Antibiotics

44 pages, 848 KB

Open AccessReview

Frog Skin Peptides: Nature’s Dual-Action Weapons Against Infection and Cancer

by Eleonora Grisard, Carlo Vetrano, Ali Benour, Eeva Tortellini, Dania Al Ismail, Giacomo Cappella, Bruno Casciaro, Maria Luisa Mangoni and Milena Mechkarska

Antibiotics 2026, 15(3), 324; https://doi.org/10.3390/antibiotics15030324 - 23 Mar 2026

Cited by 1 | Viewed by 2574

Abstract

The rise of antimicrobial resistance and the global burden of cancer demand innovative therapeutic strategies. Frog skin secretions offer a rich source of bioactive peptides, some of which exhibit remarkable dual functionality—potent antimicrobial activity coupled with selective anticancer effects. This review highlights frog [...] Read more.

The rise of antimicrobial resistance and the global burden of cancer demand innovative therapeutic strategies. Frog skin secretions offer a rich source of bioactive peptides, some of which exhibit remarkable dual functionality—potent antimicrobial activity coupled with selective anticancer effects. This review highlights frog skin-derived peptides that bridge the gap between antimicrobial and anticancer therapeutics, emphasizing their structural diversity, mechanisms of action, and translational potential. A comprehensive literature search was conducted to identify peptides isolated from diverse anuran species, with emphasis on studies reporting structural features, activity against Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolates, anticancer effects, and underlying molecular mechanisms of cytotoxicity. Peptides such as dermaseptins, temporins, and brevinins disrupt microbial membranes while triggering apoptosis or necrosis in cancer cells. Key physicochemical characteristics, including net positive charge, amphipathicity, and α-helical conformation, contribute to their dual functionality. Recent advances in peptide engineering and delivery have improved stability, selectivity, and therapeutic efficacy, enhancing the clinical prospects of these naturally occurring bioactive molecules. Frog skin peptides represent promising candidates for the development of next-generation antimicrobial and anticancer therapeutics. Full article

(This article belongs to the Special Issue Development of Antimicrobial Peptides from Amphibian, 2nd Edition)

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23 pages, 1321 KB

Open AccessArticle

Antimicrobial Resistance and ESBL-Associated Predictors Among Uropathogens: A 2019–2024 Isolate-Level Study

by Raul-Lucian Ene, Roxana Popescu, Aurica Elisabeta Cobec, Daniela Puscasiu, Ileana-Adriana Ene, Daliborca Cristina Vlad, Ionut Marcel Cobec and Peter Seropian

Antibiotics 2026, 15(3), 323; https://doi.org/10.3390/antibiotics15030323 - 23 Mar 2026

Cited by 1 | Viewed by 1864

Abstract

Background/Objectives: Urinary tract infections (UTIs) are among the most common bacterial infections and represent a major source of antimicrobial use. Increasing antimicrobial resistance among uropathogens, particularly the emergence of extended-spectrum beta-lactamase (ESBL)-producing organisms, complicates empiric treatment strategies. ESBL-producing organisms are clinically relevant because [...] Read more.

Background/Objectives: Urinary tract infections (UTIs) are among the most common bacterial infections and represent a major source of antimicrobial use. Increasing antimicrobial resistance among uropathogens, particularly the emergence of extended-spectrum beta-lactamase (ESBL)-producing organisms, complicates empiric treatment strategies. ESBL-producing organisms are clinically relevant because they are frequently associated with multidrug resistance and significantly limit empiric antimicrobial treatment options in urinary tract infections. The study period starting in 2019 was selected to reflect contemporary resistance patterns and to ensure consistency with the updated EUCAST antimicrobial susceptibility interpretation criteria introduced at that time. This study aimed to characterize antimicrobial resistance patterns among uropathogens isolated from lower UTIs and to identify independent predictors of antimicrobial resistance using isolate-level analyses. Methods: This retrospective observational study included 1470 patients and isolates with clinically suspected lower UTIs who underwent urine culture and antimicrobial susceptibility testing between 2019 and 2024 at a single clinical center. Antimicrobial susceptibility was interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, and ESBL production was assessed among Gram-negative (GN) isolates. Multivariable generalized estimating equation (GEE) logistic regression models accounting for patient clustering were used to identify predictors of resistance. Results: A total of 1470 patients and isolates were included. Escherichia coli was the most frequent uropathogen (66.0%), followed by Klebsiella pneumoniae and Enterococcus faecalis. Among Gram-negative isolates, 17.3% were ESBL-positive. Resistance rates were highest for ciprofloxacin (35.4%) and trimethoprim/sulfamethoxazole (31.7%), while fosfomycin and nitrofurantoin retained high activity against E. coli. In multivariable analyses, ESBL production was the strongest independent predictor of resistance to several antimicrobials, including ciprofloxacin (aOR 9.83), amoxicillin/clavulanic acid (aOR 3.22), trimethoprim/sulfamethoxazole (aOR 2.89), and cefotaxime (aOR 1337). Pathogen identity was also independently associated with resistance. Conclusions: Antimicrobial resistance among uropathogens was heterogeneous and predominantly driven by pathogen identity and ESBL production. ESBL status emerged as the most consistent and powerful predictor of resistance across multiple antimicrobials, underscoring its clinical relevance for empiric treatment decisions and antimicrobial stewardship in urinary tract infections. Full article

(This article belongs to the Special Issue Urinary Tract Infections: Diagnosis, Etiology, Antibiotic Treatment, and Current Trends in Antimicrobial Resistance)

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12 pages, 1012 KB

Open AccessArticle

A Risk Model Incorporating the Novel Inflammatory Biomarker CD64 for Predicting Bloodstream Infection in Suspected Cases

by Teng Xu, Yu Zhou, Bei Wang, Li Wang, Yinglu Wan, Shi Wu and Haihui Huang

Antibiotics 2026, 15(3), 322; https://doi.org/10.3390/antibiotics15030322 - 23 Mar 2026

Viewed by 716

Abstract

Background/Objectives: Bloodstream infection (BSI) is a significant cause of mortality. The availability of a convenient tool for predicting the risk of BSI at the early stage would be beneficial for clinicians, allowing them to improve the outcomes of BSI and avoid antibiotic [...] Read more.

Background/Objectives: Bloodstream infection (BSI) is a significant cause of mortality. The availability of a convenient tool for predicting the risk of BSI at the early stage would be beneficial for clinicians, allowing them to improve the outcomes of BSI and avoid antibiotic overuse. Methods: A multivariate prediction model was constructed based on conventional laboratory test results and novel serum inflammatory markers in a cohort of patients with suspected BSI over a one-year period using least absolute shrinkage and selection operator (LASSO) and logistic regression. Results: BSI was confirmed in 99 (32.0%) of the 309 enrolled patients. Five readily available markers were identified as independent predictors: the presence of local infection, platelet count, and C-reactive protein, procalcitonin (PCT), and CD64 levels. A nomogram based on these five variables achieved an area under the receiver operating characteristic curve of 0.85 in predicting the risk of BSI. The nomogram was superior to PCT alone in terms of the net clinical benefits obtained in a rather wide range of threshold probabilities. Conclusions: The simple five-variable nomogram developed in this study is useful for timely prediction of individuals at high risk of BSI. It may be used in clinical practice to facilitate timely decision-making on antimicrobial treatment and avoid inappropriate overuse of antibiotics. Full article

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17 pages, 1341 KB

Open AccessArticle

New Chemical Scaffold with Antimicrobial Activity Identified in a Screening of Industrial Photoactive Compounds

by José Manuel Ezquerra-Aznárez, Raquel Alonso-Román, Ainhoa Lucía, Raquel Andreu, Santiago Franco, José A. Aínsa and Santiago Ramón-García

Antibiotics 2026, 15(3), 321; https://doi.org/10.3390/antibiotics15030321 - 20 Mar 2026

Viewed by 1055

Abstract

Background/Objectives: The emergence of antimicrobial resistance threatens advances achieved by medicine in the last century. This situation has been exacerbated by the suboptimal outcome of screening campaigns to provide novel antimicrobials. Methods: An alternative strategy was employed to identify new chemical [...] Read more.

