Antibiotics

19 pages, 1580 KiB

Open AccessEditor’s ChoiceArticle

Fitness Burden for the Stepwise Acquisition of First- and Second-Line Antimicrobial Reduced-Susceptibility in High-Risk ESKAPE MRSA Superbugs

by Eleonora Chines, Gaia Vertillo Aluisio, Maria Santagati, Maria Lina Mezzatesta and Viviana Cafiso

Antibiotics 2025, 14(3), 244; https://doi.org/10.3390/antibiotics14030244 - 28 Feb 2025

Cited by 1 | Viewed by 2487

Abstract

Background: The fitness costs (FCs) of antimicrobial resistance (AMR) are crucial issues in antimicrobial resistance (AMR) onset, spread, and, consequently, public health. In Staphylococcus aureus, AMR can induce significant FCs due to slow growth, low competitiveness, and virulence. Here, we investigated the [...] Read more.

Background: The fitness costs (FCs) of antimicrobial resistance (AMR) are crucial issues in antimicrobial resistance (AMR) onset, spread, and, consequently, public health. In Staphylococcus aureus, AMR can induce significant FCs due to slow growth, low competitiveness, and virulence. Here, we investigated the genomics and FCs emerging for progressively acquiring daptomycin (DAP) and glycopeptide (GLY) reduced susceptibility in MRSA. Methods: Genomics was carried out using Illumina-MiSeq Whole-genome sequencing and bioinformatics. The biological FCs of isogenic MRSA strain pairs progressively acquiring DAP and GLY-reduced susceptibility, under DAP/GLY mono or combined therapy, were performed by in-vitro independent and competitive mixed growth, phenotypic in-vitro virulence analysis, and in-vivo G. mellonella larvae killing. Results: Genomics evidenced four different extremely resistant high-risk clones, i.e., ST-5 N315 HA-MRSA, ST-398 LA-MRSA, ST-22 USA-100 HA-EMRSA-15, and ST-1 MW2 CA-MRSA. In-vitro fitness assays revealed slow growth, lower competitiveness, and reduced virulence, predominantly in Galleria mellonella killing ability, in DAP-S hGISA, DAP-R GSSA, DAP-R hGISA, and DAP-R GISA strains. Conclusions: The occurrence of glycopeptide and daptomycin reduced susceptibility conferred increasing FCs, paid as a gradual reduction in virulence, competitiveness, and slow growth performance. Full article

(This article belongs to the Special Issue Spread of Multidrug-Resistant Microorganisms, 2nd Edition)

► Show Figures

Figure 1

12 pages, 545 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of the Use of Preventive Antibiotic Therapy in Patients Undergoing One-Step Prosthetic Revision Surgery with Low Preoperative Infectious Risk

by Leonardo Motta, Giacomo Stroffolini, Stefania Marocco, Giulia Bertoli, Gianluca Piovan, Lorenzo Povegliano, Claudio Zorzi and Federico Gobbi

Antibiotics 2025, 14(3), 224; https://doi.org/10.3390/antibiotics14030224 - 21 Feb 2025

Viewed by 520

Abstract

Introduction: The prosthetic knee infection (PKI) rate in most centers ranges from 0.5 to 2% for knee replacements, depending on risk factors. Current PKI definitions may miss the identification of both early and late complications. There is no consensus on preventive or early [...] Read more.

Introduction: The prosthetic knee infection (PKI) rate in most centers ranges from 0.5 to 2% for knee replacements, depending on risk factors. Current PKI definitions may miss the identification of both early and late complications. There is no consensus on preventive or early empiric antibiotic therapy (EEAT) in the one-step exchange strategy for low-risk patients pending microbiology results. The aim of the study was to evaluate the potential role of EEAT in patients with comorbidities in preventing PKI and to evaluate differences in septic failure at 3, 6 and 9 months after prosthetic revision between patients undergoing EEAT and patients not undergoing EEAT. Methods: All adult patients undergoing one-step knee revision surgery at IRCCS Sacro-Cuore Don Calabria Negrar, from January 2018 to February 2021, were retrospectively included in a cohort observational study. Patients on antibiotic therapy before surgery or with preoperative ascertained PKI were excluded. Demographic characteristics, Charlson score, comorbidities, inflammatory markers, microbiological tests, imaging, infectious disease risk score and EEAT data were collected. Any postoperative complication or modification of antibiotic therapy at 14, 30, 90, 180 and 270 days after surgery was collected. Results: A total of 227 patients were included: 114 comorbid low-risk patients received EEAT after surgery, pending microbiological results; while 113 non-comorbid low-risk patients did not receive any antibiotic therapy in the postoperative period. Among the EEAT group, 16 were diagnosed with PKI, compared with 10 in the untreated group. Regarding septic failure during the 9-month follow-up after revision surgery, we registered nine cases in the EEAT arm and four in the untreated arm. In three out of nine cases treated with EEAT who had a post-revision septic failure, the causative microorganism was not successfully empirically targeted by EEAT; in the untreated group, two out of four cases had a post-revision septic failure, despite the targeted treatment of intraoperatively identified causative microorganisms. Conclusions: According to our results, EEAT after revision surgery in patients with comorbidities, who are at higher risk of infection, did not prevent prosthetic knee infections. There was also no evidence of a reduction in subsequent septic failure within nine months of revision surgery between groups. More accurate risk-defining scores are needed to identify patients at risk of PKI complications. Full article

(This article belongs to the Special Issue Epidemiology, Diagnosis and Antimicrobial Treatment of Hospital-Acquired Infections)

► Show Figures

Figure 1

13 pages, 218 KiB

Open AccessEditor’s ChoiceArticle

Predictive Factors for Risk of Reinfection in Septic Two-Stage Revision of Total Hip and Knee Arthroplasties

by Benedikt Paul Blersch, Florian Hubert Sax, Philipp Schuster and Bernd Fink

Antibiotics 2025, 14(2), 167; https://doi.org/10.3390/antibiotics14020167 - 8 Feb 2025

Viewed by 703

Abstract

Background: The two-stage septic exchange is the most common therapy concept in the treatment of periprosthetic hip and knee infections. However, before the second-stage reimplantation can be carried out, the physician has to assess whether or not the eradication of the periprosthetic joint [...] Read more.

Background: The two-stage septic exchange is the most common therapy concept in the treatment of periprosthetic hip and knee infections. However, before the second-stage reimplantation can be carried out, the physician has to assess whether or not the eradication of the periprosthetic joint infection (PJI) has been successful. Therefore, the aim of this study was to evaluate possible predictive parameters for the successful treatment of PJI before and at the time of reimplantation. Methods: This study investigated a total of 145 patients with periprosthetic hip infection and 93 patients with periprosthetic knee infection, who all underwent a two-stage septic exchange between 2017 and 2021. In order to identify possible risk factors for reinfections, the patients underwent preoperative examination of serological inflammatory parameters, microbiological and histological examination of the periprosthetic membrane at the time of reimplantation, as well as postoperative evaluations at regular intervals for a period of at least 24 months. Results: During the follow-up period, reinfection occurred in 11.3% of cases after the two-stage septic revision. None of the serological, microbiological, or histological parameters were able to significantly predict the risk of reinfection. Risk factors associated with reinfection were BMI and previous revision surgery. Conclusions: Currently, there is no reliable predictive factor indicating the risk of reinfection at the time of reimplantation. New diagnostic methods need to be developed to evaluate the possibility and timing of endoprosthesis reimplantation. Full article

(This article belongs to the Special Issue Prevention, Diagnostic and Antibiotic Treatment of Periprosthetic Joint and Fracture Related Infection, 2nd Edition)

17 pages, 7112 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial and Antibiofilm Activity of Auranofin and Its Two Derivatives Bearing Naproxen and Acetylcysteine as Ligands Against Staphylococci

by Caterina Ferretti, Lorenzo Chiaverini, Noemi Poma, Andrea Dalli, Riccardo Di Leo, Laura Rindi, Alessandro Marrone, Iogann Tolbatov, Diego La Mendola, Arianna Tavanti, Tiziano Marzo and Mariagrazia Di Luca

Antibiotics 2025, 14(2), 118; https://doi.org/10.3390/antibiotics14020118 - 23 Jan 2025

Cited by 1 | Viewed by 1165

Abstract

Background/Objectives: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid [...] Read more.

Background/Objectives: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid arthritis, shows promising antibacterial activity. This study investigates the antimicrobial and antibiofilm activity of AF and its two derivatives in which the thiosugar ligand is replaced by acetylcysteine (AF-AcCys) or naproxen (AF-Napx), against Staphylococcus aureus and Staphylococcus epidermidis. Methods: AF was conjugated by transmetalation with either naproxen or acetylcysteine. Assessments of their stability in DMSO/H₂O and lipophilicity expressed as the LogP were performed. The antimicrobial activity of AF and its analogues were investigated by broth microdilution assay to determine the minimum inhibitory concentration (MIC) and versus biofilm to obtain the minimum bactericidal biofilm concentration (MBBC) and minimum biofilm eradication concentration (MBEC). Results: AF derivatives were found to be stable in a DMSO/H₂O mixture for 48 h. AF-Napx showed a LogP = 1.25 ± 0.22, close to AF, while AF-AcCys had a LogP = −0.95. MIC values of S. aureus and S. epidermidis were ranging from 2 µM to 0.25 µM, and ≤0.12 µM, respectively. Both AF and AF-Napx maintained efficacy against biofilm-embedded S. aureus and S. epidermidis at non-cytotoxic concentrations, with AF-Napx demonstrating lower MBBC values for S. epidermidis. Conclusions: AF, and especially its naproxen conjugate, holds potential as a therapeutic agent for treating biofilm-associated infections caused by S. aureus and S. epidermidis, particularly in device-related infections where both infection and inflammation are present. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Evolution and New Strategies to Fight It)

► Show Figures

Figure 1

17 pages, 1902 KiB

Open AccessEditor’s ChoiceArticle

Controlling Oral Polymicrobial Biofilm Using Usnic Acid on the Surface of Titanium in the Artificial Saliva Media

by Nazia Tabassum, Fazlurrahman Khan, Geum-Jae Jeong, Do Kyung Oh and Young-Mog Kim

Antibiotics 2025, 14(2), 115; https://doi.org/10.3390/antibiotics14020115 - 22 Jan 2025

Viewed by 1263

Abstract

Background/Objectives: Titanium dental implants, while highly successful, face challenges due to polymicrobial infections leading to peri-implantitis and implant failure. Biofilm formation on implant surfaces is the primary cause of these infections, with factors such as matrix production and cross-kingdom interactions contributing to the [...] Read more.

Background/Objectives: Titanium dental implants, while highly successful, face challenges due to polymicrobial infections leading to peri-implantitis and implant failure. Biofilm formation on implant surfaces is the primary cause of these infections, with factors such as matrix production and cross-kingdom interactions contributing to the microbial accumulation of bacterial and fungal pathogens species. To combat this issue, naturally derived molecules have been reported to overcome the hurdle of antimicrobial resistance against the application of conventional antibiotics and antifungals. Methods: The present study aimed to employ the lichen-derived molecules, usnic acid (UA), to retard the development of biofilms of bacterial and fungal pathogens on the surface of titanium kept in the human artificial saliva (HAS) working as a growth-supporting, host-mimicking media. Results: The minimum inhibitory concentration of UA in HAS towards Candida albicans was >512 µg/mL, whereas against Staphylococcus aureus and Streptococcus mutans, it was determined to be 512 µg/mL. Whereas, in the standard growth media, the MIC value of UA towards S. mutans and S. aureus were 8 and 16 µg/mL; however, against C. albicans, it was 512 µg/mL. UA synergistically enhanced the efficacy of the antibiotics toward bacterial pathogens and the efficacy of antifungals against C. albicans. The antibiofilm results depict the fact that in the HAS, UA significantly reduced both mono-species of S. mutans, S. aureus, and C. albicans and mixed-species biofilm of C. albicans with S. mutans and S. aureus on the surface of the titanium. Conclusions: The present study showed that UA is a promising natural drug that can control oral polymicrobial disease as a result of the application of dental implants. Full article

(This article belongs to the Special Issue Strategies for Combatting Multidrug-Resistant and Extensively Drug-Resistant Bacteria, 2nd Edition)

► Show Figures

Figure 1

17 pages, 5886 KiB

Open AccessEditor’s ChoiceArticle

Interference of Celastrol with Cell Wall Synthesis and Biofilm Formation in Staphylococcus epidermidis

by Leandro de León Guerra, Nayely Padilla Montaño and Laila Moujir

Antibiotics 2025, 14(1), 26; https://doi.org/10.3390/antibiotics14010026 - 3 Jan 2025

Viewed by 950

Abstract

Background: The emergence of antibiotic-resistant bacteria, including Staphylococcus epidermidis, underscores the need for novel antimicrobial agents. Celastrol, a natural compound derived from the plants of the Celastraceae family, has demonstrated promising antibacterial and antibiofilm properties against various pathogens. Objectives: This study [...] Read more.

