model for understanding E. coli ecology. Further large-scale research is crucial to confirm the environmental impacts on AMR prevalence in bacteria.
]]>Antibiotics doi: 10.3390/antibiotics13030222
Authors: Fátima Cerqueira Rui Medeiros Inês Lopes Carla Campos Maria Pia Ferraz Fernando Silva Luís G. Alves Eugénia Pinto
The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.
]]>Antibiotics doi: 10.3390/antibiotics13030221
Authors: Robert Penchovsky Antoniya V. Georgieva Vanya Dyakova Martina Traykovska Nikolet Pavlova
This review is focused on antisense and functional nucleic acid used for completely rational drug design and drug target assessment, aiming to reduce the time and money spent and increase the successful rate of drug development. Nucleic acids have unique properties that play two essential roles in drug development as drug targets and as drugs. Drug targets can be messenger, ribosomal, non-coding RNAs, ribozymes, riboswitches, and other RNAs. Furthermore, various antisense and functional nucleic acids can be valuable tools in drug discovery. Many mechanisms for RNA-based control of gene expression in both pro-and-eukaryotes and engineering approaches open new avenues for drug discovery with a critical role. This review discusses the design principles, applications, and prospects of antisense and functional nucleic acids in drug delivery and design. Such nucleic acids include antisense oligonucleotides, synthetic ribozymes, and siRNAs, which can be employed for rational antibacterial drug development that can be very efficient. An important feature of antisense and functional nucleic acids is the possibility of using rational design methods for drug development. This review aims to popularize these novel approaches to benefit the drug industry and patients.
]]>Antibiotics doi: 10.3390/antibiotics13030220
Authors: Diego E. Navarro-López Yocanxóchitl Perfecto-Avalos Araceli Zavala Marco A. de Luna Araceli Sanchez-Martinez Oscar Ceballos-Sanchez Naveen Tiwari Edgar R. López-Mena Gildardo Sanchez-Ante
The rise in antibiotic-resistant bacteria is a global health challenge. Due to their unique properties, metal oxide nanoparticles show promise in addressing this issue. However, optimizing these properties requires a deep understanding of complex interactions. This study incorporated data-driven machine learning to predict bacterial survival against lanthanum-doped ZnO nanoparticles. The effect of incorporation of lanthanum ions on ZnO was analyzed. Even with high lanthanum concentration, no significant variations in structural, morphological, and optical properties were observed. The antibacterial activity of La-doped ZnO nanoparticles against Gram-positive and Gram-negative bacteria was qualitatively and quantitatively evaluated. Nanoparticles induce 60%, 95%, and 55% bacterial death against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, respectively. Algorithms such as Multilayer Perceptron, K-Nearest Neighbors, Gradient Boosting, and Extremely Random Trees were used to predict the bacterial survival percentage. Extremely Random Trees performed the best among these models with 95.08% accuracy. A feature relevance analysis extracted the most significant attributes to predict the bacterial survival percentage. Lanthanum content and particle size were irrelevant, despite what can be assumed. This approach offers a promising avenue for developing effective and tailored strategies to reduce the time and cost of developing antimicrobial nanoparticles.
]]>Antibiotics doi: 10.3390/antibiotics13030219
Authors: Hajime Nakashima Motoyasu Miyazaki Tsuneo Kuwamura Kazutaka Oda Yumi Haga Osamu Imakyure
Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02–245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.
]]>Antibiotics doi: 10.3390/antibiotics13030218
Authors: Gloria Zaragoza María Pérez-Vázquez Laura Villar-Gómara Andrea González-Prieto Jesús Oteo-Iglesias Juan-Ignacio Alós
Escherichia coli isolates that are resistant to cefixime and amoxicillin/clavulanic acid, but apparently susceptible to cefuroxime, with no ESBL identified, were initially detected in Madrid from urine samples in 2019. Throughout 2020 and 2021, all cases of community UTI by E. coli from six health areas in Madrid were studied. A representative sample of 23 cases was selected for further studies. The broth microdilution method and the agar diffusion method were performed to determine the antibiotic susceptibility. WGS was carried out for phylogeny, resistome and virulome analysis. Community consumption of third-generation oral cephalosporins in Madrid (2017–2021) was analyzed. A total of 582 (1.3%) E. coli isolates had the mentioned resistance profile. The mutation at position –32 (T > A) of the AmpC promoter was found in 21 isolates. No plasmid AmpC- or ESBL-encoding genes were detected. A cluster of 20 ST12 isolates was detected by cgMLST. A 6.2% increase in the consumption of third-generation oral cephalosporins, especially cefixime, was observed in Madrid. Chromosomal AmpC-hyperproducing ST12 E. coli isolates could be implicated in the increase in community UTI cases by cefixime-resistant isolates, which correlates with an increasing trend of cefixime consumption.
]]>Antibiotics doi: 10.3390/antibiotics13030216
Authors: Ibraheem Altamimi Khalifa Binkhamis Abdullah Alhumimidi Ibrahim M. Alabdulkarim Abdulrahman Almugren Hadi Alhemsi Abdulaziz Altamimi Abeer Almazyed Seham Elbih Razan Alghunaim Abdullah Altamimi
The COVID-19 pandemic has led to significant changes in healthcare practices, including increased antibiotic usage. This study aimed to investigate the impact of the pandemic on the prevalence of extended-spectrum β-lactamase (ESBL) production and carbapenem resistance among key bacterial species causing urinary tract infections (UTIs). Conducted at King Fahad Medical City in Riyadh from January 2018 to December 2022, the study analyzed urine samples from 9697 UTI patients. Patients were categorized into ‘pre-COVID-19’ and ‘during COVID-19’ groups. Bacterial isolates were identified, and antimicrobial susceptibility testing was performed following guidelines. ESBL production was detected using the Double-Disc Synergy Test. Escherichia coli and Klebsiella pneumoniae were the main pathogens. During the pandemic, ESBL production decreased in E. coli by 1.9% and in K. pneumoniae by 6.0%. Carbapenem resistance also declined, with E. coli displaying a 1.2% reduction and K. pneumoniae and Pseudomonas aeruginosa displaying 10.7% and 7.9% reductions, respectively. Notably, logistic regression analysis revealed that the odds of ESBL presence were 10% lower during the COVID-19 pandemic (OR 0.91; 95% CI 0.83–0.99; p = 0.040), and there was a significant reduction in the odds of carbapenem resistance (OR 0.43; 95% CI 0.37–0.51; p < 0.001). This study reveals a significant decrease in ESBL production and carbapenem resistance among UTI pathogens during the COVID-19 pandemic, hinting at the impact of modified antibiotic and healthcare approaches. It emphasizes the need for persistent antimicrobial resistance surveillance and policy adaptation to address resistance challenges, offering key directions for future public health actions.
]]>Antibiotics doi: 10.3390/antibiotics13030217
Authors: Yuxin Gong Qing Peng Yu Qiao Dandan Tian Yuwei Zhang Xiaoyan Xiong Mengxin He Xiaoqing Xu Bo Shi
In recent years, traditional antibiotic efficacy outcomes have rapidly diminished due to the advent of drug resistance, and the dose limitation value has increased due to the severe side effect of globalized healthcare. Therefore, novel strategies are required to resensitize resistant pathogens to antibiotics existing in the field and prevent the emergence of drug resistance. In this study, cationic hyperbranched polylysine (HBPL-6) was synthesized using the one-pot polymerization method. HBPL-6 exhibited excellent non-cytotoxicity and bio-solubility properties. The present study also showed that HBPL-6 altered the outer membrane (OM) integrity of Escherichia coli O157:H7, Salmonella typhimurium, and Pseudomonas aeruginosa PAO1 by improving their permeability levels. When administered at a safe dosage, HBPL-6 enhanced the accumulation of rifampicin (RIF) and erythromycin (ERY) in bacteria to restore the efficacy of the antibiotics used. Moreover, the combination of HBPL-6 with colistin (COL) reduced the antibiotic dosage, which was helpful in preventing further drug-resistance outcomes. Therefore, this research provides a new strategy for reducing the dosage of drugs used to combat Gram-negative (G−) bacteria through their synergistic effects.