Background/Objectives: The emergence of antimicrobial resistance threatens advances achieved by medicine in the last century. This situation has been exacerbated by the suboptimal outcome of screening campaigns to provide novel antimicrobials. Methods: An alternative strategy was employed to identify new chemical scaffolds with antimicrobial activity. A collection of photoactive compounds originally synthesized for industrial purposes was screened for antibacterial activity. Results: 4H-pyran-4-ylidenes were identified as active against Gram-positive bacteria. Compounds belonging to this family displayed dose-dependent bactericidal activity against both wild-type and methicillin-resistant Staphylococcus aureus. No cytotoxicity was observed in the HepG2 hepatic cell line at the concentrations required for antimicrobial activity against S. aureus. Resistance to 4H-pyran-4-ylidenes in S. aureus was associated with point mutations in the rny locus, which encodes for a ribonuclease that plays a key role in RNA homeostasis. Conclusions: These findings indicate that chemical libraries not originally intended for drug discovery can be an innovative source of chemical diversity for the development of novel antimicrobials. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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12 pages, 263 KB

Open AccessArticle

Balancing Speed and Cost: Economic Insights from Rapid Diagnostic Testing in Bloodstream Infections

by Gergana Lengerova, Ralitsa Raycheva, Michael M. Petrov and Todor Kantardjiev

Antibiotics 2026, 15(3), 320; https://doi.org/10.3390/antibiotics15030320 - 20 Mar 2026

Viewed by 891

Abstract

Background: Rapid diagnostic tests (RDTs) for bloodstream infections (BSIs) reduce time to pathogen identification, yet evidence on their real-world economic and clinical value remains inconsistent. This study aimed to compare clinical outcomes, antibiotic utilization, and hospital costs associated with different rapid microbiological identification [...] Read more.

Background: Rapid diagnostic tests (RDTs) for bloodstream infections (BSIs) reduce time to pathogen identification, yet evidence on their real-world economic and clinical value remains inconsistent. This study aimed to compare clinical outcomes, antibiotic utilization, and hospital costs associated with different rapid microbiological identification methods versus standard culture. Methods: A retrospective observational study was conducted in a tertiary university hospital including 115 hospitalized patients with suspected or confirmed BSIs. Multiplex PCR (mPCR), fluorescence in situ hybridization (FISH), and MALDI-TOF MS were compared with conventional culture. Outcomes included mortality, length of stay, antibiotic-days, and direct and indirect hospital costs. Nonparametric and exploratory adjusted analyses were performed. Results: No significant differences were observed across diagnostic groups for age, sex, mortality, or length of stay. Patients tested with mPCR showed higher empirical and total antibiotic-days and increased antibiotic-related costs (p < 0.05). Median direct and indirect hospital costs were numerically lower with FISH and mPCR but did not reach statistical significance. Adjusted analyses confirmed that diagnostic modality was not independently associated with mortality or costs. Conclusions: Rapid diagnostics accelerate identification but demonstrate heterogeneous downstream clinical and economic effects. Their value appears to depend more on local implementation and antimicrobial stewardship integration than on diagnostic speed alone. Full article

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

33 pages, 6207 KB

Open AccessReview

Mechanisms of Bacterial Resistance and Innovative Strategies to Overcome Antimicrobial Resistance

by Irene Dini

Antibiotics 2026, 15(3), 319; https://doi.org/10.3390/antibiotics15030319 - 20 Mar 2026

Cited by 4 | Viewed by 4238

Abstract

Widespread, sometimes careless use of antibiotics has accelerated the rise and spread of antibiotic-resistant pathogens. These resistant bacteria are now often found in animal-based foods like meat, milk, and eggs, as well as in plant-based foods such as fruits and vegetables. Contaminated food [...] Read more.

Widespread, sometimes careless use of antibiotics has accelerated the rise and spread of antibiotic-resistant pathogens. These resistant bacteria are now often found in animal-based foods like meat, milk, and eggs, as well as in plant-based foods such as fruits and vegetables. Contaminated food is a key way these bacteria travel through the food chain and eventually reach people. This review brings together global trends in antibiotic contamination, explains the molecular mechanisms underlying antimicrobial resistance, and examines current approaches to addressing this problem. It also highlights new technologies that could work alongside or improve on traditional antibiotics. Some promising options are antimicrobial peptides, natural bioactive compounds, nanomaterials, and monoclonal antibody-based therapies. Tackling antimicrobial resistance requires teamwork across fields such as microbiology, food science, pharmacology, environmental science, and public health. Future research should strengthen global surveillance, standardize resistance-assessment methods, expand studies on non-bacterial pathogens, and ensure rigorous evaluation of novel therapies for pharmacokinetics, toxicity, scalability, and regulatory compliance. Ongoing global cooperation and new scientific ideas are crucial to slow the spread of resistant microbes and protect food safety and human health. Full article

(This article belongs to the Special Issue The Antimicrobial Resistance in the Food Chain)

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14 pages, 1748 KB

Open AccessArticle

Molecular Characterization of Colistin-Resistant Clinical Acinetobacter baumannii from Northern Greece: Phenotypic Colistin Susceptibility and lpx/pmrCAB Mutational Profiles

by Dimitrios Karakalpakidis, Michaela-Eftychia Tsitlakidou, Michalis Paraskeva, Maria Nikoleta Mavidi, Maria Marinou, Kassandra Procter, Apostolos Beloukas and Christine Kottaridi

Antibiotics 2026, 15(3), 318; https://doi.org/10.3390/antibiotics15030318 - 20 Mar 2026

Cited by 1 | Viewed by 1466

Abstract

Background: Acinetobacter baumannii (A. baumannii) is a formidable nosocomial pathogen and is classified by the World Health Organization (WHO) as a critical-priority pathogen, owing to its rapid evolution into extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains. Colistin remains one of [...] Read more.

Background: Acinetobacter baumannii (A. baumannii) is a formidable nosocomial pathogen and is classified by the World Health Organization (WHO) as a critical-priority pathogen, owing to its rapid evolution into extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains. Colistin remains one of the last-resort therapeutic options, although resistance rates are increasing in endemic regions such as Greece. In this study, we investigated the molecular basis of colistin resistance and characterized the clonal backgrounds of clinical XDR/PDR A. baumannii isolates collected between January and June 2022 from two tertiary-care hospitals in Thessaloniki, Northern Greece. Methods: We analyzed forty non-duplicate XDR/PDR clinical isolates. Antimicrobial susceptibility was determined using the VITEK 2 system, broth microdilution, and gradient diffusion methods. The lipid A biosynthesis genes (lpxA, lpxC, lpxD) and the pmrCAB operon were amplified by PCR and sequenced for all isolates. A representative subset of strains (n = 10/40) underwent multilocus sequence typing (MLST) according to the Pasteur MLST scheme. Results: All isolates proved colistin-resistant (MIC ≥ 4 µg/mL), and 95% were classified as PDR. Sequence analysis revealed multiple nonsynonymous mutations in the pmrCAB operon, with the PmrB A226V substitution predominating and extensive amino-acid changes observed in PmrC. In contrast, lpx genes exhibited limited protein-level variation, limited to lineage-associated polymorphisms (LpxC N287D, LpxD E117K). A novel six-nucleotide insertion in pmrB was identified in one isolate. MLST demonstrated a predominance of ST2 (International Clone 2), with single representatives of ST115 (IC2) and ST1 (IC1). Conclusions: In this cohort from Northern Greece, chromosomal mutations in the pmrCAB operon, within a predominantly ST2/IC2 background, were strongly associated with colistin resistance. These findings underscore the urgent need for continued molecular surveillance and targeted infection-control measures to limit further spread of PDR A. baumannii. Full article

(This article belongs to the Special Issue Epidemiology and Genomics of Antimicrobial Resistance of Difficult-to-Treat Pathogens)

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21 pages, 836 KB

Open AccessReview

Bacteriophage Therapy Against Shigella spp.: A Precision Antimicrobial Strategy

by Giuseppe Guido Maria Scarlata, Andrej Belančić, Davor Štimac, Almir Fajkić, Tomislav Meštrović and Ludovico Abenavoli

Antibiotics 2026, 15(3), 317; https://doi.org/10.3390/antibiotics15030317 - 20 Mar 2026

Cited by 3 | Viewed by 1464

Abstract

Shigellosis remains a significant global cause of infectious colitis, increasingly complicated by multidrug-resistant strains and the microbiota-disrupting effects of broad-spectrum antibiotics. Although conventional antimicrobial therapy can reduce symptom duration and bacterial shedding, it also contributes to gut dysbiosis, loss of colonization resistance, and [...] Read more.

