Antibiotics

19 pages, 11797 KB

Open AccessEditor’s ChoiceArticle

Benzoxaborole-Based Inhibitors Block LexA Autocleavage and Suppress SOS-Dependent Adaptive Phenotypes in Escherichia coli

by Pierangelo Bellio, Lisaurora Nazzicone, Lorenza Fagnani, Eleonora Scarsella, Donatella Tondi, Laura Bertarini and Giuseppe Celenza

Antibiotics 2026, 15(5), 437; https://doi.org/10.3390/antibiotics15050437 - 27 Apr 2026

Viewed by 516

Abstract

Background/Objectives: The rapid emergence of antimicrobial resistance (AMR) is driven not only by antibiotic selective pressure but also by bacterial adaptive responses that enhance genetic diversification under stress. The SOS response, regulated by the RecA-LexA axis, plays a central role in coordinating [...] Read more.

Background/Objectives: The rapid emergence of antimicrobial resistance (AMR) is driven not only by antibiotic selective pressure but also by bacterial adaptive responses that enhance genetic diversification under stress. The SOS response, regulated by the RecA-LexA axis, plays a central role in coordinating DNA repair, mutagenesis, and phenotypic adaptation. Targeting this pathway represents a promising strategy to limit bacterial adaptability without directly affecting viability. This study aimed to evaluate benzoxaborole-based compounds as potential inhibitors of the LexA regulatory pathway. Methods: A drug repurposing approach was employed to investigate the benzoxaborole scaffold and the clinically approved derivatives tavaborole and crisaborole. Biochemical assays were used to assess LexA autocleavage in a RecA-dependent co-protease system. Molecular docking analyses were performed to evaluate compound binding within the LexA catalytic site. Microbiological assays were conducted to examine the effects on antibiotic-induced filamentation and biofilm formation under different growth conditions. Results: Selected benzoxaboroles inhibited LexA autocleavage, with tavaborole showing the strongest inhibitory profile in the biochemical assay. Docking analyses supported these findings, indicating stable binding within the LexA catalytic site near the catalytic serine residue. At the cellular level, tavaborole and benzoxaborole significantly reduced levofloxacin-induced filamentation at sub-inhibitory concentrations. Both compounds also decreased biofilm formation under nutrient-limited conditions, while no significant effects were observed on preformed biofilms. Crisaborole showed limited cellular activity despite measurable biochemical effects. Conclusions: These findings identify benzoxaboroles as modulators of the LexA-dependent SOS response and support the potential repurposing of clinically approved compounds as adjuvants to limit bacterial adaptive responses associated with antimicrobial resistance. Full article

(This article belongs to the Special Issue New Inhibitors for Overcoming Antimicrobial Resistance)

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25 pages, 6231 KB

Open AccessEditor’s ChoiceReview

How Glyphosate and Its Derivatives Influence Antimicrobial Resistance Emergence and Transmission: A One Health Perspective

by Leticia Malinoski, Gilmar Gonçalves Silva, Larissa Kaniak Ikeda Rodrigues, Leandro Flávio Carneiro and Marcelo Pedrosa Gomes

Antibiotics 2026, 15(4), 419; https://doi.org/10.3390/antibiotics15040419 - 21 Apr 2026

Cited by 4 | Viewed by 1997

Abstract

Background/Objectives: Glyphosate-based formulations are globally pervasive pollutants increasingly recognized as potential contributors to antimicrobial resistance (AMR) in environmental microbiomes. Although glyphosate is designed to inhibit plant 5-enolpyruvylshikimate-3-phosphate synthase, it also affects microbial metabolism, stress response, and genetic exchange. This review synthesizes the pathways [...] Read more.

Background/Objectives: Glyphosate-based formulations are globally pervasive pollutants increasingly recognized as potential contributors to antimicrobial resistance (AMR) in environmental microbiomes. Although glyphosate is designed to inhibit plant 5-enolpyruvylshikimate-3-phosphate synthase, it also affects microbial metabolism, stress response, and genetic exchange. This review synthesizes the pathways through which glyphosate, its metabolite aminomethylphosphonic acid (AMPA), and commercial mixtures influence resistance-associated phenotypes and the dissemination of antibiotic resistance (ABR). Methods: A critical synthesis of the literature was conducted to evaluate the mechanistic and ecological interactions between glyphosate exposure and bacterial resistance in soil, aquatic, and host-associated microbiomes. Results: Experimental evidence showed that sublethal glyphosate exposure induced oxidative stress, altered membrane permeability, activated multidrug efflux pumps, and promoted tolerance phenotypes that could modify antibiotic susceptibility. It also enhances mutation rates and horizontal gene transfer processes associated with the emergence of resistance under controlled conditions. At the community level, glyphosate exposure is associated with microbiome restructuring and enrichment of resistance determinants, often without major shifts in overall diversity of the microbiome. These effects have been reported at environmentally relevant concentrations, although the evidence remains largely derived from laboratory and mesocosm studies. Conclusions: Glyphosate acts as both a biochemical modulator of resistance-related phenotypes and an environmental selective pressure that shapes microbial communities. Its widespread use and environmental persistence position it as a context-dependent contributor to the emergence and dissemination of AMR through interacting mechanistic and ecological pathways. Integrating AMR endpoints into pesticide risk assessments and surveillance frameworks is warranted, in addition to expanded field-based validation. Full article

(This article belongs to the Special Issue Antibiotics in the Environment and Antimicrobial Resistance: A One Health Perspective)

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30 pages, 1286 KB

Open AccessEditor’s ChoiceArticle

Large Language Model Recommendations for Empiric Antibiotics Versus Clinician Prescribing: A Non-Interventional Paired Retrospective Antimicrobial Stewardship Analysis

by Ninel Iacobus Antonie, Vlad Alexandru Ionescu, Gina Gheorghe, Loredana-Crista Tiucă and Camelia Cristina Diaconu

Antibiotics 2026, 15(4), 368; https://doi.org/10.3390/antibiotics15040368 - 2 Apr 2026

Cited by 3 | Viewed by 1104

Abstract

Background/Objectives: Antimicrobial resistance (AMR) remains a major global health threat, strengthening the case for antimicrobial stewardship strategies that limit unnecessary broad-spectrum empiric therapy while preserving timely escalation when clinically warranted. Before any clinical deployment of large language model (LLM)-based antibiotic decision support [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) remains a major global health threat, strengthening the case for antimicrobial stewardship strategies that limit unnecessary broad-spectrum empiric therapy while preserving timely escalation when clinically warranted. Before any clinical deployment of large language model (LLM)-based antibiotic decision support can be considered, structured offline evaluation is needed to assess whether model outputs align with auditable stewardship constraints under real-world admission contexts. We therefore evaluated whether post hoc LLM-generated empiric antibiotic recommendations showed greater concordance with a pre-specified stewardship benchmarking framework than clinician-initiated regimens in a retrospective shadow-mode setting. Methods: Single-center retrospective paired evaluation at Clinical Emergency Hospital of Bucharest (Internal Medicine, 2020–2024). The unit of analysis was the admission (N = 493), with paired 24 h empiric regimens (clinician-prescribed vs. post hoc LLM-recommended via OpenAI API; not visible to clinicians; no influence on care). Local laboratory-derived epidemiology was precomputed from microbiology exports and provided as structured prompt context to approximate information parity with clinicians’ implicit local ecology knowledge. Primary (prespecified) endpoint: any contextual guardrail violation (unjustified carbapenem/antipseudomonal/anti-MRSA under prespecified structured severity/MDR-risk rules), exact McNemar. Key secondary (prespecified): Δ contextual guardrail penalty (LLM − Clin), sign test and Wilcoxon signed-rank (ties reported). Ethics committee approval was obtained. Results: Guardrail violations occurred in 17.0% of clinician regimens vs. 4.9% of LLM regimens (paired RD −12.2%; matched OR 0.216, 95% CI 0.127–0.367; McNemar exact p = 1.60 × 10⁻¹⁰). Δ penalty had median 0 with 398/493 ties; among non-ties, improvements (Δ < 0) exceeded adverse shifts (79 vs. 16; sign-test p = 3.47 × 10⁻¹¹). Conclusions: In this offline, non-interventional paired evaluation, LLM-generated empiric regimens showed greater concordance with a pre-specified stewardship benchmarking framework than clinician empiric regimens for the same admissions. These findings should not be interpreted as evidence of clinical superiority, patient safety, or causal effectiveness, but rather as process-level benchmarking within a rule-based stewardship construct. As such, reproducible guardrail-based benchmarking may serve as an early pre-implementation step to identify alignment and potential failure modes before prospective, safety-governed evaluation. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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15 pages, 1000 KB

Open AccessEditor’s ChoiceArticle

Deciphering the Emergence of Biofilm-Independent Colistin Persistence and Resistance in A. baumannii: Toxin–Antitoxin Omics and Novel T/A mRNA-asRNA Balance Regulatory Models

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

Antibiotics 2026, 15(4), 337; https://doi.org/10.3390/antibiotics15040337 - 26 Mar 2026

Viewed by 1188

Abstract

Background: Persistence represents a critical evolutionary reservoir for the development of antimicrobial resistance in Acinetobacter baumannii (Ab). Understanding the basal mechanisms that enable this survival strategy is crucial for elucidating how high-risk clones evolve resistance during therapy. Methods: High-dose [...] Read more.

Background: Persistence represents a critical evolutionary reservoir for the development of antimicrobial resistance in Acinetobacter baumannii (Ab). Understanding the basal mechanisms that enable this survival strategy is crucial for elucidating how high-risk clones evolve resistance during therapy. Methods: High-dose colistin time-kill assays were performed in ten ST2 clinical colistin-susceptible (COL-S) Carbapenem-Resistant Ab (CRAB) developing in vivo stable and full-colistin resistance to detect persisters. Genomics and basal transcriptomics of chromosomal/plasmid toxin–antitoxin systems (T/As) were performed, as duplicates for each sample, in two ST2 COL-S CRAB to investigate the genomics and basal T/A transcriptomic backgrounds. Results: Phenotypically, all strains showed a persistent subpopulation (~1% survival at 8 h) under 5× COL MIC exposure. Genomics identified 10 type-II and one type-IV T/A systems. Basal transcriptomics revealed active expression patterns mainly of GNAT superfamily T/A systems, with consistently low toxin mRNA levels associated with toxin- or antitoxin-directed asRNAs in chromosomal modules. This architecture defined new dual-combined regulatory models in which asRNAs acted as primary T/A mRNA balance modulators, putatively impacting on the T/A mRNA ratio. Conversely, the plasmid-encoded BrnT/A module showed a highly balanced expression. Conclusions: Our findings revealed, for the first time, the role of the type-II GNAT T/A superfamily as putative molecular switchers via a fine-tuning transcript balance regulation, impacting the transition from a metabolically active cell state to a dormant one in developing colistin persistence and in vivo resistance CRAB. Full article

(This article belongs to the Special Issue Mechanisms of Microbial Biofilm Resistance and New Methods for Biofilm Control)

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25 pages, 2146 KB

Open AccessEditor’s ChoiceArticle

Characterizing Aeromonas spp. as a Potential Sentinel Organism for Antimicrobial Resistance Dissemination in Wastewater and Drinking Water Treatment Systems: A Case Study in the Barcelona Metropolitan Area, Spain

by Laura Mondéjar, Victoria Ballén, Yaiza Gabasa, Laura Castellsagués, Anna Pinar-Méndez, Carles Vilaró, Belén Galofré, Aida González-Díaz, Sara Martí, Sergi Sanz and Sara M. Soto

Antibiotics 2026, 15(3), 301; https://doi.org/10.3390/antibiotics15030301 - 17 Mar 2026

Viewed by 1465

Abstract

Background: Wastewater treatment plants (WWTPs) are hotspots of antimicrobial resistance (AMR) due to inputs from diverse anthropogenic sources. Aeromonas spp., ubiquitous in aquatic environments, often carry clinically relevant antibiotic resistance genes (ARGs) and can persist beyond fecal contamination indicators, making them promising sentinel [...] Read more.