]]>Antibiotics doi: 10.3390/antibiotics13030215
Authors: Javiera Parada Gonzalo Tortella Amedea B. Seabra Paola Fincheira Olga Rubilar
Copper oxide nanoparticles (NCuO) have emerged as an alternative to pesticides due to their antifungal effect against various phytopathogens. Combining them with fungicides represents an advantageous strategy for reducing the necessary amount of both agents to inhibit fungal growth, simultaneously reducing their environmental release. This study aimed to evaluate the antifungal activity of NCuO combined with three fungicide models separately: Iprodione (IPR), Tebuconazole (TEB), and Pyrimethanil (PYR) against two phytopathogenic fungi: Botrytis cinerea and Fusarium oxysporum. The fractional inhibitory concentration (FIC) was calculated as a synergism indicator (FIC ≤ 0.5). The NCuO interacted synergistically with TEB against both fungi and with IPR only against B. cinerea. The interaction with PYR was additive against both fungi (FIC > 0.5). The B. cinerea biomass was inhibited by 80.9% and 93% using 20 mg L−1 NCuO + 1.56 mg L−1 TEB, and 40 mg L−1 NCuO + 12 µg L−1 IPR, respectively, without significant differences compared to the inhibition provoked by 160 mg L−1 NCuO. Additionally, the protein leakage and nucleic acid release were also evaluated as mechanisms associated with the synergistic effect. The results obtained in this study revealed that combining nanoparticles with fungicides can be an adequate strategy to significantly reduce the release of metals and agrochemicals into the environment after being used as antifungals.
]]>Antibiotics doi: 10.3390/antibiotics13030214
Authors: Tatjana Mrvič Sintija Stevanoska Bojana Beović Mateja Logar Sergeja Gregorčič Benica Žnidaršič Katja Seme Ivana Velimirović Nataša Švent Kučina Polona Maver Vodičar Veronika Križan Hergouth Sašo Džeroski Mateja Pirs
The COVID-19 pandemic has strained healthcare systems globally. Shortages of hospital beds, reassignment of healthcare workers to COVID-19-dedicated wards, an increased workload, and evolving infection prevention and control measures have potentially contributed to the spread of multidrug-resistant bacteria (MDRB). To determine the impact of the COVID-19 pandemic at the University Medical Center Ljubljana, a tertiary teaching hospital, we analyzed the monthly incidence of select bacterial species per patient from 2018 to 2022. The analysis was performed for all isolates and for MDRB isolates. The data were analyzed separately for isolates from all clinical samples, from blood culture only, and from clinical and surveillance samples. Our findings revealed an increased incidence density of patients with Enterococcus faecium, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa isolates from clinical samples during the COVID-19 period in the studied hospital. Notably, the incidence density of MDRB isolates—vancomycin-resistant E. faecium, extended-spectrum betalactamase-producing K. pneumoniae, and betalactam-resistant P. aeruginosa—from clinical samples increased during the COVID-19 period. There were no statistically significant differences in the incidence density of patients with blood culture MDRB isolates. We observed an increase in the overall MDRB burden (patients with MDRB isolates from both clinical and surveillance samples per 1000 patient days) in the COVID-19 period in the studied hospital for vancomycin-resistant E. faecium, carbapenem-resistant K. pneumoniae, and betalactam-resistant P. aeruginosa and a decrease in the methicillin-resistant S. aureus burden.
]]>Antibiotics doi: 10.3390/antibiotics13030213
Authors: Luz Abarca-Coloma Miguel Puga-Tejada Tamara Nuñez-Quezada Otilia Gómez-Cruz Carlos Mawyin-Muñoz Shivan Barungi Macarena Perán
Antibiotic overuse and the resulting antimicrobial resistance pose significant global public health challenges, providing an avenue for opportunistic pathogens like Acinetobacter baumannii to thrive. This study will report the trends of Acinetobacter baumannii antimicrobial resistance patterns at the Hospital Teodoro Maldonado Carbo, Ecuador. An observational, analytical, longitudinal, and prospective study was conducted involving patients diagnosed with hospital-acquired infections. Antimicrobial susceptibility testing was performed, followed by molecular analysis of carbapenemase genes in Acinetobacter baumannii isolates. We included 180 patients aged from 16 to 93 years. The hospital mortality rate was 63/180 (35%). Invasive mechanical ventilation (IMV) was indicated in 91/180 patients (50.4%). The overall survival (OS) rate in patients on IMV was 49.5% (45/91), with a median survival of 65 days. The OS rate in patients not on IMV was 80.9% (72/89), with a median survival of 106 days (HR 2.094; 95% CI 1.174–3.737; p = 0.012). From multivariate analysis, we conclude that ventilator-associated pneumonia is the most related factor to OS.
]]>Antibiotics doi: 10.3390/antibiotics13030212
Authors: Ilinca Margareta Vlad Diana Camelia Nuță Miron Theodor Căproiu Florea Dumitrașcu Eleonóra Kapronczai Georgiana Ramona Mük Speranta Avram Adelina Gabriela Niculescu Irina Zarafu Vanesa Alexandra Ciorobescu Ana Maria Brezeanu Carmen Limban
N-acyl hydrazone (NAH) is recognized as a promising framework in drug design due to its versatility, straightforward synthesis, and attractive range of biological activities, including antimicrobial, antitumoral, analgesic, and anti-inflammatory properties. In the global context of increasing resistance of pathogenic bacteria to antibiotics, NAHs represent potential solutions for developing improved treatment alternatives. Therefore, this research introduces six novel derivatives of (EZ)-N’-benzylidene-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide, synthesized using a microwave-assisted method. In more detail, we joined two pharmacophore fragments in a single molecule, represented by an NSAID-type carprofen structure and a hydrazone-type structure, obtaining a new series of NSAID-N-acyl hydrazone derivatives that were further characterized spectrally using FT-IR, NMR, and HRMS investigations. Additionally, the substances were assessed for their tuberculostatic activity by examining their impact on four strains of M. tuberculosis, including two susceptible to rifampicin (RIF) and isoniazid (INH), one susceptible to RIF and resistant to INH, and one resistant to both RIF and INH. The results of our research highlight the potential of the prepared compounds in fighting against antibiotic-resistant M. tuberculosis strains.
]]>Antibiotics doi: 10.3390/antibiotics13030211
Authors: Sumaira Khadim Iyad Naeem Muhammad Tanveer Alam Shahnaz Usman Hina Rehman Sajjad Haider
Growing antibiotic resistance complicates H. pylori eradication, posing a public health challenge. Inconclusive research on sociodemographic and clinical factors emphasizes the necessity for further investigations. Hence, this study aims to evaluate the correlation between demographic and clinical factors and the success rates of H. pylori eradication. A group of 162 H. pylori-positive patients were allocated randomly to receive either a ten-day moxifloxacin-based triple therapy or a levofloxacin-based sequential therapy. Eradication success was determined through the stool antigen test. Logistic regression analysis was utilized to figure out potential factors that contribute to H. pylori eradication success. Significantly higher H. pylori eradication rates were observed in the middle age group (COR: 3.671, p = 0.007), among females (p = 0.035), those with BMI ≥ 25 (COR: 2.011, p = 0.045), and non-smokers (COR: 2.718, p = 0.018). In multivariate analysis, age and smoking emerged as significant predictors (p < 0.05). Patients with comorbidities, excluding diabetes and hypertension (COR: 4.432, p = 0.019), dyspepsia (COR: 0.178, p < 0.001), and moxifloxacin triple therapy (COR: 0.194, p = 0.000), exhibited higher chances of eradication (p < 0.05). Further research is vital for tailored approaches to enhance eradication success.
]]>Antibiotics doi: 10.3390/antibiotics13030210
Authors: Taciana Freire de Oliveira Taís Mayumi Kuniyoshi Elionio Galvão Frota Sebastián Bermúdez-Puga Letícia Naomy Sakaue Luara Lucena Cassiano Leonardo Tachibana Rosane Aparecida Moniz Piccoli Attilio Converti Ricardo Pinheiro de Souza Oliveira
Listeria monocytogenes is a foodborne pathogen that contaminates food-processing environments and persists within biofilms on equipment, thus reaching final products by cross-contamination. With the growing demand for clean-label products, the search for natural antimicrobials as biopreservants, such as bacteriocins, has shown promising potential. In this context, this study aimed to evaluate the anti-listerial action of bacteriocins produced by Enterococcus lactis LBM BT2 in an alternative medium containing sugarcane molasses (SCM). Molecular analyses were carried out to characterize the strain, including the presence of bacteriocin-related genes. In the kinetic study on SCM medium E. lactis, LBM BT2 showed biomass and bacteriocin productions similar to those observed on a sucrose-based medium (control), highlighting the potential of the sugarcane molasses as a low-cost substrate. Stability tests revealed that the molecule remained active in wide ranges of pH (4–10) and temperature (60–100 °C). Furthermore, the proteolytic treatment reduced the biomolecule’s antimicrobial activity, highlighting its proteinaceous nature. After primary purification by salting out and tangential flow filtration, the bacteriocin-like inhibitory substance (BLIS) showed bacteriostatic activity on suspended L. monocytogenes cells and against biofilm formation at a concentration of 0.625 mg/mL. These results demonstrate the potential of the produced BLIS as a biopreservative in the food industry.