Shigellosis remains a significant global cause of infectious colitis, increasingly complicated by multidrug-resistant strains and the microbiota-disrupting effects of broad-spectrum antibiotics. Although conventional antimicrobial therapy can reduce symptom duration and bacterial shedding, it also contributes to gut dysbiosis, loss of colonization resistance, and further selection for antimicrobial resistance. These challenges have renewed interest in precision antimicrobial strategies, particularly bacteriophage therapy, which provides strain-level specificity and preserves the gut microbiota. This narrative review evaluates the biological rationale, preclinical and early clinical evidence, safety considerations, and translational challenges associated with bacteriophage therapy targeting Shigella spp. The historical development and mechanistic basis of phage therapy are summarized, with emphasis on the advantages of obligately lytic phages, receptor-specific targeting, self-amplification at infection sites, and activity against both planktonic and biofilm-associated bacteria. Recent microbiota research indicates that shigellosis is closely associated with early and persistent disruption of gut ecology, including depletion of short-chain fatty acids-producing taxa and reduced microbial resilience. Phage-based approaches may reduce pathogen burden while preserving beneficial microbial communities. Evidence from in vitro systems, animal models, human intestinal organoids, and a Phase 1 clinical trial demonstrates targeted efficacy and favorable safety profiles for Shigella-specific phages and phage cocktails. Major barriers to clinical adoption include immune interactions, phage resistance dynamics, genomic safety screening, regulatory classification, and the need for standardized susceptibility testing. Future directions emphasize the development of personalized phage therapy platforms that integrate rapid diagnostics, phage libraries, metagenomics, and artificial intelligence-assisted matching to enable scalable, precision treatment. Full article

(This article belongs to the Special Issue New Advances in Antibiotic Therapy in the Gastroenterology Field)

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11 pages, 1404 KB

Open AccessCommunication

Enhanced In Vitro Stability of Bedaquiline with Ascorbic Acid and Pyruvate During Long-Term Incubation in Mycobacterium Species

by Sara Batista, Jordi Lamata, Lidia Feliu, Marta Planas, Mariana Fernandez-Pittol, Diego Martinez, Lorena San Nicolás, Griselda Tudó and Julian Gonzalez-Martin

Antibiotics 2026, 15(3), 316; https://doi.org/10.3390/antibiotics15030316 - 20 Mar 2026

Viewed by 790

Abstract

Background: Drug susceptibility testing in Mycobacterium species typically requires prolonged incubation periods during which the chemical integrity of antibiotics may not be maintained, potentially compromising the reliability and accuracy of minimum inhibitory concentration (MIC) determinations. Objectives: This study evaluated the in vitro stability [...] Read more.

Background: Drug susceptibility testing in Mycobacterium species typically requires prolonged incubation periods during which the chemical integrity of antibiotics may not be maintained, potentially compromising the reliability and accuracy of minimum inhibitory concentration (MIC) determinations. Objectives: This study evaluated the in vitro stability of several antibiotics, including recently introduced agents (bedaquiline [BDQ], pretomanid, delamanid and clofazimine) used for treating multidrug-resistant mycobacteriosis (linezolid and moxifloxacin), and those commonly included in combination regimens (rifampicin, isoniazid, ethambutol and clarithromycin). Methods: Antibiotics were pre-incubated at 37 °C before MIC determination and those exhibiting two or more dilutions in MIC were further tested in combination with ascorbic acid (AA) and pyruvate (P). Results: All antibiotics demonstrated stability except BDQ, which showed significant MIC variation after pre-incubation, which was prevented when BDQ was combined with AA and P. Conclusions: These findings suggest that the combined use of AA and P may serve as an effective stabilizing strategy for BDQ during MIC determination. Full article

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15 pages, 523 KB

Open AccessArticle

Pharmacokinetic/Pharmacodynamic Analysis of High-Dose Daptomycin in Combination with Continuous Infusion Ceftobiprole in a Case Series of Documented Staphylococcal Bacteremia or Endocarditis: Is There Any Room for TDM-Guided Dosing Reduction?

by Pier Giorgio Cojutti, Renato Pascale, Andrea Grechi, Simone Ambretti, Pierluigi Viale and Federico Pea

Antibiotics 2026, 15(3), 315; https://doi.org/10.3390/antibiotics15030315 - 19 Mar 2026

Viewed by 882

Abstract

Background: Staphylococcal bloodstream infections (BSIs) and infective endocarditis (IE) are associated with high morbidity and mortality. Among the different antimicrobial combination strategies proposed to enhance antibacterial activity, the association of daptomycin and ceftobiprole may be valuable. The aim of this study was to [...] Read more.

Background: Staphylococcal bloodstream infections (BSIs) and infective endocarditis (IE) are associated with high morbidity and mortality. Among the different antimicrobial combination strategies proposed to enhance antibacterial activity, the association of daptomycin and ceftobiprole may be valuable. The aim of this study was to assess the PK/PD target attainment, safety, and clinical outcomes of such combination therapy for BSI and IE treatment. Methods: This retrospective monocentric study included adult patients with targeted treatment of staphylococcal BSI or IE with daptomycin plus continuous infusion (CI) ceftobiprole. Therapeutic drug monitoring (TDM) was performed for both agents, including Bayesian estimation of daptomycin 24 h area under the concentration–time curve (AUC_24h). PK/PD targets were defined as daptomycin AUC_24h/MIC ≥ 666 and ≥1081, and ceftobiprole steady-state concentration/MIC ≥ 4. Dose adjustments, safety, microbiological response, and clinical outcomes were assessed. Results: Twenty-three patients (11 BSI and 12 IE) were included. Methicillin-resistant Staphylococci were identified in 91.3% of cases. At first TDM assessment, daptomycin PK/PD targets were achieved in all patients, while ceftobiprole targets were achieved in 91.6% of BSI cases and in all IE cases. PK-/PD-guided dose de-escalation was frequently feasible. Clinical cure was observed in 77.8% of evaluable patients with BSI and in 91.7% with IE. Creatine phosphokinase elevations occurred in two patients, while hyper-eosinophilia was observed in 69.6% and was manageable with monitoring. Conclusions: Targeted therapy with daptomycin plus CI ceftobiprole achieved high PK/PD target attainment and favorable clinical outcomes in staphylococcal BSI and IE. TDM and model-informed precision dosing may enable dose optimization and may improve the balance between efficacy and safety. Multicenter studies are warranted. Full article

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

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22 pages, 3364 KB

Open AccessArticle

Evolutionary and Mobile Genetic Element Analysis of a Multidrug-Resistant ST398-MRSA-Vc Isolate from Ready-to-Eat Pork Products

by Jinqi Wan, Xiaoru Wang, Kaifen Wang, Qiuyi Feng, Ruihua Yuan, Xiaojing Qi, Yidong Lai and He Yan

Antibiotics 2026, 15(3), 314; https://doi.org/10.3390/antibiotics15030314 - 19 Mar 2026

Viewed by 961

Abstract

Background: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398 poses a significant zoonotic threat, largely due to its capacity to acquire and disseminate antimicrobial resistance through mobile genetic elements (MGEs). Ready-to-eat (RTE) foods may serve as critical interfaces for zoonotic spillover. However, genomic data on [...] Read more.

Background: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398 poses a significant zoonotic threat, largely due to its capacity to acquire and disseminate antimicrobial resistance through mobile genetic elements (MGEs). Ready-to-eat (RTE) foods may serve as critical interfaces for zoonotic spillover. However, genomic data on ST398-MRSA-Vc isolates from RTE foods remain scarce, leaving the characteristics of their MGEs largely unresolved. Methods: This study performed whole-genome sequencing and comparative genomic analysis of an ST398-MRSA-Vc isolate (NPREF115) from an RTE pork product in China. Using NPREF115 and 134 publicly available S. aureus genomes from diverse sources, we constructed a core genome phylogeny and conducted SNP and pangenome analyses, with a focus on MGEs. Results: Phylogenetic analysis revealed that our foodborne ST398-MRSA-Vc isolate clustered with human, Capra pyrenaica, bovine, and swine-derived ST398-MRSA-Vc isolates. SNP analysis indicated NPREF115 was most closely related to human clinical isolates (132 and 140 SNPs, respectively), consistent with shared ancestry rather than recent cross-host transmission. Genomic divergence was largely confined to MGEs, including SCCmec, prophages, genomic islands, and a chromosomally integrated Tn560 carrying the ant(9)-Ia-lsa(E)-lnu(B) multidrug resistance cluster. Notably, NPREF115 harbored a unique metabolic gene that may facilitate persistence in high-osmolarity food environments. Conclusions: The successful colonization of food by the ST398-MRSA-Vc isolate is likely associated with the acquisition of multiple MGEs harboring antimicrobial resistance genes. Transmission of ST398-MRSA-Vc between food, human, and livestock hosts was accompanied by changes in genes involved in metabolism. These findings underscore the importance of monitoring MGEs in genomic surveillance of foodborne MRSA. Full article

(This article belongs to the Special Issue Antimicrobial Resistance of Staphylococcus spp. in Animals: A One Health Perspective)

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24 pages, 2655 KB

Open AccessReview

Antimicrobial Resistance in Rhodococcus equi and the Promise of Synergistic Therapies

by Farzaneh Javadimarand, Pablo Castañera, Blanca Lorente-Torres, Negar Mortazavi, Jesús Llano-Verdeja, Sergio Fernández-Martínez, Helena Á. Ferrero, Luis M. Mateos, Álvaro Mourenza and Michal Letek

Antibiotics 2026, 15(3), 313; https://doi.org/10.3390/antibiotics15030313 - 19 Mar 2026

Viewed by 1492

Abstract

Rhodococcus equi is an opportunistic intracellular pathogen responsible for severe pneumonia in foals and has emerged as an important cause of infection in immunocompromised humans. The treatment of R. equi infections in foals relies mainly on the combination of macrolides and rifampin. However, [...] Read more.

