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Antibiotics, Volume 11, Issue 9 (September 2022) – 134 articles

Cover Story (view full-size image): Multidrug-resistant (MDR) E. faecium is a challenging nosocomial pathogen known to colonize medical device surfaces and form biofilms. Daptomycin (DAP) is the first line for serious MDR E. faecium infections; however, resistant phenotypes are quickly emerging. Bacteriophages may constitute an emerging anti-infective option for refractory, biofilm-mediated infections. Phage–antibiotic synergy and bacterial killing were assessed with a modified checkerboard minimum biofilm inhibitory concentration (MBIC) and 24-hour time kill assays. Against DAP-resistant R497 and DAP-susceptible dose-dependent HOU503 E. faecium clinical blood isolates, the use of DAP + ampicillin (AMP) combined with three- and four-phage cocktails effectively eradicated biofilm-embedded MDR E. faecium without altering antibiotic MBIC or phage susceptibility compared to the baseline. View this paper
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11 pages, 302 KiB  
Article
Influence of Probiotic Strains Bifidobacterium, Lactobacillus, and Enterococcus on the Health Status and Weight Gain of Calves, and the Utilization of Nitrogenous Compounds
by Luboš Zábranský, Anna Poborská, Branislav Gálik, Miloslav Šoch, Petr Brož, Martin Kantor, Naděžda Kernerová, Ivan Řezáč, Michal Rolinec, Ondrej Hanušovský, Ladislav Strnad and Nikola Havrdová
Antibiotics 2022, 11(9), 1273; https://doi.org/10.3390/antibiotics11091273 - 19 Sep 2022
Cited by 6 | Viewed by 1615
Abstract
The aim of this study was to monitor the effect of Bifidobacterium bifidum (BB) and the combination of Lactobacillus sporogenes, Enterococcus faecium, and Bifidobacterium bifidum (LEB) on the health status and weight gain of calves, and the utilisation of nitrogenous substances. [...] Read more.
The aim of this study was to monitor the effect of Bifidobacterium bifidum (BB) and the combination of Lactobacillus sporogenes, Enterococcus faecium, and Bifidobacterium bifidum (LEB) on the health status and weight gain of calves, and the utilisation of nitrogenous substances. The experiment was performed in the period from April 2020 to September 2020. A total of 90 Holstein heifers, which were one to 56 days old, were used as experimental animals. Differences in live weight gain were significant if we compared the LEB vs. BB group and the LEB vs. C, the control group (86.23 ± 5.49 kg vs. 84.72 ± 6.22 kg, p < 0.05; 86.23 ± 5.49 kg vs. 82.86 ± 5.35 kg, p < 0.01). Considering the live weight gain, group BB was heavier than group C only (84.72 ± 6.22 kg vs. 82.86 ± 5.35 kg, p < 0.05). An effect on reducing the incidence and duration of diarrheal diseases was not demonstrated in this study (p = 0.1957). The administration of feed additives had no statistically significant effect on the amount of N excreted in the feces. The values of hematological and biochemical parameters were unaffected except for the first sampling of urea. Other blood parameters were not affected by the addition of probiotic feed additives. The bacterial populations in the feces 5 days and 56 days after birth were not affected by the inclusion of feed additives. Full article
7 pages, 625 KiB  
Brief Report
Quercetin Is a Novel Inhibitor of the Choline Kinase of Streptococcus pneumoniae
by Tahl Zimmerman and Salam A. Ibrahim
Antibiotics 2022, 11(9), 1272; https://doi.org/10.3390/antibiotics11091272 - 19 Sep 2022
Cited by 2 | Viewed by 1617
Abstract
The effectiveness of current antimicrobial methods for addressing for food-borne Gram-positive pathogens has dropped with the emergence of resistant strains. Consequently, new methods for addressing Gram-positive strains have to be developed continuously. This includes establishing novel targets for antimicrobial discovery efforts. Eukaryotic choline [...] Read more.
The effectiveness of current antimicrobial methods for addressing for food-borne Gram-positive pathogens has dropped with the emergence of resistant strains. Consequently, new methods for addressing Gram-positive strains have to be developed continuously. This includes establishing novel targets for antimicrobial discovery efforts. Eukaryotic choline kinases have been highly developed as drug targets for the treatment of cancer, rheumatoid arthritis, malaria and many other conditions and diseases. Recently, choline kinase (ChoK) has been proposed as a drug target for Gram-positive species generally. The aim of this work was to discover novel, natural sources of inhibitors for bacterial ChoK from tea extracts. We report the first natural bacterial ChoK inhibitor with antimicrobial activity against Streptococcus pneumoniae: quercetin. Full article
(This article belongs to the Special Issue Advances in the Discovery of Novel Antibiotics)
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15 pages, 19850 KiB  
Article
Resistance to Fluoroquinolones in Pseudomonas aeruginosa from Human, Animal, Food and Environmental Origin: The Role of CrpP and Mobilizable ICEs
by María López, Beatriz Rojo-Bezares, Gabriela Chichón and Yolanda Sáenz
Antibiotics 2022, 11(9), 1271; https://doi.org/10.3390/antibiotics11091271 - 19 Sep 2022
Cited by 4 | Viewed by 2384
Abstract
Fluoroquinolone resistance and the associated genetic mechanisms were assessed by antimicrobial susceptibility and whole genome sequencing in 56 Pseudomonas aeruginosa strains from human, animal, food and environmental origins. P. aeruginosa PAO1, PA7 and PA14 reference strains were also included in the study. Twenty-two [...] Read more.
Fluoroquinolone resistance and the associated genetic mechanisms were assessed by antimicrobial susceptibility and whole genome sequencing in 56 Pseudomonas aeruginosa strains from human, animal, food and environmental origins. P. aeruginosa PAO1, PA7 and PA14 reference strains were also included in the study. Twenty-two strains (37%) were resistant to, at least, one fluoroquinolone agent. Correlation between the number of changes in GyrA and ParC proteins and the level of fluoroquinolone resistance was observed. Mutations or absence of genes, such as mexZ, mvaT and nalD encoding efflux pumps regulators, were also found in resistant strains. The crpP gene was detected in 43 strains (72.9%; 17 of them non-clinical strains), and coded seven different CrpP variants, including a novel one (CrpP-7). The crpP gene was located in 23 different chromosomal mobile integrative and conjugative elements (ICEs), inserted in two tRNAs integration sites. A great variety of structures was detected in the crpP-ICEs elements, e.g., the fimbriae related cup clusters, the mercury resistance mer operon, the pyocin S5 or S8 bacteriocin encoding genes, and mobilization genes. The location of crpP-like genes in mobilizable ICEs and linked to heavy metal resistance and virulence factors is of significant concern in P. aeruginosa. This work provides a genetic explanation of the fluoroquinolone resistance and crpP-associated pathogenesis of P. aeruginosa from a One-Health approach. Full article
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17 pages, 3847 KiB  
Article
Clinical Prevalence, Antibiogram Profiling and Gompertz Growth Kinetics of Resistant Staphylococcus epidermidis Treated with Nanoparticles of Rosin Extracted from Pinus roxburghii
by Zahid Majeed, Muhammad Qudir Javid, Shamyla Nawazish, Basharat Ahmad, Abu ul Hassan Faiz, Ayesha Baig, Sofia Baig, Mater H. Mahnashi, Naif A. Jalal, Abdulaziz Asiri and Amer Al Ali
Antibiotics 2022, 11(9), 1270; https://doi.org/10.3390/antibiotics11091270 - 19 Sep 2022
Cited by 1 | Viewed by 1629
Abstract
The rise of methicillin-resistant Staphylococcus epidermidis (MRSE) makes it difficult to treat infections that increase morbidity and mortality rates in various parts of the world. The study’s objectives include identifying the clinical prevalence, antibiogram profile, and Gompertz growth kinetics of MRSE treated with [...] Read more.