Background: The emergence of antibiotic-resistant bacteria, including Staphylococcus epidermidis, underscores the need for novel antimicrobial agents. Celastrol, a natural compound derived from the plants of the Celastraceae family, has demonstrated promising antibacterial and antibiofilm properties against various pathogens. Objectives: This study aims to evaluate the antibacterial effects, mechanism of action, and antibiofilm activity of celastrol against S. epidermidis, an emerging opportunistic pathogen. Methods: To investigate the mechanism of action of celastrol, its antibacterial activity was evaluated by determining the time–kill curves, assessing macromolecular synthesis, and analysing its impact on the stability and functionality of the bacterial cell membrane. Additionally, its effect on biofilm formation and disruption was examined. Results: Celastrol exhibited significant antibacterial activity with a minimal inhibitory concentration (MIC) of 0.31 μg/mL and minimal bactericidal concentration (MBC) of 15 μg/mL, which is superior to conventional antibiotics used as control. Time–kill assays revealed a concentration-dependent bactericidal effect, with a shift from bacteriostatic activity at lower concentrations to bactericidal and lytic effect at higher concentrations. Celastrol inhibited cell wall biosynthesis by blocking the incorporation of N-acetylglucosamine (NAG) into peptidoglycan. In contrast, the cytoplasmic membrane was only affected at higher concentrations of the compound or after prolonged exposure times. Additionally, celastrol was able to disrupt biofilm formation at concentrations of 0.9 μg/mL and to eradicate pre-formed biofilms at 7.5 μg/mL in S. epidermidis. Conclusions: Celastrol exhibits significant antibacterial and antibiofilm activities against S. epidermidis, with a primary action on cell wall synthesis. Its efficacy in disrupting the formation of biofilms and pre-formed biofilms suggests its potential as a therapeutic agent for infections caused by biofilm-forming S. epidermidis resistant to conventional treatments. Full article

(This article belongs to the Special Issue Antimicrobial and Antibiofilm Activity by Natural Compounds)

► Show Figures

Graphical abstract

20 pages, 2256 KiB

Open AccessEditor’s ChoiceArticle

Tracking the Prevalence of Antibiotic Resistance in Enterococcus Within the Spanish Poultry Industry: Insights from a One Health Approach

by Josep Garcia-Llorens, Isaac Monroy, Jan Torres-Boncompte, Jose M. Soriano, Pablo Catalá-Gregori and Sandra Sevilla-Navarro

Antibiotics 2025, 14(1), 16; https://doi.org/10.3390/antibiotics14010016 - 30 Dec 2024

Viewed by 1407

Abstract

Background/Objectives: Antimicrobial resistance (AMR) in Enterococcus species from poultry production represents a significant public health threat due to the potential transmission of AMR through the food chain. This study aimed to examine the relative prevalence, resistance patterns, and mannitol fermentation [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) in Enterococcus species from poultry production represents a significant public health threat due to the potential transmission of AMR through the food chain. This study aimed to examine the relative prevalence, resistance patterns, and mannitol fermentation capacity of Enterococcus isolates from various poultry production systems in Spain over a seven-year period (2017–2023). Methods: A total of 215 Enterococcus isolates were analyzed. Phenotypic assessments were conducted to determine resistance rates and metabolic capacities, while genotypic characterization focused on detecting vancomycin-resistance genes (vanA, vanB, vanC, and vanD). Results: Enterococcus faecalis (62.3%) and Enterococcus faecium (29.77%) were the predominant species, primarily isolated from broilers (74.88%), with the highest frequency observed in one-week-old chicks (31.16%). High resistance rates to tetracyclines and streptogramins were identified, while resistance to vancomycin (0.47%) and tigecycline (3.03%) was low. Interestingly, a significant reduction in tetracyclines resistance was shown in this period for Enterococcus faecalis (from 100% to 70% (2017–2023) and Enterococcus faecium (from 100% to 40% (2018–2023)). Multidrug resistance (MDR) was detected in 26.98% of isolates. Mannitol fermentation tests revealed high metabolic capacity in Enterococcus faecalis (99.25%) and Enterococcus faecium (96.88%), associated with adaptability and virulence potential. Genotypic analysis showed a very low prevalence of vanB and vanC genes. Conclusions: These findings highlight the critical need for targeted surveillance and intervention strategies in poultry production to mitigate the risks posed by MDR Enterococcus to public health. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in One Health Perspective: New Insights in Human, Animal, and Environment Interlace, 2nd Edition)

► Show Figures

Figure 1

10 pages, 195 KiB

Open AccessEditor’s ChoiceArticle

Safety and Effectiveness of BPaL-Based Regimens to Treat Multidrug-Resistant TB: First Experience of an Italian Tuberculosis Referral Hospital

by Gina Gualano, Maria Musso, Paola Mencarini, Silvia Mosti, Carlotta Cerva, Pietro Vittozzi, Antonio Mazzarelli, Angela Cannas, Assunta Navarra, Stefania Ianniello, Paolo Faccendini and Fabrizio Palmieri

Antibiotics 2025, 14(1), 7; https://doi.org/10.3390/antibiotics14010007 - 25 Dec 2024

Viewed by 1577

Abstract

Background/Objectives: Tuberculosis (TB) is preventable and curable, but multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose significant challenges worldwide due to the limited treatment options, lengths of therapies, and high rates of treatment failure. The management of MDR-TB has been revolutionized [...] Read more.

Background/Objectives: Tuberculosis (TB) is preventable and curable, but multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose significant challenges worldwide due to the limited treatment options, lengths of therapies, and high rates of treatment failure. The management of MDR-TB has been revolutionized by all oral anti-TB drug regimens that are likely to improve adherence and treatment outcomes. These regimes include bedaquiline (B), pretomanid (P), and linezolid (L) (BPaL), and moxifloxacin if resistance to fluoroquinolones is not detected (BPaLM). Based on the evidence generated by the TB-PRACTECAL and ZeNix randomized controlled trials, BPaL/BPaLM regimens are recommended over the currently recommended longer regimens in patients with MDR-TB or monoresistance to rifampin (RR). To our knowledge, no data are currently available on the implementation of BPaL/BPaLM regimens in Italy. Results: Seventeen patients completed the BPaL/BPaLM regimen, with a treatment success rate of 90% (17/19), consistent with the literature data. Eleven patients out of the nineteen retained in care (58%) complained about symptoms consistent with adverse events (AEs). No treatment interruption was necessary due to AEs. Methods: Here, we report the real-world experience of a tertiary referral hospital for TB in Italy, from 2022 to 2024, in the management, outcomes, and adverse drug reactions of a cohort of twenty-two MDR/RR patients treated with BPaL and BPaLM regimens. Conclusions: BPaL-containing regimens also serve as promising options for patients with RR/MDR-TB in terms of real-life experience, but further multicentric studies are required in Europe to confirm the efficacy of shorter regimens to eliminate MDR TB. Full article

(This article belongs to the Special Issue Antibiotics Use for Respiratory Diseases)

17 pages, 631 KiB

Open AccessEditor’s ChoiceArticle

Pooled Antibiotic Susceptibility Testing Performs Within CLSI Standards for Validation When Measured Against Broth Microdilution and Disk Diffusion Antibiotic Susceptibility Testing of Cultured Isolates

by Emery Haley, Frank R. Cockerill, Rick L. Pesano, Richard A. Festa, Natalie Luke, Mohit Mathur, Xiaofei Chen, Jim Havrilla and David Baunoch

Antibiotics 2024, 13(12), 1214; https://doi.org/10.3390/antibiotics13121214 - 14 Dec 2024

Cited by 2 | Viewed by 1943

Abstract

Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay [...] Read more.

Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay for complicated and recurrent urinary tract infections (UTIs): pooled antibiotic susceptibility testing (P-AST). This assay was compared to broth microdilution (BMD) and disk diffusion (DD), following Clinical and Laboratory Standards Institute (CLSI) guidelines for assessment of error rates and agreement. Methods: This study analyzed consecutive fresh clinical urine specimens submitted for UTI diagnostic testing. Upon receipt, the urine samples were subjected in parallel to standard urine culture and multiplex polymerase chain reaction (M-PCR) for microbial identification and quantification. Specimens with the same monomicrobial non-fastidious bacteria detected by both M-PCR and standard urine culture (SUC) underwent standard antibiotic susceptibility testing (AST) and P-AST antibiotic susceptibility testing. Analysis was also undertaken to assess the presence of heteroresistance for specimens with P-AST-resistant and BMD/DD consensus-susceptible results. Results: The performance measures without correction for heteroresistance showed essential agreement (EA%) of ≥90%, very major errors (VMEs) of <1.5%, and major errors (MEs) of <3.0% for P-AST, all meeting the threshold guidelines established by CLSI for AST. The categorical agreement (CA%) also met acceptable criteria (>88%), as the majority of the errors were minor (mEs) with essential agreement. The very major and major error rates for P-AST decreased to <1.0% when heteroresistance was accounted for. Conclusions: The P-AST assay methodology is validated within acceptable parameters when compared to broth microdilution and disk diffusion using CLSI criteria. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

► Show Figures

Figure 1

18 pages, 4858 KiB

Open AccessEditor’s ChoiceArticle

Does Antibiotic Use Contribute to Biofilm Resistance in Sink Drains? A Case Study from Four German Hospital Wards

by Nicole van Leuven, Ralf Lucassen, Anna Dicks, Patrick Braß, André Lipski and Dirk P. Bockmühl

Antibiotics 2024, 13(12), 1148; https://doi.org/10.3390/antibiotics13121148 - 1 Dec 2024

Viewed by 1282

Abstract

Backgound. As biofilms are known to harbour (multi-)resistant species, their presence in health settings must be considered critical. Although there is evidence that bacteria spread from drains to the outside, there is still a lack of research data focusing on drain biofilms [...] Read more.