Rhodococcus equi is an opportunistic intracellular pathogen responsible for severe pneumonia in foals and has emerged as an important cause of infection in immunocompromised humans. The treatment of R. equi infections in foals relies mainly on the combination of macrolides and rifampin. However, the increasing incidence of multidrug-resistant (MDR) isolates has raised significant therapeutic challenges. The mechanisms underlying this resistance include mutations in target genes, activation of efflux pumps, and biofilm formation, which collectively compromise the efficacy of conventional antibiotics. Recently, growing concern over antibiotic failure has accelerated research into alternative and synergistic strategies to enhance antibacterial efficacy and reduce the development of resistance. Natural and synthetic compounds, as well as optimized antibiotic combinations, have shown promising synergistic effects by enhancing intracellular accumulation, disrupting redox homeostasis, or inhibiting efflux systems. Experimental models employing checkerboard and time-kill assays, as well as redox-sensitive biosensors, have demonstrated that certain antibiotic combinations can influence bacterial susceptibility to antibiotic exposure. Furthermore, integrating molecular tools provides valuable insight into bacterial responses to oxidative and antibiotic stress, paving the way for novel therapeutic designs. This review summarizes the current understanding of the molecular factors contributing to antimicrobial resistance in R. equi and assesses new therapeutic approaches aimed at overcoming these challenges. It highlights recent findings on strategies to improve treatment outcomes and manage antimicrobial resistance. Full article

(This article belongs to the Special Issue Virulence, Antimicrobial Resistance and Biofilm Production in Veterinary, Zoonotic and Food-Related Pathogens, 2nd Edition)

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33 pages, 959 KB

Open AccessReview

Essential Oils for Flea and Tick Control in Companion Animals: A Critical Review of Efficacy, Safety, Resistance Mitigation and Integrated Pest Management

by Roberto Bava, Rosa Maria Bulotta, Fabio Castagna, Stefano Ruga, Carmine Lupia, Filomena Conforti, Giancarlo Statti, Rosalia Crupi, Vincenzo Musella and Ernesto Palma

Antibiotics 2026, 15(3), 312; https://doi.org/10.3390/antibiotics15030312 - 19 Mar 2026

Cited by 3 | Viewed by 6102

Abstract

Background: The control of fleas and ticks in companion animals is a persistent challenge with animal welfare and public health implications. The increasing resistance to antiparasitic treatments, coupled with concerns over the environmental impact and non-target effects of synthetic acaricides, has driven interest [...] Read more.

Background: The control of fleas and ticks in companion animals is a persistent challenge with animal welfare and public health implications. The increasing resistance to antiparasitic treatments, coupled with concerns over the environmental impact and non-target effects of synthetic acaricides, has driven interest in sustainable alternatives. Essential oils (EOs) have emerged as potential candidates due to their complex chemistry and modes of action. Methods: This review critically analyzes the scientific literature on essential oils for ectoparasite control in companion animals. Specifically, it examines their chemical composition, multi-target mechanisms of action, laboratory and field efficacy, role in resistance mitigation, and integration into IPM strategies. Results: Several EOs, particularly those rich in phenolic compounds (thymol, carvacrol, eugenol, and cinnamaldehyde), demonstrate promising in vitro insecticidal and acaricidal activity. Their multi-target mechanisms, affecting neuronal, respiratory, and cuticular functions, not only provide efficacy but also represent a significant barrier to rapid resistance development. However, their translation to reliable field performance is hampered by high volatility, formulation instability, and innate variability. Conclusions: EOs represent a valuable source of bioactive compounds for reducing reliance on conventional acaricides and can play a key role within IPM strategies. To realize their full potential in mitigating resistance, focused advancements are needed in standardized testing, formulation science to enhance stability and residual activity, and rigorous field studies to confirm safety and efficacy. Full article

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26 pages, 393 KB

Open AccessReview

Antimicrobial Resistance Along the Food Chain: Spread and Integrated Strategies for Mitigation and Control

by Anna Maria Spagnolo, Francesco Palma, Giulia Amagliani, Michele Fernando Panunzio, Maria Teresa Montagna, Elena Alonzo, Guglielmo Bonaccorsi, Giulia Cairella, Emilia Guberti and Giuditta Fiorella Schiavano

Antibiotics 2026, 15(3), 311; https://doi.org/10.3390/antibiotics15030311 - 19 Mar 2026

Cited by 3 | Viewed by 2255

Abstract

The development of antimicrobial resistance (AMR) and the emergence of multiresistant pathogens represent a growing global threat to both human and animal health. Beyond the excessive and improper use of antimicrobials in human medicine, irrational use in veterinary medicine, agriculture, and aquaculture significantly [...] Read more.

The development of antimicrobial resistance (AMR) and the emergence of multiresistant pathogens represent a growing global threat to both human and animal health. Beyond the excessive and improper use of antimicrobials in human medicine, irrational use in veterinary medicine, agriculture, and aquaculture significantly contributes to the selection and spread of resistant microorganisms, which can enter the food chain and reach humans through food consumption or handling. Based on results from a recent meta-analysis, the prevalence of antimicrobial-resistant foodborne pathogens in food samples exceeds 10%. The veterinary sector is of particular concern, as a large proportion of antimicrobials are used in animal production, generating strong selective pressure and favoring the dissemination of AMR along the food chain. In an increasingly interconnected global context, resistant pathogens and resistance determinants can disseminate rapidly across sectors and national borders, making strategies confined to a single sector insufficient; therefore, effectively addressing AMR requires a One Health approach encompassing the human, veterinary, and environmental domains. Key mitigation strategies include strengthening antimicrobial stewardship programs, also in animal production, reducing routine prophylactic use of antimicrobials, and improving surveillance, coordinated across sectors and, where possible, further supported by advanced technologies such as artificial intelligence and machine learning. Further efforts are also needed to improve microbiological diagnostics, particularly through rapid and molecular methods, to support timely, targeted therapies and reduce inappropriate empirical treatments. In parallel, investment in new therapeutic options, including innovative molecules, drug combinations, and alternative approaches, remains crucial to effectively countering the growing burden of antimicrobial resistance. Full article

(This article belongs to the Special Issue The One Health Action Plan Against Antimicrobial Resistance)

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25 pages, 1958 KB

Open AccessArticle

Microwave-Assisted Synthesis of Imidazole-Based Chalcones: Modulating Antimicrobial Activity Through Alkoxy Substitutions

by Elnar Mammadov, Nilüfer Bayrak, Neslihan Beyazit, Emel Mataraci-Kara and Amaç Fatih TuYuN

Antibiotics 2026, 15(3), 310; https://doi.org/10.3390/antibiotics15030310 - 18 Mar 2026

Cited by 1 | Viewed by 1033

Abstract

Background/Objectives: The emergence of antimicrobial resistance necessitates the development of new and effective antimicrobial agents. In this study, three different series of imidazole-based chalcones (IBC1-25) were designed and synthesised using a sustainable approach, with the aim of identifying compounds with [...] Read more.