]]>Antibiotics doi: 10.3390/antibiotics13030209
Authors: Eric J. Bryan Qi Qiao Yuxuan Wang Jacques Y. Roberge Edmond J. LaVoie Daniel S. Pilch
The global threat of multidrug-resistant Gram-negative bacterial pathogens necessitates the development of new and effective antibiotics. FtsZ is an essential and highly conserved cytoskeletal protein that is an appealing antibacterial target for new antimicrobial therapeutics. However, the effectiveness of FtsZ inhibitors against Gram-negative species has been limited due in part to poor intracellular accumulation. To address this limitation, we have designed a FtsZ inhibitor (RUP4) that incorporates a chlorocatechol siderophore functionality that can chelate ferric iron (Fe3+) and utilizes endogenous siderophore uptake pathways to facilitate entry into Gram-negative pathogens. We show that RUP4 is active against both Klebsiella pneumoniae and Acinetobacter baumannii, with this activity being dependent on direct Fe3+ chelation and enhanced under Fe3+-limiting conditions. Genetic deletion studies in K. pneumoniae reveal that RUP4 gains entry through the FepA and CirA outer membrane transporters and the FhuBC inner membrane transporter. We also show that RUP4 exhibits bactericidal synergy against K. pneumoniae when combined with select antibiotics, with the strongest synergy observed with PBP2-targeting β-lactams or MreB inhibitors. In the aggregate, our studies indicate that incorporation of Fe3+-chelating moieties into FtsZ inhibitors is an appealing design strategy for enhancing activity against Gram-negative pathogens of global clinical significance.
]]>Antibiotics doi: 10.3390/antibiotics13030208
Authors: Elliot Simpson Humera Sarwar Iain Jack Deborah Lowry
Chitosan nanoparticle delivery systems have the potential for enhancing bone healing and addressing osteomyelitis. The objective was to deliver antimicrobial agents capable of preventing or treating osteomyelitis. Each formulation was optimized to achieve desired characteristics in terms of size (ranging from 100 to 400 nm), PDI (less than 0.5), zeta potential (typically negative), and in vitro release profiles for gentamicin. Entrapment percentages varied with gentamicin ranging from 10% to 65%. The chitosan nanoparticles exhibited substantial antimicrobial efficacy, particularly against P. aeruginosa and MRSA, with zones of inhibition ranging from 13 to 24 mm and a complete reduction in colony forming units observed between 3 and 24 h. These chitosan nanoparticle formulations loaded with antimicrobials hold promise for addressing orthopedic complications.
]]>Antibiotics doi: 10.3390/antibiotics13030207
Authors: Bakhtiyar Mahmood Ana Paunkov Malgorzata Kupc Katalin Burián Elisabeth Nagy David Leitsch József Sóki
Previously, we reported that metronidazole MICs are not dependent on the expression levels of nim genes in B. fragilis strains and we compared the proteomes of metronidazole-resistant laboratory B. fragilis strains to those of their susceptible parent strains. Here, we used RT-qPCR to correlate the expression levels of 18 candidate genes in a panel of selected, clinical nim gene-positive and -negative B. fragilis strains to their metronidazole MICs. Metronidazole MICs were correlated with the expression of certain tested genes. Specifically, lactate dehydrogenase expression correlated positively, whereas cytochrome fumarate reductase/succinate dehydrogenase, malate dehydrogenase, phosphoglycerate kinase redox and gat (GCN5-like acetyltransferase), and relA (stringent response) regulatory gene expressions correlated negatively with metronidazole MICs. This result provides evidence for the involvement of carbohydrate catabolic enzymes in metronidazole resistance in B. fragilis. This result was supported by direct substrate utilization tests. However, the exact roles of these genes/proteins should be determined in deletion–complementation tests. Moreover, the exact redox cofactor(s) participating in metronidazole activation need to be identified.
]]>Antibiotics doi: 10.3390/antibiotics13030206
Authors: Yu Qiu Jorge Pinto Ferreira Riasat Wasee Ullah Peter Flanagan Muhammad Usman Zaheer Muhammad Farooq Tahir Javaria Alam Armando E. Hoet Junxia Song Muhammad Akram
The agriculture and food (agrifood) sectors play key roles in the emergence, spread, and containment of antimicrobial resistance (AMR). Pakistan’s first National Action Plan (NAP) on AMR was developed to guide One Health interventions to combat AMR through 2017–2022. To improve subsequent iterations, we assessed the implementation of Pakistan’s NAP in the agrifood sectors (NAPag) in October 2022, using the Progressive Management Pathway on AMR tool developed by the Food and Agriculture Organization of the United Nations (FAO). The assessment tool addressed four crucial focus areas of the NAPag: governance, awareness, evidence, and practices. Each focus area contains multiple topics, which involve four sequential stages of activities to progressively achieve systematic management of AMR risk in the agrifood sectors. High-level representatives of the NAPag stakeholders provided information for the assessment through pre-event documentary review and workshop discussions. The assessment results showed that Pakistan’s NAPag had an overall moderate coverage (59%) of the anticipated activities. Gaps were particularly notable in strengthening governance, good practices, and interventions in non-livestock sectors. Furthermore, only 12% of the evaluated activities were fully executed and documented, consistently remaining at the planning and piloting stages in the livestock sector across all the examined topics. Insufficient attention to non-livestock sectors, inadequate regulation and enforcement capacity, and resource constraints have hindered scalable and sustainable interventions under the current plan. This assessment provides valuable insights to strengthen the inclusiveness and contribution of the agrifood sectors in the next NAP iteration. In the short-to-medium term, strategic prioritization is necessary to optimize the use of limited resources and target the most critical gaps, such as improving awareness among key stakeholders and fortifying regulations for prudent antimicrobial use. In the long term, integration of AMR into the country’s broader health, development, and agricultural transformation agendas will be needed to generate sustainable benefits.
]]>Antibiotics doi: 10.3390/antibiotics13030205
Authors: Gabriel da Silva Oliveira Concepta McManus Vinícius Machado dos Santos
Pathogens, such as Escherichia coli (E. coli), have been identified as significant causes of poultry mortality. Poultry can serve as potential sources of E. coli transmission, even when asymptomatic, posing a substantial threat to food safety and human health. The in ovo administration of antimicrobials is crucial for preventing and/or effectively combating acute and chronic infections caused by poultry pathogens. To achieve this goal, it is critical that antimicrobials are properly injected into embryonic fluids, such as the amnion, to reach target tissues and trigger robust antimicrobial responses. Several protocols based on antimicrobials were evaluated to meet these requirements. This review analyzed the impacts of antimicrobial substances injected in ovo on the control of E. coli in poultry. The reduction in infection rates, resulting from the implementation of in ovo antimicrobials, combined with efforts aimed at hygienic-sanitary action plans in poultry sheds, reinforces confidence that E. coli can be contained before causing large scale damage. For example, antimicrobial peptides and probiotics have shown potential to provide protection to poultry against infections caused by E. coli. Issues related to the toxicity and bacterial resistance of many synthetic chemical compounds represent challenges that need to be overcome before the commercial application of in ovo injection protocols focused on microbiological control.