The rise of methicillin-resistant Staphylococcus epidermidis (MRSE) makes it difficult to treat infections that increase morbidity and mortality rates in various parts of the world. The study’s objectives include identifying the clinical prevalence, antibiogram profile, and Gompertz growth kinetics of MRSE treated with synthetically created nanoparticles of rosin obtained from Pinus roxburghii. A total of 64 of 200 clinical isolates of S. epidermidis (32% of the total) displayed sensitivity (40.62%) and resistance (59.37%) to seven different antibiotic classes. The most sensitive patterns of antibiotic resistance were seen in 20 (78.95%) and 24 (94.74%) isolates of MRSE against piperacillin/tazobactam and cephradine, respectively. Fosfomycine was found to be the most effective antibiotic against MRSE in 34 (89.47%) isolates, followed by amoxicillin. Successfully produced, described, and used against MRSE were rosin maleic anhydride nanoparticles with a size range of 250 nm to 350 nm. Five different concentrations of 25, 50, 75, 100, and 150 mg mL−1 rosin maleic anhydride nanoparticles were investigated to treat MRSE resistance. According to Gompertz growth kinetics, the maximal growth response was 32.54% higher and the lag phase was also 10.26% longer compared to the control when the amount of rosin maleic anhydride nanoparticles was increased in the MRSE. Following the application of rosin maleic anhydride nanoparticles, the growth period is extended from 6 to 8 h. A potential mechanism for cell disintegration and distortion is put forth. This investigation came to the conclusion that rosin maleic anhydride nanoparticles better interfere with the surface of MRSE and demonstrated a preferred bacteriostatic action. Full article
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8 pages, 478 KiB  
Article
Impact of Discontinuing Levofloxacin Prophylaxis on Bloodstream Infections in Neutropenic Hematopoietic Stem Cell Transplantation Patients
by Thaís Guimarães, Igor Carmo Borges, Fernanda de Souza Spadão, Livia Mariano, Marina de Mattos Nascimento, Hermes Higashino, Flavia Rossi, Vanderson Rocha and Silvia Figueiredo Costa
Antibiotics 2022, 11(9), 1269; https://doi.org/10.3390/antibiotics11091269 - 19 Sep 2022
Cited by 3 | Viewed by 2010
Abstract
Multidrug-resistant pathogens have emerged worldwide. We have driven the hypothesis that the non-use of fluoroquinolone prophylaxis during neutropenia could reduce antibiotic resistance in Gram-negative bacteria that cause bloodstream infections (BSIs) in hematopoietic stem cell transplantation (HSCT) patients and that this change in resistance [...] Read more.
Multidrug-resistant pathogens have emerged worldwide. We have driven the hypothesis that the non-use of fluoroquinolone prophylaxis during neutropenia could reduce antibiotic resistance in Gram-negative bacteria that cause bloodstream infections (BSIs) in hematopoietic stem cell transplantation (HSCT) patients and that this change in resistance pattern could lead to an impact on BSI mortality. This is a quasi-experimental study comparing BSI incidence, resistance patterns of bacteria that cause BSI, and BSI mortality when levofloxacin prophylaxis was routine for neutropenic HSCT patients (2016–2018) to when fluoroquinolone prophylaxis was discontinued in our center (2019). Bivariate comparisons and multivariate logistic regression models were used for analyses. A total of 310 HSCTs (66 (21%) allogeneic and 244 (79%) autologous) were performed during the study period. Sixty (19%) patients had BSIs, 30 in each evaluated period. The discontinuation of levofloxacin prophylaxis was associated with an increase in BSI incidence and a decrease in the resistance rates of causative BSI bacteria and in BSI 30-day mortality. The increase in the rate of resistant bacteria causing BSI and in BSI mortality might outweigh the benefits of a decrease in BSI incidence caused by fluoroquinolone prophylaxis in neutropenic HSCT patients. We suggest that the routine use of fluoroquinolone in this context be revisited. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Healthcare Associated Infections)
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12 pages, 1769 KiB  
Article
Homocysteine and Inflammatory Cytokines in the Clinical Assessment of Infection in Venous Leg Ulcers
by Ilaria Cavallo, Ilaria Lesnoni La Parola, Francesca Sivori, Luigi Toma, Tatiana Koudriavtseva, Isabella Sperduti, Daniela Kovacs, Giovanna D’Agosto, Elisabetta Trento, Norma Cameli, Anna Mussi, Alessandra Latini, Aldo Morrone, Fulvia Pimpinelli and Enea Gino Di Domenico
Antibiotics 2022, 11(9), 1268; https://doi.org/10.3390/antibiotics11091268 - 18 Sep 2022
Cited by 3 | Viewed by 1965
Abstract
Inflammation and biofilm-associated infection are common in chronic venous leg ulcers (VU), causing deep pain and delayed healing. Albeit important, clinical markers and laboratory parameters for identifying and monitoring persistent VU infections are limited. This study analyzed 101 patients with infected (IVU) and [...] Read more.
Inflammation and biofilm-associated infection are common in chronic venous leg ulcers (VU), causing deep pain and delayed healing. Albeit important, clinical markers and laboratory parameters for identifying and monitoring persistent VU infections are limited. This study analyzed 101 patients with infected (IVU) and noninfected VUs (NVU). Clinical data were collected in both groups. The serum homocysteine (Hcys) and inflammatory cytokines from the wound fluid were measured. In addition, microbial identification, antibiotic susceptibility, and biofilm production were examined. IVU were 56 (55.4%) while NVU were 45 (44.5%). IVUs showed a significant increase in the wound’s size and depth compared to NVUs. In addition, significantly higher levels of interleukin (IL)-6, IL-10, IL17A, and tumor necrosis factor-alpha (TNF-α) were found in patients with IVUs compared to those with NVUs. Notably, hyperhomocysteinemia (HHcy) was significantly more common in patients with IVUs than NVUs. A total of 89 different pathogens were identified from 56 IVUs. Gram-negative bacteria were 51.7%, while the Gram-positives were 48.3%. At the species level, Staphylococcus aureus was the most common isolate (43.8%), followed by Pseudomonas aeruginosa (18.0%). Multidrug-resistant organisms (MDROs) accounted for 25.8% of the total isolates. Strong biofilm producers (SBPs) (70.8%) were significantly more abundant than weak biofilm producers (WBP) (29.2%) in IVUs. SBPs were present in 97.7% of the IVUs as single or multispecies infections. Specifically, SBPs were 94.9% for S. aureus, 87.5% for P. aeruginosa, and 28.6% for Escherichia coli. In IVU, the tissue microenvironment and biofilm production can support chronic microbial persistence and a most severe clinical outcome even in the presence of an intense immune response, as shown by the high levels of inflammatory molecules. The measurement of local cytokines in combination with systemic homocysteine may offer a novel set of biomarkers for the clinical assessment of IVUs caused by biofilm-producing bacteria. Full article
(This article belongs to the Special Issue Multi-Drug Resistant Gram-Negative Microorganisms, 2nd Volume)
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11 pages, 2247 KiB  
Article
Photodynamic Therapy by Mean of 5-Aminolevulinic Acid for the Management of Periodontitis and Peri-Implantitis: A Retrospective Analysis of 20 Patients
by Roberto Rossi, Lorena Rispoli, Michele Antonio Lopez, Andrea Netti, Morena Petrini and Adriano Piattelli
Antibiotics 2022, 11(9), 1267; https://doi.org/10.3390/antibiotics11091267 - 18 Sep 2022
Cited by 5 | Viewed by 2130
Abstract
Periodontitis and peri-implantitis are common in the population worldwide. Periodontal diseases affect approximately 50% of adults, while mucositis affects 80% of patients with implants, turning into peri-implantitis at a rate varying from 28 to 58%. If standardized treatments for all degrees and variety [...] Read more.