Background/Objectives: The emergence of antimicrobial resistance necessitates the development of new and effective antimicrobial agents. In this study, three different series of imidazole-based chalcones (IBC1-25) were designed and synthesised using a sustainable approach, with the aim of identifying compounds with enhanced antimicrobial activity. Methods: A series of monoalkoxy, dialkoxy, and trialkoxy imidazole-based chalcones (IBC1–25) were synthesised and evaluated for their antimicrobial and antifungal activities against a range of microbial strains. Structure-activity relationships were analysed, and molecular docking studies were performed to investigate potential binding interactions with biofilm-associated regulatory proteins. In addition, ADME properties were predicted to assess drug-likeness. Results: Among the monoalkoxy derivatives (IBC1-14), IBC5 exhibited the broadest spectrum of activity, particularly against S. epidermidis. Several dialkoxy analogues (IBC17-21) demonstrated improved potency, with IBC20 showing notably high activity. While IBC22 and IBC25 were largely ineffective, IBC23 and IBC24 displayed significant antibacterial and antifungal activities. Overall, dialkoxy and trialkoxy derivatives exhibited enhanced efficacy, whereas monoalkoxy compounds with bulky or long-chain substituents were generally less active. The presence of multiple alkoxy substituents, such as methoxy and ethoxy groups, on the phenyl ring significantly improved activity, particularly against fungi and Gram-positive bacteria. Molecular docking studies revealed that IBC20 and IBC23 showed favourable binding to the biofilm-associated regulator TcaR, suggesting a potential allosteric inhibition mechanism, while weak interactions were observed with TagF. ADME predictions indicated good oral absorption and compliance with key drug-likeness criteria. Conclusions: The results demonstrate that both the number and type of alkoxy substituents play a critical role in antimicrobial activity. In particular, IBC20 and IBC23 emerge as promising candidates for further development as antimicrobial agents targeting biofilm-associated pathways. Full article

(This article belongs to the Special Issue Discovery and Development of Novel Antibacterial Agents—2nd Edition)

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16 pages, 271 KB

Open AccessArticle

Antibiotic Resistance Awareness and Prescribing Behavior Among General Practitioners in Kazakhstan, Kyrgyzstan, Uzbekistan, and Tajikistan

by Yuliya Semenova, Kamila Akhmetova, Shakhnoza Rakhmatullaeva, Makhbuba Muminova, Dilafruz Fakhriddinova, Kenesh Dzhusupov, Asel Kanymetova, Damira Ashyralieva, Mukhabbat Saidova, Shakhlo Yakubova, Lyudmila Pivina and Zaituna Khismetova

Antibiotics 2026, 15(3), 309; https://doi.org/10.3390/antibiotics15030309 - 18 Mar 2026

Cited by 1 | Viewed by 1081

Abstract

Background/Objectives: Despite a wide range of international studies examining antibiotic prescribing practices among physicians, research from Central Asia remains scarce. To address this gap, the present study aimed to investigate antibiotic resistance awareness and prescribing practices among general practitioners (GPs) in Kazakhstan, Kyrgyzstan, [...] Read more.

Background/Objectives: Despite a wide range of international studies examining antibiotic prescribing practices among physicians, research from Central Asia remains scarce. To address this gap, the present study aimed to investigate antibiotic resistance awareness and prescribing practices among general practitioners (GPs) in Kazakhstan, Kyrgyzstan, Uzbekistan, and Tajikistan. Methods: The online questionnaire was completed by 1231 GPs, including 469 from Kazakhstan, 274 from Kyrgyzstan, 369 from Uzbekistan, and 119 from Tajikistan. Results: Most physicians (71.1%) acknowledged that their antibiotic prescribing behavior influences the development of antibiotic resistance in their regions. More than half reported discussing antibiotic resistance with their patients often or very often. However, the strategy of delayed antibiotic prescribing was unknown to 27.1% of GPs. Factors associated with good knowledge of indications for antibiotic prescribing included female sex, older age, working in Uzbekistan, practicing in urban areas, seeing 20 or more patients per day, and use of practice guidelines. Clinical practice guidelines were the most frequently reported source of current information on antibiotic therapy and resistance (20.4%), followed by continuing professional education (15.9%) and textbooks (14.1%). The vast majority of GPs (94.4%) indicated a need for additional information resources to support more rational antibiotic prescribing. The most commonly cited needs were higher-quality clinical practice guidelines (22.5%) and better access to existing guidelines (17.7%). Conclusions: These findings suggest that, despite generally high awareness of antibiotic resistance, important knowledge gaps remain among GPs in Central Asia. Strengthening access to clinical guidelines and continuing professional education may support more rational antibiotic prescribing. Full article

(This article belongs to the Special Issue Antibiotic Use and the Emergence of Antibiotic Resistance in Clinical Settings, 2nd Edition)

12 pages, 938 KB

Open AccessArticle

Restricting C-Reactive Protein Use in Early-Onset Neonatal Sepsis Reduces Unnecessary Antibiotic Exposure

by Valeria Capone, Sophie Venturelli, Eleonora Cresta, Francesca Miselli, Martina Buttera, Licia Lugli, Eugenio Spaggiari and Alberto Berardi

Antibiotics 2026, 15(3), 308; https://doi.org/10.3390/antibiotics15030308 - 18 Mar 2026

Cited by 2 | Viewed by 1094

Abstract

Background: some consensus guidelines include C-reactive protein (CRP) in the diagnostic workup of early-onset neonatal sepsis (EOS), but its routine use remains debated due to variable diagnostic performance. The experiences and data from individual centers can help clarify its clinical utility and inform [...] Read more.

Background: some consensus guidelines include C-reactive protein (CRP) in the diagnostic workup of early-onset neonatal sepsis (EOS), but its routine use remains debated due to variable diagnostic performance. The experiences and data from individual centers can help clarify its clinical utility and inform local practice. Methods: Retrospective analysis at a level III center assessing the impact of discontinuing routine C-reactive protein (CRP) testing for suspected early-onset sepsis (EOS). Laboratory use, antibiotic therapy, and outcomes in neonates of all gestational ages were compared before (2021–2022) and after (2024–2025) the policy change. Results: A total of 638 neonates were included (period 1, n = 348; period 2, n = 290). CRP testing decreased markedly (218/348 in period 1 vs. 40/290 in period 2; p < 0.001), alongside a significant reduction in the number of complete blood counts performed (285/348 vs. 214/290; p = 0.02). Concurrently, both the proportion of short antibiotic courses (≤48 h) initiated within the first 3 days of life (98/181 vs. 88/133) and the median duration of antibiotic therapy (48.0 h vs. 40.0 h; p < 0.001) decreased without worsening outcomes. The duration of antibiotic therapy was even shorter in infants born before 34 weeks’ gestation (48.0 h vs. 37.5 h; p < 0.001). Conclusions: Restricting the use of CRP in the evaluation of EOS was associated with a reduction in unnecessary antibiotic exposure. This strategy may be considered a core component of neonatal antibiotic stewardship programs. Full article

(This article belongs to the Special Issue Neonatal Infection: Antibiotics for Prevention and Treatment)

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19 pages, 322 KB

Open AccessArticle

Drug-Resistant Infections in Burn Patients: A One-Year Analysis of Microbiological Trends and Predictive Risk Factors in a Romanian Tertiary Care Centre

by Oana Izmendi, Baditoiu Luminita, Corina Musuroi, Silvana Vulpie, Delia Muntean, Adela Voinescu, Silvia Ioana Musuroi, Zorin Petrisor Crainiceanu, Panche Taskov, Romanita Jumanca and Monica Licker

Antibiotics 2026, 15(3), 307; https://doi.org/10.3390/antibiotics15030307 - 18 Mar 2026

Cited by 1 | Viewed by 872

Abstract

Background and Objectives: The susceptibility of burn patients to infections with multidrug-resistant organisms (MDROs) is high. The aim of this study is to describe the local patterns of antimicrobial resistance in a Romanian burn unit and to identify risk factors associated with the [...] Read more.

Background and Objectives: The susceptibility of burn patients to infections with multidrug-resistant organisms (MDROs) is high. The aim of this study is to describe the local patterns of antimicrobial resistance in a Romanian burn unit and to identify risk factors associated with the acquisition of extensively drug-resistant (XDR) pathogens. Materials and Methods: We conducted a one-year, observational, retrospective single-centre cohort study including all burn patients with at least one positive culture admitted to our unit during 2024. In order to identify the pathogens and perform antibiograms, we used routine microbiological diagnostic tests. A multivariable logistic regression model was used to identify XDR risk factors. We also compiled a cumulative antibiogram using the first non-duplicate isolate per patient, following the CLSI M39 guidelines. Results: Among the 180 total admissions, 128 (71.1%) had at least one positive microbiological culture, resulting in 643 bacterial isolates out of 559 samples. The most frequently identified species were A. baumannii, P. aeruginosa, S. aureus, and K. pneumoniae. We isolated MDROs in 59.37% of patients, and 26.56% had at least one XDR pathogen isolated during hospitalisation. We identified three independent predictors for the isolation of XDR pathogens: a higher Abbreviated Burn Severity Index (ABSI) score (aOR 6.12; p = 0.001), hospital length of stay (LOS) (aOR 1.02; p = 0.030), and the number of bacterial species identified per sample, representing polymicrobial growth (aOR 5.91; p = 0.001). Conclusions: Our findings highlight a significant percentage of MDR and XDR pathogens and provide the foundation for antimicrobial stewardship measures, using the local cumulative antibiogram for empirical therapy. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Epidemiological Study of Clinically Relevant Pathogens, 2nd Edition)

17 pages, 304 KB

Open AccessReview

Antibiotic Prophylaxis and Treatment of Neonatal Group B Streptococcus Disease in the Era of Antimicrobial Resistance

by Chryssoula Tzialla, Serena Salomè, Vito Mondì, Vincenzo Salvo and Alberto Berardi

Antibiotics 2026, 15(3), 306; https://doi.org/10.3390/antibiotics15030306 - 18 Mar 2026

Viewed by 1797

Abstract

Group B Streptococcus (GBS) remains a major cause of early- and late-onset neonatal sepsis worldwide, despite the widespread use of intrapartum antibiotic prophylaxis (IAP). β-lactam antibiotics, including penicillin G and ampicillin, remain the cornerstone of both GBS prophylaxis and neonatal treatment, supported by [...] Read more.