Background: Wastewater treatment plants (WWTPs) are hotspots of antimicrobial resistance (AMR) due to inputs from diverse anthropogenic sources. Aeromonas spp., ubiquitous in aquatic environments, often carry clinically relevant antibiotic resistance genes (ARGs) and can persist beyond fecal contamination indicators, making them promising sentinel organisms for AMR dissemination. The aim of this study was to assess the suitability of Aeromonas spp. in this role by characterizing resistance profiles, associated virulence factor genes (VFGs), genetic mobility, and persistence across wastewater and drinking water treatment processes in the Barcelona metropolitan area, Spain. Methods: Isolates were phenotypically characterized and screened for ARGs, VFGs, integrons, and heavy metal tolerance genes, followed by whole-genome sequencing (WGS). Biofilm formation was assessed in vitro. Conjugation assays with Escherichia coli evaluated horizontal gene transfer (HGT) potential. Results: A total of 428 antibiotic-resistant Aeromonas spp., the most abundant antibiotic-resistant bacteria isolated during the 2023 sampling campaigns from two WWTPs and one drinking water treatment plant (DWTP), were characterized. Trimethoprim/sulfamethoxazole (SXT) non-susceptibility was most frequent (72%), followed by cefoxitin resistance (65.4%). The sul1 (57.5%) and bla_MOX (78.6%) genes predominated among SXT- and β-lactam-resistant isolates. The merA gene was detected in 23.6%; 97.9% harbored at least one VFG (aerA, act, fla, alt, or hlyA), and 70.3% carried intI1. Half formed biofilm. Conjugation confirmed bi-directional HGT, and WGS revealed persistent ST3458 clones across treatment stages. Conclusions: WWTPs and DWTPs act as reservoirs of antibiotic-resistant Aeromonas spp., demonstrating persistence and HGT potential. Findings support their use as sentinel organisms for AMR surveillance in aquatic environments and for assessing treatment efficacy, highlighting variability across treatment types and locations, and reinforcing their relevance for urban water reclamation monitoring. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Wastewater Treatment Plants)

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31 pages, 487 KB

Open AccessEditor’s ChoiceReview

Cefepime Combined with Late-Generation β-Lactamase Inhibitors: Mechanisms of Action, In Vitro Activity, PK/PD Characteristics, Clinical Evidence and Resistance Mechanisms

by Sara Comini, Matteo Boattini, Paolo Gaibani and Gabriele Bianco

Antibiotics 2026, 15(3), 263; https://doi.org/10.3390/antibiotics15030263 - 3 Mar 2026

Cited by 5 | Viewed by 3136

Abstract

Cefepime combined with late-generation β-lactamase inhibitors—enmetazobactam, zidebactam, and taniborbactam—represents a promising strategy to treat multidrug-resistant Gram-negative infections. These combinations expand the therapeutic armamentarium beyond established β-lactam/β-lactamase inhibitor regimens, offering targeted activity against ESBL-, AmpC-, and carbapenemase-producing Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa [...] Read more.

Cefepime combined with late-generation β-lactamase inhibitors—enmetazobactam, zidebactam, and taniborbactam—represents a promising strategy to treat multidrug-resistant Gram-negative infections. These combinations expand the therapeutic armamentarium beyond established β-lactam/β-lactamase inhibitor regimens, offering targeted activity against ESBL-, AmpC-, and carbapenemase-producing Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. In vitro studies highlight potent and broad activity, with mechanisms including β-lactamase inhibition and, in the case of zidebactam, dual β-lactam enhancement through PBP2 binding. Clinical evidence demonstrates efficacy in complicated urinary tract infections and suggests potential for treating extensively drug-resistant infections, including those unresponsive to conventional β-lactam/β-lactamase inhibitors. Emerging resistance mechanisms—such as PBP alterations, porin loss, efflux pump overexpression, and evolving KPC or NDM variants—underscore the need for ongoing surveillance and robust susceptibility testing. This review provides a comprehensive overview of the mechanisms of action, in vitro activity, pharmacokinetic/pharmacodynamic properties, clinical outcomes, and resistance patterns of these cefepime-based combinations. It also highlights future directions, including the establishment of clinical breakpoints, evaluation in severe infections, and exploration of combination strategies to counteract complex resistance. Overall, these agents exemplify a strategic evolution in β-lactam therapy, offering versatile options to reduce carbapenem reliance while maintaining high efficacy against multidrug-resistant Gram-negative pathogens. Full article

(This article belongs to the Special Issue Bacterial Detection, Identification, and Antimicrobial Susceptibility Testing, 2nd Edition)

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17 pages, 1700 KB

Open AccessEditor’s ChoiceArticle

Risk Factors Associated with the Emergence of Multidrug-Resistant Bacteria and Fungal Infections in Walled-Off Pancreatic Necrosis

by Michael Fernandez Y Viesca, Alia Hadefi, Lukas Otero Sanchez, Martina Pezzullo, Morgane Van Wettere, Eleni Karakike, Maya Hites, Viviane De Maertelaer, Myriam Delhaye and Marianna Arvanitakis

Antibiotics 2026, 15(2), 220; https://doi.org/10.3390/antibiotics15020220 - 17 Feb 2026

Cited by 2 | Viewed by 1485

Abstract

Background: Infected pancreatic necrosis (IPN) is a serious complication of moderate-to-severe acute pancreatitis (AP), associated with high morbidity, intensive care unit (ICU) admission, organ failure, and mortality. Initial management relies on antibiotics and drainage of walled-off necrosis (WON). In the context of increasing [...] Read more.

Background: Infected pancreatic necrosis (IPN) is a serious complication of moderate-to-severe acute pancreatitis (AP), associated with high morbidity, intensive care unit (ICU) admission, organ failure, and mortality. Initial management relies on antibiotics and drainage of walled-off necrosis (WON). In the context of increasing multidrug-resistant (MDR) bacteria, identifying risk factors for MDR emergence is crucial. The impact of fungal infections (FIs) on outcomes also remains unclear. This study aimed to identify risk factors associated with the emergence of MDR bacteria and FIs during intervention for IPN. Methods: This retrospective study included 71 consecutive patients undergoing intervention for suspected IPN or symptomatic WON. Results: At first intervention, IPN was confirmed in 52 patients (73%), MDR bacteria in 19 (27%), extensively drug-resistant (XDR) bacteria in 4 (5.6%), and FI in 21 (30%). After all interventions, MDR/XDR bacteria and fungi were detected in 25 (35%)/11 (15.5%) and 42 (59%) patients, respectively. Independent risk factors for MDR emergence were the number of antibiotic changes (b, 1.70; 95% CI 1.18–2.43; p = 0.004) and need for nutritional support (NS) (b, 5.69; 95% CI 1.52–20.50; p = 0.010). No independent factor was associated with FI. The 180-day mortality did not differ across groups. The 90-day cumulative ICU admission rate was higher in IPN vs. non-IPN (63.1% vs. 29.4%, p = 0.030) and in MDR vs. non-MDR (72.2% vs. 37.1%, p = 0.005). Conclusions: Antibiotic changes and NS were independently associated with MDR emergence in IPN. No independent factors were linked to FI. ICU admission was significantly higher in IPN and MDR cases. Full article

(This article belongs to the Special Issue Therapy of Infectious Diseases Among Children and Adults: The Role of Antibiotics in Daily Practice)

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16 pages, 1440 KB

Open AccessEditor’s ChoiceArticle

TDM-Guided Dalbavancin Treatment for Complex Staphylococcus aureus Osteoarticular Infections in Children

by Silvia Garazzino, Giulia Mazzetti, Matteo Sandei, Raffaele Vitale, Camilla Martino, Alice Palermiti, Amedeo De Nicolò, Elisa Funiciello, Alessandro Aprato, Alessia Gerace, Alessandro Bondi, Antonio Curtoni, Antonio D’Avolio and Marco Denina

Antibiotics 2026, 15(2), 162; https://doi.org/10.3390/antibiotics15020162 - 3 Feb 2026

Viewed by 1393

Abstract

Background/Objectives: Dalbavancin is approved for pediatric acute bacterial skin and skin structure infections (ABSSSIs), yet real-world practice frequently necessitates off-label use for deep-seated infections requiring prolonged suppression. While adult data support therapeutic drug monitoring (TDM)-guided maintenance, the pediatric evidence for repeated-dose pharmacokinetics [...] Read more.

Background/Objectives: Dalbavancin is approved for pediatric acute bacterial skin and skin structure infections (ABSSSIs), yet real-world practice frequently necessitates off-label use for deep-seated infections requiring prolonged suppression. While adult data support therapeutic drug monitoring (TDM)-guided maintenance, the pediatric evidence for repeated-dose pharmacokinetics (PK) is limited. We evaluated the efficacy, safety, multi-dose PK, and pharmacoeconomic impact of dalbavancin in a complex pediatric cohort. Methods: A retrospective study (2023–2025) of enrolled patients < 18 years treated with dalbavancin. A subgroup receiving ≥3 doses underwent PK analysis to assess concentration decay against conservative efficacy targets (4 and 8 mg/L). A pharmacoeconomic analysis compared resource utilization against the standard of care. Results: Sixteen patients (median age 12) were included, primarily treated for Staphylococcus aureus (S. aureus) osteoarticular infections (75%), and frequently device-associated (66.7%). Clinical success was 93.8% (15/16) with no adverse events. A PK analysis (n = 9; 78 samples) ruled out dangerous accumulation but revealed a significant concentration drop at week 4 (mean 6.06 mg/L; p = 0.005). Logistic regression identified the time since the previous dose as the sole predictor of sub-therapeutic levels, with >50% of the patients dropping below 8 mg/L by the fourth week. An analysis showed median net savings of EUR 3215.84 per patient (p = 0.004). Conclusions: Dalbavancin is effective and cost-saving for complex pediatric infections. However, due to distinct pediatric PK, dosing regimens extrapolated from adults may result in sub-therapeutic concentrations by week 4. We recommend TDM around week 3 to tailor dosing or limiting maintenance intervals to a maximum of 4 weeks. Full article

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13 pages, 343 KB

Open AccessEditor’s ChoiceArticle

Timing of Antimicrobial Lock Replacement for Gram-Positive Port Infections: Results of a Randomized Trial

by César Bustos, José R. Yuste, Aitziber Aguinaga, Asunción Parra, Francisco Carmona-Torre, José R. Azanza, Carlos Lacasa and José L. Del Pozo

Antibiotics 2026, 15(2), 157; https://doi.org/10.3390/antibiotics15020157 - 2 Feb 2026

Viewed by 1555

Abstract

Background: Conservative management of port-related bacteremia often includes locally administered antimicrobials, known as antimicrobial lock therapy (ALT). Current guidelines recommend daily replacement of antimicrobial lock solutions (ALSs). We aimed to evaluate whether ALSs could remain effective with extended dwell times of up [...] Read more.