Periodontitis and peri-implantitis are common in the population worldwide. Periodontal diseases affect approximately 50% of adults, while mucositis affects 80% of patients with implants, turning into peri-implantitis at a rate varying from 28 to 58%. If standardized treatments for all degrees and variety of periodontal diseases are known and codified, a consensus on the treatment of peri-implantitis still has to be found. Photodynamic therapy (PDT) has been used successfully in the medical field and was recently introduced as supportive therapy in dentistry. This paper reviews the results on 20 patients, 10 affected by periodontal disease (grades II to III) and 10 by peri-implantitis. Application of 5% 5-aminolevulinic acid gel (ALAD), as a support of causal therapy, in periodontal pockets and areas of peri-implantitis favored the maintenance of severely compromised teeth and significantly improved compromised implant conditions. Between baseline and 6 months, all teeth and implants remained functional. All patients confirmed that the scaling and root planning (SRP)+ALAD-PDT was not painful, and all perceived a benefit after the treatment at all timing points. For periodontal patients, a significant decrease in PPD after 3 (p < 0.001) and 6 months after SRP+ALAD-PDT respect baseline values were observed. For the implant patients, the SRP+ALAD-PDT was correlated to a decrease in PPD and BOP, and a slight increase in the number of exposed threads. However, the results were statistically significant only for PPD (p < 0.001). Full article
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14 pages, 631 KiB  
Article
Effects of One-Stage Full-Mouth Scaling and Root Planing with Azithromycin on Diabetes and Periodontal Disease: A Randomized Controlled Trial
by Sho Komatsu, Shotaro Oshikiri, Takatoshi Nagano, Akihiro Yashima, Yuji Matsushima, Satoshi Shirakawa, Katsutoshi Komatsu, Akiko Mokubo and Kazuhiro Gomi
Antibiotics 2022, 11(9), 1266; https://doi.org/10.3390/antibiotics11091266 - 18 Sep 2022
Cited by 1 | Viewed by 1829
Abstract
Recent reports show that hemoglobin A1c (HbA1c) can be lowered by improving chronic inflammation in periodontal patients with diabetes mellitus and that full-mouth scaling and root planing (FM-SRP), in combination with azithromycin (AZM) treatment, can reduce early periodontal inflammation. However, the association of [...] Read more.
Recent reports show that hemoglobin A1c (HbA1c) can be lowered by improving chronic inflammation in periodontal patients with diabetes mellitus and that full-mouth scaling and root planing (FM-SRP), in combination with azithromycin (AZM) treatment, can reduce early periodontal inflammation. However, the association of FM-SRP and AZM with periodontitis and HbA1c in patients with diabetes is largely unknown. This study investigated periodontitis and HbA1c in patients with diabetes after receiving FM-SRP and AZM to evaluate which clinical parameters most reflect the diabetic condition. Fifty-one periodontal patients with diabetes mellitus were included in this study. In total, 25 patients were assigned to the FM-SRP group in which patients were treated with FM-SRP in combination with AZM, and 26 patients were assigned to the control group in which only supragingival calculus removal was performed along with the provision of oral hygiene instructions. We evaluated periodontal parameters (probing pocket depth, periodontal inflamed surface area (PISA), bleeding on probing), and periodontal bacteria and biochemical parameters (HbA1c, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)) at baseline (BL) and 1, 3, 6, and 9 months after treatment. Compared with BL values, the FM-SRP group showed improved clinical parameters, reduced periodontal pathogens, and significantly lower HbA1c. Inflammatory cytokines (hs-CRP, TNF-α, IL-6) were significantly reduced one month after treatment and remained low thereafter. MCP-1 did not change significantly during the experimental period. PISA showed a strong correlation with HbA1c, hs-CRP, and TNF-α. FM-SRP, in combination with AZM, produced clinical, microbiological, and HbA1c improvements in periodontal patients with previously diagnosed diabetes mellitus. Additionally, PISA was shown to be a useful index for assessing the diabetic status of patients with periodontal disease. Full article
(This article belongs to the Section The Global Need for Effective Antibiotics)
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17 pages, 107429 KiB  
Article
The Feed Additive Potassium Diformate Prevents Salmonella enterica Serovar Pullorum Infection and Affects Intestinal Flora in Chickens
by Yufan Sun, Panyuan Yu, Yiluo Cheng, Jiahui Liu, Xiabing Chen, Tengfei Zhang, Ting Gao, Rui Zhou and Lu Li
Antibiotics 2022, 11(9), 1265; https://doi.org/10.3390/antibiotics11091265 - 18 Sep 2022
Cited by 6 | Viewed by 2103
Abstract
Extensive studies have shown that potassium diformate (KDF), an antibiotic substitute used as a feed additive, improves animal growth performance, although there is less direct evidence of its preventive effect on bacterial infections and its influence on the intestinal flora of animals. In [...] Read more.
Extensive studies have shown that potassium diformate (KDF), an antibiotic substitute used as a feed additive, improves animal growth performance, although there is less direct evidence of its preventive effect on bacterial infections and its influence on the intestinal flora of animals. In this study, the inhibition effect of KDF on Salmonella enterica serovar Pullorum, an important enteric pathogen causing pullorum disease, was investigated in vitro and on a chicken infection model. The effect of KDF on the diversities and structures of chicken duodenal and cecum flora were also investigated using 16S rRNA gene sequencing. The results showed that addition of 0.5% KDF in feed or 0.1% KDF in drinking water significantly reduced the bacterial loads and the degree of pathological changes in the cecum, improved digestion and reduced the pH of the gastrointestinal tract of chickens infected with S. pullorum. KDF also significantly modified the diversity and abundance of intestinal microflorae in chickens. In particular, it promoted the colonization of several probiotics, such as Bacteroides, Blautia, Ruminococcus_torques_group and Faecalibacteriumm, which are involved in maintenance of the intestinal barrier, modulation of inflammation, energy supply for intestinal cells and pathogen resistance. These results enrich the theoretical basis for the clinical application of KDF in chickens. Full article
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11 pages, 1644 KiB  
Article
Prolongation of Fate of Bacteriophages In Vivo by Polylactic-Co-Glycolic-Acid/Alginate-Composite Encapsulation
by Sang-Guen Kim, Sib Sankar Giri, Su-Jin Jo, Jeong-Woo Kang, Sung-Bin Lee, Won-Joon Jung, Young-Min Lee, Hee-Jin Kim, Ji-Hyung Kim and Se-Chang Park
Antibiotics 2022, 11(9), 1264; https://doi.org/10.3390/antibiotics11091264 - 17 Sep 2022
Cited by 5 | Viewed by 1781
Abstract
With concern growing over antibiotics resistance, the use of bacteriophages to combat resistant bacteria has been suggested as an alternative strategy with which to enable the selective control of targeted pathogens. One major challenge that restrains the therapeutic application of bacteriophages as antibacterial [...] Read more.
With concern growing over antibiotics resistance, the use of bacteriophages to combat resistant bacteria has been suggested as an alternative strategy with which to enable the selective control of targeted pathogens. One major challenge that restrains the therapeutic application of bacteriophages as antibacterial agents is their short lifespan, which limits their antibacterial effect in vivo. Here, we developed a polylactic-co-glycolic acid (PLGA)/alginate-composite microsphere for increasing the lifespan of bacteriophages in vivo. The alginate matrix in PLGA microspheres encapsulated the bacteriophages and protected them against destabilization by an organic solvent. Encapsulated bacteriophages were detected in the tissue for 28 days post-administration, while the bacteriophages administered without advanced encapsulation survived in vivo for only 3–5 days. The bacteriophages with extended fate showed prophylaxis against the bacterial pathogens for 28 days post-administration. This enhanced prophylaxis is presumed to have originated from the diminished immune response against these encapsulated bacteriophages because of their controlled release. Collectively, composite encapsulation has prophylactic potential against bacterial pathogens that threaten food safety and public health. Full article
(This article belongs to the Special Issue Phage Therapy to Control Pathogenic Bacteria, 2nd Edition)
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28 pages, 634 KiB  
Review
Epidemiology, Mechanisms of Resistance and Treatment Algorithm for Infections Due to Carbapenem-Resistant Gram-Negative Bacteria: An Expert Panel Opinion
by Nicola Coppola, Alberto Enrico Maraolo, Lorenzo Onorato, Riccardo Scotto, Federica Calò, Luigi Atripaldi, Anna Borrelli, Antonio Corcione, Maria Giovanna De Cristofaro, Emanuele Durante-Mangoni, Amelia Filippelli, Gianluigi Franci, Maria Galdo, Gaspare Guglielmi, Pasquale Pagliano, Alessandro Perrella, Ornella Piazza, Marco Picardi, Rodolfo Punzi, Ugo Trama and Ivan Gentileadd Show full author list remove Hide full author list
Antibiotics 2022, 11(9), 1263; https://doi.org/10.3390/antibiotics11091263 - 17 Sep 2022
Cited by 14 | Viewed by 5677
Abstract
Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are [...] Read more.
Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence. Full article
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8 pages, 901 KiB  
Article
Gastrointestinal Carriage of Antimicrobial Resistance in School-Aged Children in Three Municipalities of Timor-Leste
by Tessa Oakley, Brandon Le, Virginia da Conceicao, Ian Marr, Carolina Maia, Messias Soares, Joana Correia Belo, Nevio Sarmento, Endang da Silva, Salvador Amaral, Susana Vaz Nery, Sarah Lynar, Joshua R. Francis and Jennifer Yan
Antibiotics 2022, 11(9), 1262; https://doi.org/10.3390/antibiotics11091262 - 16 Sep 2022
Cited by 2 | Viewed by 1589
Abstract
Invasive bacterial infections are a leading cause of death in children, primarily in low- and middle-income countries (LMIC). Links between carriage of antimicrobial-resistant organisms and more resistant infections have been established; however, little has been reported regarding community carriage of antibiotic-resistant organisms such [...] Read more.
Invasive bacterial infections are a leading cause of death in children, primarily in low- and middle-income countries (LMIC). Links between carriage of antimicrobial-resistant organisms and more resistant infections have been established; however, little has been reported regarding community carriage of antibiotic-resistant organisms such as extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in LMIC. The aim of this study was to determine colonic carriage of ESBL-producing fluoroquinolone- and aminoglycoside-resistant Enterobacterales in healthy children in three municipalities of Timor-Leste. In November 2020, 621 stool samples were collected from school-aged children and underwent screening for the presence of Enterobacterales species and antimicrobial resistance (AMR). Ciprofloxacin-resistant Gram-negative organisms were cultured from 16.5% (95% CI 6.2–26.9), and gentamicin resistance was identified in 6.8% (95% CI 2.8–10.7). Compared to the prevalence of ciprofloxacin resistance in Dili (36.1%), there was significantly lower prevalence in the rural municipalities of Ermera (12.9%; AOR 0.38, 95% CI 0.24–0.60, p < 0.001) and Manufahi (4.5%; AOR 0.07, 95% CI 0.01–0.51, p = 0.009). The overall cluster-adjusted prevalence of ESBL-producing bacteria was 8.3%, with no significant differences between municipalities. This study demonstrates high rates of carriage of AMR among school-aged children in Timor-Leste, with higher rates observed in Dili compared to rural municipalities. Empiric antibiotic guidelines should include recommendations for treating community-acquired infections that account for the possibility of antimicrobial resistance. Full article
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20 pages, 3841 KiB  
Article
Enrofloxacin and Sulfamethoxazole Sorption on Carbonized Leonardite: Kinetics, Isotherms, Influential Effects, and Antibacterial Activity toward S. aureus ATCC 25923
by Chanat Chokejaroenrat, Chainarong Sakulthaew, Khomson Satchasataporn, Daniel D. Snow, Tarik E. Ali, Mohammed A. Assiri, Apichon Watcharenwong, Saksit Imman, Nopparat Suriyachai and Torpong Kreetachat
Antibiotics 2022, 11(9), 1261; https://doi.org/10.3390/antibiotics11091261 - 16 Sep 2022
Cited by 6 | Viewed by 1755
Abstract
Excessive antibiotic use in veterinary applications has resulted in water contamination and potentially poses a serious threat to aquatic environments and human health. The objective of the current study was to quantify carbonized leonardite (cLND) adsorption capabilities to remove sulfamethoxazole (SMX)- and enrofloxacin [...] Read more.
Excessive antibiotic use in veterinary applications has resulted in water contamination and potentially poses a serious threat to aquatic environments and human health. The objective of the current study was to quantify carbonized leonardite (cLND) adsorption capabilities to remove sulfamethoxazole (SMX)- and enrofloxacin (ENR)-contaminated water and to determine the microbial activity of ENR residuals on cLND following adsorption. The cLND samples prepared at 450 °C and 850 °C (cLND450 and cLND550, respectively) were evaluated for structural and physical characteristics and adsorption capabilities based on adsorption kinetics and isotherm studies. The low pyrolysis temperature of cLND resulted in a heterogeneous surface that was abundant in both hydrophobic and hydrophilic functional groups. SMX and ENR adsorption were best described using a pseudo-second-order rate expression. The SMX and ENR adsorption equilibrium data on cLND450 and cLND550 revealed their better compliance with a Langmuir isotherm than with four other models based on 2.3-fold higher values of qmENR than qmSMX. Under the presence of the environmental interference, the electrostatic interaction was the main contributing factor to the adsorption capability. Microbial activity experiments based on the growth of Staphylococcus aureus ATCC 25923 revealed that cLND could successfully adsorb and subsequently retain the adsorbed antibiotic on the cLND surface. This study demonstrated the potential of cLND550 as a suitable low-cost adsorbent for the highly efficient removal of antibiotics from water. Full article
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8 pages, 265 KiB  
Article
Microbiological Characterization of Cutibacterium acnes Strains Isolated from Prosthetic Joint Infections
by Llanos Salar-Vidal, John Jairo Aguilera-Correa, Holger Brüggemann, Yvonne Achermann and Jaime Esteban
Antibiotics 2022, 11(9), 1260; https://doi.org/10.3390/antibiotics11091260 - 16 Sep 2022
Cited by 5 | Viewed by 2011
Abstract
Aims: This study aimed to characterize 79 Cutibacterium acnes strains isolated from prosthetic joint infections (PJIs) originated from eight European hospitals. Methods: Isolates were phylotyped according to the single-locus sequence typing (SLST) scheme. We evaluated the ability of the biofilm formation of C. [...] Read more.
Aims: This study aimed to characterize 79 Cutibacterium acnes strains isolated from prosthetic joint infections (PJIs) originated from eight European hospitals. Methods: Isolates were phylotyped according to the single-locus sequence typing (SLST) scheme. We evaluated the ability of the biofilm formation of C. acnes strains isolated from PJIs and 84 isolates recovered from healthy skin. Antibiotic susceptibility testing of planktonic and biofilm cells of PJI isolates and skin isolates was performed. Results: Most of the isolates from PJIs belonged to the SLST class H/phylotype IB (34.2%), followed by class D/phylotype IA1 (21.5%), class A/phylotype IA1 (18.9%), and class K/phylotype II (13.9%). All tested isolates were biofilm producers; no difference in biofilm formation was observed between the healthy skin group and the PJI group of strains. Planktonic and sessile cells of C. acnes remained highly susceptible to a broad spectrum of antibiotics, including beta-lactams, clindamycin, fluoroquinolones, linezolid, rifampin, and vancomycin. The minimal inhibitory concentrations (MICs) for planktonic and biofilm states coincided in most cases. However, the minimal biofilm eradication concentration (MBEC) was high for all antimicrobial drugs tested (>32 mg/L), except for rifampin (2 mg/L). Conclusions: C. acnes strains isolated from healthy skin were able to produce biofilm to the same extent as isolates recovered from PJIs. All C. acnes strains in planktonic and sessile states were susceptible to most antibiotics commonly used for PJI treatment, although rifampin was the only antimicrobial agent able to eradicate C. acnes embedded in biofilm. Full article
16 pages, 4224 KiB  
Article
Antimicrobial Functionalization of Prolamine–Silica Hybrid Coatings with Fumaric Acid for Food Packaging Materials and Their Biocompatibility
by Franziska Trodtfeld, Tina Tölke and Cornelia Wiegand
Antibiotics 2022, 11(9), 1259; https://doi.org/10.3390/antibiotics11091259 - 16 Sep 2022
Cited by 3 | Viewed by 1747
Abstract
The interest of the food packaging industry in biodegradable, recyclable, and functional materials has steadily increased in recent years. The use of hydrogels in the food sector holds great potential for use in packaging systems or as carriers for bioactive substances. The synthesis [...] Read more.