]]>Antibiotics doi: 10.3390/antibiotics13030204
Authors: Federico Scali Sandra Ganio Claudio Roullet Mauro Ruffier Stefania Bergagna Giulia Pagliasso Claudia Romeo Nicoletta Formenti Antonio Marco Maisano Giovanni Santucci Matteo Tonni Federica Guadagno Francesca Mazza Flavia Guarneri Giorgio Bontempi Loredana Candela Giovanni Loris Alborali
Optimising antimicrobial usage (AMU) in livestock is pivotal to counteract the emergence of antimicrobial resistance. We analysed AMU in more than 1000 cattle herds over 11 years (2008–2018) in the Aosta Valley (Italy), a region where 80% of farms house less than 50 cattle. Dairy cows accounted for over 95% of AMU. AMU was estimated using the defined daily dose animal for Italy (DDDAit) per biomass for the whole herd and a treatment incidence 100 (TI100) for cows. Average annual herd-level AMU was low, with 3.6 DDDAit/biomass (range: 3.2–4.0) and 1.2 TI100 in cows (range: 1.1–1.3). Third and fourth generation cephalosporins, which are critical for human medicine, represented almost 10% of usage, and intramammary antimicrobials accounted for over 60%. We detected significant downward temporal trends in total AMU, as well as a positive relationship with herd size. The magnitude of such effects was small, leaving scant room for further reduction. However, the frequent use of critical antimicrobials and intramammary products should be addressed, following the principles of prudent AMU. Our findings highlight the importance of monitoring AMU even in low-production, smallholding contexts where a low usage is expected, to identify any deficiencies and implement interventions for further AMU optimisation.
]]>Antibiotics doi: 10.3390/antibiotics13030203
Authors: Hassan Al Mana Hamad Abdel Hadi Godwin Wilson Muna A. Almaslamani Sulieman H. Abu Jarir Emad Ibrahim Nahla O. Eltai
Antimicrobial resistance (AMR) is a global healthcare challenge with substantial morbidity, mortality, and management costs. During the COVID-19 pandemic, there was a documented increase in antimicrobial consumption, particularly for severe and critical cases, as well as noticeable travel and social restriction measures that might influenced the spectrum of AMR. To evaluate the problem, retrospective data were collected on bacterial infections and antimicrobial susceptibility patterns in Qatar before and after the pandemic from 1 January 2019 to 31 December 2021, covering 53,183 pathogens isolated from reported infection episodes. The findings revealed a significant resistance pattern for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EBC), carbapenem-resistant Enterobacteriaceae (CR-EBC), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), ciprofloxacin-resistant Salmonella and methicillin-resistant Staphylococcus aureus (MRSA). For correlation with social restrictions, ESBL-EBC and MRSA were positively correlated with changing patterns of international travel (ρ = 0.71 and 0.67, respectively; p < 0.05), while CRPA was moderately correlated with the number of COVID-19 hospitalized patients (ρ = 0.49; p < 0.05). CREBC and CRPA respiratory infections were associated with hospitalized patients (OR: 3.08 and 2.00, respectively; p < 0.05). The findings emphasize the challenges experienced during the COVID-19 pandemic and links to international travel, which probably will influence the local epidemiology of AMR that needs further surveillance and control strategies.
]]>Antibiotics doi: 10.3390/antibiotics13030202
Authors: Galina Satchanska Slavena Davidova Alexandra Gergova
Antimicrobial peptides (AMPs) are usually made up of fewer than 100 amino acid residues. They are found in many living organisms and are an important factor in those organisms’ innate immune systems. AMPs can be extracted from various living sources, including bacteria, plants, animals, and even humans. They are usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi, and other pathogens. They can act against both Gram-negative and Gram-positive pathogens and have various modes of action against them. Some attack the pathogens’ membranes, while others target their intracellular organelles, as well as their nucleic acids, proteins, and metabolic pathways. A crucial area of AMP use is related to their ability to help with emerging antibiotic resistance: some AMPs are active against resistant strains and are susceptible to peptide engineering. This review considers AMPs from three key sources—plants, animals, and humans—as well as their modes of action and some AMP sequences.
]]>Antibiotics doi: 10.3390/antibiotics13030201
Authors: Dimitra Kostoglou Athina Vass Efstathios Giaouris
Campylobacter spp. are significant zoonotic agents, which cause annually millions of human cases of foodborne gastroenteritis worldwide. Their inclusion in biofilms on abiotic surfaces seems to play a pivotal role in their survival outside of the host, growth, and spread. To successfully mitigate the risks that arise with these bacteria, it is crucial to decrease their prevalence within the food production chain (from farm to the table), alongside the successful treatment of the resulting illness, known as campylobacteriosis. For this, the use of various antimicrobial agents remains actively in the foreground. A general-purpose biocide and cationic surfactant (benzalkonium chloride; BAC), a widely used macrolide antibiotic (erythromycin; ERY), and a naturally occurring organic acid (L(+)-lactic acid; LA) were comparatively evaluated in this work for their potential to inhibit both the planktonic and biofilm growth of 12 selected Campylobacter spp. (of which, seven were C. jejuni and five were C. coli) raw chicken meat isolates, all grown in vitro as monocultures. The inhibitory action of LA was also studied against four mixed-culture Campylobacter biofilms (each composed of three different isolates). The results showed that the individual effectiveness of the agents varied significantly depending on the isolate, growth mode (planktonic, biofilm), intercellular interactions (monocultures, mixed cultures), and the growth medium used (with special focus on blood presence). Thus, BAC exhibited minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), and minimum biofilm inhibitory concentrations (MBICs) that ranged from 0.5 to 16 μg/mL. Interestingly enough, these values varied widely from 0.25 to 1024 μg/mL for ERY. Concerning LA, the MICs, MBCs, and MBICs varied from 1024 to 4096 μg/mL, with mixed-culture biofilm formation always being more difficult to suppress when compared to biofilm monocultures. In addition, it was evident that intercellular interactions encountered within mixed-culture Campylobacter biofilms significantly influenced both the population dynamics and the tolerance of each consortium member to acid exposure. Overall, the findings of this study provide useful information on the comparative effectiveness of three well-known antimicrobial agents for the control of Campylobacter spp. under various growth modes (i.e., planktonic, biofilm, monocultures, mixed cultures) that could potentially be encountered in food production and clinical settings.
]]>Antibiotics doi: 10.3390/antibiotics13030200
Authors: Javier Blanco-Blanco María Bravo Irene Simón Pedro Fernández-Llario Miguel Fajardo-Olivares María Coronada Fernández-Calderón Rosario Cerrato
Antimicrobial resistance is a critical challenge due to the overuse of conventional antimicrobials, and alternative solutions are urgently needed. This study investigates the efficacy of compounds derived from lactic acid bacteria (LAB) fermentation combined with antibiotics against multidrug-resistant pathogens isolated from clinical cases in a hospital setting. Strains of Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium and faecalis were isolated and selected from blood, respiratory, and urine samples. They were tested against the fermentation products from the Ingulados LAB collection (BAL5, BAL6, BAL8, BAL13, and BAL16), recognized for their antimicrobial efficacy against veterinary pathogens. The activity against multidrug-resistant (MDR) pathogens was evaluated initially, followed by synergy tests using checkerboard assays and subsequent analysis. Bioinformatic assessments and supernatant treatments were performed to characterize the nature of the compounds responsible for the antimicrobial activity. Notably, BAL16 exhibited significant growth inhibition against multidrug-resistant E. faecium. Synergy tests highlighted its combined activity with tetracycline through FICI and surface analysis and bioinformatic analysis unveiled the protein fraction containing bacteriocins as the underlying mechanism. This study highlights BAL16 fermentation products potential as valuable antimicrobial agents against MDR E. faecium infections, attributed to bacteriocins. Further in-depth studies are necessary for complete bacteriocin characterization.
]]>Antibiotics doi: 10.3390/antibiotics13030199
Authors: Xiaoxia Li Zhi Chen Xiuwen Zhang Zimei Zhou Maureen Boost Taomin Huang Xingtao Zhou
Aims: The aims of this study are to investigate the etiology, microbiological spectrum, and risk factors associated with visual outcomes of fungal endophthalmitis (FE) in a tertiary eye specialty hospital in Shanghai, China. Methods: This was a retrospective, single-center case series. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. Logistic regression was used to analyze the factors related to visual outcomes. Results: This study involved 102 eyes of 92 patients with FE, including 63 males (66.3%). The mean age was 44.4 ± 19.8 years. The most common etiology of FE was trauma (56.5%). The predominant fungal species isolated were Aspergillus spp. (31/93, 33.3%). Pars plana vitrectomy (PPV) and intravitreal antifungal agents was performed initially in 86 (84.3%) and 83 (81.4%) eyes, respectively. Only 35 (34.3%) eyes achieved final best corrected visual acuity (BCVA) of 20/400 or better. Ten (9.8%) eyes had a final BCVA of light perception or worse, and five (4.9%) had to be enucleated. The factors determining better visual outcomes included initial visual acuity better than finger-counting (FC) (odds ratio (OR) 5.811, p = 0.036), the absence of corneal infiltrate (OR 10.131, p = 0.002), and Candida species infection (OR 6.325, p = 0.011). Conclusions: Early diagnosis of FE and a timely vitrectomy, combined with an intravitreal injection of an antifungal drug, can mitigate the devastating results of intraocular fungal infection. Not being infected by Aspergillus spp., an initial BCVA that was no worse than FC, and the absence of corneal involvement were related to better visual prognosis.