Background: Conservative management of port-related bacteremia often includes locally administered antimicrobials, known as antimicrobial lock therapy (ALT). Current guidelines recommend daily replacement of antimicrobial lock solutions (ALSs). We aimed to evaluate whether ALSs could remain effective with extended dwell times of up to 10 days. Methods: In this randomized clinical trial, patients with noninfected, recently implanted ports were assigned to one of five ALS dwell-time groups, ranging from 1 to 10 days. Each ALS contained heparin plus an antimicrobial at standard intraluminal concentrations: vancomycin 2 mg/mL, teicoplanin 10 mg/mL, linezolid 1.8 mg/mL, daptomycin 5 mg/mL, or tigecycline 4.5 mg/mL. The primary endpoint was the time at which intraluminal drug concentrations decreased below 1 mg/mL (ClinicalTrials.gov NCT01592032). Results: Vancomycin and linezolid concentrations fell significantly below 1 mg/mL after 3 days of dwell time. Daptomycin and tigecycline concentrations decreased significantly after 7 days but remained above 1 mg/mL. Teicoplanin concentrations did not decline significantly after 7 days. Conclusions: Optimal ALS dwell time depends on the antimicrobial agent. Vancomycin and linezolid locks require daily replacement, whereas daptomycin, tigecycline, and teicoplanin locks maintain therapeutic concentrations for up to 7 days. These findings support individualized ALS replacement strategies, potentially reducing the need for daily interventions. Full article

(This article belongs to the Special Issue Progress and Challenges in the Antibiotic Treatment of Infections)

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14 pages, 653 KB

Open AccessEditor’s ChoiceArticle

Impact of High-Dose Cefepime During the Initial 48 h on Intensive Care Unit Survival in Sepsis: A Retrospective Observational Study

by Tsukasa Kuwana, Kosaku Kinoshita, Yuma Kanai, Yurina Yamaya, Ken Takahashi, Satoshi Ishizuka and Toru Imai

Antibiotics 2026, 15(1), 88; https://doi.org/10.3390/antibiotics15010088 - 15 Jan 2026

Viewed by 1492

Abstract

Background/Objectives: Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients [...] Read more.

Background/Objectives: Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients is unclear. This study aimed to evaluate whether high-dose CFPM administration during the first 48 h improves survival in patients with sepsis, irrespective of renal function. Methods: This single-center, retrospective, observational study included adult intensive care unit (ICU) patients with sepsis who received CFPM as initial therapy between January 2017 and December 2024. Patients were categorized into High-dose (12 g within 48 h; 2 g every 8 h) and Low-dose (<12 g/48 h) groups. The primary outcome was ICU survival. To address confounding, inverse probability of treatment weighting (IPTW) based on serum creatinine was applied, with sensitivity analyses using 1% trimmed and stabilized IPTW. Results: Of 122 eligible patients, 84 were analyzed (High-dose: n = 27; Low-dose: n = 57). After IPTW adjustment, high-dose CFPM was significantly associated with improved ICU survival (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.60–18.39, p = 0.0066). This association remained consistent in the 1% trimmed IPTW analysis (OR 4.07, 95% CI 1.19–13.97, p = 0.0256). Stabilized IPTW yielded a similar effect estimate, though without statistical significance (OR 5.43, 95% CI 0.72–41.16, p = 0.1017). Overall, results were consistent in direction and magnitude across models. Conclusions: High-dose CFPM administration during the initial 48 h was associated with improved ICU survival in patients with sepsis, independent of renal function. Full article

(This article belongs to the Special Issue Antibiotic Stewardship and Infection Control Strategies in Critical Care)

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25 pages, 2831 KB

Open AccessEditor’s ChoiceReview

Ellagic Acid as a Promising Antifungal Agent: A Review of Mechanisms, Synergy, and Formulation Strategies

by Amanda Graziela G. Mendes, Carmem D. L. Campos, José L. Pereira-Filho, Viviane S. S. Almeida, Israel V. Moreira, Raphael F. Marques, Mayara Cristina P. Silva and Valério Monteiro-Neto

Antibiotics 2026, 15(1), 72; https://doi.org/10.3390/antibiotics15010072 - 9 Jan 2026

Cited by 6 | Viewed by 2454

Abstract

Ellagic acid (EA), a naturally occurring phenolic compound, has garnered significant interest as a potential antifungal agent owing to increasing fungal resistance and a scarce therapeutic pipeline. This review consolidates the evidence of the broad-spectrum activity of EA against critical priority pathogens, including [...] Read more.

Ellagic acid (EA), a naturally occurring phenolic compound, has garnered significant interest as a potential antifungal agent owing to increasing fungal resistance and a scarce therapeutic pipeline. This review consolidates the evidence of the broad-spectrum activity of EA against critical priority pathogens, including Candida auris and Cryptococcus neoformans. We highlight its multi-target mechanisms of action, such as the impairment of cell wall integrity and plasma membrane disruption resulting from the inhibition of ergosterol biosynthesis, and inhibition of key enzymes, such as laccase. In addition to its direct growth-inhibitory effects, EA exhibits antivirulence properties, reducing biofilm formation and hyphal morphogenesis. Notably, it demonstrates synergistic potential with conventional antifungals, such as fluconazole, enhancing efficacy and potentially hindering the emergence of resistance. Although its poor solubility and bioavailability pose therapeutic challenges, advanced formulations such as liposomal systems show promise for improving its delivery. We conclude that EA is a promising candidate for developing new antifungal strategies, particularly as a synergistic agent or in nanoformulations, warranting further investigation to translate its potential into clinical practice. Full article

(This article belongs to the Special Issue Bioactive Natural Products in Antimicrobial Resistance Management)

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16 pages, 234 KB

Open AccessEditor’s ChoiceArticle

Community Pharmacists’ Perspectives on Antibiotic Misuse and Antimicrobial Resistance in Cyprus: A Reflexive Thematic Analysis

by Mark J. M. Sullman and Timo J. Lajunen

Antibiotics 2026, 15(1), 45; https://doi.org/10.3390/antibiotics15010045 - 2 Jan 2026

Cited by 2 | Viewed by 1583

Abstract

Background: Antimicrobial resistance (AMR) is a major global health threat, and Cyprus reports one of the highest levels of community antibiotic consumption in the EU. Despite their central role in antibiotic access and counselling, the stewardship practices and perspectives of community pharmacists in [...] Read more.

Background: Antimicrobial resistance (AMR) is a major global health threat, and Cyprus reports one of the highest levels of community antibiotic consumption in the EU. Despite their central role in antibiotic access and counselling, the stewardship practices and perspectives of community pharmacists in this regulated setting are not well documented. Methods: We conducted semi-structured qualitative interviews with 20 community pharmacists to explore their perspectives on antibiotic use and AMR. Results: We analysed the data using reflexive thematic analysis, revealing five key themes: regulation and control of dispensing; pharmacist–patient interaction and misuse; antimicrobial stewardship and public education; safety and professional responsibility; and systemic barriers. Pharmacists reported strict adherence to prescription-only rules, and described regulation and e-prescribing as a practical ‘shield’ that legitimised refusals and redirected some misuse from overt non-prescription requests towards attempts to reuse, extend, or ‘top up’ prior prescriptions and household leftovers. They described managing frequent patient demands for antibiotics for self-limiting conditions and using brief counselling scripts, written aids, and symptomatic alternatives to promote appropriate use. Participants emphasised the risks of antibiotic-related harms, including AMR and other health consequences, while also highlighting workload, access constraints, and communication difficulties as barriers to effective counselling. Overall, the findings indicate that community pharmacists in Cyprus function as front-line antimicrobial stewards. Conclusions: These accounts position community pharmacists in Cyprus as front-line antimicrobial stewards. Policy should consider supporting this function by providing enhanced communication tools, improving access pathways for timely prescriber review (including outside routine hours), and strengthening links between community pharmacy and national AMR action plans. Full article

(This article belongs to the Special Issue Antibiotic Use in the Communities—2nd Edition)

27 pages, 1445 KB

Open AccessEditor’s ChoiceReview

Smart Healing for Wound Repair: Emerging Multifunctional Strategies in Personalized Regenerative Medicine and Their Relevance to Orthopedics

by Carla Renata Arciola, Veronica Panichi, Gloria Bua, Silvia Costantini, Giulia Bottau, Stefano Ravaioli, Eleonora Capponi and Davide Campoccia

Antibiotics 2026, 15(1), 36; https://doi.org/10.3390/antibiotics15010036 - 1 Jan 2026

Cited by 5 | Viewed by 3767

Abstract

To address the challenges in wound healing, clinical management increasingly demands targeted, adaptive, responsive, and patient-centered strategies. This is especially true for wounds characterized by delayed healing and a high risk of infection. Advances in regenerative medicine and biomaterial technologies are fostering the [...] Read more.