The interest of the food packaging industry in biodegradable, recyclable, and functional materials has steadily increased in recent years. The use of hydrogels in the food sector holds great potential for use in packaging systems or as carriers for bioactive substances. The synthesis of an oxygen barrier coating of prolaminic silica material and antimicrobial functionalization with fumaric acid for packaging materials described here is an elegant way to meet these requirements. The developed material achieved a significant antimicrobial activity against Escherichia coli and Staphylococcus aureus, two common clinical pathogens. Another pre-requisite of such materials is a high biocompatibility, which can be assessed using human cell models, to help ensure consumer safety. The biocompatibility was determined by luminescence adenosine triphosphate and photometric lactate dehydrogenase assays. No cytotoxic effects on human keratinocytes in vitro were found for the test materials. Full article
(This article belongs to the Special Issue Non-antibiotic Approaches to Control Food-Borne Pathogens)
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11 pages, 250 KiB  
Article
A Point Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in Public Acute Care Hospitals in Crete, Greece
by Petros Ioannou, Eirini Astrinaki, Efsevia Vitsaxaki, Emmanouil Bolikas, Despoina Christofaki, Apostolia Salvaraki, Eirini Lagoudaki, Eleni Ioannidou, Stamatis Karakonstantis, Stamatina Saplamidou, Christos Cleovoulou, Eleni Stamataki, Stavroula Ilia, Argyri Messaritaki, Michaela Avdi, Anthoula Chalkiadaki, Styliani Papathanasaki, Chrisanthi Markopoulou, Evagelia Magouli, Maria Moustaki, Vasileia-Athina Kataxaki, Panagiotis Skevakis, Nikolaos Spernovasilis, Georgios Chamilos and Diamantis P. Kofteridisadd Show full author list remove Hide full author list
Antibiotics 2022, 11(9), 1258; https://doi.org/10.3390/antibiotics11091258 - 16 Sep 2022
Cited by 6 | Viewed by 2599
Abstract
Background: Both healthcare-associated infections (HAIs) and antimicrobial resistance are associated with an increased length of stay and hospital costs, while they have also been linked to high morbidity and mortality rates. In 2016 and 2017, the latest point prevalence survey (PPS) of HAIs [...] Read more.
Background: Both healthcare-associated infections (HAIs) and antimicrobial resistance are associated with an increased length of stay and hospital costs, while they have also been linked to high morbidity and mortality rates. In 2016 and 2017, the latest point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals highlighted an HAI prevalence of 6.5%, while Greece had a higher HAI prevalence of 10%. The aim of this PPS was to record the prevalence of HAIs and antimicrobial use in all eight public acute care hospitals in Crete, Greece during the COVID-19 pandemic in order to highlight the types of infections and antimicrobial practices that need to be prioritized for infection control initiatives. Methods: The PPS was conducted between 30 March and 15 April 2022, according to the ECDC standardized relevant protocol (version 5.3). Statistics were extracted using the ECDC Helics.Win.Net application (software version 4.1.0). Results: A total of 1188 patients were included. The overall point prevalence of patients with at least one HAI was 10.6%. The most frequent types of infections were pneumonia (34.3%), bloodstream infections (10.5%), systemic infections and urinary tract infections (10.5% and 9.1%, respectively). In 14 (12.4%) cases, the pathogen responsible for HAI was SARS-CoV-2 following onsite spread, accounting for almost 10% of all HAIs. Microorganisms were identified in 60.1% of HAIs. Antimicrobials were administered in 711 (59.8%) patients, with 1.59 antimicrobials used per patient. Conclusion: The prevalence of HAI and antimicrobial use among hospitalized patients in Crete, Greece was similar to the national HAI prevalence in 2016 despite the enormous pressure on public hospitals due to the COVID-19 pandemic. Nevertheless, both HAI prevalence and antimicrobial use remain high, underlining the need to implement adequate infection control and antimicrobial stewardship interventions. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Humans: The Final Frontier)
7 pages, 527 KiB  
Perspective
Tailoring Antimicrobial Stewardship (AMS) Interventions to the Cultural Context: An Investigation of AMS Programs Operating in Northern Italian Acute-Care Hospitals
by Costanza Vicentini, Valentina Blengini, Giulia Libero, Manuela Martella and Carla Maria Zotti
Antibiotics 2022, 11(9), 1257; https://doi.org/10.3390/antibiotics11091257 - 16 Sep 2022
Cited by 1 | Viewed by 1347
Abstract
Antibiotic misuse and overuse are important contributors to the development of antimicrobial resistance (AMR). Antimicrobial stewardship (AMS) programs are coordinated sets of actions aiming to promote appropriate antibiotic use, improving patient outcomes whilst reducing AMR. Two main organizational models for AMS programs have [...] Read more.
Antibiotic misuse and overuse are important contributors to the development of antimicrobial resistance (AMR). Antimicrobial stewardship (AMS) programs are coordinated sets of actions aiming to promote appropriate antibiotic use, improving patient outcomes whilst reducing AMR. Two main organizational models for AMS programs have been described: restrictive strategies (RS) vs. enabling strategies (ES). Evaluating and understanding social and cultural influences on antibiotic decision-making are critical for the development of successful and sustainable context-specific AMS programs. Characteristics and surrogate outcomes of AMS programs operating in acute-care hospitals of Piedmont in north-western Italy were investigated. The aim of this study was assessing whether RS vs. ES operating in our context were associated with different outcomes in terms of total antimicrobial usage and percentage of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteria (CRE) over invasive isolates. In total, 24 AMS programs were assessed. ES were more frequently chosen compared to RS, with the latter being implemented only in broader AMS programs involving enabling components (combined strategy, CS). This study found no difference in evaluated outcomes among hospitals implementing ES vs. CS, suggesting both approaches could be equally valid in our context. Full article
(This article belongs to the Special Issue Optimization of Antimicrobial Stewardship in Public Health)
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12 pages, 3288 KiB  
Article
Activity of Phage–Lactoferrin Mixture against Multi Drug Resistant Staphylococcus aureus Biofilms
by Katarzyna Kosznik-Kwaśnicka, Natalia Kaźmierczak and Lidia Piechowicz
Antibiotics 2022, 11(9), 1256; https://doi.org/10.3390/antibiotics11091256 - 16 Sep 2022
Cited by 3 | Viewed by 1768
Abstract
Biofilms are complex bacterial structures composed of bacterial cells embedded in extracellular polymeric substances (EPS) consisting of polysaccharides, proteins and lipids. As a result, biofilms are difficult to eradicate using both mechanical methods, i.e., scraping, and chemical methods such as disinfectants or antibiotics. [...] Read more.
Biofilms are complex bacterial structures composed of bacterial cells embedded in extracellular polymeric substances (EPS) consisting of polysaccharides, proteins and lipids. As a result, biofilms are difficult to eradicate using both mechanical methods, i.e., scraping, and chemical methods such as disinfectants or antibiotics. Bacteriophages are shown to be able to act as anti-biofilm agents, with the ability to penetrate through the matrix and reach the bacterial cells. However, they also seem to have their limitations. After several hours of treatment with phages, the biofilm tends to grow back and phage-resistant bacteria emerge. Therefore, it is now recommended to use a mixture of phages and other antibacterial agents in order to increase treatment efficiency. In our work we have paired staphylococcal phages with lactoferrin, a protein with proven anti-biofilm proprieties. By analyzing the biofilm biomass and metabolic activity, we have observed that the addition of lactoferrin to phage lysate accelerated the anti-biofilm effect of phages and also prevented biofilm re-growth. Therefore, this combination might have a potential use in biofilm eradication procedures in medical settings. Full article
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10 pages, 566 KiB  
Communication
The Epidemiology of Multidrug-Resistant Sepsis among Chronic Hemodialysis Patients
by Shani Zilberman-Itskovich, Yazid Elukbi, Roni Weinberg Sibony, Michael Shapiro, Dana Zelnik Yovel, Ariela Strulovici, Amin Khatib and Dror Marchaim
Antibiotics 2022, 11(9), 1255; https://doi.org/10.3390/antibiotics11091255 - 15 Sep 2022
Cited by 3 | Viewed by 1454
Abstract
Sepsis is one of the leading causes of hospitalization and death among hemodialysis patients. Infections due to multidrug-resistant organisms (MDROs) are common among these patients, but empiric broad-spectrum coverage for every septic patient is associated with unfavorable outcomes. A retrospective case–control study was [...] Read more.