]]>Antibiotics doi: 10.3390/antibiotics13030198
Authors: Yasmin Youssef Elisabeth Roschke Nadine Dietze Anna-Judith Dahse Iris F. Chaberny Donald Ranft Christina Pempe Szymon Goralski Mohamed Ghanem Regine Kluge Christoph Lübbert Arne C. Rodloff Andreas Roth
Periprosthetic joint infections (PJI) are serious complications after arthroplasty, associated with high morbidity, mortality, and complex treatment processes. The outcomes of different PJI entities are largely unknown. The aim of this study was to access the early outcomes of different PJI entities. A retrospective, single-center study was conducted. The characteristics and outcomes of patients with PJI treated between 2018 and 2019 were evaluated 12 months after the completion of treatment. Primary endpoints were mortality, relapse free survival (RFS) and postoperative complications (kidney failure, sepsis, admission to ICU). A total of 115 cases were included [19.1% early (EI), 33.0% acute late (ALI), and 47.8% chronic infections (CI)]. Patients with ALI were older (p = 0.023), had higher ASA scores (p = 0.031), preoperative CRP concentrations (p = 0.011), incidence of kidney failure (p = 0.002) and sepsis (p = 0.026). They also tended towards higher in-house mortality (ALI 21.1%, 13.6% EI, 5.5% CI) and admission to ICU (ALI 50.0%, 22.7% EI, 30.9% CI). At 12 months, 15.4% of patients with EI had a relapse, compared to 38.1% in ALI and 36.4% in CI. There are differences in patient characteristics and early outcomes between PJI entities. Patients with EI have better early clinical outcomes. Patients with ALI require special attention during follow-up because they have higher occurrences of relapses and postoperative complications than patients with EI and CI.
]]>Antibiotics doi: 10.3390/antibiotics13030197
Authors: Aarman Sohaili Judith Asin Pierre P. M. Thomas
Antimicrobial resistance (AMR) jeopardizes the effectiveness of essential antimicrobial agents in treating infectious diseases. Accelerated by human activities, AMR is prevalent in Sub-Saharan Africa, including Kenya, due to indiscriminate antibiotic use and limited diagnostics. This study aimed to assess Kenya’s AMR efforts through a situational analysis of policy efficacy, interventions, and implementation, culminating in recommendations for strengthening mitigation. Employing two methodologies, this study evaluated Kenya’s AMR endeavors. A systematic scoping review summarized AMR dynamic, and an expert validated the findings, providing an on-the-ground perspective. Antibiotic resistance is driven by factors including widespread misuse in human medicine due to irrational practices, consumer demand, and substandard antibiotics. Heavy antibiotic use in the agricultural sector leads to contamination of the food chain. The National Action Plan (NAP) reflects a One Health approach, yet decentralized healthcare and funding gaps hinder its execution. Although AMR surveillance includes multiple facets, diagnostic deficiencies persist. Expert insights recognize proactive NAP but underscore implementation obstacles. Kenya grapples with escalating resistance, but commendable policy efforts exist. However, fragmented implementations and complexities persist. Addressing this global threat demands investment in healthcare infrastructure, diagnostics, international partnerships, and sustainable strategies.
]]>Antibiotics doi: 10.3390/antibiotics13030196
Authors: José R. Almeida
The pioneering medical application of peptides as therapeutics began approximately a century ago; however, they remain clinically relevant candidates garnering more attention on the drug development agenda [...]
]]>Antibiotics doi: 10.3390/antibiotics13020195
Authors: João Duarte Carolina Máximo Pedro Costa Vanessa Oliveira Newton C. M. Gomes Jesús L. Romalde Carla Pereira Adelaide Almeida
Urinary tract infections (UTIs) caused by resistant Klebsiella pneumoniae can lead to severe clinical complications and even death. An alternative treatment option for infected patients is using bacteriophages. In the present study, we isolated phage VB_KPM_KP1LMA (KP1LMA) from sewage water using a K. pneumoniae strain as a host. Whole-genome analysis indicated that the genome was a double-stranded linear 176,096-bp long DNA molecule with 41.8% GC content and did not contain virulence or antibiotic resistance genes. The inactivation potential of phage KP1LMA was assessed in broth at an MOI of 1 and 10, and a maximum inactivation of 4.9 and 5.4 log CFU/mL, respectively, was observed after 9 h. The efficacy at an MOI of 10 was also assessed in urine to evaluate the phage’s performance in an acidic environment. A maximum inactivation of 3.8 log CFU/mL was observed after 9 h. The results suggest that phage KP1LMA could potentially control a UTI caused by this strain of K. pneumoniae, indicating that the same procedure can be used to control UTIs caused by other strains if new specific phages are isolated. Although phage KP1LMA has a narrow host range, in the future, efforts can be made to expand its spectrum of activity and also to combine this phage with others, potentially enabling its use against other K. pneumoniae strains involved in UTIs.
]]>Antibiotics doi: 10.3390/antibiotics13020194
Authors: Mohammed Nasser-Ali Pablo Aja-Macaya Kelly Conde-Pérez Noelia Trigo-Tasende Soraya Rumbo-Feal Ana Fernández-González Germán Bou Margarita Poza Juan A. Vallejo
Wastewater treatment plants (WWTPs) are recognized as important niches of antibiotic-resistant bacteria that can be easily spread to the environment. In this study, we collected wastewater samples from the WWTP of A Coruña (NW Spain) from April 2020 to February 2022 to evaluate the presence of Gram-negative bacteria harboring carbapenemase genes. Bacteria isolated from wastewater were classified and their antimicrobial profiles were determined. In total, 252 Gram-negative bacteria carrying various carbapenemase genes were described. Whole-genome sequencing was conducted on 55 selected carbapenemase producing isolates using Oxford Nanopore technology. This study revealed the presence of a significant population of bacteria carrying carbapenemase genes in WWTP, which constitutes a public health problem due to their risk of dissemination to the environment. This emphasizes the usefulness of WWTP monitoring for combating antibiotic resistance. Data revealed the presence of different types of sequences harboring carbapenemase genes, such as blaKPC-2, blaGES-5, blaGES-6, blaIMP-11, blaIMP-28, blaOXA-24, blaOXA-48, blaOXA-58, blaOXA-217, and blaVIM-2. Importantly, the presence of the blaKPC-2 gene in wastewater, several months before any clinical case was detected in University Hospital of A Coruña, suggests that wastewater-based epidemiology can be used as an early warning system for the surveillance of antibiotic-resistant bacteria.
]]>Antibiotics doi: 10.3390/antibiotics13020193
Authors: Povilas Kavaliauskas Birutė Grybaitė Birutė Sapijanskaitė-Banevič Rita Vaickelionienė Vidmantas Petraitis Rūta Petraitienė Ethan Naing Andrew Garcia Ramunė Grigalevičiūtė Vytautas Mickevičius
Infections caused by multidrug-resistant bacterial and fungal pathogens represent a significant global health concern, contributing to increased morbidity and mortality rates. Therefore, it is crucial to develop novel compounds targeting drug-resistant microbial strains. Herein, we report the synthesis of amino acid derivatives bearing an incorporated 4-hydroxyphenyl moiety with various substitutions. The resultant novel 3-((4-hydroxyphenyl)amino)propanoic acid derivatives 2–37 exhibited structure-dependent antimicrobial activity against both ESKAPE group bacteria and drug-resistant Candida species. Furthermore, these derivatives demonstrated substantial activity against Candida auris, with minimum inhibitory concentrations ranging from 0.5 to 64 µg/mL. Hydrazones 14–16, containing heterocyclic substituents, showed the most potent and broad-spectrum antimicrobial activity. This activity extended to methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1 to 8 µg/mL, vancomycin-resistant Enterococcus faecalis (0.5–2 µg/mL), Gram-negative pathogens (MIC 8–64 µg/mL), and drug-resistant Candida species (MIC 8–64 µg/mL), including Candida auris. Collectively, these findings underscore the potential utility of the novel 3-((4-hydroxyphenyl)amino)propanoic acid scaffold for further development as a foundational platform for novel antimicrobial agents targeting emerging and drug-resistant bacterial and fungal pathogens.