To address the challenges in wound healing, clinical management increasingly demands targeted, adaptive, responsive, and patient-centered strategies. This is especially true for wounds characterized by delayed healing and a high risk of infection. Advances in regenerative medicine and biomaterial technologies are fostering the development of multifunctional approaches that integrate tissue regeneration, antibacterial/antibiofilm activity, immunomodulation, and real-time monitoring. This paper surveys emerging platforms, including both natural and synthetic scaffolds, hydrogels enriched with platelet-derived growth factors, glycosaminoglycan mimetics, bioactive peptides (such as GHK-Cu and antimicrobial peptides), nanoscaffolds, and stimuli-responsive systems. The paper also explores cutting-edge technologies such as water-powered, electronics-free dressings that deliver localized electrical stimulation; biodegradable bioelectric sutures that produce self-sustained mechano-electrical signals; and sensory bandages that monitor pH, moisture, temperature, and bacterial contamination in real-time while enabling on-demand drug release with pro-regenerative, antibacterial, and other therapeutic functionalities. Further therapeutic approaches include natural matrices, exosomes, gene editing, 3D bioprinting, and AI-assisted design. Particular attention is paid to orthopedic applications and orthopedic implant infection. A brief section addresses the still unresolved challenge of articular cartilage regeneration. Interdisciplinary innovation, integrating insights from molecular biology through engineering, plays a central role in translating novel strategies into tailored, clinically effective wound management solutions. Full article

(This article belongs to the Special Issue Advances in the Field of Biofilm-Associated Musculoskeletal Infections)

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15 pages, 2081 KB

Open AccessEditor’s ChoiceArticle

Clinical and Environmental Plasmids: Antibiotic Resistance, Virulence, Mobility, and ESKAPEE Pathogens

by Célia P. F. Domingues, João S. Rebelo, Francisco Dionisio and Teresa Nogueira

Antibiotics 2026, 15(1), 29; https://doi.org/10.3390/antibiotics15010029 - 31 Dec 2025

Viewed by 1887

Abstract

Background/Objectives: Plasmids are autonomous DNA molecules that can replicate independently and transfer horizontally between bacterial cells. They play a key role in disseminating adaptive traits, such as antimicrobial resistance and virulence. Our study investigates the fundamental differences between plasmid populations originating from clinical/isolates [...] Read more.

Background/Objectives: Plasmids are autonomous DNA molecules that can replicate independently and transfer horizontally between bacterial cells. They play a key role in disseminating adaptive traits, such as antimicrobial resistance and virulence. Our study investigates the fundamental differences between plasmid populations originating from clinical/isolates and environmental/metagenomes. Methods: We compare three distinct plasmid genome datasets—the NCBI Reference Sequence Database (RefSeq), the Integrated Microbial Genomes & Microbiomes system (IMG/PR) from bacterial isolates (I) and microbiomes (M)—to assess how plasmid origin shapes their characteristics, including mobility types, antimicrobial resistance genes (ARGs), virulence genes (VGs) and host taxonomy. Results: We show that plasmids originating from bacterial isolates, more enriched in clinical samples, are fundamentally distinct from recovered from metagenomic data. Plasmids from isolates are larger, enriched in conjugative plasmids and display a higher frequency of ARGs and VGs than the ones assembled from metagenomes. Furthermore, ARGs are more frequently associated with highly mobile plasmids, particularly pCONJ. Conclusions: These findings highlight the importance of plasmid origins in studies of plasmid epidemiology, functional potential and mobility. Full article

(This article belongs to the Special Issue Drivers of Virulence and Antimicrobial Resistance in Emerging and Re-Emerging Pathogens)

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13 pages, 388 KB

Open AccessEditor’s ChoiceArticle

Occurrence of Antibiotic Resistance in Lacticaseibacillus paracasei and Lactiplantibacillus plantarum Strains Isolated from Traditional Sardinian Fermented Food

by Gavino Carboni, Maria E. Mura, Margherita Chessa, Giuseppe Blaiotta, Anna Nudda and Nicoletta P. Mangia

Antibiotics 2026, 15(1), 18; https://doi.org/10.3390/antibiotics15010018 - 22 Dec 2025

Cited by 4 | Viewed by 1624

Abstract

Background: This study investigated the phenotypic and genotypic antibiotic resistance profiles of 50 Lactic Acid Bacteria (LAB) strains—25 Lactiplantibacillus plantarum and 25 Lacticaseibacillus paracasei—isolated from traditional Sardinian fermented foods of animal origin. Methods: The sensitivity of the isolates to antibiotics such as [...] Read more.

Background: This study investigated the phenotypic and genotypic antibiotic resistance profiles of 50 Lactic Acid Bacteria (LAB) strains—25 Lactiplantibacillus plantarum and 25 Lacticaseibacillus paracasei—isolated from traditional Sardinian fermented foods of animal origin. Methods: The sensitivity of the isolates to antibiotics such as β-lactams, tetracyclines, aminoglycosides, macrolides, phenicols, and glycopeptides was initially assessed using disc diffusion and minimum inhibitory concentration (MIC) tests. Subsequently, PCR analyses were performed on both genomic DNA and plasmid DNA to detect blaZ, tet(W), strA, aac(6′)-Ie–aph(2″)-Ia, and vanX genes associated with resistance to ampicillin, tetracycline, streptomycin, gentamicin, and vancomycin. Results: The analysis revealed that L. plantarum strains frequently carried the tet(W) gene on the chromosome and strA on plasmids, while vanX was detected in most strains as a chromosomal determinant. By contrast, L. paracasei strains exhibited a predominantly plasmid-mediated distribution of resistance genes. For example, strA, aac(6′)-Ie–aph(2″)-Ia and blaZ were often found on plasmids, whereas vanX remained chromosomally encoded. Phenotypic assays confirmed high intrinsic resistance to vancomycin in both species, with L. plantarum showing a higher overall frequency and diversity of resistant phenotypes compared to L. paracasei. Conclusions: The co-occurrence of multiple resistance determinants, including plasmid-encoded ones, in most strains suggests that even autochthonous isolates from artisanal products may represent potential reservoirs for transmissible resistance genes. Full article

(This article belongs to the Special Issue Animal-Origin Bacteria: Diversity, Pathogenicity and Antimicrobial Resistance)

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14 pages, 1218 KB

Open AccessEditor’s ChoiceArticle

Resistance to Clarithromycin and Fluoroquinolones in Helicobacter pylori Isolates: A Prospective Molecular Analysis in Western Romania

by Patricia Serena, Ruxandra Mare, Bogdan Miutescu, Renata Bende, Alexandru Popa, Giovanni Aragona, Edward Seclăman, Luca Serena, Andreea Barbulescu and Roxana Sirli

Antibiotics 2025, 14(12), 1223; https://doi.org/10.3390/antibiotics14121223 - 4 Dec 2025

Cited by 1 | Viewed by 1282

Abstract

Background and Objectives: Helicobacter pylori (H. pylori) infection remains one of the most common chronic bacterial infections worldwide and is associated with a wide range of gastrointestinal disorders, including gastritis, peptic ulcer disease, and gastric cancer. Increasing rates of antibiotic [...] Read more.

Background and Objectives: Helicobacter pylori (H. pylori) infection remains one of the most common chronic bacterial infections worldwide and is associated with a wide range of gastrointestinal disorders, including gastritis, peptic ulcer disease, and gastric cancer. Increasing rates of antibiotic resistance, particularly to clarithromycin and fluoroquinolones, represent a major therapeutic challenge. The objective of this study was to determine the prevalence of resistance-associated mutations in H. pylori-positive gastric biopsy samples from western Romania. Materials and Methods: We conducted a prospective study from January to December 2024, enrolling 138 patients undergoing gastroscopy. Biopsies were collected from the gastric antrum, and H. pylori infection was confirmed using the rapid urease test (RUT). Positive samples were further analyzed with the GenoType HelicoDR assay to detect mutations in the 23S rRNA gene (clarithromycin resistance) and gyrA gene (fluoroquinolone resistance). Clinical, demographic, and endoscopic data were also collected. Results:H. pylori infection was confirmed in 41.3% of the patients (57), of whom 63.2% (36) were treatment-naïve and 36.8% (21) had prior eradication therapy. Among treatment-naïve patients, clarithromycin resistance was identified in 19.4%, whereas previously treated patients showed a markedly higher resistance rate of 47.6% (p = 0.018). All clarithromycin-resistant cases carried the A2147G (23S MUT3) mutation. Fluoroquinolone resistance was present in 13.9% of naïve patients and increased to 23.8% in those with prior eradication therapy, with resistance linked to gyrA mutations at codons 87 (N87K) and 91 (D91 variants). Combined resistance to both antibiotics was observed only in a subset of previously treated patients. Conclusions: Primary resistance to clarithromycin in western Romania exceeds the 15% threshold defined by international guidelines, making clarithromycin-based triple therapy unsuitable as an empirical first-line option. The findings support the use of bismuth quadruple therapy as the preferred empirical regimen in this region. Also, molecular testing proved effective for rapid identification of resistance-associated mutations. Full article

(This article belongs to the Special Issue Helicobacter pylori Virulence Factors, Antibiotic Susceptibility and Persistent Infection)

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26 pages, 2475 KB

Open AccessEditor’s ChoiceReview

Current Advances in Developing New Antimicrobial Agents Against Non-Tuberculous Mycobacterium

by Jane Cross, Nupur Gargate and Khondaker Miraz Rahman

Antibiotics 2025, 14(12), 1189; https://doi.org/10.3390/antibiotics14121189 - 21 Nov 2025

Cited by 3 | Viewed by 3173

Abstract

Non-tuberculous mycobacteria (NTM) comprise more than 190 species capable of causing severe pulmonary, lymphatic, cutaneous, and disseminated infections, particularly in immunocompromised populations. Over the past two decades, the global incidence of NTM infections has risen steadily, underscoring an urgent unmet medical need. Treatment [...] Read more.

Non-tuberculous mycobacteria (NTM) comprise more than 190 species capable of causing severe pulmonary, lymphatic, cutaneous, and disseminated infections, particularly in immunocompromised populations. Over the past two decades, the global incidence of NTM infections has risen steadily, underscoring an urgent unmet medical need. Treatment remains highly challenging due to intrinsic antimicrobial resistance and the requirement for prolonged multidrug regimens that are often poorly tolerated and associated with unsatisfactory outcomes. At the same time, the development of novel therapies has lagged behind other disease areas, hindered by the high costs of antimicrobial drug discovery and the relatively low commercial return compared with treatments for chronic conditions. Over the past decade, discovery and development have diversified across novel small molecules, next-generation analogues of existing classes, and adjunctive or host-directed strategies. While most candidates remain preclinical, several agents have advanced clinically in other infections, including gepotidacin (topoisomerase inhibitor; FDA-approved 2025 for urinary tract infection (UTI)), sulbactam–durlobactam (DBO β-lactamase inhibitor; FDA-approved 2023 for Acinetobacter baumannii complex), and contezolid, supporting repurposing opportunities for NTM. Conversely, SPR720 (gyrase B prodrug) was suspended after not meeting its Phase 2 endpoint in 2024, underscoring translational risk. Overall, the NTM pipeline is expanding, with near-term progress most likely from repurposed agents and optimised combinations, alongside earlier-stage candidates that target biofilms or resistance mechanisms. This review aims to provide a critical and up-to-date overview of emerging antimicrobial strategies against NTM, highlighting recent advances, translational challenges, and opportunities to accelerate the development of effective therapeutics. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Evaluation of Antibacterial Compounds)

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12 pages, 537 KB

Open AccessEditor’s ChoiceArticle

Clinical Characteristics and Treatment Strategies in a Cohort of Patients with Tularemia: A Retrospective Multicenter Analysis of 65 Cases in Germany

by Benjamin Arnold, Henning Trawinski, Nils Kellner, Hans-Martin Orth, Daniela Tominski, Agata Mikolajewska, Katja Rothfuss, Gesa Grupe, Dominik Ruf, Friedrich Reichert, Daniela Jacob, Klaus Heuner, Kathrin Marx and Christoph Lübbert

Antibiotics 2025, 14(11), 1169; https://doi.org/10.3390/antibiotics14111169 - 20 Nov 2025

Cited by 1 | Viewed by 1788

Abstract

Background: In recent years, there has been a significant increase in cases of tularemia, a rare zoonotic disease caused by Francisella tularensis, in Europe. Methods: To investigate the epidemiological, clinical, and therapeutic characteristics of tularemia patients in Germany, we performed a retrospective [...] Read more.