Sepsis is one of the leading causes of hospitalization and death among hemodialysis patients. Infections due to multidrug-resistant organisms (MDROs) are common among these patients, but empiric broad-spectrum coverage for every septic patient is associated with unfavorable outcomes. A retrospective case–control study was conducted at Shamir Medical Center, Israel (July 2016–April 2020), to determine predictors of MDRO infections among septic (per SEPSIS-3) ambulatory adult hemodialysis patients with permanent dialysis access (i.e., fistula, graft, or tunneled Perm-A-Cath). MDROs were determined according to established definitions. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prediction score and determine its performance. Of 509 patients, 225 (44%) had microbiologically confirmed infection, and 79 patients (35% of 225) had MDROs. The eventual independent predictors of MDRO infections were Perm-A-Cath access (vs. fistula or graft, aOR = 3, CI-95% = 2.1–4.2) and recent hospitalization in the previous three months (aOR = 2.3, CI-95% = 1.6–3.3). The score to predict MDRO sepsis with the highest performances contained seven parameters and displayed an area under the receiver operating characteristic curve (ROC AUC) of 0.74. This study could aid in defining a group of hemodialysis patients for which empiric broad-spectrum agents could be safely avoided. Full article
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8 pages, 1162 KiB  
Case Report
Dual Infection of an Open Fracture Caused by Mycobacterium setense and Clostridium celerecrescens
by Lenka Ryskova, Jan Zahradnicek, Rudolf Kukla, Radka Bolehovska, Milan Vajda, Ivo Pavlik, Pavel Bostik and Pavel Ryska
Antibiotics 2022, 11(9), 1254; https://doi.org/10.3390/antibiotics11091254 - 15 Sep 2022
Cited by 1 | Viewed by 1429
Abstract
Infections caused by Mycobacterium setense or Clostridium celerecrescens are extremely rare. In this report, for the first time a dual infection with these two pathogens is described. An 18-year-old female suffered multiple injuries, including an open comminuted fracture of the right humeral diaphysis [...] Read more.
Infections caused by Mycobacterium setense or Clostridium celerecrescens are extremely rare. In this report, for the first time a dual infection with these two pathogens is described. An 18-year-old female suffered multiple injuries, including an open comminuted fracture of the right humeral diaphysis after falling from a fifth-floor balcony in January 2019. Five months after the accident, a fistula appeared in the scar, reaching the bone tissue. M. setense and C. celerecrescens were cultured from sinus swabs and subsequently from perioperative samples. The patient was initially treated with a combination of intravenous antibiotics (ATBs): imipenem, amikacin, and ciprofloxacin. One month after the fracture fixation with a titanium nail, C. celerecrescens was again detected; therefore, metronidazole was added to the therapy. A triple combination of oral (PO) ATBs (trimethoprim–sulfamethoxazole, moxifloxacin, and metronidazole) followed, 8 weeks after the initial intravenous therapy. C. celerecrescens was cultured again two times, most recently in November 2019, when surgical debridement was supplemented by the topical administration of cancellous bone impregnated with vancomycin. Signs of bone healing were found at follow-ups and ATB treatment was finished in March 2020 after a total of 9 months of therapy. To this day, there have been no signs of reinfection. This case thus illustrates the need for a combination of systemic and individualized local therapy in the treatment of complicated cases of dual infections with rare pathogens. Full article
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14 pages, 1738 KiB  
Article
First Belgian Report of Ertapenem Resistance in an ST11 Klebsiella Pneumoniae Strain Isolated from a Dog Carrying blaSCO-1 and blaDHA-1 Combined with Permeability Defects
by Hanne Debergh, Margo Maex, Cristina Garcia-Graells, Cécile Boland, Marc Saulmont, Koenraad Van Hoorde and Claude Saegerman
Antibiotics 2022, 11(9), 1253; https://doi.org/10.3390/antibiotics11091253 - 15 Sep 2022
Cited by 5 | Viewed by 2653
Abstract
Klebsiella pneumoniae of sequence type (ST) 11 is a hyper-epidemic nosocomial clone, which is spreading worldwide among humans and emerging in pets. This is the first report, to the best of our knowledge, of multidrug-resistant (MDR) K. pneumoniae ST11 carrying blaSCO-1 and [...] Read more.
Klebsiella pneumoniae of sequence type (ST) 11 is a hyper-epidemic nosocomial clone, which is spreading worldwide among humans and emerging in pets. This is the first report, to the best of our knowledge, of multidrug-resistant (MDR) K. pneumoniae ST11 carrying blaSCO-1 and blaDHA-1, isolated from a four-month-old dog in Belgium. Antimicrobial susceptibility testing (AST) of the isolate, performed via broth microdilution following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, revealed resistance to eight different classes of antimicrobials, including carbapenems, in particular ertapenem, third-generation cephalosporins and fluoroquinolones. A hybrid approach, combining long- and short-read sequencing, was employed for in silico plasmid characterization, multi-locus sequence typing (MLST) and the identification and localization of antimicrobial resistance (AMR) and virulence-associated genes. Three plasmids were reconstructed from the whole-genome sequence (WGS) data: the conjugative IncFIB(K), the non-mobilizable IncR and the mobilizable but unconjugative ColRNAI. The IncFIB(K) plasmid carried the blaSCO-1 gene, whereas IncR carried blaDHA-1, both alongside several other antimicrobial resistance genes (ARGs). No virulence genes could be detected. Here, we suggest that the resistance to ertapenem associated with susceptibility to imipenem and meropenem in K. pneumoniae could be related to the presence of blaSCO-1 and blaDHA-1, combined with permeability defects caused by point mutations in an outer membrane porin (OmpK37). The presence of the blaSCO-1 gene on a conjugative IncFIB(K) plasmid is worrisome as it can increase the risk of transmission to humans, to animals and to the environment. Full article
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19 pages, 7737 KiB  
Article
In Situ Biosynthesis of Reduced Alpha Hematite (α-Fe2O3) Nanoparticles by Stevia Rebaudiana L. Leaf Extract: Insights into Antioxidant, Antimicrobial, and Anticancer Properties
by Samar Zuhair Alshawwa, Eman J. Mohammed, Nada Hashim, Mohamed Sharaf, Samy Selim, Hayaa M. Alhuthali, Hind A. Alzahrani, Alsayed E. Mekky and Mohamed G. Elharrif
Antibiotics 2022, 11(9), 1252; https://doi.org/10.3390/antibiotics11091252 - 15 Sep 2022
Cited by 12 | Viewed by 2061
Abstract
In the present study, we utilized Stevia rebaudiana L. (SRLe) extract to in situ biosynthesize nanoscale alpha hematite (α-Fe2O3) nanoparticles (NPs) with potent antioxidant, antimicrobial, and anticancer properties. SRLe-α-Fe2O3 was characterized using physiochemical analyses, including UV/Vis, [...] Read more.
In the present study, we utilized Stevia rebaudiana L. (SRLe) extract to in situ biosynthesize nanoscale alpha hematite (α-Fe2O3) nanoparticles (NPs) with potent antioxidant, antimicrobial, and anticancer properties. SRLe-α-Fe2O3 was characterized using physiochemical analyses, including UV/Vis, FTIR, XRD, DLS, EDX, SEM, and TEM studies. Among tested solvents, CHCl3/MeOH (2:1 v/v) SRL extract (least polar solvent) contained the highest EY, TPC, and antioxidant capacity of ~3.5%, ~75 mg GAE/g extract, and IC50 = 9.87 ± 0.7 mg/mL, respectively. FTIR confirmed the engagement of coating operation to the colloidal α-Fe2O3 NPs. TEM, SEM, and DLS revealed that SRLe-α-Fe2O3 has a spherical shape, uniform size distribution with aggregation for an average size of ~18.34 nm, and ζ = −19.4 mV, forming a repulsive barrier that helped to improve stability. The synthesized nanoparticles displayed considerable antibacterial activity against E. coli and S. aureus bacterial growth, and exhibited superior activity against the A549 lung cancer cell lines. These findings indicate that the increased availability of bioactive substances with antioxidant properties of SRLe makes it a potentially interesting material for the preparation of biologically active compounds and green synthesis of nanoparticles. Full article
(This article belongs to the Special Issue Non-antibiotic Approaches to Control Food-Borne Pathogens)
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13 pages, 1861 KiB  
Article
Minocycline and the SPR741 Adjuvant Are an Efficacious Antibacterial Combination for Acinetobacter baumannii Infections
by Yonas A. Alamneh, Vlado Antonic, Brittany Garry, Michael J. Pucci, Rania Abu-Taleb, Jonathan P. Shearer, Samandra T. Demons, Derese Getnet, Brett E. Swierczewski, Troy Lister and Daniel V. Zurawski
Antibiotics 2022, 11(9), 1251; https://doi.org/10.3390/antibiotics11091251 - 15 Sep 2022
Cited by 3 | Viewed by 1961
Abstract
Antibiotic resistance, when it comes to bacterial infections, is not a problem that is going to disappear anytime soon. With the lack of larger investment in novel antibiotic research and the ever-growing increase of resistant isolates amongst the ESKAPEE pathogens (Enterobacter cloacae [...] Read more.