]]>Antibiotics doi: 10.3390/antibiotics13020192
Authors: Lenka Doubravská Miroslava Htoutou Sedláková Kateřina Fišerová Olga Klementová Radovan Turek Kateřina Langová Milan Kolář
The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence of bacterial community- and hospital-acquired pneumonia (CAP and HAP) and its effect on mortality in critically ill COVID-19 patients admitted to the intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 and 31 December 2022. The secondary objectives of this study include identifying the bacterial etiology of CAP and HAP and exploring the capabilities of diagnostic tools, with a focus on inflammatory biomarkers. Data were collected from the electronic information hospital system, encompassing biomarkers, microbiological findings, and daily visit records, and subsequently evaluated by ICU physicians and clinical microbiologists. Out of 171 patients suffering from critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically ill COVID-19 patients who experienced bacterial CAP and HAP exhibited higher mortality compared to COVID-19 patients without any bacterial infection, with rates of 38% and 56% versus 11%, respectively. In CAP, the most frequent causative agents were chlamydophila and mycoplasma; Enterobacterales, which were multidrug-resistant in 71% of cases; Gram-negative non-fermenting rods; and Staphylococcus aureus. Notably, no strains of Streptococcus pneumoniae were detected, and only a single strain each of Haemophilus influenzae and Moraxella catarrhalis was isolated. The most frequent etiologic agents causing HAP were Enterobacterales and Gram-negative non-fermenting rods. Based on the presented results, commonly used biochemical markers demonstrated poor predictive and diagnostic accuracy. To confirm the diagnosis of bacterial CAP in our patient cohort, it was necessary to assess the initial values of inflammatory markers (particularly procalcitonin), consider clinical signs indicative of bacterial infection, and/or rely on positive microbiological findings. For HAP diagnostics, it was appropriate to conduct regular detailed clinical examinations (with a focus on evaluating respiratory functions) and closely monitor the dynamics of inflammatory markers (preferably Interleukin-6).
]]>Antibiotics doi: 10.3390/antibiotics13020191
Authors: Aamir Jamal Gondal Nakhshab Choudhry Ammara Niaz Nighat Yasmin
Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains have become a global threat due to their remarkable capability to survive and disseminate successfully by the acquisition of resistance genes. As a result, the treatment strategies have been severely compromised. Due to the insufficient available data regarding P. aeruginosa resistance from Pakistan, we aimed to investigate the resistance mechanisms of 249 P. aeruginosa strains by antimicrobial susceptibility testing, polymerase chain reaction for the detection of carbapenemases, aminoglycoside resistance genes, extended-spectrum beta-lactamases (ESBLs), sequence typing and plasmid typing. Furthermore, we tested silver nanoparticles (AgNPs) to evaluate their in vitro sensitivity against antimicrobial-resistant P. aeruginosa strains. We observed higher resistance against antimicrobials in the general surgery ward, general medicine ward and wound samples. Phenotypic carbapenemase-producer strains comprised 80.7% (201/249) with 89.0% (179/201) demonstrating genes encoding carbapenemases: blaNDM-1 (32.96%), blaOXA48 (37.43%), blaIMP (7.26%), blaVIM (5.03%), blaKPC-2 (1.12%), blaNDM-1/blaOXA48 (13.97%), blaOXA-48/blaVIM (1.68%) and blaVIM/blaIMP (0.56%). Aminoglycoside-modifying enzyme genes and 16S rRNA methylase variants were detected in 43.8% (109/249) strains: aac(6′)-lb (12.8%), aac(3)-lla (12.0%), rmtB (21.1%), rmtC (11.0%), armA (12.8%), rmtD (4.6%), rmtF (6.4%), rmtB/aac(3)-lla (8.2%), rmtB/aac(6′)-lla (7.3%) and rmtB/armA (3.6%). In total, 43.0% (77/179) of the strains coharbored carbapenemases and aminoglycoside resistance genes with 83.1% resistant to at least 1 agent in 3 or more classes and 16.9% resistant to every class of antimicrobials tested. Thirteen sequence types (STs) were identified: ST235, ST277, ST234, ST170, ST381, ST175, ST1455, ST1963, ST313, ST207, ST664, ST357 and ST348. Plasmid replicon types IncFI, IncFII, IncA/C, IncL/M, IncN, IncX, IncR and IncFIIK and MOB types F11, F12, H121, P131 and P3 were detected. Meropenem/AgNPs and Amikacin/AgNPs showed enhanced antibacterial activity. We reported the coexistence of carbapenemases and aminoglycoside resistance genes among carbapenem-resistant P. aeruginosa with diverse clonal lineages from Pakistan. Furthermore, we highlighted AgNP’s potential role in handling future antimicrobial resistance concerns.
]]>Antibiotics doi: 10.3390/antibiotics13020190
Authors: Vagif Gasanov Ekaterina Vorotelyak Andrey Vasiliev
In this study, we developed a method for the expression of the antimicrobial peptide SE-33-A2P in E. coli bacterial cells. The SE-33-A2P peptide consists of A2P and SE-33 peptides and is a retro analog of cathelicidin possessing antimicrobial activity against both Gram-positive and Gram-negative bacteria. Furthermore, the A2P peptide is a self-cleaving peptide. For an efficient expression of the SE-33-A2P peptide, a gene encoding several repetitive sequences of the SE-33 peptide separated by A2P sequences was created. The gene was cloned into a plasmid, with which E. coli cells were transformed. An induction of the product expression was carried out by IPTG after the cell culture gained high density. The inducible expression product, due to the properties of the A2P peptide, was cleaved in the cell into SE-33-A2P peptides. As the next step, the SE-33-A2P peptide was purified using filtration and chromatography. Its activity against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant bacteria, was proved. The developed approach for obtaining a prokaryotic system for the expression of a highly active antimicrobial peptide expands the opportunities for producing antimicrobial peptides via industrial methods.
]]>Antibiotics doi: 10.3390/antibiotics13020189
Authors: Luca Sbricoli Giulio Grisolia Edoardo Stellini Christian Bacci Marco Annunziata Eriberto Bressan
The problem of antibiotic resistance is becoming increasingly serious worldwide due to uncontrolled prescription. Dentists are among the groups that prescribe the most antibiotics, often to delay urgent treatment. The purpose of the present study is to investigate the prescribing protocols adopted by dentists for prophylaxis and antibiotic therapy in major clinical surgical indications. Methods: A ten-question survey was administered to a group of Italian dentists. The participants were asked about their preferences for antibiotic administration for the prevention of infective endocarditis, the administration of antibiotics to patients allergic to penicillin, the insertion of implants, and the extraction of third molars. The retrieved data were screened and analyzed. Results: A total of 298 surveys were filled out. The most-prescribed antibiotic was amoxicillin or amoxicillin with clavulanic acid or macrolides for allergic patients. The administration of two grams of amoxicillin one hour before surgery was the most widely used prescriptive protocol for prophylaxis. International guidelines on antibiotic prophylaxis for infective endocarditis were only partially followed. The most heterogeneous results emerged for prophylaxis associated with dental implants or provided prior to surgical third-molar extraction. Conclusions: The present study shows widespread antibiotic prescriptive heterogeneity among the sample of dentists analyzed, especially in conditions where international guidelines are lacking. An evidence-based consensus on prescriptive modalities in dentistry would be desirable in the near future.
]]>Antibiotics doi: 10.3390/antibiotics13020188
Authors: Thibaut Vanbaelen Jolein Laumen Christophe Van Dijck Tessa De Block Sheeba Santhini Manoharan-Basil Chris Kenyon
Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV preexposure prophylaxis (PrEP) have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6 months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high-antimicrobial-consumption populations, the association between antimicrobial consumption and resistance may be attenuated. This conclusion would not apply to lower-consumption populations.
]]>Antibiotics doi: 10.3390/antibiotics13020187
Authors: Juan Carlos Ruiz-Rodríguez Luis Chiscano-Camón Carolina Maldonado Adolf Ruiz-Sanmartin Laura Martin Ivan Bajaña Juliana Bastidas Rocio Lopez-Martinez Clara Franco-Jarava Juan José González-López Vicent Ribas Nieves Larrosa Jordi Riera Xavier Nuvials-Casals Ricard Ferrer
Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d’Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles—hyperinflammatory, low perfusion, and hypogammaglobulinemic—which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition.