Background: In recent years, there has been a significant increase in cases of tularemia, a rare zoonotic disease caused by Francisella tularensis, in Europe. Methods: To investigate the epidemiological, clinical, and therapeutic characteristics of tularemia patients in Germany, we performed a retrospective evaluation of tularemia cases treated between 2010 and 2025 at selected treatment centers of the Permanent Working Group of Competence and Treatment Centers for High Consequence Infectious Diseases (STAKOB) at the Robert Koch Institute. Results: A total of 65 patients (median age: 48.5 years; 66.2% male) were identified. Most common manifestation was ulceroglandular (70.7%), followed by oropharyngeal (13.8%), pulmonary (10.8%), oculoglandular (7.7%), typhoidal (4.6%), and meningitic (4.6%). Serological confirmation of the diagnosis was achieved in all patients (90.8% ELISA, 46.2% Western blot). PCR-based direct pathogen detection was successful in 26.2%. Bloodstream infection was detected in 4.6%. Median incubation period was 7 days (IQR: 4–10), with fever being the most common symptom in 96.9% and lymphadenopathy in 46.2%. Median time to recovery was 56 days (IQR: 37–80) in patients diagnosed and treated early (≤3 weeks after symptom onset), compared to 84 days (IQR: 66–182) in patients with late diagnosis (>3 weeks after symptom onset; p = 0.015). Empirical therapy with beta-lactam antibiotics was initiated in 49.2% of cases. Following suspicion of tularemia, 96.9% received recommended treatment with fluoroquinolones, tetracyclines, or aminoglycosides. Conclusions: Delayed diagnosis and inappropriate initial therapy can significantly prolong disease courses and increase morbidity. Early treatment with effective antibiotics, considering the intrinsic beta-lactam resistance of Francisella tularensis, leads to faster recovery. Full article

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

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17 pages, 3008 KB

Open AccessEditor’s ChoiceArticle

Synthesis and Structure–Activity Relationship Study of 2-(amino)quinazolin-4(3H)-one Derivatives as Potential Inhibitors of Methicillin-Resistant Staphylococcus aureus (MRSA)

by Jun Young Lee, Hyunjung Lee, Sungmin Kim, Jihwan Gim, Yunmi Lee, Chae Jo Lim, Hyun-Seob Song, Hyeung-geun Park, Soojin Jang and Chul Min Park

Antibiotics 2025, 14(10), 967; https://doi.org/10.3390/antibiotics14100967 - 25 Sep 2025

Cited by 1 | Viewed by 1671

Abstract

Background/Objectives: The rise in methicillin-resistant Staphylococcus aureus (MRSA) demands new therapeutic strategies. In this study, a series of 2-(amino)quinazolin-4(3H)-one derivatives were synthesized and evaluated for antistaphylococcal activity. Methods/Results: Through screening against S. aureus ATCC25923 and USA300 JE2, several submicromolar inhibitors were [...] Read more.

Background/Objectives: The rise in methicillin-resistant Staphylococcus aureus (MRSA) demands new therapeutic strategies. In this study, a series of 2-(amino)quinazolin-4(3H)-one derivatives were synthesized and evaluated for antistaphylococcal activity. Methods/Results: Through screening against S. aureus ATCC25923 and USA300 JE2, several submicromolar inhibitors were identified. Among them, compound 6l, which contains a 7-chloro substituent on the key parental scaffold, exhibited strong overall antibacterial activity (MIC₅₀: 1.0 µM, ATCC25923; 0.6 µM, JE2) and served as a lead for further structural optimization. Structure–activity relationship analysis showed that substitution at the 2-position was critical, with its optimized analog 6y (3,4-difluorobenzylamine) exhibiting the highest potency (MIC₅₀: 0.36 µM, ATCC25923; 0.02 µM, JE2). Cytotoxicity assays in HepG2 cells revealed six compounds with IC₅₀ values above 20 µM, yielding efficacy windows greater than 10. Compound 6y exhibited an exceptional index (~885). Consistently, in an H460 lung epithelial infection model mimicking MRSA pneumonia, 6y significantly reduced intracellular bacterial loads with minimal host cell damage, outperforming comparator compounds. Conclusions: These findings highlight 2-(amino)quinazolin-4(3H)-one derivatives, particularly 6y, as promising leads for the development of new antistaphylococcal agents. Full article

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20 pages, 4943 KB

Open AccessEditor’s ChoiceArticle

Phage Resistance Modulates Escherichia coli B Response to Metal-Based Antimicrobials

by Franklin C. Ezeanowai, Akamu J. Ewunkem, Ugonna C. Morikwe, Larisa C. Kiki, Lindsey W. McGee, Joseph L. Graves, Jr. and Liesl K. Jeffers-Francis

Antibiotics 2025, 14(9), 942; https://doi.org/10.3390/antibiotics14090942 - 18 Sep 2025

Cited by 2 | Viewed by 2281

Abstract

Background/Objective: The rise of multidrug-resistant bacteria underscores the urgent need for alternative antimicrobial strategies. Metal-based compounds and bacteriophage (phage) therapy have emerged as promising candidates, but the evolutionary trade-offs associated with these selective pressures and their combination remain poorly understood. This study [...] Read more.

Background/Objective: The rise of multidrug-resistant bacteria underscores the urgent need for alternative antimicrobial strategies. Metal-based compounds and bacteriophage (phage) therapy have emerged as promising candidates, but the evolutionary trade-offs associated with these selective pressures and their combination remain poorly understood. This study aimed to investigate how prior exposure to T4 phage influences Escherichia coli B’s subsequent adaptation to iron (III) stress and to assess the resulting phenotypic and genomic signatures of dual resistance. Method: In this study, we performed experimental evolution using Escherichia coli B to investigate adaptive responses under four conditions: control (LB broth), T4 phage-only, iron (III) sulfate-only, and sequential phage followed by iron (III) exposure. Each treatment consisted of ten independently evolved populations (biological replicates), all derived from a common ancestral strain and passaged daily for 35 days. Phage resistance evolved rapidly, with complete resistance observed within 24 h of exposure. Results: In contrast, iron-selected populations evolved tolerance to high iron concentrations (1000–1750 mg/L) over time at a cost to resistance in other metals (gallium and iron (II) and antibiotics (tetracycline). Notably, prior phage exposure altered these outcomes: phage/iron-selected populations retained phage resistance and iron tolerance but showed diminished resistance to iron (II) and distinct antibiotic sensitivity profiles. Whole-genome sequencing revealed stressor-specific adaptations: large deletions in phage receptor-related genes (waaA and waaG) under phage pressure, and selective sweeps in iron-adapted populations affecting regulatory and membrane-associated genes (qseB, basR, aroK, fieF, rseB, and cpxP). Conclusions: These results demonstrate that the sequence of environmental stressors significantly shapes phenotypic and genetic resistance outcomes. Our findings highlight the importance of fitness epistasis and historical contingency in microbial adaptation, with implications for the design of evolution-informed combination therapies. Full article

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11 pages, 863 KB

Open AccessEditor’s ChoiceArticle

Testing Analytical Methods for Antibiotic Detection in Tenebrio molitor Larvae: A Controlled Feeding Trial

by Tomke Asendorf, Christine Wind and Andreas Vilcinskas

Antibiotics 2025, 14(9), 909; https://doi.org/10.3390/antibiotics14090909 - 9 Sep 2025

Cited by 1 | Viewed by 1551

Abstract

Background: As edible insects gain importance as sustainable protein sources, their integration into the food system requires that they meet the same safety standards as conventional animal products. This includes systematic testing for residues of pharmacologically active substances, such as antibiotics. To enable [...] Read more.

Background: As edible insects gain importance as sustainable protein sources, their integration into the food system requires that they meet the same safety standards as conventional animal products. This includes systematic testing for residues of pharmacologically active substances, such as antibiotics. To enable such monitoring, validated analytical methods for insect matrices are essential—but currently lacking. This study evaluates whether LC-MS/MS methods already validated for conventional animal products are suitable for detecting antibiotics in edible insects. Methods:Tenebrio molitor larvae were fed wheat flour containing 10 mg of tiamulin or chloramphenicol and 31.3 mg erythromycin per 100 g flour. The antibiotics were mixed into the feed, and their homogeneity and stability were confirmed. After seven days of feeding and a 24-h fasting period, larval samples were analyzed by LC-MS/MS. Results: All three antibiotics were detected in the insects. After seven days, mealworms contained 6.8 ± 0.3 mg/kg tiamulin, 1.4 ± 0.2 mg/kg chloramphenicol, and 224.5 ± 111 mg/kg erythromycin. Following the 24-hour fasting period, concentrations declined markedly to 0.6 ± 0.03 mg/kg, 0.2 ± 0.002 mg/kg, and 130.5 ± 0.7 mg/kg, respectively. Conclusions: The detection of all three antibiotics demonstrates that existing LC-MS/MS methods can be applied to insect matrices. Owing to the small number of replicates and the exploratory nature of the trial, these residue levels should be interpreted qualitatively as a proof of concept. The study provides a reproducible model for further feeding trials and underscores the need for more comprehensive validation. Potential drivers of antibiotic misuse in insect farming are discussed as a basis for developing and expanding testing methods to ensure the food safety of edible insects. Full article

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20 pages, 2009 KB

Open AccessEditor’s ChoiceArticle

Optimizing the Routine Use of Clinical Guidelines by Addition of Supplements (Probiotics and/or Bismuth) to Helicobacter pylori Eradication Protocols in a Clarithromycin Resistant and Tetracycline/Bismuth Naive Area: A Real-World Data Retrospective Analysis of 402 Cases (2016–24) in a Single Gastroenterology Unit

by András Gelley, Noémi Kéri, Péter Birinyi, Kinga Komka, Vajk Hardy, László Döngölő, Dóra Szeli and Ibolya Czegle

Antibiotics 2025, 14(9), 870; https://doi.org/10.3390/antibiotics14090870 - 29 Aug 2025

Viewed by 3247

Abstract

Background: The official current guideline for Helicobacter pylori (H. pylori) eradication is to use tetracycline–bismuth-based protocols as first line treatment due to the increasing incidence of clarithromycin resistance in the last decade. The unavailability of tetracycline and bismuth-containing medicines, however, is [...] Read more.