Backgound. As biofilms are known to harbour (multi-)resistant species, their presence in health settings must be considered critical. Although there is evidence that bacteria spread from drains to the outside, there is still a lack of research data focusing on drain biofilms from hospitals. Methods. We sampled biofilms from various wards of Helios Hospital Krefeld (Germany), where comprehensive antibiotic consumption data were available. Biofilms were analysed by cell counting, isolation of relevant bacterial groups and genetic and phenotypical resistance parameters. Data were correlated with the prescribed antibiotics of the respective ward. Furthermore, an ex situ biofilm model was employed to investigate the influence of sub-inhibitory antibiotics on the bacterial community and the prevalence of class 1 integrons. Results. Our results show that every ward harboured medically relevant bacterial species. While no significant differences were found in cell counts, the median prevalence of the resistance marker gene intI1 correlated with the amount of prescribed antibiotics. In contrast, phenotypical resistances showed no similar tendency. In addition, melting curve analysis data and changes in intI1 prevalence show that the composition of the bacterial community shifted depending on the biofilm and antibiotic. Conclusions. To the best of our knowledge, our study is the first considering possible correlations between the consumption data of hospital wards and resistances in drain biofilms the way we did. Based on our results, we conclude that sub-inhibitory concentrations of antibiotics have no general effect on biofilms in terms of bacterial community shift and occurrence of antibiotic-resistant species. Amongst other things, the effect depends on the initial composition of the bacterial community, the antibiotic used and the intrinsic bacterial resistance, e.g., prevalence of class 1 integrons. Full article

► Show Figures

Figure 1

17 pages, 2849 KiB

Open AccessEditor’s ChoiceArticle

Microbiome and Resistome Studies of the Lithuanian Baltic Sea Coast and the Curonian Lagoon Waters and Sediments

by Greta Gyraitė, Marija Kataržytė, Rafael Picazo Espinosa, Greta Kalvaitienė and Eglė Lastauskienė

Antibiotics 2024, 13(11), 1013; https://doi.org/10.3390/antibiotics13111013 - 28 Oct 2024

Cited by 1 | Viewed by 1371

Abstract

Background: the widespread use of antibiotics in human and veterinary medicine has contributed to the global challenge of antimicrobial resistance, posing significant environmental and public health risks. Objectives: this study aimed to examine the microbiome and resistome dynamics across a salinity gradient, analyzing [...] Read more.

Background: the widespread use of antibiotics in human and veterinary medicine has contributed to the global challenge of antimicrobial resistance, posing significant environmental and public health risks. Objectives: this study aimed to examine the microbiome and resistome dynamics across a salinity gradient, analyzing water and sediment samples from the Baltic Sea coast and the Curonian Lagoon between 2017 and 2023. Methods: the composition of the water and sediment bacterial community was determined by Full-Length Amplicon Metagenomics Sequencing, while ARG detection and quantification were performed using the SmartChipTM Real-Time PCR system. Results: the observed differences in bacterial community composition between the Baltic Sea coast and the Curonian Lagoon were driven by variations in salinity and chlorophyll a (chl a) concentration. The genera associated with infectious potential were observed in higher abundances in sediment than in water samples. Over 300 genes encoding antibiotic resistance (ARGs), such as aminoglycosides, beta-lactams, and multidrug resistance genes, were identified. Of particular interest were those ARGs that have previously been detected in pathogens and those currently classified as a potential future threat. Furthermore, our findings reveal a higher abundance and a distinct profile of ARGs in sediment samples from the lagoon compared to water. Conclusions: these results suggest that transitional waters such as lagoons may serve as reservoirs for ARGs, and might be influenced by anthropogenic pressures and natural processes such as salinity fluctuation and nutrient cycling. Full article

► Show Figures

Figure 1

25 pages, 1091 KiB

Open AccessEditor’s ChoiceArticle

Combinations of Terminalia bellirica (Gaertn.) Roxb. and Terminalia chebula Retz. Extracts with Selected Antibiotics Against Antibiotic-Resistant Bacteria: Bioactivity and Phytochemistry

by Gagan Tiwana, Ian Edwin Cock and Matthew James Cheesman

Antibiotics 2024, 13(10), 994; https://doi.org/10.3390/antibiotics13100994 - 19 Oct 2024

Cited by 1 | Viewed by 1849

Abstract

Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates [...] Read more.

Antimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates the antibacterial activity of solvent extracts prepared using Terminalia bellirica and Terminalia chebula fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of T. bellirica and T. chebula showed substantial zones of inhibition (ZOIs) against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The activity against those bacteria was strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the T. bellirica methanolic extract showed noteworthy antibacterial activity against Escherichia coli and an extended spectrum β-lactamase (ESBL) E. coli strain (MIC values of 755 µg/mL for both). The aqueous T. bellirica and T. chebula extracts also inhibited Klebsiella pneumoniae growth (MIC values of 784 µg/mL and 556 µg/mL, respectively). The corresponding methanolic extracts also inhibited ESBL K. pneumoniae growth (MIC values of 755 µg/mL and 1509 µg/mL, respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Strong antagonism occurred when any of the extracts were mixed with polymyxin B. Liquid chromatography-mass spectroscopy (LC-MS) analysis of the extracts revealed several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities, suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Natural Products and Plants Extracts)

► Show Figures

Graphical abstract

21 pages, 1022 KiB

Open AccessEditor’s ChoiceArticle

Genomic Analyses of Methicillin-Resistant Staphylococcus pseudintermedius from Companion Animals Reveal Changing Clonal Populations, Multidrug Resistance, and Virulence

by Mattias Myrenås, Karl Pedersen and Ulrika Windahl

Antibiotics 2024, 13(10), 962; https://doi.org/10.3390/antibiotics13100962 - 12 Oct 2024

Viewed by 1402

Abstract

Background/Objectives: Staphylococcus pseudintermedius is part of the normal microbiota in dogs. Since 2006, an increase in multidrug-resistant clones of methicillin-resistant S. pseudintermedius has been reported, as well as zoonotic transmission. Longitudinal investigations into clonal population structures, antibiotic resistance patterns, and the presence of [...] Read more.

Background/Objectives: Staphylococcus pseudintermedius is part of the normal microbiota in dogs. Since 2006, an increase in multidrug-resistant clones of methicillin-resistant S. pseudintermedius has been reported, as well as zoonotic transmission. Longitudinal investigations into clonal population structures, antibiotic resistance patterns, and the presence of resistance and virulence genes are important tools for gaining knowledge of the mechanisms behind the emergence of such clones. Methods: We investigated 87% of all non-repetitive MRSP isolates from dogs and cats in Sweden over a ten-year period (n = 356). All isolates were subjected to staphylococcal chromosomal cassette mec identification, whole-genome sequencing, multi-locus sequence typing, and analyses of genomic relatedness, as well as investigation of phenotypical resistance patterns and the presence of antibiotic resistance genes and virulence genes. Results: A considerable increase over time in the number of clonal lineages present was observed, indicating genomic diversification, and four clones became dominant: ST71, ST258, ST265, and ST551. In total, 96% of the isolates were multidrug-resistant. Statistically significant differences in resistance to several antibiotic classes between the four dominant clones were present. All isolates carried several virulence genes encoding factors associated with attachment, colonization, toxin synthesis, quorum sensing, antibiotic resistance, and immune evasion. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Companion and Food-Producing Animals, 2nd Edition)

► Show Figures

Figure 1

32 pages, 6288 KiB

Open AccessEditor’s ChoiceReview

A Decade of Antimicrobial Resistance in Human and Animal Campylobacter spp. Isolates

by Rita Barata, Maria José Saavedra and Gonçalo Almeida

Antibiotics 2024, 13(9), 904; https://doi.org/10.3390/antibiotics13090904 - 21 Sep 2024

Cited by 5 | Viewed by 3970

Abstract

Objectives: Campylobacter spp. remain a leading cause of bacterial gastroenteritis worldwide, with resistance to antibiotics posing significant challenges to treatment and public health. This study examines profiles in antimicrobial resistance (AMR) for Campylobacter isolates from human and animal sources over the past [...] Read more.

Objectives: Campylobacter spp. remain a leading cause of bacterial gastroenteritis worldwide, with resistance to antibiotics posing significant challenges to treatment and public health. This study examines profiles in antimicrobial resistance (AMR) for Campylobacter isolates from human and animal sources over the past decade. Methods: We conducted a comprehensive review of resistance data from studies spanning ten years, analyzing profiles in resistance to key antibiotics, ciprofloxacin (CIP), tetracycline (TET), erythromycin (ERY), chloramphenicol (CHL), and gentamicin (GEN). Data were collated from various regions to assess global and regional patterns of resistance. Results: The analysis reveals a concerning trend of increasing resistance patterns, particularly to CIP and TET, across multiple regions. While resistance to CHL and GEN remains relatively low, the high prevalence of CIP resistance has significantly compromised treatment options for campylobacteriosis. Discrepancies in resistance patterns were observed between human and animal isolates, with variations across different continents and countries. Notably, resistance to ERY and CHL showed regional variability, reflecting potential differences in antimicrobial usage and management practices. Conclusions: The findings underscore the ongoing challenge of AMR in Campylobacter, highlighting the need for continued surveillance and research. The rising resistance prevalence, coupled with discrepancies in resistance patterns between human and animal isolates, emphasize the importance of a One Health approach to address AMR. Enhanced monitoring, novel treatment strategies, and global cooperation are crucial for mitigating the impact of resistance and ensuring the effective management of Campylobacter-related infections. Full article

(This article belongs to the Special Issue Challenges and Emerging Strategies to Tackle the Global Burden of Antimicrobial Resistance)

► Show Figures

Figure 1

16 pages, 5378 KiB

Open AccessEditor’s ChoiceArticle

Alkyl Pyridinol Compounds Exhibit Antimicrobial Effects against Gram-Positive Bacteria

by Juan Canchola, Gracious Yoofi Boafo Donkor, Patrick Ofori Tawiah, Ayoola Fasawe, Emmanuel Ayim, Martin F. Engelke and Jan-Ulrik Dahl

Antibiotics 2024, 13(9), 897; https://doi.org/10.3390/antibiotics13090897 - 20 Sep 2024

Viewed by 1321

Abstract

Background/Objectives. The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen, causing infections in multiple organs and tissues [...] Read more.

Background/Objectives. The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen, causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit the growth or impair the survival of bacterial pathogens. Given their large structural and chemical diversity, as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against Gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin-resistant S. aureus (MRSA) and the multi-drug-resistant community-acquired strain USA300LAC. Methods. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Results/Conclusions. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 μg/mL), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane-associated mechanism of action. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery, 2nd Edition)

► Show Figures

Figure 1

21 pages, 5445 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Two Novel Endolysins from Bacteriophage PEF1 and Evaluation of Their Combined Effects on the Control of Enterococcus faecalis Planktonic and Biofilm Cells

by Chen Wang, Junxin Zhao, Yunzhi Lin, Su Zar Chi Lwin, Mohamed El-Telbany, Yoshimitsu Masuda, Ken-ichi Honjoh and Takahisa Miyamoto

Antibiotics 2024, 13(9), 884; https://doi.org/10.3390/antibiotics13090884 - 13 Sep 2024

Viewed by 1763

Abstract

Endolysin, a bacteriophage-derived lytic enzyme, has emerged as a promising alternative antimicrobial agent against rising multidrug-resistant bacterial infections. Two novel endolysins LysPEF1-1 and LysPEF1-2 derived from Enterococcus phage PEF1 were cloned and overexpressed in Escherichia coli to test their antimicrobial efficacy against multidrug-resistant [...] Read more.

Endolysin, a bacteriophage-derived lytic enzyme, has emerged as a promising alternative antimicrobial agent against rising multidrug-resistant bacterial infections. Two novel endolysins LysPEF1-1 and LysPEF1-2 derived from Enterococcus phage PEF1 were cloned and overexpressed in Escherichia coli to test their antimicrobial efficacy against multidrug-resistant E. faecalis strains and their biofilms. LysPEF1-1 comprises an enzymatically active domain and a cell-wall-binding domain originating from the NLPC-P60 and SH3 superfamilies, while LysPEF1-2 contains a putative peptidoglycan recognition domain that belongs to the PGRP superfamily. LysPEF1-1 was active against 89.86% (62/69) of Enterococcus spp. tested, displaying a wider antibacterial spectrum than phage PEF1. Moreover, two endolysins demonstrated lytic activity against additional gram-positive and gram-negative species pretreated with chloroform. LysPEF1-1 showed higher activity against multidrug-resistant E. faecalis strain E5 than LysPEF1-2. The combination of two endolysins effectively reduced planktonic cells of E5 in broth and was more efficient at inhibiting biofilm formation and removing biofilm cells of E. faecalis JCM 7783^T than used individually. Especially at 4 °C, they reduced viable biofilm cells by 4.5 log after 2 h of treatment on glass slide surfaces. The results suggest that two novel endolysins could be alternative antimicrobial agents for controlling E. faecalis infections. Full article

(This article belongs to the Special Issue Phage Applications from Diagnostics to Treatment of Bacterial Infections in a One Health World)

► Show Figures

Figure 1

21 pages, 11964 KiB

Open AccessEditor’s ChoiceArticle

Novel Antimicrobial Agents Based on Zinc-Doped Hydroxyapatite Loaded with Tetracycline

by Simona Liliana Iconaru, Daniela Predoi, Carmen Steluta Ciobanu, Catalin Constantin Negrila, Roxana Trusca, Steinar Raaen, Krzysztof Rokosz, Liliana Ghegoiu, Monica Luminita Badea and Carmen Cimpeanu

Antibiotics 2024, 13(9), 803; https://doi.org/10.3390/antibiotics13090803 - 25 Aug 2024

Cited by 1 | Viewed by 1462

Abstract

In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron [...] Read more.