Antibiotic resistance, when it comes to bacterial infections, is not a problem that is going to disappear anytime soon. With the lack of larger investment in novel antibiotic research and the ever-growing increase of resistant isolates amongst the ESKAPEE pathogens (Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus sp., and Escherichia coli), it is inevitable that more and more infections caused by extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains will arise. One strategy to counteract the growing threat is to use antibiotic adjuvants, a drug class that on its own lacks significant antibiotic activity, but when mixed with another antibiotic, can potentiate increased killing of bacteria. Antibiotic adjuvants have various mechanisms of action, but polymyxins and polymyxin-like molecules can disrupt the Gram-negative outer membrane and allow other drugs better penetration into the bacterial periplasm and cytoplasm. Previously, we showed that SPR741 had this adjuvant effect with regard to rifampin; however, rifampin is often not used clinically because of easily acquired resistance. To find additional, appropriate clinical partners for SPR741 with respect to pulmonary and wound infections, we investigated tetracyclines and found a previously undocumented synergy with minocycline in vitro and in vivo in murine models of infection. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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13 pages, 1388 KiB  
Article
A Threshold Logistic Modelling Approach for Identifying Thresholds between Antibiotic Use and Methicillin-Resistant Staphylococcus aureus Incidence Rates in Hospitals
by Mamoon A. Aldeyab, Stuart E. Bond, Barbara R. Conway, Jade Lee-Milner, Jayanta B. Sarma and William J. Lattyak
Antibiotics 2022, 11(9), 1250; https://doi.org/10.3390/antibiotics11091250 - 15 Sep 2022
Cited by 3 | Viewed by 1673
Abstract
The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also [...] Read more.
The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also aimed to assess the impact of exceeding those thresholds that resulted in increased MRSA rates. The study was undertaken in a 700-bed hospital in England between January 2015 and December 2021 (84 monthly observations). By employing the threshold logistic modelling approach, we: (i) determined the cut-off percentile value of MRSA incidence that defines a critical level of MRSA; (ii) identified thresholds for fluoroquinolone and co-amoxiclav use that would accelerate MRSA incidence rates and increase the probability of reaching critical incidence levels; (iii) enabled a better understanding of the effect of antibiotic use on the probability of reaching a critical level of resistant pathogen incidence; (iv) developed a near real-time performance monitoring feedback system; (v) provided risk scores and alert signals for antibiotic use, with the ability to inform hospital policies, and control MRSA incidence; and (vi) provided recommendations and an example for the management of pathogen incidence in hospitals. Threshold logistic models can help hospitals determine quantitative targets for antibiotic usage and can also inform effective antimicrobial stewardship to control resistance in hospitals. Studies should work toward implementing and evaluating the proposed approach prospectively, with the aim of determining the best counter-measures to mitigate the risk of increased resistant pathogen incidence in hospitals. Full article
(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship, 2nd Volume)
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13 pages, 1031 KiB  
Article
Antifungal Effect of Brassica Tissues on the Mycotoxigenic Cereal Pathogen Fusarium graminearum
by Samina Ashiq, Simon Edwards, Andrew Watson, Emma Blundell and Matthew Back
Antibiotics 2022, 11(9), 1249; https://doi.org/10.3390/antibiotics11091249 - 15 Sep 2022
Cited by 1 | Viewed by 1808
Abstract
Fusarium graminearum is a globally important cereal pathogen, causing head blight in wheat, resulting in yield losses and mycotoxin contamination. Currently, triazole fungicides are used to suppress Fusarium graminearum, however, the declining effectiveness of triazoles and concerns over the safety of pesticides [...] Read more.
Fusarium graminearum is a globally important cereal pathogen, causing head blight in wheat, resulting in yield losses and mycotoxin contamination. Currently, triazole fungicides are used to suppress Fusarium graminearum, however, the declining effectiveness of triazoles and concerns over the safety of pesticides have led to the pursuit of safe alternative crop protection strategies such as biofumigation. In the present study, species belonging to Brassicaceae (Brassica juncea, Raphanus sativus, Eruca sativa) were assessed for their biofumigation potential against F. graminearum and the glucosinolate profile of the brassicas was determined. In Petri dishes, mycelial plugs of Fusarium graminearum were exposed to frozen/defrosted leaf discs of brassicas collected at early-leaf, stem-extension, and early-bud stages. Additionally, F. graminearum inoculum was incubated in soil amended with chopped tissues of brassicas in a closed jar experiment. Glucosinolate analysis of the leaf tissue of brassicas revealed that the total glucosinolate concentration of B. juncea ‘Brons’ increased with advancing growth stage (24.5–51.9 µmol g−1). Brassica juncea leaf discs were effective against mycelial growth, while the sinigrin content in the leaf tissue corresponded to the level of suppression. At the stem-extension and early-bud stages, B. juncea ‘Brons’ showed 87–90% suppression with four leaf discs, and 100% suppression with eight leaf discs. Brassica juncea ‘Caliente Rojo’ leaf discs collected at the stem-extension stage showed 94% inhibition with eight discs. In the closed jar experiment, each brassica species significantly suppressed F. graminearum inoculum by 41–55%. The findings suggest that the brassica species investigated in the present study could be effective in reducing the inoculum of F. graminearum in soil prior to cereal production. Full article
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23 pages, 2181 KiB  
Article
Occurrence of Antimicrobial-Resistant Escherichia coli in Marine Mammals of the North and Baltic Seas: Sentinels for Human Health
by Stephanie Gross, Anja Müller, Diana Seinige, Peter Wohlsein, Manuela Oliveira, Dieter Steinhagen, Corinna Kehrenberg and Ursula Siebert
Antibiotics 2022, 11(9), 1248; https://doi.org/10.3390/antibiotics11091248 - 14 Sep 2022
Cited by 5 | Viewed by 2330
Abstract
Antimicrobial resistance is a global health threat that involves complex, opaque transmission processes in the environment. In particular, wildlife appears to function as a reservoir and vector for antimicrobial-resistant bacteria as well as resistance genes. In the present study, the occurrence of antimicrobial-resistant [...] Read more.
Antimicrobial resistance is a global health threat that involves complex, opaque transmission processes in the environment. In particular, wildlife appears to function as a reservoir and vector for antimicrobial-resistant bacteria as well as resistance genes. In the present study, the occurrence of antimicrobial-resistant Escherichia coli was determined in marine mammals and various fish species of the North and Baltic Seas. Rectal or faecal swabs were collected from 66 live-caught or stranded marine mammals and 40 fish specimens. The antimicrobial resistance phenotypes and genotypes of isolated E. coli were determined using disk diffusion tests and PCR assays. Furthermore, isolates were assigned to the four major phylogenetic groups of E. coli. Additionally, post mortem examinations were performed on 41 of the sampled marine mammals. The investigations revealed resistant E. coli in 39.4% of the marine mammal samples, while no resistant isolates were obtained from any of the fish samples. The obtained isolates most frequently exhibited resistance against aminoglycosides, followed by β-lactams. Of the isolates, 37.2% showed multidrug resistance. Harbour porpoises (Phocoena phocoena) mainly carried E. coli isolates belonging to the phylogenetic group B1, while seal isolates were most frequently assigned to group B2. Regarding antimicrobial resistance, no significant differences were seen between the two sampling areas or different health parameters, but multidrug-resistant isolates were more frequent in harbour porpoises than in the sampled seals. The presented results provide information on the distribution of antimicrobial-resistant bacteria in the North and Baltic Seas, and highlight the role of these resident marine mammal species as sentinels from a One Health perspective. Full article
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11 pages, 387 KiB  
Review
Is Three Company or a Crowd? Comparing and Contrasting U.S. and European Clostridioidesdifficile Clinical Practice Guidelines
by Jordan Jones, Aditya Pradhan, Morgan E. Pizzuti, Christopher M. Bland and P. Brandon Bookstaver
Antibiotics 2022, 11(9), 1247; https://doi.org/10.3390/antibiotics11091247 - 14 Sep 2022
Cited by 1 | Viewed by 2262
Abstract
In 2021, the American College of Gastroenterology (ACG), the Infectious Diseases Society of America in conjunction with the Society for Healthcare Epidemiology of America (IDSA/SHEA), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published updated clinical practice guidelines (CPGs) for [...] Read more.