Group B Streptococcus (GBS) remains a major cause of early- and late-onset neonatal sepsis worldwide, despite the widespread use of intrapartum antibiotic prophylaxis (IAP). β-lactam antibiotics, including penicillin G and ampicillin, remain the cornerstone of both GBS prophylaxis and neonatal treatment, supported by sustained susceptibility, favorable pharmacokinetics, and extensive clinical experience. However, increasing global resistance to macrolides and lincosamides has markedly reduced the reliability of clindamycin and erythromycin, which are commonly used as second-line agents in women with severe penicillin allergy. This narrative review summarizes current evidence on antibiotic strategies for the prevention and treatment of neonatal GBS disease, with a particular focus on antimicrobial resistance patterns and their clinical implications. Available surveillance data demonstrate substantial geographic variability in resistance but consistently low resistance to β-lactams and vancomycin. These trends have expanded the role of vancomycin in IAP for women with high-risk β-lactam allergy and in neonatal treatment when first-line agents are contraindicated. Alternative agents such as linezolid and teicoplanin exhibit activity against GBS, but their use remains limited by sparse neonatal data and pharmacokinetic variability. Ongoing antimicrobial surveillance, susceptibility-guided therapy, and stewardship initiatives are essential to preserve effective GBS prevention and treatment strategies. Full article

(This article belongs to the Special Issue Neonatal Infection: Antibiotics for Prevention and Treatment)

17 pages, 681 KB

Open AccessReview

Treatment of Syphilis in Pregnancy and Congenital Syphilis: Current Evidence, Challenges, and Future Directions

by Serena Salomè and Chryssoula Tzialla

Antibiotics 2026, 15(3), 305; https://doi.org/10.3390/antibiotics15030305 - 18 Mar 2026

Viewed by 4150

Abstract

Syphilis remains a global public health concern, with maternal infection posing a substantial risk for congenital syphilis, a preventable condition associated with severe morbidity and mortality. Penicillin, particularly benzathine penicillin G, remains the cornerstone of treatment and the only therapy with proven efficacy [...] Read more.

Syphilis remains a global public health concern, with maternal infection posing a substantial risk for congenital syphilis, a preventable condition associated with severe morbidity and mortality. Penicillin, particularly benzathine penicillin G, remains the cornerstone of treatment and the only therapy with proven efficacy in preventing vertical transmission during pregnancy. However, recurrent global shortages, limited manufacturing capacity, mislabeling of penicillin allergy, and the absence of validated alternative regimens for pregnant women and neonates threaten progress toward elimination goals. This review summarizes current evidence on the treatment of syphilis in pregnancy and congenital syphilis, highlighting the established maternal and neonatal regimens, diagnostic and therapeutic challenges, and clinical consequences of delayed or inadequate treatment. We examine the scope and drivers of benzathine penicillin G shortages, the overestimation of penicillin allergy and its impact on care, and the role of neonatal management when maternal therapy is suboptimal. Emerging data on alternative antimicrobial agents, including cephalosporins, tetracyclines, lipoglycopeptides, and novel compounds are discussed considering recent advances in Treponema pallidum culture and susceptibility testing. While several non-penicillin agents show promise for non-pregnant populations, robust evidence supporting their use during pregnancy and for the prevention of congenital syphilis is lacking. Addressing these gaps through coordinated supply chain strategies, guideline harmonization, and targeted clinical research is essential to ensure resilient and equitable syphilis control and advance global efforts toward the elimination of congenital syphilis. Full article

(This article belongs to the Special Issue Neonatal Infection: Antibiotics for Prevention and Treatment)

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16 pages, 1981 KB

Open AccessArticle

Genomic Insights into Ciprofloxacin-Resistant Enteropathogenic Escherichia coli ST752 in Republic of Korea: A One Health Perspective on Its Emergence and Transmission

by Yeongeun Seo, Wooju Kang, Eunkyung Shin, Jungsun Park, Mooneui Hong, Dong-Hyun Roh and Junyoung Kim

Antibiotics 2026, 15(3), 304; https://doi.org/10.3390/antibiotics15030304 - 17 Mar 2026

Viewed by 686

Abstract

Background/Objectives: We analyzed the whole-genome sequences of ciprofloxacin-resistant (CIP-R) enteropathogenic Escherichia coli (EPEC) ST752 isolates in South Korea to characterize their molecular epidemiology. This lineage has emerged as the predominant CIP-R EPEC clone in South Korea, accounting for 28.8% of human clinical [...] Read more.

Background/Objectives: We analyzed the whole-genome sequences of ciprofloxacin-resistant (CIP-R) enteropathogenic Escherichia coli (EPEC) ST752 isolates in South Korea to characterize their molecular epidemiology. This lineage has emerged as the predominant CIP-R EPEC clone in South Korea, accounting for 28.8% of human clinical isolates and circulating within the One Health interface. Methods: We performed whole-genome sequencing (WGS) and reference-based core-genome single-nucleotide polymorphism (SNP) analysis on 26 CIP-R EPEC ST752 isolates (19 human clinical and 7 poultry-derived isolates). To elucidate their evolutionary history and transmission dynamics, Bayesian phylodynamic and phylogeographic reconstructions were implemented by integrating domestic isolates with a global genome dataset (n = 508). Results: Isolates from human and poultry sources clustered together with an identical virulence profile and minimal genetic distance. The Bayesian molecular clock analysis estimated that the time to the most recent common ancestor of the South Korean clade was 2000.65. Moreover, the phylogeographic analysis supported statistical evidence (Bayes factor 32.16) for the introduction of this lineage into South Korea from Denmark and revealed a strongly supported host transition from humans to poultry (Bayes factor > 10,000), although this requires cautious interpretation due to limited temporal sampling of poultry isolates. Conclusions: Continued integrated One Health surveillance across human, animal, and environmental reservoirs is needed to monitor and prevent the spread of high-risk antimicrobial-resistant clones. Full article

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

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12 pages, 229 KB

Open AccessArticle

Prescribing Patterns and Clinical Outcomes of Ceftolozane/Tazobactam by Renal Function and Body Mass Index: A SPECTRA Real-World Multi-Country Analysis

by Emre Yucel, Alex Soriano, Florian Thalhammer, Stefan Kluge, Mike Allen, Jessica Levy, Huina Yang and Sunny Kaul

Antibiotics 2026, 15(3), 303; https://doi.org/10.3390/antibiotics15030303 - 17 Mar 2026

Cited by 1 | Viewed by 885

Abstract

Background: Antimicrobial resistance is a global health crisis associated with high mortality and economic burden. Patients with renal dysfunction and obesity have increased susceptibility to infections and may experience different real-world outcomes, including clinical success and mortality, but are often under-represented in clinical [...] Read more.

Background: Antimicrobial resistance is a global health crisis associated with high mortality and economic burden. Patients with renal dysfunction and obesity have increased susceptibility to infections and may experience different real-world outcomes, including clinical success and mortality, but are often under-represented in clinical trials. Ceftolozane/tazobactam (C/T) is an innovative therapy used to treat resistant Gram-negative infections. We aimed to describe real-world clinical outcomes in hospitalized adults treated with C/T across categories of renal function and BMI in the SPECTRA study. Methods: SPECTRA was a multi-national observational study on 617 patients who received C/T for ≥48 h. Outcomes included clinical success, all-cause in-hospital mortality, readmission, and ICU admission and length of stay (LOS), with sub-analysis of patients across BMI and renal function strata. Results: Renal function and weight were reported in 597 and 469 patients, respectively, of which 51.9% had lower creatine clearance (<80 mL/min) and 50.7% were overweight. Clinical success and all-cause in-hospital mortality ranged at 59.1–77.8% and 11.1–29.2% across renal function strata and 64.6–68.6% and 18.6–21.4% across weight subgroups. Across renal function and weight subgroups, 38.9–54.2% and 45.9–53.5% of patients were admitted to ICU. Median ICU LOS was 8–21.5 and 14–20 days, respectively. Readmission (30-day all-cause) occurred in 4.5–11.8% and 8.2–11.9% of patients across renal function and weight strata. Conclusions: Results from this sub-analysis suggest real-world clinical effectiveness of C/T across patients with renal impairment and obesity, highlighting C/T as a component within treatment guidelines for resistant Gram-negative infections. Full article

13 pages, 849 KB

Open AccessArticle

Goondoxazoles A–C: Anthelmintic Spiroketal Polyketide Alkaloids and Other Benzoxazoles from Australian Pasture Soil-Derived Streptomyces spp.

by Shengbin Jin, David F. Bruhn, Erica J. Burkman, Cynthia T. Childs, Jianying Han, Zeinab G. Khalil, Yovany Moreno, Angela A. Salim, Kaumadi Samarasekera, Marcelo M. P. Tangerina and Robert J. Capon

Antibiotics 2026, 15(3), 302; https://doi.org/10.3390/antibiotics15030302 - 17 Mar 2026

Cited by 1 | Viewed by 1023

Abstract

Background/Objectives/Methods: A bioassay-informed investigation of the Australian pasture soil-derived Streptomyces sp. S4S-00193A39 yielded the anthelmintic principals as three new spiroketal polyketide alkaloids, goondoxazoles A–C (1–3), with structures assigned by detailed spectroscopic analysis. Results: A structure–activity relationship based on the [...] Read more.