In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were used for the sample’s complex evaluation. Moreover, the biocompatibility of zinc-doped hydroxyapatite (ZnHAp) and ZnHApTe nanoparticles was evaluated with the aid of human fetal osteoblastic cells (hFOB 1.19 cell line). The results of the biological assays suggested that these nanoparticles hold great promise as potential candidates for the future development of novel biocompatible and antimicrobial agents for biomedical applications. The antimicrobial properties of the ZnHAp and ZnHApTe nanoparticles were assessed using the standard reference microbial strains Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231. The results of the in vitro antimicrobial assay demonstrated that both tested materials exhibited good antimicrobial activity. Additionally, these data also indicated that the antimicrobial effects of the ZnHAp nanoparticles were intensified by the presence of tetracycline (Te). Furthermore, the results also suggested that the antimicrobial activity of the samples increased with the incubation time. Full article

(This article belongs to the Special Issue Nanomaterials as Antimicrobial Agents for Biomedical Applications)

► Show Figures

Figure 1

23 pages, 4568 KiB

Open AccessEditor’s ChoiceArticle

Bacteriophage Therapy on an In Vitro Wound Model and Synergistic Effects in Combination with Beta-Lactam Antibiotics

by Guillermo Santamaría-Corral, John Jairo Aguilera-Correa, Jaime Esteban and Meritxell García-Quintanilla

Antibiotics 2024, 13(9), 800; https://doi.org/10.3390/antibiotics13090800 - 24 Aug 2024

Viewed by 1551

Abstract

One of the primary opportunistic pathogens that can cause a wide range of diseases is Pseudomonas aeruginosa. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, [...] Read more.

One of the primary opportunistic pathogens that can cause a wide range of diseases is Pseudomonas aeruginosa. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, among other things, the failure of antimicrobial therapies. Due to a variety of virulence factors and host immune system modifications, P. aeruginosa is one of the most significant and common bacteria that colonize wounds and burns. A novel therapeutic option for treating these multidrug-resistant (MDR) bacterial infections is the combination of antibiotics and bacteriophages. This approach has been linked to improved biofilm penetration, a decreased selection of antibiotic and bacteriophage resistance, and an enhanced antibacterial impact. Combining the F1Pa bacteriophage and beta-lactam antibiotics reduced the viability of the mature biofilm of MDR P. aeruginosa strains and suppressed bacterial growth in vitro. F1Pa critically reduced the amount of biofilm that MDR P. aeruginosa clinical strains formed in the in vitro wound model. These findings highlight the bacteriophage F1Pa’s therapeutic potential as a prophylactic topical treatment against MDR pseudomonal infections in wounds and burns. Full article

(This article belongs to the Special Issue Bacteriophage Therapy a Renaissance Weapon Recent Developments and Application, 2nd Edition)

► Show Figures

Figure 1

14 pages, 3106 KiB

Open AccessEditor’s ChoiceArticle

Development of a Galleria mellonella Infection Model to Evaluate the Efficacy of Antibiotic-Loaded Polymethyl Methacrylate (PMMA) Bone Cement

by You Zhao, Gopala Krishna Mannala, Raphaëlle Youf, Markus Rupp, Volker Alt and Martijn Riool

Antibiotics 2024, 13(8), 692; https://doi.org/10.3390/antibiotics13080692 - 25 Jul 2024

Viewed by 1591

Abstract

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and [...] Read more.

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus. Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches. Full article

(This article belongs to the Special Issue Local Antibiotics: Antibiotic Loaded Bone Cement and Drug Containing Medical Devices in Orthopaedic Surgery)

► Show Figures

Figure 1

18 pages, 14184 KiB

Open AccessEditor’s ChoiceArticle

Isolation and Characterization of Novel Bacteriophages to Target Carbapenem-Resistant Acinetobacter baumannii

by Yoon-Jung Choi, Shukho Kim, Minsang Shin and Jungmin Kim

Antibiotics 2024, 13(7), 610; https://doi.org/10.3390/antibiotics13070610 - 29 Jun 2024

Cited by 6 | Viewed by 2856

Abstract

The spread of multidrug-resistant Acinetobacter baumannii in hospitals and nursing homes poses serious healthcare challenges. Therefore, we aimed to isolate and characterize lytic bacteriophages targeting carbapenem-resistant Acinetobacter baumannii (CRAB). Of the 21 isolated A. baumannii phages, 11 exhibited potent lytic activities against clinical [...] Read more.

The spread of multidrug-resistant Acinetobacter baumannii in hospitals and nursing homes poses serious healthcare challenges. Therefore, we aimed to isolate and characterize lytic bacteriophages targeting carbapenem-resistant Acinetobacter baumannii (CRAB). Of the 21 isolated A. baumannii phages, 11 exhibited potent lytic activities against clinical isolates of CRAB. Based on host spectrum and RAPD-PCR results, 11 phages were categorized into four groups. Three phages (vB_AbaP_W8, vB_AbaSi_W9, and vB_AbaSt_W16) were further characterized owing to their antibacterial efficacy, morphology, and whole-genome sequence and were found to lyse 37.93%, 89.66%, and 37.93%, respectively, of the 29 tested CRAB isolates. The lytic spectrum of phages varied depending on the multilocus sequence type (MLST) of the CRAB isolates. The three phages contained linear double-stranded DNA genomes, with sizes of 41,326–166,741 bp and GC contents of 34.4–35.6%. Genome-wide phylogenetic analysis and single gene-based tree construction revealed no correlation among the three phages. Moreover, no genes were associated with lysogeny, antibiotic resistance, or bacterial toxins. Therefore, the three novel phages represent potential candidates for phage therapy against CRAB infections. Full article

(This article belongs to the Special Issue Bacteriophages and Other Alternative Antimicrobials to Combat Multidrug Resistance)

► Show Figures

Figure 1

12 pages, 1466 KiB

Open AccessEditor’s ChoiceArticle

Implementation of a Multifaceted Program to Improve the Rational Use of Antibiotics in Children under 3 Years of Age in Primary Care

by Santiago Alfayate-Miguélez, Gema Martín-Ayala, Casimiro Jiménez-Guillén, Manuel Alcaraz-Quiñonero, Rafael Herrero Delicado and José Arnau-Sánchez

Antibiotics 2024, 13(7), 572; https://doi.org/10.3390/antibiotics13070572 - 21 Jun 2024

Viewed by 1723

Abstract

A multifaceted, participatory, open program based on a qualitative and quantitative approach was developed in the Region of Murcia (Spain) aimed to reduce antibiotic use in children under 3 years of age diagnosed with upper respiratory tract infections (acute otitis media, pharyngitis, and [...] Read more.

A multifaceted, participatory, open program based on a qualitative and quantitative approach was developed in the Region of Murcia (Spain) aimed to reduce antibiotic use in children under 3 years of age diagnosed with upper respiratory tract infections (acute otitis media, pharyngitis, and common cold). Antibiotic consumption was measured using the defined daily dose per 1000 inhabitants per day (DHD). Pre-intervention data showed a prevalence of antibiotic prescriptions in the primary care setting of 45.7% and a DHD of 19.05. In 2019, after the first year of implementation of the program, antibiotic consumption was 10.25 DHD with an overall decrease of 48% as compared with 2015. Although antibiotic consumption decreased in all health areas, there was a large variability in the magnitude of decreases across health areas (e.g., 12.97 vs. 4.77 DHD). The intervention program was effective in reducing the use of antibiotics in children under 3 years of age with common upper respiratory diseases, but reductions in antibiotic consumption were not consistent among all health areas involved. Full article

(This article belongs to the Special Issue Inappropriate Use of Antibiotics in Pediatrics)

► Show Figures

Figure 1

12 pages, 1553 KiB

Open AccessEditor’s ChoiceArticle

Demographic Characteristics and Economic Burden of Clostridioides difficile Infection in Korea: A Nationwide Population-Based Study after Propensity Score Matching

by Jae Myung Cha, Jin Young Yoon, Min Seob Kwak, Moonhyung Lee and Young-Seok Cho

Antibiotics 2024, 13(6), 542; https://doi.org/10.3390/antibiotics13060542 - 10 Jun 2024

Cited by 1 | Viewed by 1422

Abstract

Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of [...] Read more.

Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×10³), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 3rd Edition)

► Show Figures

Graphical abstract

17 pages, 2142 KiB

Open AccessEditor’s ChoiceArticle

Impact of Soil Fertilization with Pig Slurry on Antibiotic Residues and Resistance Genes: A Longitudinal Study

by Luisa Massaccesi, Elisa Albini, Francesca Romana Massacci, Danilo Giusepponi, Fabiola Paoletti, Stefano Sdogati, Francesco Morena, Alberto Agnelli, Angelo Leccese, Chiara Francesca Magistrali and Roberta Galarini

Antibiotics 2024, 13(6), 486; https://doi.org/10.3390/antibiotics13060486 - 24 May 2024

Cited by 1 | Viewed by 1692

Abstract

The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add knowledge about persistence and correlations between antibiotic residues and antibiotic resistance genes (ARGs) in fertilized soil, [...] Read more.

The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add knowledge about persistence and correlations between antibiotic residues and antibiotic resistance genes (ARGs) in fertilized soil, a longitudinal soil mesocosm study was conducted. Soil samples were collected from the mesocosms immediately before spreading and then afterward at fifteen time points during a 320-day observation period. Eight ARGs (ermB, sul1, tetA, tetG, tetM, cfr, fexA, and optrA) and the class 1 integron-integrase gene, intI1, were determined in both pig slurry and soil, as well as residues of 36 antibiotics. Soil chemical and biochemical parameters were also measured. Twelve antibiotics were detected in the slurry in the range of 3 µg kg⁻¹–3605 µg kg⁻¹, with doxycycline, lincomycin, and tiamulin being the most abundant, whereas ermB, sul1, and tetM were the predominant ARGs. Before spreading, neither antibiotic residues nor ARGs were detectable in the soil; afterwards, their concentrations mirrored those in the slurry, with a gradual decline over the duration of the experiment. After about three months, the effect of the amendment was almost over, and no further evolution was observed. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Monitoring in Food-Producing Animals)

► Show Figures

Figure 1

30 pages, 5934 KiB

Open AccessEditor’s ChoiceArticle

The MraY Inhibitor Muraymycin D2 and Its Derivatives Induce Enlarged Cells in Obligate Intracellular Chlamydia and Wolbachia and Break the Persistence Phenotype in Chlamydia

by Iris Löckener, Lara Vanessa Behrmann, Jula Reuter, Andrea Schiefer, Anna Klöckner, Sebastian Krannich, Christian Otten, Katja Mölleken, Satoshi Ichikawa, Achim Hoerauf, Tanja Schneider, Kenneth M. Pfarr and Beate Henrichfreise

Antibiotics 2024, 13(5), 421; https://doi.org/10.3390/antibiotics13050421 - 4 May 2024

Cited by 1 | Viewed by 2263

Abstract

Chlamydial infections and diseases caused by filarial nematodes are global health concerns. However, treatment presents challenges due to treatment failures potentially caused by persisting Chlamydia and long regimens against filarial infections accompanied by low compliance. A new treatment strategy could be the targeting [...] Read more.