]]>Antibiotics doi: 10.3390/antibiotics13020186
Authors: Tim Niklas Bewersdorf Jakob Hofmann Sebastian Findeisen Christian Schamberger Thomas Lingner Ulrike Sommer Gerhard Schmidmaier Tobias Grossner
The treatment of fungal bone infections and infected non-unions is a huge challenge in modern trauma and orthopedics, which normally contain the local and systemic administration of anti-fungal drugs. Although frequently used, little is known about the impact of systemic and locally administered fungicides on the osteogenic regenerative capabilities of infected bone tissue, especially upon the osteogenesis of human bone marrow mesenchymal stem cells (BM-hMSCs). This study evaluates the effects of the three most common fungicides for the systemic treatment of bone infections, Voriconazole (VOR), liposomal Amphotericin B (LAMB), and Fluconazole (FLU), as well as the effects of VOR and LAMB-loaded Polymethylmethacrylate (PMMA) cement chips in different concentrations upon the osteogenic response of BM-hMSCs in vitro. Within this study, we compared the ability of BM-hMSC to differentiate into osteoblast-like cells and synthesize hydroxyapatite as assessed by radioactive 99mTechnetium-Hydroxydiphosphonate (99mTc-HDP) labeling, cell proliferation, and analyses of supernatants upon various osteogenic parameters. Our results revealed that VOR added to the cell culture medium affects the osteogenic potential of BM-hMSC negatively, while there were no detectable effects of LAMB and FLU. Moreover, we showed dose-dependent negative effects of high- and extended-dose fungicide-loaded PMMA cement due to cytotoxicity, with a higher cytotoxic potential of VOR than LAMB, while low-dose fungicide-loaded PMMA had no significant effect on the osteogenic potential of BM-hMSC in vitro.
]]>Antibiotics doi: 10.3390/antibiotics13020185
Authors: Cody A. Black Raymond Benavides Sarah M. Bandy Steven D. Dallas Gerard Gawrys Wonhee So Alvaro G. Moreira Samantha Aguilar Kevin Quidilla Dan F. Smelter Kelly R. Reveles Christopher R. Frei Jim M. Koeller Grace C. Lee
Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term “non-carbapenemase (NCP)”, particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.
]]>Antibiotics doi: 10.3390/antibiotics13020184
Authors: Rasoul Mirzaei Davide Campoccia Stefano Ravaioli Carla Renata Arciola
Bacterial biofilms, enigmatic communities of microorganisms enclosed in an extracellular matrix, still represent an open challenge in many clinical contexts, including orthopedics, where biofilm-associated bone and joint infections remain the main cause of implant failure. This study explores the scenario of biofilm infections, with a focus on those related to orthopedic implants, highlighting recently emerged substantial aspects of the pathogenesis and their potential repercussions on the clinic, as well as the progress and gaps that still exist in the diagnostics and management of these infections. The classic mechanisms through which biofilms form and the more recently proposed new ones are depicted. The ways in which bacteria hide, become impenetrable to antibiotics, and evade the immune defenses, creating reservoirs of bacteria difficult to detect and reach, are delineated, such as bacterial dormancy within biofilms, entry into host cells, and penetration into bone canaliculi. New findings on biofilm formation with host components are presented. The article also delves into the emerging and critical concept of immunometabolism, a key function of immune cells that biofilm interferes with. The growing potential of biofilm metabolomics in the diagnosis and therapy of biofilm infections is highlighted, referring to the latest research.
]]>Antibiotics doi: 10.3390/antibiotics13020183
Authors: Sinazo Z. Z. Cobongela Maya M. Makatini Bambesiwe May Zikhona Njengele-Tetyana Mokae F. Bambo Nicole R. S. Sibuyi
The continuous rise in bacterial infections and antibiotic resistance is the driving force behind the search for new antibacterial agents with novel modes of action. Antimicrobial peptides (AMPs) have recently gained attention as promising antibiotic agents with the potential to treat drug-resistant infections. Several AMPs have shown a lower propensity towards developing resistance compared to conventional antibiotics. However, these peptides, especially acyldepsipeptides (ADEPs) present with unfavorable pharmacokinetic properties, such as high toxicity and low bioavailability. Different ways to improve these peptides to be drug-like molecules have been explored, and these include using biocompatible nano-carriers. ADEP1 analogues (SC005-8) conjugated to gelatin-capped Silver/Indium/Sulfide (AgInS2) quantum dots (QDs) improved the antibacterial activity against Gram-negative (Escherichia coli and Pseudomonas aeruginosa), and Gram-positive (Bacillus subtilis, Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus) bacteria. The ADEP1 analogues exhibited minimum inhibition concentrations (MIC) between 63 and 500 µM, and minimum bactericidal concentrations (MBC) values between 125 and 750 µM. The AgInS2-ADEP1 analogue conjugates showed enhanced antibacterial activity as evident from the MIC and MBC values, i.e., 1.6–25 µM and 6.3–100 µM, respectively. The AgInS2-ADEP1 analogue conjugates were non-toxic against HEK-293 cells at concentrations that showed antibacterial activity. The findings reported herein could be helpful in the development of antibacterial treatment strategies.
]]>Antibiotics doi: 10.3390/antibiotics13020182
Authors: Mayra Paola Mena Navarro Merle Ariadna Espinosa Bernal Claudia Alvarado Osuna Miguel Ángel Ramos López Aldo Amaro Reyes Jackeline Lizzeta Arvizu Gómez Juan Ramiro Pacheco Aguilar Carlos Saldaña Gutiérrez Victor Pérez Moreno José Alberto Rodríguez Morales María Carlota García Gutiérrez Erika Álvarez Hidalgo Jorge Nuñez Ramírez José Luis Hernández Flores Juan Campos Guillén
Chili powder is an important condiment around the world. However, according to various reports, the presence of pathogenic microorganisms could present a public health risk factor during its consumption. Therefore, microbiological quality assessment is required to understand key microbial functional traits, such as antibiotic resistance genes (ARGs). In this study, metagenomic next-generation sequencing (mNGS) and bioinformatics analysis were used to characterize the comprehensive profiles of the bacterial community and antibiotic resistance genes (ARGs) in 15 chili powder samples from different regions of Mexico. The initial bacterial load showed aerobic mesophilic bacteria (AMB) ranging between 6 × 103 and 7 × 108 CFU/g, sporulated mesophilic bacteria (SMB) from 4.3 × 103 to 2 × 109 CFU/g, and enterobacteria (En) from <100 to 2.3 × 106 CFU/g. The most representative families in the samples were Bacillaceae and Enterobacteriaceae, in which 18 potential pathogen-associated species were detected. In total, the resistome profile in the chili powder contained 68 unique genes, which conferred antibiotic resistance distributed in 13 different classes. Among the main classes of antibiotic resistance genes with a high abundance in almost all the samples were those related to multidrug, tetracycline, beta-lactam, aminoglycoside, and phenicol resistance. Our findings reveal the utility of mNGS in elucidating microbiological quality in chili powder to reduce the public health risks and the spread of potential pathogens with antibiotic resistance mechanisms.