Background/Objectives/Methods: A bioassay-informed investigation of the Australian pasture soil-derived Streptomyces sp. S4S-00193A39 yielded the anthelmintic principals as three new spiroketal polyketide alkaloids, goondoxazoles A–C (1–3), with structures assigned by detailed spectroscopic analysis. Results: A structure–activity relationship based on the ability to inhibit the motility of Dirofilaria immitis microfilariae (mf) revealed a positive correlation for the benzoxazole moiety present in 2 and 3 (EC₅₀ 55–85 nM) versus the ring-opened aminobenzoic acid moiety evident in 1 (EC₅₀ 1.38 µM). This hypothesis was strengthened by extension of the SAR assessment to the known benzoxazole natural products A-33583 (12), UK-1 (13) and nataxazole (14), and the new analogue 5-hydroxynataxazole (15), which were isolated in our lab from three additional Australian pasture soil-derived Streptomyces spp. Of note, while the benzoxazole methyl esters 13–15 exhibited approximately 9- to 65-fold lower potency against D. immitis mf compared with 2 and 3, the carboxylic acid substituted benzoxazole 12 displayed comparable activity (EC₅₀ 72 nM) against D. immitis mf, and >5-fold improved potency against D. immitis L4 larvae (EC₅₀ 0.43 µM). Conclusions: These observations reveal the promising anthelmintic potential (against D. immitis) for the new structurally complex and chiral goondoxazoles (e.g., 2 and 3), and demonstrate that this effect can be replicated, even improved, by simpler, achiral benzoxazole microbial natural products (e.g., 12). Full article

(This article belongs to the Collection Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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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 1228

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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19 pages, 1729 KB

Open AccessArticle

Genetic Characterization and Biofilm-Forming Capacity of Bacterial Population Isolated from Conjunctival Samples

by Adela Voinescu, Silvia-Ioana Musuroi, Monica Licker, Delia Muntean, Florin-George Horhat, Luminita Mirela Baditoiu, Oana Izmendi, Andrei Cosnita, Mihnea Munteanu, Mihai Poenaru-Sava, Valentin Ordodi, Petrinela Ceachir, Tudor Rareș Olariu and Corina Musuroi

Antibiotics 2026, 15(3), 300; https://doi.org/10.3390/antibiotics15030300 - 15 Mar 2026

Viewed by 889

Abstract

Background/Objectives: Bacterial conjunctivitis is a common ocular infection requiring prompt treatment, particularly in vulnerable patients, and may influence perioperative outcomes. This study aimed to characterize conjunctival bacterial isolates phenotypically and genotypically, to evaluate their biofilm-forming capacity, and to investigate the relationship between resistance [...] Read more.

Background/Objectives: Bacterial conjunctivitis is a common ocular infection requiring prompt treatment, particularly in vulnerable patients, and may influence perioperative outcomes. This study aimed to characterize conjunctival bacterial isolates phenotypically and genotypically, to evaluate their biofilm-forming capacity, and to investigate the relationship between resistance gene carriage, resistance phenotypes, and biofilm-associated antimicrobial resistance (AMR). Methods: A prospective, single-center, cross-sectional study was conducted on bacterial isolates from conjunctival samples of patients examined in an ophthalmology department. Antimicrobial susceptibility testing (AST) was performed to determine the minimum inhibitory concentrations (MICs). Resistance genes were detected by quantitative PCR. Biofilm-forming capacity was assessed using the microtiter plate assay, and biofilm susceptibility to amikacin (AK) and levofloxacin (LEV) was evaluated using a biofilm susceptibility assay. Results: A total of 78 isolates were analyzed; Gram-positive cocci prevailed (GPC, 84.6%), being significantly more frequent than Gram-negative bacilli (GNB, p < 0.001). Among GPC, 65.2% were multidrug-resistant, with Staphylococcus epidermidis emerging as the most frequent species (p < 0.001). Resistance gene carriage was detected in 33.3% of GNB. Strong biofilm formation was observed in 22.7% of GPC versus 58.3% of GNB. It should be noted that the relatively small number of GNB may limit the statistical robustness of comparisons between Gram-positive and Gram-negative groups. A statistically significant association between resistance genes and biofilm capacity was found only in Staphylococcus aureus (p = 0.027). Biofilm-embedded bacteria showed increased antimicrobial tolerance, particularly for AK in S. aureus and for both AK and LEV in S. epidermidis (p < 0.001). Conclusions: The prevalence of multidrug-resistant conjunctival isolates and their biofilm-forming capacity highlights the clinical importance of biofilm-related resistance and support integrating AMR profiling with biofilm assessment to optimize empirical therapy in bacterial conjunctivitis. Full article

(This article belongs to the Section Antibiofilm Strategies)

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18 pages, 1834 KB

Open AccessArticle

Imipenem-Induced Transcriptional Responses of Porin, Efflux Pumps, and Carbapenemase Genes in Clinical Carbapenem-Resistant Acinetobacter baumannii

by Suna Sibel Rizvanoglu, Basar Karaca and Mujde Eryilmaz

Antibiotics 2026, 15(3), 299; https://doi.org/10.3390/antibiotics15030299 - 15 Mar 2026

Cited by 1 | Viewed by 1133

Abstract

Background/Objectives: Carbapenem-resistant Acinetobacter baumannii poses a critical threat due to its ability to acquire multiple resistance mechanisms and persist under antibiotic pressure. This study aimed to elucidate the molecular basis of imipenem resistance in clinical A. baumannii isolates by integrating phenotypic, molecular, [...] Read more.

Background/Objectives: Carbapenem-resistant Acinetobacter baumannii poses a critical threat due to its ability to acquire multiple resistance mechanisms and persist under antibiotic pressure. This study aimed to elucidate the molecular basis of imipenem resistance in clinical A. baumannii isolates by integrating phenotypic, molecular, transcriptional, and clonal analyses. Methods: Eleven A. baumannii isolates identified by MALDI-TOF MS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were investigated. Antimicrobial susceptibility to imipenem and meropenem was assessed, followed by polymerase chain reaction (PCR) detection of Ade efflux pump, outer membrane porin, and OXA-type carbapenemase genes. Transcriptional responses to sub-inhibitory imipenem exposure were evaluated using quantitative real-time PCR, and clonal relatedness was assessed by arbitrarily primed PCR. Results: All isolates were carbapenem-resistant, with bla_OXA-23 detected in all isolates and bla_OXA-24 absent in one isolate. Transcriptional analysis revealed isolate-specific responses to imipenem exposure. Among Ade efflux pump components, only adeR exhibited expression changes, displaying either downregulation or upregulation depending on the isolate, whereas adeA, adeB, adeC, and adeS transcripts were not detected under the tested conditions. Outer membrane porin genes showed heterogeneous regulation, with ompA and carO downregulated, while some isolates showed increased expression. Expression of oprD varied among isolates, and omp33–36 transcripts were detected in a single isolate and were reduced after exposure. Clonal analysis identified nine distinct genotypes, indicating genetic diversity and the absence of clonal dominance. Conclusions: These findings highlight the multifactorial and heterogeneous nature of carbapenem resistance in A. baumannii, emphasizing the interplay between regulatory efflux mechanisms, porin modulation, and carbapenemase carriage. Full article

(This article belongs to the Special Issue Genetic Mechanisms of Bacterial Survival: Antibiotic Resistance and Defense Strategies)

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19 pages, 6554 KB

Open AccessArticle

Iron(III)–Tropolone Complex as a Topical Agent Against Drug-Resistant MRSA Skin Infections

by Nalin Abeydeera, Guanyu Chen, Khalil Zarea, Bishnu D. Pant, Bogdan M. Benin, Kalpani M. Ratnayake, Min-Ho Kim, Woo Shik Shin and Songping D. Huang

Antibiotics 2026, 15(3), 298; https://doi.org/10.3390/antibiotics15030298 - 14 Mar 2026

Cited by 2 | Viewed by 1780

Abstract

Background/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. [...] Read more.