Chlamydial infections and diseases caused by filarial nematodes are global health concerns. However, treatment presents challenges due to treatment failures potentially caused by persisting Chlamydia and long regimens against filarial infections accompanied by low compliance. A new treatment strategy could be the targeting of the reduced peptidoglycan structures involved in cell division in the obligate intracellular bacteria Chlamydia and Wolbachia, the latter being obligate endosymbionts supporting filarial development, growth, and survival. Here, cell culture experiments with C. trachomatis and Wolbachia showed that the nucleoside antibiotics muraymycin and carbacaprazamycin interfere with bacterial cell division and induce enlarged, aberrant cells resembling the penicillin-induced persistence phenotype in Chlamydia. Enzymatic inhibition experiments with purified C. pneumoniae MraY revealed that muraymycin derivatives abolish the synthesis of the peptidoglycan precursor lipid I. Comparative in silico analyses of chlamydial and wolbachial MraY with the corresponding well-characterized enzyme in Aquifex aeolicus revealed a high degree of conservation, providing evidence for a similar mode of inhibition. Muraymycin D2 treatment eradicated persisting non-dividing C. trachomatis cells from an established penicillin-induced persistent infection. This finding indicates that nucleoside antibiotics may have additional properties that can break bacterial persistence. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

► Show Figures

Figure 1

16 pages, 3192 KiB

Open AccessEditor’s ChoiceArticle

Bacitracin Methylene Disalicylate (BMD) Treatment Affects Spleen Proteome in Broiler Chicks Infected with Salmonella enteritidis

by Adedeji Adetunji, Theresa Casey, Uma K. Aryal, Tunde Ogundare, Jackeline Franco and Yewande Fasina

Antibiotics 2024, 13(5), 414; https://doi.org/10.3390/antibiotics13050414 - 1 May 2024

Cited by 1 | Viewed by 2727

Abstract

Bacitracin Methylene Disalicylate (BMD), as a feed additive to poultry diets, enhances digestion, prevents Salmonella enteritidis (SE) colonization, and treats current infections. The objective of this study was to utilize a quantitative proteomic approach to determine the effect of BMD feed additive on [...] Read more.

Bacitracin Methylene Disalicylate (BMD), as a feed additive to poultry diets, enhances digestion, prevents Salmonella enteritidis (SE) colonization, and treats current infections. The objective of this study was to utilize a quantitative proteomic approach to determine the effect of BMD feed additive on broiler chickens challenged with SE in the spleen proteome. At 1 d of age, chicks were randomly allocated into four groups: control with and without SE challenge (CON, n = 60; CON-SE, n = 60), BMD with and without SE challenge (BMD, n = 60; BMD-SE, n = 60). Birds in the CON-SE and BMD-SE treatment were administered SE inoculum by oral gavage. On day three and day seven post-gavage, the spleen was collected aseptically from birds in each treatment group (CON, n = 4/day; CON-SE, n = 4/day; BMD, n = 4/day; BMD-SE, n = 4/day). Proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed an increased abundance of 115 proteins and decreased of 77 due to the BMD. Proteins that decreased in abundance were enriched for fibrinogen complex and extracellular space, whereas proteins that increased in abundance were enriched for proteasome-mediated ubiquitin-dependent protein catabolic process and mitochondrion. Analysis of the interaction between BMD and the Salmonella challenge found 230 differentially abundant proteins including proteins associated with RNA binding, spliceosome, protein transport, and cell adhesion among the upregulated proteins, and those associated with protein folding, carbon metabolism, biosynthesis of nucleotide sugars, response to oxidative stress, positive regulation of NIK/NF-kappaB signaling, and inflammatory response among the downregulated proteins. The impact of BMD treatment on spleen proteome indicates an anti-apoptotic effect. BMD also modified the response of the spleen to the SE challenge with a marked decrease in proteins that prompt cytokine synthesis and an increase in proteins involved in the selective removal of unfolded proteins. Full article

(This article belongs to the Topic Animal Diseases in Agricultural Production Systems: Their Veterinary, Zoonotic, and One Health Importance, 2nd Edition)

► Show Figures

Figure 1

19 pages, 4683 KiB

Open AccessEditor’s ChoiceArticle

Efficacy of Tamoxifen Metabolites in Combination with Colistin and Tigecycline in Experimental Murine Models of Escherichia coli and Acinetobacter baumannii

by Soraya Herrera-Espejo, Andrea Vila-Domínguez, Tania Cebrero-Cangueiro, Younes Smani, Jerónimo Pachón, Manuel E. Jiménez-Mejías and María E. Pachón-Ibáñez

Antibiotics 2024, 13(5), 386; https://doi.org/10.3390/antibiotics13050386 - 24 Apr 2024

Cited by 2 | Viewed by 1909

Abstract

This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and [...] Read more.

This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on E. coli (colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and A. baumannii (tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both E. coli strains, especially E. coli MCR-1+ (−2.86 log₁₀ CFU/g lungs, −5.88 log₁₀ CFU/mL blood, and −50% mortality), and against the Ab#186 strain when combined with CMS (−2.27 log₁₀ CFU/g lungs, −2.73 log₁₀ CFU/mL blood, and −40% mortality) or tigecycline (−3.27 log₁₀ CFU/g lungs, −4.95 log₁₀ CFU/mL blood, and −50% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both A. baumannii strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible E. coli C1-7-LE strain (−3.32 log₁₀ CFU/g lung, −6.06 log₁₀ CFU/mL blood, and −79% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically A. baumannii. Full article

(This article belongs to the Special Issue Advancing the Discovery and Development of New Antibiotics through Drug Repurposing)

► Show Figures

Figure 1

10 pages, 228 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Clinical Relevance of Routine Sonication for Periprosthetic Hip or Knee Joint Infection Diagnosis

by Anas Zouitni, Jakob van Oldenrijk, P. Koen Bos, Peter D. Croughs, Erlangga Yusuf and Ewout S. Veltman

Antibiotics 2024, 13(4), 366; https://doi.org/10.3390/antibiotics13040366 - 17 Apr 2024

Cited by 1 | Viewed by 1972

Abstract

Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. PJI screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique for PJI diagnosis. This study aims to determine the clinical relevance of routine sonication [...] Read more.

Periprosthetic joint infection (PJI) is a serious complication after joint arthroplasty. PJI screening and conventional cultures may be inconclusive. Sonication fluid culturing stands out as a valuable adjunct technique for PJI diagnosis. This study aims to determine the clinical relevance of routine sonication for all (a)septic revisions. All patients who underwent (partial) hip or knee revision arthroplasty between 2012 and 2021 were retrospectively reviewed. We formed three groups based on the European Bone and Joint Society PJI criteria: infection confirmed, likely, and unlikely. We analyzed clinical, laboratory, and radiological screening. Sensitivity and specificity were calculated for synovial fluid (preoperative), tissue, and sonication fluid cultures. We determined the clinical relevance of sonication as the percentage of patients for whom sonication confirmed PJI; 429 patients who underwent (partial) revision of hip or knee arthroplasty were included. Sensitivity and specificity were 69% and 99% for synovial fluid cultures, 76% and 92% for tissue cultures, and 80% and 89% for sonication fluid cultures, respectively. Sonication fluid cultures improved tissue culture sensitivity and specificity to 83% and 99%, respectively. In 11% of PJIs, sonication fluid cultures were decisive for diagnosis. This is applicable to acute and chronic infections. Sonication fluid cultures enhanced the sensitivity and specificity of PJI diagnostics. In 11% of PJI cases, causative pathogens were confirmed by sonication fluid culture results. Sonication fluid culture should be performed in all revision arthroplasties. Full article

(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)

22 pages, 6012 KiB

Open AccessEditor’s ChoiceArticle

Repurposing Farnesol for Combating Drug-Resistant and Persistent Single and Polymicrobial Biofilms

by Li Tan, Rong Ma, Tony Reeves, Adam J. Katz and Nicole Levi

Antibiotics 2024, 13(4), 350; https://doi.org/10.3390/antibiotics13040350 - 11 Apr 2024

Cited by 4 | Viewed by 2097

Abstract

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the [...] Read more.

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, including their polymicrobial biofilms, and, moreover, kills S. aureus persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for S. aureus after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy—including ability to reduce persistent and resistant microbial populations—farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

► Show Figures

Figure 1

17 pages, 2227 KiB

Open AccessEditor’s ChoiceArticle

Insights into the Evolution of IncR Plasmids Found in the Southern European Clone of the Monophasic Variant of Salmonella enterica Serovar Typhimurium

by Xenia Vázquez, Javier Fernández, Jürgen J. Heinisch, Rosaura Rodicio and M. Rosario Rodicio

Antibiotics 2024, 13(4), 314; https://doi.org/10.3390/antibiotics13040314 - 29 Mar 2024

Viewed by 2034

Abstract

Salmonella enterica subspecies enterica serovar 4,[5],12:i:- is a monophasic variant of S. Typhimurium which has emerged as a world-wide distributed pathogen in the last decades. Several clones have been identified within this variant, the European clone, the Spanish clone, the Southern European [...] Read more.

Salmonella enterica subspecies enterica serovar 4,[5],12:i:- is a monophasic variant of S. Typhimurium which has emerged as a world-wide distributed pathogen in the last decades. Several clones have been identified within this variant, the European clone, the Spanish clone, the Southern European clone and the U.S./American clone. The present study focused on isolates of the Southern European clone that were obtained from clinical samples at Spanish hospitals. The selected isolates were multidrug resistant, with most resistance genes residing on IncR plasmids that also carried virulence genes. These plasmids had a mosaic structure, comprising a highly reduced IncR backbone, which has acquired a large amount of exogenous DNA mostly derived from pSLT and IncI1-I(alfa) plasmids. Although composed of approximately the same elements, the investigated plasmids displayed a high diversity, consistent with active evolution driven by a wealth of mobile genetic elements. They comprise multiple intact or truncated insertion sequences, transposons, pseudo-compound transposons and integrons. Particularly relevant was the role of IS26 (with six to nine copies per plasmid) in generating insertions, deletions and inversions, with many of the rearrangements uncovered by tracking the patterns of eight bp target site duplications. Most of the resistance genes detected in the analyzed isolates have been previously associated with the Southern European clone. However, erm(B), lnu(G) and bla_TEM-1B are novel, with the last two carried by a second resistance plasmid found in one of the IncR-positive isolates. Thus, evolution of resistance in the Southern European clone is not only mediated by diversification of the IncR plasmids, but also through acquisition of additional plasmids. All isolates investigated in the present study have the large deletion affecting the fljBA region previously found to justify the monophasic phenotype in the Southern European and U.S./American clones. An SNP-based phylogenetic analysis revealed the close relationship amongst our isolates, and support that those sharing the large fljBA deletion could be more heterogeneous than previously anticipated. Full article

(This article belongs to the Special Issue The Evolution of Plasmid-Mediated Antimicrobial Resistance)

► Show Figures

Figure 1

16 pages, 989 KiB

Open AccessEditor’s ChoiceArticle

Comparative Impact of an Optimized PK/PD Target Attainment of Piperacillin-Tazobactam vs. Meropenem on the Trend over Time of SOFA Score and Inflammatory Biomarkers in Critically Ill Patients Receiving Continuous Infusion Monotherapy for Treating Documented Gram-Negative BSIs and/or VAP

by Milo Gatti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Pierluigi Viale and Federico Pea

Antibiotics 2024, 13(4), 296; https://doi.org/10.3390/antibiotics13040296 - 25 Mar 2024

Cited by 2 | Viewed by 2189

Abstract

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over [...] Read more.