]]>Antibiotics doi: 10.3390/antibiotics13020181
Authors: Melinda Héjja Emőke Mihok Amina Alaya Maria Jolji Éva György Noemi Meszaros Violeta Turcus Neli Kinga Oláh Endre Máthé
Nowadays, unprecedented health challenges are urging novel solutions to address antimicrobial resistance as multidrug-resistant strains of bacteria, yeasts and moulds are emerging. Such microorganisms can cause food and feed spoilage, food poisoning and even more severe diseases, resulting in human death. In order to overcome this phenomenon, it is essential to identify novel antimicrobials that are naturally occurring, biologically effective and increasingly safe for human use. The development of gemmotherapy extracts (GTEs) using plant parts such as buds and young shoots has emerged as a novel approach to treat/prevent human conditions due to their associated antidiabetic, anti-inflammatory and/or antimicrobial properties that all require careful evaluations. Seven GTEs obtained from plant species like the olive (Olea europaea L.), almond (Prunus amygdalus L.), black mulberry (Morus nigra L.), walnut (Juglans regia L.), blackberry (Rubus fruticosus L.), blackcurrant (Ribes nigrum L.) and bilberry (Vaccinium myrtillus L.) were tested for their antimicrobial efficiency via agar diffusion and microbroth dilution methods. The antimicrobial activity was assessed for eight bacterial (Bacillus cereus, Staphylococcus aureus, Salmonella enterica subsp. enterica, Proteus vulgaris, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes), five moulds (Aspergillus flavus, Aspergillus niger, Aspergillus ochraceus, Penicillium citrinum, Penicillium expansum) and one yeast strain (Saccharomyces cerevisiae). The agar diffusion method revealed the blackberry GTE as the most effective since it inhibited the growth of three bacterial, four moulds and one yeast species, having considered the total number of affected microorganism species. Next to the blackberry, the olive GTE appeared to be the second most efficient, suppressing five bacterial strains but no moulds or yeasts. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were then determined for each GTE and the microorganisms tested. Noticeably, the olive GTE appeared to feature the strongest bacteriostatic and bactericidal outcome, displaying specificity for S. aureus, E. faecalis and L. monocytogenes. The other GTEs, such as blueberry, walnut, black mulberry and almond (the list indicates relative strength), were more effective at suppressing microbial growth than inducing microbial death. However, some species specificities were also evident, while the blackcurrant GTE had no significant antimicrobial activity. Having seen the antimicrobial properties of the analysed GTEs, especially the olive and black mulberry GTEs, these could be envisioned as potential antimicrobials that might enhance antibiotic therapies efficiency, while the blackberry GTE would act as an antifungal agent. Some of the GTE mixtures analysed have shown interesting antimicrobial synergies, and all the antimicrobial effects observed argue for extending these studies to include pathological microorganisms.
]]>Antibiotics doi: 10.3390/antibiotics13020180
Authors: Pierre-Marie Roger Diane Lesselingue Anouk Gérard Jacques Roghi Pauline Quint Sophie Un Agnès Chincholle Assi Assi Odile Bouchard Véronique Javaudin Eric Denes
Our aim was to determine the impact of antimicrobial stewardship tools (ASTs) and the COVID-19 pandemic on antibiotic consumption (AC). We used the national software Consores® to determine AC in DDD/1000 days of hospitalization from 2017 to 2022 in voluntary private hospitals in France. The ASTs considered were: 1. internal guidelines; 2. the list of antibiotics with restricted access; 3. the presence of an antibiotic referent or 4. an ID specialist; and 5. proof of an annual meeting on antimicrobial resistance. Institutions with dedicated units for COVID-19 patients were specified. In 30 institutions, the total AC varied from (means) 390 to 405 DDD/1000 DH from 2017 to 2022. Fluoroquinolones and amoxicillin/clavulanate consumption decreased from 50 to 36 (p = 0.003) and from 112 to 77 (p = 0.025), respectively, but consumption of piperacillin/tazobactam increased from 9 to 21 (p < 0.001). Over the study period, 10 institutions with ≤2 AST had lower AC compared to 20 institutions with ≥3 AST (p < 0.01). COVID-19 units opened in 10 institutions were associated with a trend toward higher macrolide consumption from 15 to 25 from 2017 to 2020 (p = 0.065) and with an acceleration of piperacillin/tazobactam consumption from 2020 to 2022 (p ≤ 0.003). Antibiotic consumption in 30 private hospitals in France was inversely related to the number of AST. The COVID-19 pandemic was associated with limited impact on AC, but special attention should be paid to piperacillin/tazobactam consumption.
]]>Antibiotics doi: 10.3390/antibiotics13020179
Authors: Sebastian M. Klim Jürgen Prattes Florian Amerstorfer Tobias Niedrist Christoph Zurl Martin Stradner Barbara Dreo Gunther Glehr Andreas Leithner Mathias Glehr Patrick Reinbacher Patrick Sadoghi Georg Hauer
Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden’s J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated.
]]>Antibiotics doi: 10.3390/antibiotics13020178
Authors: Elda Carolina Dávila-López María Guadalupe Berumen-Lechuga Carlos José Molina-Pérez Rodolfo Norberto Jimenez-Juarez Alfredo Leaños-Miranda Natali Robles-Ordoñez María Isabel Peña-Cano German Alberto Venegas-Esquivel
Background: Antimicrobial resistance is a global health problem, due to morbidity, mortality, and healthcare costs. The misuse of antimicrobials is the main cause of antimicrobial resistance. The aim of this study was to report antimicrobial resistance and antibiotic consumption in a secondary care hospital in Mexico. Methods: Within a cross-sectional study, antimicrobial resistance data on ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and antibiotic consumption from 2020 to 2022 were collected. Antimicrobial resistance was reported based on percentages of resistance and consumption was analyzed using the defined daily dose (DDD)/100 bed days and the AWaRe (Access, Surveillance, Reservation) antibiotic group. Results: Antibiotic consumption in 2020, 2021 and 2022 was 330, 175 and 175 DDD/100 beds day, respectively. The rate of ceftriaxone resistance in E. coli (n = 526) and K. pneumoniae (n = 80) was 76% and 69%, respectively, the rate of carbapenem resistance in A. baumannii (n = 168) and P. aeruginosa (n = 108) was 92% and 52%, respectively; the rate of oxacillin resistance in S. aureus (n = 208) was 27%; and the rate of vancomycin resistance in E. faecium (n = 68) was 47%. Conclusion: The reported results are congruent with global estimates of antibiotic resistance and consumption, providing an overview that could generate actions for antimicrobial optimization at the local and regional levels.
]]>Antibiotics doi: 10.3390/antibiotics13020177
Authors: Elin Svedholm Benjamin Bruce Benjamin J. Parcell Peter J. Coote
The aims of this study were (i) to determine if the combination of mitomycin C with pentamidine or existing antibiotics resulted in enhanced efficacy versus infections with MDR P. aeruginosa in vivo; and (ii) to determine if the doses of mitomycin C and pentamidine in combination can be reduced to levels that are non-toxic in humans but still retain antibacterial activity. Resistant clinical isolates of P. aeruginosa, a mutant strain over-expressing the MexAB-OprM resistance nodulation division (RND) efflux pump and a strain with three RND pumps deleted, were used. MIC assays indicated that all strains were sensitive to mitomycin C, but deletion of three RND pumps resulted in hypersensitivity and over-expression of MexAB-OprM caused some resistance. These results imply that mitomycin C is a substrate of the RND efflux pumps. Mitomycin C monotherapy successfully treated infected Galleria mellonella larvae, albeit at doses too high for human administration. Checkerboard and time–kill assays showed that the combination of mitomycin C with pentamidine, or the antibiotic gentamicin, resulted in synergistic inhibition of most P. aeruginosa strains in vitro. In vivo, administration of a combination therapy of mitomycin C with pentamidine, or gentamicin, to G. mellonella larvae infected with P. aeruginosa resulted in enhanced efficacy compared with monotherapies for the majority of MDR clinical isolates. Notably, the therapeutic benefit conferred by the combination therapy occurred with doses of mitomycin C close to those used in human medicine. Thus, repurposing mitomycin C in combination therapies to target MDR P. aeruginosa infections merits further investigation.
]]>Antibiotics doi: 10.3390/antibiotics13020176
Authors: Alejandro Quiñonez-Flores Bernardo A. Martinez-Guerra Carla M. Román-Montes Karla M. Tamez-Torres María F. González-Lara Alfredo Ponce-de-León Sandra Rajme-López
Background: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia. Methods: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality. Results: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic. Conclusions: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.
]]>Antibiotics doi: 10.3390/antibiotics13020175
Authors: Anton Smirnov Oleg Yanushevich Natella Krikheli Nestor Washington Solis Pinargote Pavel Peretyagin Sergey Grigoriev Luis Alou David Sevillano Roberto López-Piriz Francisco Guitian José Florindo Bartolomé
The surface adhesion of bacterial cells and the in vivo biocompatibility of a new ceramic–metal composite made of zirconium dioxide and tantalum were evaluated. Within the framework of an in vitro study using the crystal violet staining and colony counting methods, a relatively similar adhesion of Streptococcus oralis to the 3Y-TZP/Ta biocermet (roughness Ra = 0.12 ± 0.04 µm) and Ti-Al6-V4 titanium alloy (Ra = 0.04 ± 0.01 µm) was found. In addition, in an in vivo preliminary study focused on the histological analysis of a series of rods implanted in the jaws of beagle dogs for a six-month period, the absence of any fibrous tissue or inflammatory reaction at the interface between the implanted 3Y-TZP/Ta biocermets and the new bone was found. Thus, it can be concluded that the developed ceramic–metal biocomposite may be a promising new material for use in dentistry.
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