In 2021, the American College of Gastroenterology (ACG), the Infectious Diseases Society of America in conjunction with the Society for Healthcare Epidemiology of America (IDSA/SHEA), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published updated clinical practice guidelines (CPGs) for the management of Clostridioides difficile infections. The differences, sometimes subtle, between these guideline recommendations have caused some debate among clinicians. This paper delves into select key recommendations from each respective CPG and analyzes the differences and evidence associated with each. One primary difference between the CPGs is the preference given to fidaxomicin over vancomycin for initial treatment in non-severe and severe disease endorsed by IDSA/SHEA and ESCMID guidelines, while the ACG-sponsored CPGs do not offer a preference. The emphasis on cost effective data was also a noticeable difference between the CPGs and thus interpretation of the available evidence. When using guidelines to help support local practice or institutional treatment pathways, clinicians should carefully balance CPG recommendations with local patient populations and feasibility of implementation, especially when multiple guidelines for the same disease state exist. Full article
(This article belongs to the Special Issue Antibiotic Therapy for Clostridioides difficile Infections)
16 pages, 3167 KiB  
Article
Molecular Characterization of Extended Spectrum β-Lactamase (ESBL) and Virulence Gene-Factors in Uropathogenic Escherichia coli (UPEC) in Children in Duhok City, Kurdistan Region, Iraq
by Salwa Muhsin Hasan and Khalid S. Ibrahim
Antibiotics 2022, 11(9), 1246; https://doi.org/10.3390/antibiotics11091246 - 14 Sep 2022
Cited by 4 | Viewed by 2148
Abstract
Background: The presence of extended-spectrum β-lactamase (ESBL)-producing bacteria among uropathogens is significantly increasing in children all over the world. Thus, this research was conducted to investigate the prevalence of E. coli and their antimicrobial susceptibility pattern, and both genes of ESBL-producing E. coli [...] Read more.
Background: The presence of extended-spectrum β-lactamase (ESBL)-producing bacteria among uropathogens is significantly increasing in children all over the world. Thus, this research was conducted to investigate the prevalence of E. coli and their antimicrobial susceptibility pattern, and both genes of ESBL-producing E. coli resistant and virulence factor in UTIs patients among children in Duhok Province, Kurdistan, Iraq. Method: a total of 67 E. coli were identified from 260 urine samples of pediatric patients diagnosed with UTIs aged (0–15 years) which were collected from Heevi Pediatric Teaching Hospital, from August 2021 to the end of February 2022. Result: a high proportion of UPEC infections at ages <5 years and the rates among girls (88%) were significantly higher than those among the boys. A wide variety of E. coli are resistant to most antibiotics, such as Amoxicillin, Ampicillin and Tetracycline, and 64% of them were positive for ESBL. Interestingly, the presence of both the ESBL marker genes (blaTEM, and blaCTX-M) as well as both virulence marker genes (pai and hly) were detected in above 90% of E. coli. Conclusion: the data illustrate an alarming increase in UPEC with ESBL production and the emergence of multidrug-resistant drugs in the early age of children. The public health sectors should further monitor the guidelines of using antibiotics in Kurdistan, Iraq. Full article
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18 pages, 6753 KiB  
Article
Antimicrobial Resistance and Biofilms Underlying Catheter-Related Bloodstream Coinfection by Enterobacter cloacae Complex and Candida parapsilosis
by Matúš Štefánek, Sigurd Wenner, Vítor Borges, Miguel Pinto, João Paulo Gomes, João Rodrigues, Isabel Faria, Maria Ana Pessanha, Filomena Martins, Raquel Sabino, Cristina Veríssimo, Isabel D. Nogueira, Patrícia Almeida Carvalho, Helena Bujdáková and Luisa Jordao
Antibiotics 2022, 11(9), 1245; https://doi.org/10.3390/antibiotics11091245 - 14 Sep 2022
Cited by 6 | Viewed by 2568
Abstract
Biofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility [...] Read more.
Biofilm-associated infections are a public health concern especially in the context of healthcare-associated infections such as catheter-related bloodstream infections (CRBSIs). We evaluated the biofilm formation and antimicrobials resistance (AMR) of Enterobacter cloacae complex and Candida parapsilosis co-isolated from a CRBSI patient. Antimicrobial susceptibility of central venous catheters (CVCs) and hemoculture (HC) isolates was evaluated, including whole genome sequencing (WGS) resistome analysis and evaluation of gene expression to obtain insight into their AMR determinants. Crystal violet assay was used to assess dual biofilm biomass and microscopy was used to elucidate a microorganism’s distribution within biofilms assembled on different materials. Bacteria were multidrug-resistant including resistance to colistin and beta-lactams, likely linked to the mcr-9-like phosphoethanolamine transferase and to an ACT family cephalosporin-hydrolyzing class C beta-lactamase, respectively. The R398I and Y132F mutations in the ERG11 gene and its differential expression might account for C. parapsilosis resistance to fluconazole. The phenotype of dual biofilms assembled on glass, polystyrene and polyurethane depends on the material and how biofilms were initiated by one or both pathogens. Biofilms assembled on polyurethane were denser and richer in the extracellular polymeric matrix, and microorganisms were differently distributed on the inner/outer surface of the CVC. Full article
(This article belongs to the Special Issue Microbial Biofilms, Antimicrobials, and Virulence Determinants)
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10 pages, 476 KiB  
Article
Microbiological Trends and Antibiotic Susceptibility Patterns in Patients with Periprosthetic Joint Infection of the Hip or Knee over 6 Years
by Frank Sebastian Fröschen, Thomas Martin Randau, Alexander Franz, Ernst Molitor, Achim Hoerauf and Gunnar Thorben Rembert Hischebeth
Antibiotics 2022, 11(9), 1244; https://doi.org/10.3390/antibiotics11091244 - 13 Sep 2022
Cited by 4 | Viewed by 1391
Abstract
We sought to analyze trends of the causative pathogens and their antibiotic susceptibility patterns in patients with periprosthetic joint infections (PJI) of the hip and knee to get better insights and improve treatment. Retrospective evaluation of all consecutive patients with microbiological detection of [...] Read more.
We sought to analyze trends of the causative pathogens and their antibiotic susceptibility patterns in patients with periprosthetic joint infections (PJI) of the hip and knee to get better insights and improve treatment. Retrospective evaluation of all consecutive patients with microbiological detection of a causative pathogen at a tertiary endoprothetic referral center between January 2016 and December 2021 in Germany was performed. Overall, 612 different microorganisms could be detected in 493 patients (hip: n = 293; knee: n = 200). Evaluation did not show a change in the relative abundance of pathogens detected, with coagulase-negative staphylococci (n = 275; 44.9%) found frequently, followed by S. aureus (n = 86; 14.1%), Enterococcus species (n = 57; 9.3%), Streptococcus species (n = 48; 7.8%), and Gram-negative bacteria (n = 80; 13.1%). Evaluation of the antibiotic susceptibilities showed increasing rates of oxacillin-resistant coagulase-negative staphylococci (60.4%; 46.8–76.7%) and piperacillin-tazobactam-resistant Gram-negative bacteria (26.5%; 0–57.1%), although statistically not significant. Resistance of Gram-positive bacteria to vancomycin (<1%) and Gram-negative microorganisms to meropenem (1.25%) remained an exception. In summary, coagulase-negative staphylococci, as the most frequent pathogen, displayed a continuously high rate of oxacillin resistance. For the highest antimicrobial coverage in the case of an empiric therapy/unknown pathogen, vancomycin might be chosen. Level of evidence: IV. Full article
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