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted. Full article

(This article belongs to the Special Issue Antibacterial Resistance and Infection Control in ICU)

► Show Figures

Figure 1

12 pages, 423 KiB

Open AccessEditor’s ChoiceArticle

Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas

by Sotirios D. Georgopoulos, Elias Xirouchakis, Christos Liatsos, Pericles Apostolopoulos, Panagiotis Kasapidis, Beatriz Martinez-Gonzalez, Fotini Laoudi, Maria Stoupaki, Georgios Axiaris, Dionysios Sgouras, Andreas Mentis and Spyridon Michopoulos

Antibiotics 2024, 13(3), 280; https://doi.org/10.3390/antibiotics13030280 - 20 Mar 2024

Cited by 2 | Viewed by 2083

Abstract

Background and aim: We conducted an equivalence trial of quadruple non-bismuth “concomitant” and “hybrid” regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to [...] Read more.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth “concomitant” and “hybrid” regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

► Show Figures

Figure 1

11 pages, 3631 KiB

Open AccessEditor’s ChoiceArticle

Chestnut Honey Is Effective against Mixed Biofilms at Different Stages of Maturity

by Regina Koloh, Viktória L. Balázs, Lilla Nagy-Radványi, Béla Kocsis, Erika Beáta Kerekes, Marianna Kocsis and Ágnes Farkas

Antibiotics 2024, 13(3), 255; https://doi.org/10.3390/antibiotics13030255 - 13 Mar 2024

Cited by 3 | Viewed by 2807

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Combating Biofilm-Related Infections: Novel Therapeutics and Strategies)

► Show Figures

Graphical abstract

21 pages, 3351 KiB

Open AccessEditor’s ChoiceArticle

A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens

by Eric J. Bryan, Qi Qiao, Yuxuan Wang, Jacques Y. Roberge, Edmond J. LaVoie and Daniel S. Pilch

Antibiotics 2024, 13(3), 209; https://doi.org/10.3390/antibiotics13030209 - 22 Feb 2024

Cited by 1 | Viewed by 2640

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antibiotics)

► Show Figures

Figure 1

19 pages, 1570 KiB

Open AccessEditor’s ChoiceArticle

Diverse Role of bla_CTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

by 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 and Grace C. Lee

Antibiotics 2024, 13(2), 185; https://doi.org/10.3390/antibiotics13020185 - 13 Feb 2024

Cited by 5 | Viewed by 3113

Abstract

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 [...] Read more.

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 bla_CTX-M had, on average, 9-fold higher copies of bla_CTX-M than CP-ErMs strains as well as approximately 4-fold more copies than bla_CTX-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 bla_CTX-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 bla_CTX-M and OmpC in ErMs strains, indicating the need to reappraise the term “non-carbapenemase (NCP)”, particularly for strains highly expressing bla_CTX-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. Full article

(This article belongs to the Special Issue Carbapenem Resistant Pathogens: Epidemiology, Treatment and Prevention)

► Show Figures

Figure 1

20 pages, 623 KiB

Open AccessEditor’s ChoiceArticle

Trends in Antibiotic Use in a Large Children’s Hospital in London (United Kingdom): 5 Years of Point Prevalence Surveys

by Kevin Meesters, Faye Chappell and Alicia Demirjian

Antibiotics 2024, 13(2), 172; https://doi.org/10.3390/antibiotics13020172 - 9 Feb 2024

Cited by 4 | Viewed by 2690

Abstract

Background: Antibiotics are commonly prescribed in paediatrics. As their excessive use contributes to adverse drug events, increased healthcare costs, and antimicrobial resistance, antimicrobial stewardship initiatives are essential to optimising medical care. These single-centre point prevalence surveys aimed to provide insights into antibiotic [...] Read more.

Background: Antibiotics are commonly prescribed in paediatrics. As their excessive use contributes to adverse drug events, increased healthcare costs, and antimicrobial resistance, antimicrobial stewardship initiatives are essential to optimising medical care. These single-centre point prevalence surveys aimed to provide insights into antibiotic prescribing trends and identify targets for paediatric AMS activities. Methods: 14 point prevalence surveys were conducted from March 2016–April 2021, collecting data on antibiotic prescriptions, indication, adherence to guidelines, and route of administration. The UK adapted the World Health Organisation’s AWaRe classification-guided antibiotic categorization. Results: 32.5% of all inpatients were on at least one antimicrobial; this remained stable during all surveys (range: 20–44%, p = 0.448). Of all prescriptions, 67.2% had an end- or review-date, and the majority was for agents in the Watch category (46.8–70.5%). Amoxicillin and clavulanate were the most frequently prescribed antibiotics (20.8%), followed by gentamicin (15.3%). Approximately 28.8% of all prescriptions were for prophylactic indications, while 7.6% of the prescriptions were not adherent to the hospital guidelines. Conclusions: This study highlights the importance of ongoing monitoring and robust AMS initiatives to ensure prudent antibiotic prescribing in paediatric healthcare. It underscores the need for tailored guidelines, educational efforts, and targeted interventions to enhance the quality of antibiotic usage, ultimately benefiting both individual patients and public health. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship and Use in Healthcare Setting)

► Show Figures

Figure 1

17 pages, 1445 KiB

Open AccessEditor’s ChoiceReview

Novel Antimicrobial Approaches to Combat Bacterial Biofilms Associated with Urinary Tract Infections

by Giuseppe Mancuso, Marilena Trinchera, Angelina Midiri, Sebastiana Zummo, Giulia Vitale and Carmelo Biondo

Antibiotics 2024, 13(2), 154; https://doi.org/10.3390/antibiotics13020154 - 4 Feb 2024

Cited by 12 | Viewed by 6252

Abstract

Urinary tract infections (UTIs) are prevalent bacterial infections in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, [...] Read more.

Urinary tract infections (UTIs) are prevalent bacterial infections in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, the significant increase in antibiotic resistance in recent years has made many previously effective treatments ineffective. Biofilm on medical equipment in healthcare settings creates a reservoir of pathogens that can easily be transmitted to patients. Urinary catheter infections are frequently observed in hospitals and are caused by microbes that form a biofilm after a catheter is inserted into the bladder. Managing infections caused by biofilms is challenging due to the emergence of antibiotic resistance. Biofilms enable pathogens to evade the host’s innate immune defences, resulting in long-term persistence. The incidence of sepsis caused by UTIs that have spread to the bloodstream is increasing, and drug-resistant infections may be even more prevalent. While the availability of upcoming tests to identify the bacterial cause of infection and its resistance spectrum is critical, it alone will not solve the problem; innovative treatment approaches are also needed. This review analyses the main characteristics of biofilm formation and drug resistance in recurrent uropathogen-induced UTIs. The importance of innovative and alternative therapies for combatting biofilm-caused UTI is emphasised. Full article

(This article belongs to the Special Issue From Detection to Treatment: Navigating Urinary Tract Infections with Antibiotics)

► Show Figures

Figure 1

16 pages, 3065 KiB

Open AccessEditor’s ChoiceArticle

Influence of Dead Cells Killed by Industrial Biocides (BAC and DBNPA) on Biofilm Formation

by Ana C. Barros, Diogo A. C. Narciso, Luis F. Melo and Ana Pereira

Antibiotics 2024, 13(2), 140; https://doi.org/10.3390/antibiotics13020140 - 31 Jan 2024

Cited by 1 | Viewed by 2315

Abstract

Industrial biocides aim to keep water systems microbiologically controlled and to minimize biofouling. However, the resulting dead cells are usually not removed from the water streams and can influence the growth of the remaining live cells in planktonic and sessile states. This study [...] Read more.

Industrial biocides aim to keep water systems microbiologically controlled and to minimize biofouling. However, the resulting dead cells are usually not removed from the water streams and can influence the growth of the remaining live cells in planktonic and sessile states. This study aims to understand the effect of dead Pseudomonas fluorescens cells killed by industrial biocides—benzalkonium chloride (BAC) and 2,2-dibromo-3-nitrilopropionamide (DBNPA)—on biofilm formation. Additionally, the effect of different dead/live cell ratios (50.00% and 99.99%) was studied. The inoculum was recirculated in a Parallel Plate Flow Cell (PPFC). The overall results indicate that dead cells greatly affect biofilm properties. Inoculum with DBNPA–dead cells led to more active (higher ATP content and metabolic activity) and thicker biofilm layers in comparison to BAC–dead cells, which seems to be linked to the mechanism of action by which the cells were killed. Furthermore, higher dead cell ratios (99.99%) in the inoculum led to more active (higher culturability, metabolic activity and ATP content) and cohesive/compact and uniformly distributed biofilms in comparison with the 50.00% dead cell ratio. The design of future disinfection strategies must consider the contribution of dead cells to the biofilm build-up, as they might negatively affect water system operations. Full article

(This article belongs to the Special Issue Biofilm Formation and Control)

► Show Figures

Graphical abstract

12 pages, 848 KiB

Open AccessEditor’s ChoiceArticle

Determining Susceptibility and Potential Mediators of Resistance for the Novel Polymyxin Derivative, SPR206, in Acinetobacter baumannii

by Jacinda C. Abdul-Mutakabbir, Nana Sakyi Opoku, Karen K. Tan, Peter Jorth, Victor Nizet, Hansel M. Fletcher, Keith S. Kaye and Michael J. Rybak

Antibiotics 2024, 13(1), 47; https://doi.org/10.3390/antibiotics13010047 - 4 Jan 2024

Cited by 2 | Viewed by 2743

Abstract

With the increase in carbapenem-resistant A. baumannii (CRAB) infections, there has been a resurgence in the use of polymyxins, specifically colistin (COL). Since the reintroduction of COL-based regimens in treating CRAB infections, several COL-resistant A. baumannii isolates have been identified, with the mechanism [...] Read more.

With the increase in carbapenem-resistant A. baumannii (CRAB) infections, there has been a resurgence in the use of polymyxins, specifically colistin (COL). Since the reintroduction of COL-based regimens in treating CRAB infections, several COL-resistant A. baumannii isolates have been identified, with the mechanism of resistance heavily linked with the loss of the lipopolysaccharide (LPS) layer of the bacterial outer membrane through mutations in lpxACD genes or the pmrCAB operon. SPR206, a novel polymyxin derivative, has exhibited robust activity against multidrug-resistant (MDR) A. baumannii. However, there is a dearth of knowledge regarding its efficacy in comparison with other A. baumannii-active therapeutics and whether traditional polymyxin (COL) mediators of A. baumannii resistance also translate to reduced SPR206 activity. Here, we conducted susceptibility testing using broth microdilution on 30 A. baumannii isolates (17 COL-resistant and 27 CRAB), selected 14 COL-resistant isolates for genomic sequencing analysis, and performed time-kill analyses on four COL-resistant isolates. In susceptibility testing, SPR206 demonstrated a lower range of minimum inhibitory concentrations (MICs) compared with COL, with a four-fold difference observed in MIC₅₀ values. Mutations in lpxACD and/or pmrA and pmrB genes were detected in each of the 14 COL-resistant isolates; however, SPR206 maintained MICs ≤ 2 mg/L for 9/14 (64%) of the isolates. Finally, SPR206-based combination regimens exhibited increased synergistic and bactericidal activity compared with COL-based combination regimens irrespective of the multiple resistance genes detected. The results of this study highlight the potential utility of SPR206 in the treatment of COL-resistant A. baumannii infections. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

► Show Figures

Figure 1

19 pages, 4545 KiB

Open AccessEditor’s ChoiceArticle

Exploring Structure–Activity Relationships of Niclosamide-Based Colistin Potentiators in Colistin-Resistant Gram-Negative Bacteria

by Liam Berry, Quinn Neale, Rajat Arora, Danyel Ramirez, Marc Brizuela, Ronald Domalaon, Gilbert Arthur and Frank Schweizer

Antibiotics 2024, 13(1), 43; https://doi.org/10.3390/antibiotics13010043 - 3 Jan 2024

Cited by 3 | Viewed by 2608

Abstract

Colistin is primarily used as a last resort antibiotic against highly resistant Gram-negative bacteria (GNB). Rising rates of colistin resistance, however, may limit future use of this agent. The anthelmintic drug niclosamide has been shown to enhance colistin activity in combination therapy, but [...] Read more.