Background/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. Methods: In this study, we evaluate Fe(tropo)₃, a neutral and lipophilic iron(III)–tropolone complex, as a non-antibiotic topical antimicrobial candidate for the management of drug-resistant SA skin and soft tissue infections. Results: Fe(tropo)₃ exhibits potent in vitro activity against methicillin-susceptible SA, methicillin-resistant SA (MRSA), vancomycin-intermediate SA, and strains with high-level resistance to mupirocin and fusidate, with minimum inhibitory concentrations of 2 µg/mL across all tested isolates. The compound effectively penetrates bacterial cells, induces intracellular iron accumulation, and triggers dose-dependent reactive oxygen species generation, resulting in rapid bacterial killing and significant antibiofilm activity. Importantly, Fe(tropo)₃ shows a slower development of resistance compared with ciprofloxacin and displays synergistic activity with oxacillin against MRSA. When formulated as a 1% topical ointment, Fe(tropo)₃ significantly reduces bacterial burden in a murine excisional wound infection model, achieving a 98% ± 1% reduction in SA load without detectable hemolysis or skin irritation. Conclusions: These pilot study results support Fe(tropo)₃ as a clinically relevant, mechanism-distinct topical antimicrobial with potential utility in settings where resistance to existing topical antibiotics compromises standard care. Full article

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

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14 pages, 841 KB

Open AccessReview

From Gut Commensal to Opportunistic Pathogen: A Narrative Review of Butyricimonas Infections in Humans

by Afroditi Ziogou, Alexios Giannakodimos, Ilias Giannakodimos, Andreas G. Tsantes, Stella Baliou, Dimitrios Rigopoulos and Petros Ioannou

Antibiotics 2026, 15(3), 297; https://doi.org/10.3390/antibiotics15030297 - 14 Mar 2026

Viewed by 1283

Abstract

Background/Objectives: Butyricimonas species constitute a genus of Gram-negative, anaerobic bacteria that are part of the human gut microbiota. Infections caused by these organisms are extremely rare in clinical practice. While uncommon in the general population, their occurrence is higher among immunocompromised individuals or [...] Read more.

Background/Objectives: Butyricimonas species constitute a genus of Gram-negative, anaerobic bacteria that are part of the human gut microbiota. Infections caused by these organisms are extremely rare in clinical practice. While uncommon in the general population, their occurrence is higher among immunocompromised individuals or patients with significant underlying health conditions. This review aims to compile and analyze all reported cases of human Butyricimonas infections, focusing on epidemiology, microbiological characteristics, antimicrobial resistance patterns, treatment strategies, and associated mortality. Methods: This review was conducted using data retrieved from the PubMed/MEDLINE and Scopus databases. Results: A total of 14 publications described Butyricimonas infections affecting 14 patients. The mean age of those affected was 66.46 years, and 10 (71.4%) were male. The most frequently reported predisposing factor was a history of malignancy, observed in almost one-third of cases (30.8%). Clinically, fever, organ dysfunction, and shock were the most common presentations (fivecases), followed by sepsis and the need for ICU in fourpatients. In vitro studies indicated that the isolates were generally susceptible to carbapenems and metronidazole, with only high resistance levels observed to penicillin. Among the antimicrobial therapies used, carbapenems were the most commonly administered (50%), followed by piperacillin/tazobactam (41.7%) and metronidazole (33.3%). The overall mortality rate across the cohort was 16.7%, with infection-attributable deaths representing 8.3% of cases. Conclusions: Given the potential of Butyricimonas species to cause severe infections, clinicians should consider this organism in patients presenting with unexplained bacteremia or intra-abdominal infections, particularly in the setting of mucosal disruption or immune dysfunction. Full article

(This article belongs to the Special Issue Successful Antimicrobial Stewardship Approaches to Address Nosocomial Infections, 2nd Edition)

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17 pages, 636 KB

Open AccessArticle

Association Between Clinical Frailty and Antibiotic Resistance Among Older Patients with Fever in the Emergency Department

by Ji Yeon Lim, Dong Hoon Lee, Ho Sub Chung, Yunhyung Choi, Yoon Hee Choi, Keon Kim, Ki-Hun Hong and Sung Jin Bae

Antibiotics 2026, 15(3), 296; https://doi.org/10.3390/antibiotics15030296 - 14 Mar 2026

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Abstract

Background: Frailty may predispose older adults to antibiotic-resistant infections; however, evidence in emergency department (ED) patients with fever remains limited. Methods: We conducted a retrospective multicenter cohort study of 544 ED patients aged ≥65 years with fever (tympanic temperature ≥ 37.5 [...] Read more.

Background: Frailty may predispose older adults to antibiotic-resistant infections; however, evidence in emergency department (ED) patients with fever remains limited. Methods: We conducted a retrospective multicenter cohort study of 544 ED patients aged ≥65 years with fever (tympanic temperature ≥ 37.5 °C) between August and October 2023. The cohort included 234 men and 310 women. Frailty was assessed using the Clinical Frailty Scale (CFS) and categorized as robust (CFS 1–3), pre-frail (CFS 4–5), or frail (CFS 6–9). ED-initiated microbiological cultures were obtained in 329/544 (60.5%) patients. The primary outcome was the detection of antibiotic-resistant isolates among culture-tested patients. Results: Among culture-tested patients (n = 329), antibiotic-resistant isolates were detected in 65/329 (19.8%), with a graded increase across frailty strata: robust 13/121 (10.7%), pre-frail 16/88 (18.2%), and frail 36/120 (30.0%). In multivariable logistic regression restricted to culture-tested patients, frailty was independently associated with resistant infection (adjusted OR 2.84, 95% CI 1.15–7.04, p = 0.024). Frail patients also experienced greater therapeutic complexity, including higher rates of antibiotic regimen modification (68.1% vs. 54.5%) and longer antibiotic duration (median, 11 vs. 8 days), as well as worse clinical outcomes, including higher ICU admission (37.7% vs. 17.8%) and in-hospital mortality (7.2% vs. 1.8%) compared with robust patients. Conclusions: Frailty is independently associated with antibiotic-resistant infections in older ED patients with fever. Integrating frailty assessment into ED protocols can enhance risk stratification, inform empirical antibiotic selection, and antimicrobial stewardship strategies. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Geriatric Emergency Patients: Challenges and Strategies for Optimal Management)

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14 pages, 16335 KB

Open AccessArticle

Lemon Juice Activity Against Caprine Alphaherpesvirus-1: An In Vitro Study

by Francesco Pellegrini, Gianvito Lanave, Cristiana Catella, Vanessa Bachmann, Marinella Dibari, Maria Tempesta, Vito Martella, Nicola Decaro, Claudia Maria Trombetta and Michele Camero

Antibiotics 2026, 15(3), 295; https://doi.org/10.3390/antibiotics15030295 - 14 Mar 2026

Viewed by 925

Abstract

Caprine herpesvirus 1 (CpHV-1) is responsible for significant economic losses in goat farming. The CpHV-1 genital infection in goats has been used as a homologous animal model for the study of human herpes simplex virus type 2 (HSV-2). This study aimed to investigate [...] Read more.

Caprine herpesvirus 1 (CpHV-1) is responsible for significant economic losses in goat farming. The CpHV-1 genital infection in goats has been used as a homologous animal model for the study of human herpes simplex virus type 2 (HSV-2). This study aimed to investigate the in vitro virucidal and antiviral effect of lemon juice (LJ) and its main component, citric acid (CA), against CpHV-1 on Madin-Darby Bovine Kidney (MDBK) cells. Cytotoxicity was assessed using an XTT assay, while viral titers were determined by the Reed–Muench method and viral DNA was quantified via qPCR. Pure LJ (pH 2.3) and its corresponding CA solution demonstrated potent and rapid virucidal activity, reducing the viral titer by over 5.0 log10 TCID₅₀/50 µL within 1 min. When applied after viral entry, a non-cytotoxic dilution of LJ (pH 4.32) significantly inhibited viral replication, causing a 2.5 log10 TCID₅₀/50 µL reduction in viral titer and a corresponding decrease in viral DNA. The antiviral effects were minimal at a near-neutral pH of 6.67, probably interacting with envelope structures. These results suggest that LJ could be a potential low-cost topical agent or disinfectant for controlling CpHV-1 in goat populations and offer a basis for translational research on human herpesviruses. Full article

(This article belongs to the Special Issue Antibiotics in Pathogen Control: From Infection to Antimicrobial Resistance)

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Antibiotics, Volume 15, Issue 3 (March 2026) – 91 articles

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