Background: The official current guideline for Helicobacter pylori (H. pylori) eradication is to use tetracycline–bismuth-based protocols as first line treatment due to the increasing incidence of clarithromycin resistance in the last decade. The unavailability of tetracycline and bismuth-containing medicines, however, is an issue in many countries, limiting the routine use of these protocols. The value of using additional probiotics in eradication protocols is also unclear. Direct comparison data on the effect of available bismuth compounds and different probiotic strains on eradication outcome are limited. Goal: The aim of our investigation was to find optimal eradication protocols, supplementations and treatment duration for routine clinical use in our gastroenterology unit, located in a highly clarithromycin-resistant and tetracycline–bismuth-naïve area. Materials and Methods: We conducted a retrospective real-world data analysis of 402 H. pylori positive patients between 2016 and 2024. H. pylori infection was diagnosed using histological examination of gastroscopy samples obtained from the gastric antrum. For the evaluation of treatment success or failure, ¹⁴C breath tests and stool H. pylori antigen tests were performed. Data on patient characteristics and treatment protocols were collected from our electronic patient record system, and treatment success was compared between the different treatment regimes. Results: Despite the regional clarithromycin resistance, supplementing clarithromycin-based regimens with bismuth and probiotic during the 14-day treatment duration showed a high and comparable cure rate when compared to tetracycline-based regimens, which are the current first-line therapies. When tetracycline-based combination is available, it is recommended to use it with an additional probiotic to achieve the best possible outcome. Comparison of the effect of available bismuth preparations on treatment success showed no significant difference. Generally, probiotic-containing protocols are more successful, compared to those treatments without this supplement. There was no statistical difference in the cure rates amongst the four probiotic strains used, where sample size allowed statistical analysis. Furthermore, supplementation with probiotics Lactobacillus reuteri ATCC PTA 6475 or Lactobacillus reuteri Protectis^® DSM 17938 showed promising high treatment success rates (85.2% and 100.0%, respectively) in our study. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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25 pages, 473 KB

Open AccessEditor’s ChoiceReview

“Dusting Off the Cobwebs”: Rethinking How We Use New Antibiotics

by Jacob Myles Keck, Jacob Schultz and Alina Viteri

Antibiotics 2025, 14(9), 862; https://doi.org/10.3390/antibiotics14090862 - 27 Aug 2025

Cited by 3 | Viewed by 3349

Abstract

Antimicrobial resistance continues to escalate worldwide, threatening effective medical care, patient safety, and global health security. Traditional antibiotics are increasingly unreliable against multidrug-resistant pathogens, resulting in delayed appropriate therapy, prolonged illness, higher healthcare costs, and increased mortality. In this context, antimicrobial stewardship must [...] Read more.

Antimicrobial resistance continues to escalate worldwide, threatening effective medical care, patient safety, and global health security. Traditional antibiotics are increasingly unreliable against multidrug-resistant pathogens, resulting in delayed appropriate therapy, prolonged illness, higher healthcare costs, and increased mortality. In this context, antimicrobial stewardship must evolve beyond the preservation of older drugs to include the judicious, evidence-based use of newer antibiotics. When used empirically in high-risk scenarios, novel agents can improve clinical outcomes by ensuring timely, effective coverage against MDR organisms while reducing the need for broad-spectrum combinations that drive collateral resistance and adverse effects. A major challenge, however, is the underutilization of these agents, which not only limits patient benefit but also undermines incentives for continued pharmaceutical innovation. To address this gap, stewardship programs must incorporate strategies for appropriate empiric deployment of new antibiotics, guided by local epidemiology, risk stratification, rapid diagnostics, and multidisciplinary decision-making. A coordinated global effort, linking stewardship, innovation, and policy reform, will be critical to optimize the role of novel antimicrobials in clinical practice moving forward. Full article

(This article belongs to the Special Issue Revolutionizing Infection Treatment: Cutting-Edge Approaches in Antimicrobial Stewardship)

12 pages, 389 KB

Open AccessEditor’s ChoiceArticle

Evolution of Respiratory Pathogens and Antimicrobial Resistance over the COVID-19 Timeline: A Study of Hospitalized and Ambulatory Patient Populations

by Luigi Regenburgh De La Motte, Loredana Deflorio, Erika Stefano, Matteo Covi, Angela Uslenghi, Carmen Sommese and Lorenzo Drago

Antibiotics 2025, 14(8), 796; https://doi.org/10.3390/antibiotics14080796 - 5 Aug 2025

Cited by 4 | Viewed by 2096

Abstract

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial [...] Read more.

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies. Full article

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

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23 pages, 1310 KB

Open AccessEditor’s ChoiceReview

Evaluating Antimicrobial Susceptibility Testing Methods for Cefiderocol: A Review and Expert Opinion on Current Practices and Future Directions

by Stefania Stefani, Fabio Arena, Luigi Principe, Stefano Stracquadanio, Chiara Vismara and Gian Maria Rossolini

Antibiotics 2025, 14(8), 760; https://doi.org/10.3390/antibiotics14080760 - 28 Jul 2025

Cited by 4 | Viewed by 6169

Abstract

Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial [...] Read more.

Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial systems. Variability in interpretive criteria and areas of technical uncertainty (ATUs) further complicate assessments. Methods: This review and expert opinion presents: (1) an overview of non-susceptibility to FDC and then delves into the performance of current FDC AST methods for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex; (2) a practical decision framework to guide clinical microbiologists in making informed choices. Results and Conclusions: For Enterobacterales, including carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa, we propose disk diffusion (DD) as a preliminary screening tool to classify isolates as susceptible (S) or resistant (R). Confirmatory testing using the UMIC^® FDC system or the ID-CAMHB BMD method is recommended for R isolates. In cases of discrepancy, repeating the test with ID-CAMHB BMD is advised. Additionally, isolates falling within the ATU during DD testing should be retested using the UMIC^® system or ID-CAMHB BMD. For A. baumannii complex, since EUCAST breakpoints have not been defined yet, we propose a stepwise framework based on the first DD result: isolates with inhibition zones < 17 mm are considered non-susceptible and should be confirmed with standard BMD. Those between 17 and 22 mm require retesting with a commercial BMD method, with further confirmation recommended if S isolates with zones ≥ 23 mm may be considered S without additional testing. Full article

(This article belongs to the Special Issue Bacterial Detection, Identification, and Antimicrobial Susceptibility Testing)

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12 pages, 899 KB

Open AccessEditor’s ChoiceArticle

Antimicrobial Stewardship in Cardiac Device Surgery: Impact of Behavioural Change Interventions on Extended Prophylaxis Practices

by Li Wen Loo, Yvonne Peijun Zhou, Yi Bo Wang, Lai Wei Lee and Jasmine Shimin Chung

Antibiotics 2025, 14(8), 754; https://doi.org/10.3390/antibiotics14080754 - 25 Jul 2025

Cited by 2 | Viewed by 1617

Abstract

Background/Objectives: Single-dose pre-operative antibiotic prophylaxis for cardiac-device implantation is recommended but extending antibiotic prophylaxis is common. Locally, 50–60% of patients had extended prophylaxis after pacemaker insertion or generator change. Our antimicrobial stewardship programme (ASP) incorporated behavioural change strategies in implementing a multi-pronged intervention [...] Read more.

Background/Objectives: Single-dose pre-operative antibiotic prophylaxis for cardiac-device implantation is recommended but extending antibiotic prophylaxis is common. Locally, 50–60% of patients had extended prophylaxis after pacemaker insertion or generator change. Our antimicrobial stewardship programme (ASP) incorporated behavioural change strategies in implementing a multi-pronged intervention bundle to address this and evaluated its effectiveness and safety. Methods: This single-centre, retrospective cohort study included patients aged 21 years old or older, undergoing uncomplicated pacemaker insertion or generator change at Singapore General Hospital (SGH) from October 2022 to March 2025. To improve antibiotic use, ASP interventions incorporating behaviour change strategies were implemented, namely (1) data-driven feedback, (2) targeted education, (3) identification and engagement of ASP champion, and (4) clinical pathway revision. Results: There were 779 patients evaluated; 380 (48.8%) received standard prophylaxis while 399 (51.2%) received extended prophylaxis with oral antibiotics (mean duration, 3.3 ± 0.8 days). Following ASP interventions, the practice of extended prophylaxis declined significantly from 43.8% to 24.0% (p < 0.01). The incidence of surgical site infections was low and similar in both groups (0.8%, p = 1.000); all infections were superficial. There was also significant reduction in the proportion of patients on all antibiotics from 20.7% to 16.3% (p < 0.01). Identification and engagement of ASP champion proved pivotal in changing prescribing behaviour through peer influence and credibility. Conclusions: The bundled ASP interventions, incorporating behavioural change strategies, have effectively and safely reduced the use of extended prophylaxis post-cardiac device implantation. Behavioural change interventions are essential to achieve sustained stewardship success. Full article

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21 pages, 594 KB

Open AccessEditor’s ChoiceArticle

Trends in Positive Urine Culture Rates and Antimicrobial Resistance in Non-Hospitalized Children from Western Romania: A Retrospective Observational Study

by Constantin Catalin Marc, Maria Daniela Mot, Monica Licker, Delia Muntean, Daniela Teodora Marti, Ana Alexandra Ardelean, Alina Ciceu, Sergiu Adrian Sprintar, Daniela Adriana Oatis, Alin Gabriel Mihu and Tudor Rares Olariu

Antibiotics 2025, 14(7), 723; https://doi.org/10.3390/antibiotics14070723 - 18 Jul 2025

Cited by 3 | Viewed by 3866

Abstract

Background: Urinary tract infections (UTIs) are among the most common types of infections during childhood. Limited data are available on the prevalence of UTI in children from Romania, with most being available for hospitalized children. For this reason, we conducted a retrospective observational [...] Read more.

Background: Urinary tract infections (UTIs) are among the most common types of infections during childhood. Limited data are available on the prevalence of UTI in children from Romania, with most being available for hospitalized children. For this reason, we conducted a retrospective observational study in consecutive non-hospitalized children to assess the number of positive UTI samples and the antibacterial resistance of causative pathogens. Methods: This study included 7222 consecutive urine cultures collected from children aged 1 to 18 years who are residents of Arad County, Western Romania. Urine samples were analyzed for leukocyturia and cultures for the presence of monomorphic bacteria. Results: The overall number of positive UTI samples was 10.44%. A higher number of positive UTI samples was observed in females when compared to males and in children aged 6–12 and 12 to 18 years when compared to those aged 1–5 years. The antibiotic susceptibility testing of E. coli isolates revealed high sensitivity to most tested antibacterials. Near-complete susceptibility was observed for fosfomycin (99.71%) and nitrofurantoin (96.01%), while high susceptibility rates were also observed for ciprofloxacin (85.43%) and amoxicillin–clavulanic acid (75.05%). In contrast, high resistance was found for ampicillin (62.28% resistant) and trimethoprim–sulfamethoxazole (36.53% resistant). Conclusions: Given the clinical risks associated with UTI in children, our findings underscore the urgent need for the continued monitoring of multidrug-resistant strains. Our study provides important epidemiological and resistance data to guide empirical treatment and strengthen pediatric antimicrobial resistance surveillance. Future studies should focus on different regions and regularly update resistance patterns to keep treatment and prevention strategies aligned with local conditions. Full article

(This article belongs to the Special Issue Prevalence, Treatment and Antibacterial Resistance of Urinary Tract Infections)

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33 pages, 1374 KB

Open AccessEditor’s ChoiceReview

Antimicrobials in Livestock Farming and Resistance: Public Health Implications

by Marilena Trinchera, Silvia De Gaetano, Elenoire Sole, Angelina Midiri, Serena Silvestro, Giuseppe Mancuso, Teresa Catalano and Carmelo Biondo

Antibiotics 2025, 14(6), 606; https://doi.org/10.3390/antibiotics14060606 - 14 Jun 2025

Cited by 29 | Viewed by 14175

Abstract

The accelerated spread of bacterial resistance has been demonstrated to reduce the effectiveness of antibiotic treatments for infections, resulting in higher morbidity and mortality rates, as well as increased costs for livestock producers. It is expected that the majority of future antimicrobial use [...] Read more.

The accelerated spread of bacterial resistance has been demonstrated to reduce the effectiveness of antibiotic treatments for infections, resulting in higher morbidity and mortality rates, as well as increased costs for livestock producers. It is expected that the majority of future antimicrobial use will be in animal production. The management of antimicrobial resistance (AMR) in the livestock sector poses significant challenges due to the multifaceted nature of the problem. In order to identify appropriate solutions to the rise of antimicrobial resistance, it is imperative that we have a comprehensive understanding of the disease dynamics underpinning the ways in which antimicrobial resistance is transmitted between humans and animals. Furthermore, in consideration of the anticipated requirement to satisfy the global demand for food, it is imperative that we guarantee that resistance is not transmitted or propagated during the treatment and disposal of animal waste, particularly from intensive farming. It is also crucial to formulate a research agenda to investigate how antibiotic resistance in animal faeces from livestock farming is affected by intensified farming activities. The review analyses the environment’s role in the transmission resistance chain and reviews methodologies for disrupting the link. A particular focus is placed on the limitations of the applied methodologies to reduce antimicrobial resistance in global animal production. Full article

(This article belongs to the Special Issue Livestock Antibiotic Use and Resistance)

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18 pages, 1231 KB

Open AccessEditor’s ChoiceArticle

The Genetic Background and Culture Medium Only Marginally Affect the In Vitro Evolution of Pseudomonas aeruginosa Toward Colistin Resistance

by Matteo Cervoni, Antonio Maria Ferriero, Alessandra Lo Sciuto, Francesca Guidi, Naida Babić Jordamović, Silvano Piazza, Olivier Jousson, Alfonso Esposito and Francesco Imperi

Antibiotics 2025, 14(6), 601; https://doi.org/10.3390/antibiotics14060601 - 13 Jun 2025

Cited by 4 | Viewed by 3359

Abstract

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to [...] Read more.

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to influence the extent of colistin resistance. Here, we examined whether the genetic background and culture conditions affect the evolution of high-level colistin resistance in this bacterium. Methods: We performed in vitro evolution experiments in the presence or absence of increasing colistin concentrations with two phylogenetically distant reference strains in a standard laboratory medium and in two media mimicking P. aeruginosa growth during lung or systemic infections. Resistance-associated mutations were identified by comparative genomics, and the role of selected mutated genes was validated by allele replacement, deletion, or conditional mutagenesis. Results: Most colistin-resistant mutants carried mutations in genes belonging to four functional groups: two-component systems controlling LPS aminoarabinosylation (PmrAB, PhoPQ), LPS biosynthesis, the production of the polyamine norspermidine, and fatty acid metabolism. No mutation was exclusively and invariably associated with a specific strain or medium. We demonstrated that norspermidine is detrimental to the acquisition of colistin resistance upon PmrAB activation and that impaired fatty acid biosynthesis can promote colistin resistance, even if it increases susceptibility to other antibiotics. Conclusions: The evolution of colistin resistance in P. aeruginosa appeared to be only marginally affected by the genetic background and culture conditions. Notably, mutations in fatty acid biosynthetic genes represent a newly identified genetic determinant of P. aeruginosa colistin resistance, warranting further investigation in clinical isolates. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success)

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14 pages, 1086 KB

Open AccessEditor’s ChoiceReview

Challenges of Carbapenem-Resistant Enterobacteriaceae in the Development of New β-Lactamase Inhibitors and Antibiotics

by Pierre Leroux, Charleric Bornet, Jean-Michel Bolla and Anita Cohen

Antibiotics 2025, 14(6), 587; https://doi.org/10.3390/antibiotics14060587 - 7 Jun 2025

Cited by 12 | Viewed by 3988

Abstract

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex [...] Read more.

Nowadays, antimicrobial resistance (AMR) is a growing global health threat, with carbapenem-resistant Enterobacteriaceae (CRE) posing particular concern due to limited treatment options. In fact, CRE have been classified as a critical priority by the World Health Organization (WHO). Carbapenem resistance results from complex mechanisms, often combining the production of hydrolytic enzymes such as β-lactamases with reduced membrane permeability and efflux system induction. The Ambler classification is an effective tool for differentiating the characteristics of serine-β-lactamases (SβLs) and metallo-β-lactamases (MβLs), including ESβLs (different from carbapenemases), KPC, NDM, VIM, IMP, AmpC (different from carbapenemases), and OXA-48. Recently approved inhibitor drugs, such as diazabicyclooctanones and boronic acid derivatives, only partially address this problem, not least because of their ineffectiveness against MβLs. However, compared with taniborbactam, xeruborbactam is the first bicyclic boronate in clinical development with a pan-β-lactamase inhibition spectrum, including the IMP subfamily. Recent studies explore strategies such as chemical optimization of β-lactamase inhibitor scaffolds, novel β-lactam/β-lactamase inhibitor combinations, and siderophore–antibiotic conjugates to enhance bacterial uptake. A deeper understanding of the mechanistic properties of the active sites enables rational drug design principles to be established for inhibitors targeting both SβLs and MβLs. This review aims to provide a comprehensive overview of current therapeutic strategies and future perspectives for the development of carbapenemase inhibitor drug candidates. Full article

(This article belongs to the Special Issue Discovery and Synthesis of Antimicrobial Compounds Against Multidrug Resistance)

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21 pages, 7339 KB

Open AccessEditor’s ChoiceArticle

In Vitro Analysis of Interactions Between Staphylococcus aureus and Pseudomonas aeruginosa During Biofilm Formation

by Julia Scaffo, Rayssa Durães Lima, Cameron Dobrotka, Tainara A. N. Ribeiro, Renata F. A. Pereira, Daniela Sachs, Rosana B. R. Ferreira and Fabio Aguiar-Alves

Antibiotics 2025, 14(5), 504; https://doi.org/10.3390/antibiotics14050504 - 14 May 2025

Cited by 14 | Viewed by 5407

Abstract

Staphylococcus aureus and Pseudomonas aeruginosa are classified as ESKAPE pathogens that present a significant challenge to treatment due to their increased resistance to a considerable number of antimicrobial agents. Background/Objective: Biofilms exacerbate treatment challenges by providing enhanced antimicrobial and environmental protection. Mixed-species [...] Read more.

Staphylococcus aureus and Pseudomonas aeruginosa are classified as ESKAPE pathogens that present a significant challenge to treatment due to their increased resistance to a considerable number of antimicrobial agents. Background/Objective: Biofilms exacerbate treatment challenges by providing enhanced antimicrobial and environmental protection. Mixed-species biofilms further complicate treatment options through numerous complex interspecies interactions, leading to potentially severe adverse clinical outcomes. Methods: This study assessed the interaction between clinical S. aureus and P. aeruginosa isolates during biofilm formation using microplate biofilm formation assays, scanning electron microscopy, and confocal microscopy. Results: We identified a competitive relationship between P. aeruginosa and S. aureus, where both pathogens exhibited a reduction in biofilm formation during mixed-species biofilms compared with monocultures, although P. aeruginosa outcompeted S. aureus. Furthermore, we found that the cell-free conditioned media (CFCM) of P. aeruginosa significantly reduced the S. aureus biofilms. Using fractioned CFCM, we identified that the anti-staphylococcal activity of the >10 kDa fraction was almost identical to the non-fractioned CFCM. Our confocal microscopy results suggest that P. aeruginosa CFCM depolarize S. aureus membranes and reduces the biofilm burden. Conclusions: These findings contribute to our understanding of the mechanisms underlying the interactions between these pathogens, suggesting that there is an antagonistic relationship between S. aureus and P. aeruginosa in a biofilm setting. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Biofilm-Associated Infections)

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15 pages, 7498 KB

Open AccessEditor’s ChoiceArticle

Lack of Spontaneous and Adaptive Resistance Development in Staphylococcus aureus Against the Antimicrobial Peptide LTX-109

by Bhupender Singh, Mia Angelique Winkler, Wasifa Kabir, Johanna U Ericson and Arnfinn Sundsfjord

Antibiotics 2025, 14(5), 492; https://doi.org/10.3390/antibiotics14050492 - 11 May 2025

Cited by 1 | Viewed by 2134

Abstract

Nasal carriage of Staphylococcus aureus and its antibiotic-resistant derivative, methicillin-resistant S. aureus (MRSA), is a risk factor for nosocomial S. aureus infections. Mupirocin is a topical antibiotic and a key in the decolonization of both methicillin-susceptible S. aureus (MSSA) and MRSA carriage in [...] Read more.

Nasal carriage of Staphylococcus aureus and its antibiotic-resistant derivative, methicillin-resistant S. aureus (MRSA), is a risk factor for nosocomial S. aureus infections. Mupirocin is a topical antibiotic and a key in the decolonization of both methicillin-susceptible S. aureus (MSSA) and MRSA carriage in patients and health care personnel. Recent observations have shown a global increase in the prevalence of mupirocin-resistant MSSA and MRSA, reducing the efficacy of mupirocin in decolonization regimens. LTX-109 is a peptidomimetic synthetic compound that has shown broad-spectrum bactericidal antimicrobial activity in vitro and in animal experiments. However, the development of resistance against LTX-109 in clinical isolates of MRSA and MSSA has not been systematically examined. Background/Objectives: Here, we assess the development of spontaneous and adaptive resistance against LTX-109 in genomically diverse MRSA (n = 3) and MSSA (n = 4) strains. Methods: Adaptive and mutational resistance were examined by serial passaging strains over 60 cycles in a range of LTX-109 and mupirocin concentrations. Spontaneous resistance was examined in high-inoculum agar plates with 2–8 times the concentration above MIC. Results: Throughout serial passage, LTX-109 MICs varied less than 4-fold compared to the initial MIC of 4–8 mg/L, while mupirocin MICs increased in all susceptible strains (n = 5) from 0.25 mg/L to 16–512 mg/L. The spontaneous resistance assay demonstrated no resistance development at 4–8× MIC LTX-109 and an inoculum effect at 2× MIC. Conclusions: Our results demonstrate the novelty of LTX-109 as an antimicrobial agent with no detectable in vitro resistance development in selected clinical strains of MRSA and MSSA. Full article

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

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25 pages, 11534 KB

Open AccessEditor’s ChoiceArticle

Repurposing Mouthwashes: Antifungal and Antibiofilm Abilities of Commercially Available Mouthwashes Against Candida spp.

by Marie Maziere, Paulo Rompante, José Carlos Andrade, Beatriz S. F. De Oliveira, Mariana C. Alves and Celia Fortuna Rodrigues

Antibiotics 2025, 14(5), 483; https://doi.org/10.3390/antibiotics14050483 - 9 May 2025

Cited by 2 | Viewed by 3615

Abstract

Background/Objectives: The main objective was to evaluate and compare the antifungal efficacy against Candida spp. in commercially available mouthwashes distributed in the European market. Indeed, the solution to emerging infectious diseases may no longer lie in costly new drug development but rather [...] Read more.

Background/Objectives: The main objective was to evaluate and compare the antifungal efficacy against Candida spp. in commercially available mouthwashes distributed in the European market. Indeed, the solution to emerging infectious diseases may no longer lie in costly new drug development but rather in unlocking the untapped potential of existing substances. Materials and Methods: Eighteen mouthwashes, chosen based on their composition, were tested in vitro against ten Candida strains, including clinical isolates of oral origin and reference strains, in both planktonic and biofilm forms. The antifungal susceptibility testing was conducted using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion method and the evaluation of the kinetic growth in planktonic Candida. Biofilm reduction was determined by the evaluation of the minimal biofilm eradication concentration (MBEC). Scanning electron microscopy (SEM) analysis was performed to evaluate potential morphological alterations of Candida biofilms. Results: Most mouthwashes effectively reduced biomass production and colony-forming unit (CFU) count. Parodontax Extra showed the highest efficacy. In the disc diffusion assay, Gum Paroex 0.12% exhibited the largest average inhibition zone diameter. Some unusual trends in the data may be explained by a higher reaction of fungal cells and the release of excess biomass during co-incubation in higher concentration of mouthwashes. SEM images revealed significant morphological alterations. Conclusion: Mouthwashes containing chlorhexidine digluconate, either alone or in combination with cetylpyridinium chloride and other active compounds, emerged as a common factor among the most efficacious formulations. In vivo studies will be essential to validate these findings, but mouthwashes may serve as a valuable adjuvant in the treatment of oral candidiasis. Full article

(This article belongs to the Special Issue Microbial Biofilms: Identification, Resistance and Novel Drugs)

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12 pages, 248 KB

Open AccessEditor’s ChoiceArticle

An Outbreak of Serratia marcescens in a Cardiothoracic Surgery Unit Associated with an Infected Solution of Pre-Prepared Syringes

by Maria Papagianni, Eleni Mylona, Sofia Kostourou, Chrysoula Kolokotroni, Dimitris Kounatidis, Natalia G. Vallianou and Vasileios Papastamopoulos

Antibiotics 2025, 14(3), 319; https://doi.org/10.3390/antibiotics14030319 - 18 Mar 2025

Cited by 1 | Viewed by 4081

Abstract

Background/Objectives: The aim of the present study is to report an outbreak of bloodstream infections caused by Serratia marcescens in patients undergoing postoperational procedures in the Cardiothoracic Department and to describe the epidemiological investigations and control measures undertaken. A cluster of bacteremia due [...] Read more.

Background/Objectives: The aim of the present study is to report an outbreak of bloodstream infections caused by Serratia marcescens in patients undergoing postoperational procedures in the Cardiothoracic Department and to describe the epidemiological investigations and control measures undertaken. A cluster of bacteremia due to Serratia marcescens was identified in blood cultures from postoperative patients in the Cardiothoracic Surgery Department in November 2023. Methods: Active surveillance by the hospital’s prevention and control team was initiated. Interviews with nurses and sanitary personnel and reviews of the most common procedures, such as hand washing, bladder catheterization, and intravenous catheter care, were performed. Culturing samples from hospital personnel, postoperative patients, and the environment, including pressure transducers, tap water, soap, therapeutic solutions, antiseptics, respirators, and various intravenous preparations, were drawn up. Overall, 225 samples were collected, including 149 blood cultures, and these were all sent to the Hospital’s Microbiology Laboratory. Results: Twenty-three out of forty-seven postoperative patients had positive blood cultures for Serratia marcescens. All the postoperative patients involved in the outbreak received cefepime according to antimicrobial susceptibility testing. Three pre-prepared flushing syringes were found to be positive for Serratia marcescens as well. The Cardiothoracic Department was kept under surveillance with hand hygiene measures, infusion preparation, medical device use, and cleaning procedures reviewed by the infection’s prevention and control team. Conclusions: Undoubtedly, nosocomial outbreaks represent an important health issue regarding morbidity, mortality, and costs. Timely interventions by the hospital’s infection prevention and control team may be life-saving under these circumstances. Full article

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

24 pages, 7266 KB

Open AccessEditor’s ChoiceArticle

A Simple In Vitro Method to Determine Bactericidal Activity Against Mycobacterium abscessus Under Hypoxic Conditions

by Ruth Feilcke, Robert Eckenstaler, Markus Lang, Adrian Richter and Peter Imming

Antibiotics 2025, 14(3), 299; https://doi.org/10.3390/antibiotics14030299 - 13 Mar 2025

Cited by 1 | Viewed by 3138

Abstract

Background/Objectives: Non-replicating persisters (NRPs) of Mycobacterium abscessus are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication of these bacteria is difficult, which is one reason for the long treatment duration [...] Read more.

Background/Objectives: Non-replicating persisters (NRPs) of Mycobacterium abscessus are a bacterial subpopulation that can survive in the host under unfavorable conditions, such as hypoxia or nutrient starvation. The eradication of these bacteria is difficult, which is one reason for the long treatment duration and treatment failure. The drug discovery process should therefore contain methods to screen activity against NRPs. Methods: A hypoxic environment is used to generate NRPs of M. abscessus that are termed low-oxygen persisters (LOPs). For this, an oxidation process is used to transition a replicating culture of M. abscessus distributed in microtiter plates within a sealable box into LOPs. Colony counting, automated object counting, bactericidal activity determination of known agents, and confocal laser scanning microscopy are used to study the obtained culture. Results: The obtained culture shows typical attributes of non-replicating cells, such as significantly reduced replication, the reversibility of the LOP state under aerobic conditions, delayed regrowth on solid medium, altered morphological patterns on a single-cell level, and phenotypical resistance against a variety of clinically relevant antimycobacterial compounds. The study reveals metronidazole and niclosamide as bactericidal against M. abscessus LOPs. These compounds can be used as LOP verification compounds within the described model. Conclusions: Our model is easily implemented and quickly identifies compounds that are inactive under hypoxic conditions. It can therefore accelerate the identification of clinically effective antimycobacterial drug substances, and can be a helpful tool during the drug development process. Full article

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

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14 pages, 2459 KB

Open AccessEditor’s ChoiceArticle

Antibacterial and Antibiofilm Activities of Hydralazine, an Antihypertensive Drug: In Vitro and In Silico Approaches

by Antônio Mateus Gomes Pereira, Benise Ferreira da Silva, Ingrid Maria Frota Araujo, Francisco Kauê Carvalho Aguiar, Paulo Adenes Teixeira Coelho, Renata Albuquerque Costa, Marcia Machado Marinho, Emmanuel Silva Marinho, João Victor Serra Nunes, Victor Alves Carneiro and Hélcio Silva dos Santos

Antibiotics 2025, 14(3), 286; https://doi.org/10.3390/antibiotics14030286 - 10 Mar 2025

Cited by 4 | Viewed by 3132

Abstract

Background: The rise of multidrug-resistant (MDR) bacteria poses a significant challenge to global public health, contributing to increased morbidity and mortality rates. In this context, the repurposing of existing drugs has emerged as a promising strategy. In this study, hydralazine (HDZ), a vasodilator [...] Read more.

Background: The rise of multidrug-resistant (MDR) bacteria poses a significant challenge to global public health, contributing to increased morbidity and mortality rates. In this context, the repurposing of existing drugs has emerged as a promising strategy. In this study, hydralazine (HDZ), a vasodilator used as an antihypertensive since 1952, demonstrated antibacterial and antibiofilm activity against both Gram-positive and Gram-negative bacteria. Methods: In this study, the antibacterial activity of the antihypertensive hydralazine (HDZ) was evaluated against Gram-positive and Gram-negative strains through minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curve with MIC and sub-MIC doses, combinatorial effect with gentamicin, scanning electron microscopy (SEM), molecular docking, and antibiofilm activity. Results: The MIC and MBC values ranged from 39.5 to 1.250 μg/mL, respectively. A change in the growth kinetics of the strains was observed when exposed to MIC and 1/2 MIC values, with a delay in the phases of up to 12 h. The combinatorial effect with gentamicin demonstrated an additive and indifferent potential when combined with HDZ. Conclusions: Furthermore, hydralazine showed antibiofilm activity against the tested strains, including MRSA. Electron microscopy analysis revealed significant changes in bacterial morphology when exposed to the MIC dose of HDZ for 4 h. The overall results of the study indicate hydralazine as a potential agent in the fight against bacterial infections. Full article

(This article belongs to the Special Issue Repositioning Drugs as a Strategy to Combat Infections)

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19 pages, 1580 KB

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 4942

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)

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12 pages, 545 KB

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 2109

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)

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13 pages, 218 KB

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

Cited by 1 | Viewed by 1841

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 KB

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 7 | Viewed by 3302

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)

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17 pages, 1902 KB

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

Cited by 2 | Viewed by 3600

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)

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17 pages, 5886 KB

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

Cited by 4 | Viewed by 2909

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)

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20 pages, 2256 KB

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

Cited by 11 | Viewed by 4503

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)

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10 pages, 195 KB

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

Cited by 12 | Viewed by 6031

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 KB

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 23 | Viewed by 9341

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)

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18 pages, 4858 KB

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

Cited by 3 | Viewed by 2810

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

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17 pages, 2849 KB

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 5 | Viewed by 2651

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

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25 pages, 1091 KB

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 7 | Viewed by 4416

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)

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21 pages, 1022 KB

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

Cited by 11 | Viewed by 3207

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)

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32 pages, 6288 KB

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 25 | Viewed by 7462

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)

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