Colistin is primarily used as a last resort antibiotic against highly resistant Gram-negative bacteria (GNB). Rising rates of colistin resistance, however, may limit future use of this agent. The anthelmintic drug niclosamide has been shown to enhance colistin activity in combination therapy, but a detailed structure–activity relationship (SAR) for niclosamide against GNB has yet to be studied. A series of niclosamide analogs were synthesized to perform an SAR, leading to the discovery of a lead compound that displayed comparable colistin-potentiating activity to niclosamide with reduced cytotoxicity. Overall, this work provides important insights into synthetic strategies for the future development of new niclosamide derivatives and demonstrates that toxicity to mammalian cells can be reduced while maintaining colistin potentiation. Full article

(This article belongs to the Special Issue Antibiotics Use and Therapy in Gram-Negative Bacterial Infection)

► Show Figures

Figure 1

13 pages, 1492 KiB

Open AccessEditor’s ChoiceArticle

Searching for Antimicrobial-Producing Bacteria from Soils through an Educational Project and Their Evaluation as Potential Biocontrol Agents

by Mario Sergio Pino-Hurtado, Rosa Fernández-Fernández, Carmen Torres and Beatriz Robredo

Antibiotics 2024, 13(1), 29; https://doi.org/10.3390/antibiotics13010029 - 28 Dec 2023

Cited by 6 | Viewed by 4561

Abstract

Antimicrobial resistance (AMR) is a serious threat to public health due to the lack of effective drugs to combat infectious diseases, which generates the need to search for new antimicrobial substances. In this study, the potential of soil as a source of antimicrobial-producing [...] Read more.

Antimicrobial resistance (AMR) is a serious threat to public health due to the lack of effective drugs to combat infectious diseases, which generates the need to search for new antimicrobial substances. In this study, the potential of soil as a source of antimicrobial-producing bacteria (APB) was investigated and the importance of the connection between education and science was emphasized, using service-learning methodologies. Sixty-one soil samples were collected, and 1220 bacterial isolates were recovered. Eighteen of these isolates showed antimicrobial activity against at least 1 of the 12 indicator bacteria tested (including multidrug-resistant and relevant pathogens). The 18 APB were identified by MALDI-TOF and 6 different genera (Bacillus, Brevibacillus, Lysinobacillus, Peribacillus, Streptomyces, and Advenella) and 10 species were identified. The 18 APB were tested for antifungal activity against four phytopathogenic fungi (Botritis cynerea, Lecanicillium fungicola, Trichoderma harzianum, and Cladobotryum mycophilum). Moreover, the antibiotic susceptibility of APB was tested using the disk-diffusion method as well as their β-hemolytic activity (important safety criteria for potential future applications). A total of 10 of the 18 APB were able to inhibit at least 50% of indicator bacteria tested, including methicillin-resistant Staphylococcus aureus (MRSA), among others. A total of 4 of the 18 APB (3 Bacillus pumilus and 1 Bacillus altitudinis) showed inhibitory activity against two of the four fungal pathogens tested (B. cinerea and L. fungicola), as well as against 5–7 of the 12 bacterial pathogen indicators; these 4 isolates showed susceptibility to the antibiotics tested and lacked β-hemolytic activity and were considered promising APB for use as potential biocontrol agents. In addition, one Brevibacillus laterosporus strain had activity against 83% of indicator bacteria tested including Escherichia coli, MRSA and other methicillin-resistant staphylococci, as well as vancomycin-resistant enterococci (but not against fungi). These results show that soil is a source of APB with relevant antibacterial and antifungal activities, and also emphasize the importance of education and science to raise public awareness of the AMR problem and the strategies to control it. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance)

► Show Figures

Figure 1

16 pages, 1865 KiB

Open AccessEditor’s ChoiceArticle

Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria

by Delphine Vergoz, Hung Le, Benoit Bernay, Annick Schaumann, Magalie Barreau, Flore Nilly, Florie Desriac, Ali Tahrioui, Jean-Christophe Giard, Olivier Lesouhaitier, Sylvie Chevalier, Jean Michel Brunel, Cécile Muller and Emmanuelle Dé

Antibiotics 2024, 13(1), 8; https://doi.org/10.3390/antibiotics13010008 - 20 Dec 2023

Viewed by 2284

Abstract

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain [...] Read more.

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain on four major pathogens, i.e., carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant E. faecium (VRE) strains. We screened the effect of these derivatives on biofilm formation and eradication. Derivatives 4e (for CRAB, VRE, and MRSA) and 4f (for all the strains) were the most potent ones and displayed activities as good as those of conventional antibiotics. We also identified 11 compounds able to decrease by more than 40% the production of pyocyanin, a major virulence factor of P. aeruginosa. We demonstrated that 4f treatment acts against bacterial infections in Galleria mellonella and significantly prolonged larvae survival (from 50% to 80%) after 24 h of CRAB, VRE, and MRSA infections. As shown by proteomic studies, 4f triggered distinct cellular responses depending on the bacterial species but essentially linked to cell envelope. Its interesting antibiofilm and antivirulence properties make it a promising a candidate for use in therapeutics. Full article

(This article belongs to the Special Issue Novel and Traditional Methods to Fight Antibiotic Resistant Bacteria and Biofilm Infections)

► Show Figures

Figure 1

16 pages, 1880 KiB

Open AccessEditor’s ChoiceArticle

Acinetobacter baumannii Survival under Infection-Associated Stresses Depends on the Expression of Resistance–Nodulation–Division and Major Facilitator Superfamily Efflux Pumps

by Inga V. Leus, Marcela Olvera, Justyna W. Adamiak, Lauren L. Nguyen and Helen I. Zgurskaya

Antibiotics 2024, 13(1), 7; https://doi.org/10.3390/antibiotics13010007 - 20 Dec 2023

Cited by 3 | Viewed by 3694

Abstract

Multidrug efflux transporters are major contributors to the antibiotic resistance of Acinetobacter baumannii in clinical settings. Previous studies showed that these transporters are tightly integrated into the physiology of A. baumannii and have diverse functions. However, for many of the efflux pumps, such [...] Read more.

Multidrug efflux transporters are major contributors to the antibiotic resistance of Acinetobacter baumannii in clinical settings. Previous studies showed that these transporters are tightly integrated into the physiology of A. baumannii and have diverse functions. However, for many of the efflux pumps, such functions remain poorly defined. In this study, we characterized two putative drug efflux pumps, AmfAB and AmfCD (Acinetobacter Major Facilitator), that are homologous to EmrAB-like transporters from Escherichia coli and other Gram-negative bacteria. These pumps comprise the Major Facilitator Superfamily (MFS) transporters AmfB and AmfD and the periplasmic membrane fusion proteins AmfA and AmfC, respectively. We inactivated and overproduced these pumps in the wild-type ATCC 17978 strain and its derivative strains lacking the major efflux pumps from the Resistance–Nodulation–Division (RND) superfamily and characterized antibiotic susceptibilities and growth of the strains under stresses typical during human infections. We found that neither AmfAB nor AmfCD contribute to the antibiotic non-susceptibility phenotypes of A. baumannii. The two pumps, however, are critical for the adaptation and growth of the bacterium under acidic stress, whereas AmfCD also contributes to growth under conditions of low iron, high temperature, and in the presence of bile salts. These functions are dependent on the presence of the RND pumps, the inactivation of which further diminishes A. baumannii survival and growth. Our results suggest that MFS transporters contribute to stress survival by affecting the permeability properties of the A. baumannii cell envelope. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Drug Design—a Themed Issue in Honor of Professor Kim Lewis)

► Show Figures

Graphical abstract

17 pages, 1540 KiB

Open AccessEditor’s ChoiceReview

How We Treat Drug-Susceptible Pulmonary Tuberculosis: A Practical Guide for Clinicians

by Niccolò Riccardi, Sara Occhineri, Elisa Vanino, Roberta Maria Antonello, Agostina Pontarelli, Francesca Saluzzo, Tiziana Masini, Giorgio Besozzi, Marina Tadolini, Luigi Codecasa and on behalf of StopTB Italia

Antibiotics 2023, 12(12), 1733; https://doi.org/10.3390/antibiotics12121733 - 14 Dec 2023

Cited by 1 | Viewed by 2892

Abstract

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis [...] Read more.

Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript. Full article

(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)

► Show Figures

Figure 1

15 pages, 836 KiB

Open AccessEditor’s ChoiceArticle

Antibiotic Resistance in Helicobacter pylori Isolates from Northwestern and Central Romania Detected by Culture-Based and PCR-Based Methods

by Carmen Costache, Horațiu Alexandru Colosi, Simona Grad, Anamaria Ioana Paștiu, Mariela Militaru, Anca Paula Hădărean, Dan Alexandru Țoc, Vlad Sever Neculicioiu, Alina Mihaela Baciu, Razvan Vlad Opris, Dan Lucian Dumitrașcu and Ioana Alina Colosi

Antibiotics 2023, 12(12), 1672; https://doi.org/10.3390/antibiotics12121672 - 28 Nov 2023

Cited by 4 | Viewed by 2394

Abstract

Little evidence has been published regarding the antimicrobial resistance patterns of Helicobacter pylori (H. pylori) strains in Northwestern and Central Romania. The aim of this study was to determine the antibiotic resistance pattern of H. pylori isolates from gastric biopsies collected [...] Read more.

Little evidence has been published regarding the antimicrobial resistance patterns of Helicobacter pylori (H. pylori) strains in Northwestern and Central Romania. The aim of this study was to determine the antibiotic resistance pattern of H. pylori isolates from gastric biopsies collected from patients living in Romania using ETEST^® and GenoType HelicoDR. Gastric biopsies were obtained from 148 adult patients, 87 women and 61 men, the majority (131 patients) from Northwestern and Central Romania. Sixty-nine H. pylori strains were detected by both culture and PCR; sixty-three biopsies were negative by both techniques; one biopsy was positive by culture but negative by PCR; and fifteen biopsies were negative by culture but positive by PCR. Primary resistance against clarithromycin, fluoroquinolones, and metronidazole was found in 16.7%, 11.1%, and 13.3% of strains, respectively. No primary resistance has been detected against amoxicillin, tetracycline, and rifampicin. Secondary resistance against clarithromycin, fluoroquinolones, metronidazole, amoxicillin, tetracycline, and rifampicin was found in 75.8%, 30.3%, 65.5%, 1.8%, 1.8%, and 7.3% of the strains, respectively. The most frequent clarithromycin-resistant genotype detected by GenoType HelicoDR was A2147G (62.3%). Concordances between ETEST^® and PCR for clarithromycin and fluoroquinolones were 85.5% and 78.3%, respectively. Further investigation of H. pylori resistance should be conducted to ensure proper eradication schemes. Full article

(This article belongs to the Special Issue Helicobacter pylori Infection - New Data and Approaches on Diagnosis, Pathogenesis, Antibiotic Resistance and Advances in Therapy)

► Show Figures

Figure 1

13 pages, 457 KiB

Open AccessEditor’s ChoiceArticle

Clinical Impact of Rapid Bacterial Microbiological Identification with the MALDI-TOF MS

by Miriam Uzuriaga, José Leiva, Francisco Guillén-Grima, Marta Rua and José R. Yuste

Antibiotics 2023, 12(12), 1660; https://doi.org/10.3390/antibiotics12121660 - 25 Nov 2023

Cited by 6 | Viewed by 2162

Abstract

Rapid microbiological reports to clinicians are related to improved clinical outcomes. We conducted a 3-year quasi-experimental design, specifically a pretest–posttest single group design in a university medical center, to evaluate the clinical impact of rapid microbiological identification information using MALDI-TOF MS on optimizing [...] Read more.

Rapid microbiological reports to clinicians are related to improved clinical outcomes. We conducted a 3-year quasi-experimental design, specifically a pretest–posttest single group design in a university medical center, to evaluate the clinical impact of rapid microbiological identification information using MALDI-TOF MS on optimizing antibiotic prescription. A total of 363 consecutive hospitalized patients with bacterial infections were evaluated comparing a historical control group (CG) (n = 183), in which the microbiological information (bacterial identification and antibiotic susceptibility) was reported jointly to the clinician between 18:00 h and 22:00 h of the same day and a prospective intervention group (IG) (n = 180); the bacterial identification information was informed to the clinician as soon as it was available between 12:00 h and 14:00 h and the antibiotic susceptibility between 18:00 h and 22:00 h). We observed, in favor of IG, a statistically significant decrease in the information time (11.44 h CG vs. 4.48 h IG (p < 0.01)) from the detection of bacterial growth in the culture medium to the communication of identification. Consequently, the therapeutic optimization was improved by introducing new antibiotics in the 10–24 h time window (p = 0.05) and conversion to oral route (p = 0.01). Additionally, we observed a non-statistically significant decrease in inpatient mortality (global, p = 0.15; infection-related, p = 0.21) without impact on hospital length of stay. In conclusion, the rapid communication of microbiological identification to clinicians reduced reporting time and was associated with early optimization of antibiotic prescribing without worsening clinical outcomes. Full article

(This article belongs to the Special Issue Antibiotic Use and Stewardship in Hospital)

► Show Figures

Figure 1

24 pages, 3155 KiB

Open AccessEditor’s ChoiceArticle

Genomic Diversity, Antimicrobial Resistance, Plasmidome, and Virulence Profiles of Salmonella Isolated from Small Specialty Crop Farms Revealed by Whole-Genome Sequencing

by Menuka Bhandari, Jelmer W. Poelstra, Michael Kauffman, Binta Varghese, Yosra A. Helmy, Joy Scaria and Gireesh Rajashekara

Antibiotics 2023, 12(11), 1637; https://doi.org/10.3390/antibiotics12111637 - 18 Nov 2023

Cited by 12 | Viewed by 3409

Abstract

Salmonella is the leading cause of death associated with foodborne illnesses in the USA. Difficulty in treating human salmonellosis is attributed to the development of antimicrobial resistance and the pathogenicity of Salmonella strains. Therefore, it is important to study the genetic landscape of [...] Read more.

Salmonella is the leading cause of death associated with foodborne illnesses in the USA. Difficulty in treating human salmonellosis is attributed to the development of antimicrobial resistance and the pathogenicity of Salmonella strains. Therefore, it is important to study the genetic landscape of Salmonella, such as the diversity, plasmids, and presence antimicrobial resistance genes (AMRs) and virulence genes. To this end, we isolated Salmonella from environmental samples from small specialty crop farms (SSCFs) in Northeast Ohio from 2016 to 2021; 80 Salmonella isolates from 29 Salmonella-positive samples were subjected to whole-genome sequencing (WGS). In silico serotyping revealed the presence of 15 serotypes. AMR genes were detected in 15% of the samples, with 75% exhibiting phenotypic and genotypic multidrug resistance (MDR). Plasmid analysis demonstrated the presence of nine different types of plasmids, and 75% of AMR genes were located on plasmids. Interestingly, five Salmonella Newport isolates and one Salmonella Dublin isolate carried the ACSSuT gene cassette on a plasmid, which confers resistance to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline. Overall, our results show that SSCFs are a potential reservoir of Salmonella with MDR genes. Thus, regular monitoring is needed to prevent the transmission of MDR Salmonella from SSCFs to humans. Full article

(This article belongs to the Special Issue Antibiotic Resistance, Virulence Profile and Genomic Analysis among Multidrug-Resistant Bacteria Isolated from Humans and Animals)

► Show Figures

Figure 1

12 pages, 583 KiB

Open AccessEditor’s ChoiceArticle

Emergence of Antibiotic-Resistant Porphyromonas gingivalis in United States Periodontitis Patients

by Thomas E. Rams, Jacqueline D. Sautter and Arie J. van Winkelhoff

Antibiotics 2023, 12(11), 1584; https://doi.org/10.3390/antibiotics12111584 - 2 Nov 2023

Cited by 16 | Viewed by 6172

Abstract

Antibiotic resistance patterns of the major human periodontal pathogen Porphyromonas gingivalis were assessed over a 20-year period in the United States. Subgingival P. gingivalis was cultured pre-treatment from 2193 severe periodontitis patients during three time periods: 1999–2000 (936 patients), 2009–2010 (685 patients), and [...] Read more.

Antibiotic resistance patterns of the major human periodontal pathogen Porphyromonas gingivalis were assessed over a 20-year period in the United States. Subgingival P. gingivalis was cultured pre-treatment from 2193 severe periodontitis patients during three time periods: 1999–2000 (936 patients), 2009–2010 (685 patients), and 2019–2020 (572 patients). The clinical isolates were tested for in vitro resistance to 4 mg/L for clindamycin and doxycycline, 8 mg/L for amoxicillin, and 16 mg/L for metronidazole, with a post hoc combination of data for metronidazole plus amoxicillin. Clindamycin-resistant P. gingivalis was significantly more prevalent in 2009–2010 (9.1% of patients) and 2019–2020 (9.3%; 15-fold increase) as compared to 1999–2000 (0.6%). P. gingivalis resistance to amoxicillin also significantly increased from 0.1% of patients in 1999–2000 to 1.3% in 2009–2010 and 2.8% (28-fold increase) in 2019–2020. P. gingivalis resistance to metronidazole, metronidazole plus amoxicillin, and doxycycline was low (≤0.5% prevalence), and statistically unchanged, over the 20-year period. These findings are the first to reveal marked increases over 20 years in clindamycin-resistant and amoxicillin-resistant P. gingivalis in United States periodontitis patients. Increased antibiotic resistance of P. gingivalis and other periodontitis-associated bacteria threatens the efficacy of periodontal antimicrobial chemotherapy. Full article

► Show Figures

Figure 1

17 pages, 1019 KiB

Open AccessEditor’s ChoiceArticle

Antimicrobial Susceptibility to 27 Drugs and the Molecular Mechanisms of Macrolide, Tetracycline, and Quinolone Resistance in Gemella sp.

by Michiko Furugaito, Yuko Arai, Yutaka Uzawa, Toshinori Kamisako, Kohei Ogura, Shigefumi Okamoto and Ken Kikuchi

Antibiotics 2023, 12(10), 1538; https://doi.org/10.3390/antibiotics12101538 - 14 Oct 2023

Cited by 3 | Viewed by 3818

Abstract

Gemella is a catalase-negative, facultative anaerobic, Gram-positive coccus that is commensal in humans but can become opportunistic and cause severe infectious diseases, such as infective endocarditis. Few studies have tested the antimicrobial susceptibility of Gemella. We tested its antimicrobial susceptibility to 27 [...] Read more.

Gemella is a catalase-negative, facultative anaerobic, Gram-positive coccus that is commensal in humans but can become opportunistic and cause severe infectious diseases, such as infective endocarditis. Few studies have tested the antimicrobial susceptibility of Gemella. We tested its antimicrobial susceptibility to 27 drugs and defined the resistant genes using PCR in 58 Gemella strains, including 52 clinical isolates and six type strains. The type strains and clinical isolates included 22 G. morbillorum, 18 G. haemolysans (GH) group (genetically indistinguishable from G. haemolysans and G. parahaemolysans), 13 G. taiwanensis, three G. sanguinis, and two G. bergeri. No strain was resistant to beta-lactams and vancomycin. In total, 6/22 (27.3%) G. morbillorum strains were erythromycin- and clindamycin-resistant ermB-positive, whereas 4/18 (22.2%) in the GH group, 7/13 (53.8%) G. taiwanensis, and 1/3 (33.3%) of the G. sanguinis strains were erythromycin-non-susceptible mefE- or mefA-positive and clindamycin-susceptible. The MIC₉₀ of minocycline and the ratios of tetM-positive strains varied across the different species—G. morbillorum: 2 µg/mL and 27.3% (6/22); GH group: 8 µg/mL and 27.8% (5/18); G. taiwanensis: 8 µg/mL and 46.2% (6/13), respectively. Levofloxacin resistance was significantly higher in G. taiwanensis (9/13 69.2%) than in G. morbillorum (2/22 9.1%). Levofloxacin resistance was associated with a substitution at serine 83 for leucine, phenylalanine, or tyrosine in GyrA. The mechanisms of resistance to erythromycin and clindamycin differed across Gemella species. In addition, the rate of susceptibility to levofloxacin differed across Gemella sp., and the quinolone resistance mechanism was caused by mutations in GyrA alone. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

► Show Figures

Figure 1

18 pages, 3389 KiB

Open AccessEditor’s ChoiceArticle

Modified CLEC3A-Derived Antimicrobial Peptides Lead to Enhanced Antimicrobial Activity against Drug-Resistant Bacteria

by Denise Meinberger, Marco G. Drexelius, Joshua Grabeck, Gabriele Hermes, Annika Roth, Dzemal Elezagic, Ines Neundorf, Thomas Streichert and Andreas R. Klatt

Antibiotics 2023, 12(10), 1532; https://doi.org/10.3390/antibiotics12101532 - 11 Oct 2023

Cited by 8 | Viewed by 2366

Abstract

Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs HT-16 and HT-47. We truncated their [...] Read more.

Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics. Sequence changes can significantly improve the therapeutic properties of antimicrobial peptides. In our study, we apply different sequence modifications to enhance the performance of the CLEC3A-derived AMPs HT-16 and HT-47. We truncated their sequences, inserting a triple-glycine linker, adding an N-terminal tryptophan residue, and generating a D-amino acid variant, resulting in the generation of seven new peptides. We investigated their antimicrobial activity against gram-positive and gram-negative bacteria, their cytotoxicity to murine cells, and the biostability of the modified peptides in serum. We identified a novel antimicrobial peptide, WRK-30, with enhanced antimicrobial potency against S. aureus and MRSA. Additionally, WRK-30 was less cytotoxic to eukaryotic cells, allowing its application in higher concentrations in an in vivo setting. In conclusion, we identified a novel CLEC3A-derived antimicrobial peptide WRK-30 with significantly improved therapeutic properties and the potential to widen the repertoire of conventional antibiotics. Full article

(This article belongs to the Special Issue Design, Modification and Application of Antimicrobial Peptides)

► Show Figures

Figure 1

30 pages, 4340 KiB

Open AccessEditor’s ChoiceReview

Complementary Activities of Host Defence Peptides and Antibiotics in Combating Antimicrobial Resistant Bacteria

by Patrick R. Lennard, Pieter S. Hiemstra and Peter H. Nibbering

Antibiotics 2023, 12(10), 1518; https://doi.org/10.3390/antibiotics12101518 - 6 Oct 2023

Cited by 5 | Viewed by 3441

Abstract

Due to their ability to eliminate antimicrobial resistant (AMR) bacteria and to modulate the immune response, host defence peptides (HDPs) hold great promise for the clinical treatment of bacterial infections. Whereas monotherapy with HDPs is not likely to become an effective first-line treatment, [...] Read more.

Due to their ability to eliminate antimicrobial resistant (AMR) bacteria and to modulate the immune response, host defence peptides (HDPs) hold great promise for the clinical treatment of bacterial infections. Whereas monotherapy with HDPs is not likely to become an effective first-line treatment, combinations of such peptides with antibiotics can potentially provide a path to future therapies for AMR infections. Therefore, we critically reviewed the recent literature regarding the antibacterial activity of combinations of HDPs and antibiotics against AMR bacteria and the approaches taken in these studies. Of the 86 studies compiled, 56 featured a formal assessment of synergy between agents. Of the combinations assessed, synergistic and additive interactions between HDPs and antibiotics amounted to 84.9% of the records, while indifferent and antagonistic interactions accounted for 15.1%. Penicillin, aminoglycoside, fluoro/quinolone, and glycopeptide antibiotic classes were the most frequently documented as interacting with HDPs, and Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecium were the most reported bacterial species. Few studies formally evaluated the effects of combinations of HDPs and antibiotics on bacteria, and even fewer assessed such combinations against bacteria within biofilms, in animal models, or in advanced tissue infection models. Despite the biases of the current literature, the studies suggest that effective combinations of HDPs and antibiotics hold promise for the future treatment of infections caused by AMR bacteria. Full article

(This article belongs to the Special Issue Potential of Antimicrobial Peptides for an Exciting Future)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI