Antibiotics

14 pages, 1054 KB

Open AccessArticle

Real-World Experience on the Use of Eravacycline at Doses of 1 mg/kg Bodyweight and Fixed Dose Strategy in Two European Tertiary Centers

by Karin Oberreiter, Miriam M. Moser, Lisa Schneider, Heinz Burgmann, Chiara Moreal, Simone Giuliano, Jacopo Angelini, Carlo Tascini and Matthias G. Vossen

Antibiotics 2026, 15(4), 421; https://doi.org/10.3390/antibiotics15040421 - 21 Apr 2026

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Abstract

Background: Eravaycline is a novel fully synthetic fluorocycline that is currently approved for complicated intra-abdominal infections. However, it is sometimes also used off-label in tertiary care centers for other infection sites as an antibiotic of last resort due to its broad spectrum of [...] Read more.

Background: Eravaycline is a novel fully synthetic fluorocycline that is currently approved for complicated intra-abdominal infections. However, it is sometimes also used off-label in tertiary care centers for other infection sites as an antibiotic of last resort due to its broad spectrum of activity and efficacy against Enterobacterales, including multidrug-resistant pathogens like extended spectrum β-lactamase (ESBL) producers or carbapenem-resistant Enterobacterales, as well as all Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin- and linezolid-resistant Enterococcus faecium (VRE). Methods: We retrospectively included a total of 78 patients from Austria and Udine who received eravacycline between April 2023 and August 2024 to evaluate the real-world efficacy of eravacycline in various infection sites and pathogens using descriptive statistics. Results: Eravacycline was most commonly used in intra-abdominal infections (44.9%), followed by pneumonia (12.8%) and infections of unknown origin (7.7%). Escherichia coli, including ESBL producers, was the most common pathogen (24.4%), followed by Enterococcus spp. (12.8%) and Klebsiella pneumoniae (12.8%). Clinical cure was achieved in 65% of patients, whereas microbiological cure was documented in 46%; source control was attained in 48.7%, and 16.7% died within 30 days. A total of 48% of patients required intensive care. Conclusions: Eravacycline represents a possible therapeutic option for a wide range of pathogens, but its use must be evaluated in the context of infection site and severity. Full article

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

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29 pages, 7081 KB

Open AccessArticle

Evaluation of the Antifungal Activity of the Polyphenol Formulation Viroelixir Against Candida albicans

by Manal Dahdah, Yasmine Ettouil, Hawraa Issa, Latifa Koussih, Mikhlid H. Almutairi, Mahmoud Rouabhia and Abdelhabib Semlali

Antibiotics 2026, 15(4), 420; https://doi.org/10.3390/antibiotics15040420 - 21 Apr 2026

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Abstract

Candida albicans (C. albicans) is an opportunistic fungal pathogen capable of causing a wide range of infections, including mucosal and systemic candidiasis. In the oral cavity, fungi represent a minor component of the microbiome but can significantly contribute to morbidity, particularly [...] Read more.

Candida albicans (C. albicans) is an opportunistic fungal pathogen capable of causing a wide range of infections, including mucosal and systemic candidiasis. In the oral cavity, fungi represent a minor component of the microbiome but can significantly contribute to morbidity, particularly under conditions of dysbiosis or immunosuppression. Treatment remains challenging due to increasing multidrug resistance. This study investigates the in vitro antifungal potential of Viroelixir, a standardized polyphenol blend derived from green tea and pomegranate and enriched in catechins (including epigallocatechin gallate, EGCG), ellagitannins (notably punicalagin), ellagic acid, and flavonoids, with particular focus on its potential anti-virulence mechanisms. Methods: The effect of Viroelixir on C. albicans growth was assessed using MTT assay, optical density measurements, colony formation, carbohydrate quantification, and pH variation analysis. Biofilm formation, morphological transition, ROS production, necrosis, virulence gene expression, adhesion, and host immune responses were also evaluated. Results: Viroelixir significantly inhibited C. albicans growth and reduced colony formation compared with untreated controls. The formulation also inhibited biofilm formation and markedly reduced pseudohyphal development, reaching up to 94% reduction under specific treatment conditions. Flow cytometry analysis showed an increase in dead fungal cells, reaching approximately 88% following exposure to Viroelixir at the highest tested concentration. In addition, Viroelixir reduced the transcript levels of several virulence-associated genes, including SAP1–SAP9 and EAP1. In epithelial cell co-culture models, pre-treatment of C. albicans with Viroelixir reduced fungal adhesion and attenuated epithelial inflammatory responses, including IL-6, IL-8, and hBD-2 production, and was associated with reduced activation of the TLR4-NF-κB signaling pathway. Conclusions: These findings suggest that the antifungal and anti-virulence effects observed may be associated with the polyphenolic compounds present in the Viroelixir formulation, highlighting its potential as a promising in vitro antifungal candidate against C. albicans. Full article

(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)

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25 pages, 6231 KB

Open AccessReview

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

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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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37 pages, 4973 KB

Open AccessReview

Mobile Genetic Elements as Central Drivers of Antimicrobial Resistance: Molecular Mechanisms, Evolutionary Ecology, One Health Implications and Control Strategies

by Hemayet Hossain, Md. Hasan Ali, Tanvir Ahmad, Snigdha Sharmin Binte Sayeed, Md. Abdur Nur Sakib, Khadiza Akter Brishty, Md. Shah Jahan Saleh, Md. Mosharof Hosen, Shahabuddin Ahmed, Shihab Ahmed, Md. Shahidur Rahman Chowdhury and Md. Mahfujur Rahman

Antibiotics 2026, 15(4), 418; https://doi.org/10.3390/antibiotics15040418 - 20 Apr 2026

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Abstract

Antimicrobial resistance (AMR) represents a global health crisis, driven largely by the mobility of resistance determinants through mobile genetic elements (MGEs). These include plasmids, integrons, insertion sequences, transposons, integrative and conjugative elements (ICEs), and prophages, which together facilitate horizontal gene transfer (HGT) across [...] Read more.

Antimicrobial resistance (AMR) represents a global health crisis, driven largely by the mobility of resistance determinants through mobile genetic elements (MGEs). These include plasmids, integrons, insertion sequences, transposons, integrative and conjugative elements (ICEs), and prophages, which together facilitate horizontal gene transfer (HGT) across bacterial species and ecosystems. This review aims to provide a comprehensive synthesis of current knowledge on the types, mechanisms, ecological drivers, and impacts of MGEs in the dissemination of antibiotic resistance genes (ARGs). Methods involved critical evaluation of recent genomic, epidemiological, and ecological studies, alongside case studies of clinically significant resistance outbreaks. Findings highlight how MGEs function as hubs for ARG capture, recombination, and stabilization, enabling the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. We also explored their interactions with ecological pressures such as antibiotics, heavy metals, and biocides, as well as their role in One Health transmission pathways. The significance of this study lies in linking molecular insights with applied strategies, including genomic surveillance, MGE-targeted inhibitors, phage therapy, and CRISPR-based interventions. Understanding MGEs is essential for designing effective interventions to mitigate AMR and protect global health. Full article

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17 pages, 1089 KB

Open AccessReview

Gut Microbiota and Acute Myeloid Leukemia: State of the Art, Clinical Signals, and Translational Opportunities

by Maria Eugenia Alvaro, Santino Caserta, Enrica Antonia Martino, Mamdouh Skafi, Antonella Bruzzese, Nicola Amodio, Eugenio Lucia, Virginia Olivito, Caterina Labanca, Francesco Mendicino, Ernesto Vigna, Fortunato Morabito and Massimo Gentile

Antibiotics 2026, 15(4), 417; https://doi.org/10.3390/antibiotics15040417 - 20 Apr 2026

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Abstract

Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity—particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer [...] Read more.

Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity—particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer of host vulnerability and resilience during AML treatment. Microbiome disruption is detectable already at diagnosis, even in antibiotic-naïve patients, and is often characterized by reduced community diversity, depletion of anaerobic taxa linked to short-chain fatty acids (SCFAs) production, and enrichment of pathobiont-associated profiles. During induction, cytotoxic therapy and antimicrobials precipitates diversity loss, domination events, and persistent shifts beyond discharge. Clinically, the most consistent translational signal is the association between baseline or early-treatment microbiome features and infectious outcomes, while emerging data suggest that diagnosis-time microbiome structure may also relate to hematologic recovery kinetics. Mechanistic models converge on pathways linking barrier integrity, microbial metabolites (notably butyrate and other SCFAs), immune calibration, and inflammatory translocation of microbial products. These insights support hypotheses: antimicrobial stewardship may preserve microbiome function; ecosystem repair strategies such as autologous fecal microbiota transfer (A-FMT) are feasible and can restore community structure; and metabolite or nutritional interventions merit evaluation in immunocompromised hosts. Regimen-specific microbiome effects and microbiome–drug interactions suggest that treatment choice could have downstream microbiome-mediated consequences. We synthesize evidence, outline interventional concepts, and define methodological priorities for next-generation trials assessing causality and clinical benefit. Progress will require longitudinal sampling, multi-omic integration (metabolomics, resistomics, and barrier/inflammatory biomarkers), and interventional designs linking microbiome dynamics to clinically meaningful outcomes. Full article

(This article belongs to the Special Issue After Antibiotics: Dysbiosis and Drug Resistance in Gut Microbiota)

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12 pages, 442 KB

Open AccessArticle

Cefiderocol Targeted Treatment for Multidrug-Resistant Gram-Negative Infections: An Observational Cohort Study

by Lourdes García-Carnero, Gabriela Abelenda-Alonso, Marc Santos-Puig, Ariadna Padullés, Clara Ribera, Alberto Lamiel, Rosa Costa-Primo, Manuel González de Aledo, Rosa Granada, Víctor Daniel Gumucio, Eva Santafosta, Marc Gilabert, Alejandro Blanco-Arévalo, Mireia Puig-Asensio, Evelyn Shaw, Jordi Carratalà and Carlota Gudiol

Antibiotics 2026, 15(4), 416; https://doi.org/10.3390/antibiotics15040416 - 20 Apr 2026

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Abstract

Background/Objectives: Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major therapeutic challenge, particularly in hospitalized and critically ill patients with limited treatment options. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against a broad range of resistant Gram-negative pathogens. We aimed [...] Read more.

Background/Objectives: Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major therapeutic challenge, particularly in hospitalized and critically ill patients with limited treatment options. Cefiderocol, a novel siderophore cephalosporin, has demonstrated activity against a broad range of resistant Gram-negative pathogens. We aimed to evaluate the effectiveness and safety of cefiderocol for the treatment of MDR-GNB infection. Methods: We conducted a retrospective observational study including all adult patients who received ≥72 h of cefiderocol between November 2020 and October 2024 at a Spanish tertiary-care hospital. The primary outcome was clinical success, defined as survival and absence of clinical recurrence 30 days after cefiderocol initiation. Secondary outcomes included 30- and 90-day mortality, clinical and microbiological recurrence, emergence of resistance, and adverse events. Results: Eighty patients were included (median age 64 years [IQR 56–72]; 81.3% male). Respiratory (26.2%) and abdominal (22.5%) infections were the most common, and 20% presented with bacteremia. At infection onset, 26.2% had septic shock and 45% required intensive care unit admission. The three most frequently isolated pathogen was Pseudomonas aeruginosa (33.9%), followed by Enterobacterales (33%) and Stenotrophomonas maltophilia (30.1%). Clinical success was achieved in 67.5% of patients. Thirty and 90-day mortality rates were 27.5% and 36.5%, respectively. Recurrence within 90 days occurred in 5% of cases. Emergence of resistance was detected in one Klebsiella pneumoniae ST147 isolate, and serious adverse events occurred in 5% of patients. Conclusions: In a cohort including a substantial proportion of critically ill patients, cefiderocol was associated with favorable clinical outcomes and an acceptable safety profile. These findings suggest that cefiderocol may represent a useful therapeutic option for severe MDR-GNB infections in patients with limited treatment alternatives. Full article

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15 pages, 670 KB

Open AccessSystematic Review

Sialoendoscopy with Intraductal Irrigation in Chronic Salivary Gland Disease: A Minimally Invasive, Antibiotic-Sparing Strategy

by Riccardo Manzella, Palmira Immordino, Francesco Lorusso, Francesco Dispenza, Federico Sireci, Cosimo Galletti, Salvatore Gallina and Angelo Immordino

Antibiotics 2026, 15(4), 415; https://doi.org/10.3390/antibiotics15040415 - 20 Apr 2026

Viewed by 335

Abstract

Background/Objectives: Chronic and recurrent sialadenitis are inflammatory disorders of the major salivary glands often managed with repeated courses of systemic antibiotics, despite limited long-term efficacy and growing concerns regarding antimicrobial resistance. Minimally invasive intraductal therapies, including sialoendoscopy with irrigation, have emerged as [...] Read more.

Background/Objectives: Chronic and recurrent sialadenitis are inflammatory disorders of the major salivary glands often managed with repeated courses of systemic antibiotics, despite limited long-term efficacy and growing concerns regarding antimicrobial resistance. Minimally invasive intraductal therapies, including sialoendoscopy with irrigation, have emerged as effective alternatives aimed at addressing ductal obstruction and chronic inflammation while reducing antibiotic exposure. This study aimed to systematically review the available evidence on the effectiveness and safety of sialoendoscopy with intraductal irrigation in the management of chronic and recurrent sialadenitis, with particular attention to its potential antibiotic-sparing role. Methods: A literature review was conducted in accordance with PRISMA guidelines. Major scientific databases were searched to identify studies evaluating sialoendoscopy with intraductal irrigation in patients with chronic or recurrent sialadenitis. Study characteristics, patient populations, irrigation protocols, and clinical outcomes were extracted and qualitatively analyzed. Results: Sialoendoscopy with intraductal irrigation was associated with significant clinical improvement in more than two-thirds of patients, with complete or partial symptom resolution. The procedure demonstrated high technical feasibility and a favorable safety profile. Symptom control was maintained across most etiological subgroups. The need for prolonged or repeated systemic antibiotic treatment decreased following endoscopic intervention. Conclusions: Sialoendoscopy with intraductal irrigation may represent a promising and minimally invasive therapeutic option for chronic and recurrent sialadenitis and may contribute to improved antibiotic stewardship by reducing unnecessary systemic antibiotic use. These findings suggest that intraductal therapeutic strategies could be considered within evolving care pathways for chronic salivary gland disorders, aligning clinical management with broader public health efforts to combat antimicrobial resistance. Full article

(This article belongs to the Special Issue A Public Health Lens on Antibiotic Use: From Prescription to Resistance for ENT Infections)

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10 pages, 1317 KB

Open AccessArticle

In Vitro Restoration of Colistin Susceptibility by Ivacaftor Synergy with Limited Reproducibility in a Murine Pneumonia Model

by Ana Verónica Halperin, Franziska Schwartz, Lars Christophersen, José Pérez-del Palacio, Manuel Ponce-Alonso, José Avendaño-Ortiz, Juan de Dios Caballero, Rafael Cantón, Claus Moser and Rosa del Campo

Antibiotics 2026, 15(4), 414; https://doi.org/10.3390/antibiotics15040414 - 18 Apr 2026

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Abstract

Background: We aimed to investigate the potential synergistic effect of ivacaftor combined with colistin against Pseudomonas aeruginosa and Klebsiella pneumoniae, and to elucidate the underlying molecular mechanisms through metabolomic analysis and its reproducibility in a murine model. Methods: Six colistin-susceptible and 2 [...] Read more.

Background: We aimed to investigate the potential synergistic effect of ivacaftor combined with colistin against Pseudomonas aeruginosa and Klebsiella pneumoniae, and to elucidate the underlying molecular mechanisms through metabolomic analysis and its reproducibility in a murine model. Methods: Six colistin-susceptible and 2 colistin-resistant cystic fibrosis P. aeruginosa isolates, along with two colistin-resistant K. pneumoniae clinical isolates, were studied. Antimicrobial susceptibility was assessed by broth microdilution, and synergy by checkerboard assay. Metabolomic profiling was conducted via LC-HRMS with statistical analysis. A murine pneumonia model, induced by intranasal administration of colistin-resistant strains, was used to validate in vivo ivacaftor and colistin synergy after 24 h. Results: No previously described colistin resistance mutations were identified in P. aeruginosa strains, whereas K. pneumoniae carried mgrB variations. Ivacaftor restored colistin susceptibility at 16 mg/L concentration, and at 1–2 mg/L led to at least a twofold reduction in colistin MIC. Metabolomic analysis of colistin-resistant P. aeruginosa strains revealed that ivacaftor induced modifications in phosphoethanolamine groups of lipid A. However, no synergistic effects were observed in the short-term in vivo pneumonia model, regardless of the administration route. Conclusions: Ivacaftor exhibited no direct antimicrobial activity against P. aeruginosa and K. pneumoniae isolates in vitro but restored colistin susceptibility through synergistic interactions. The lack of synergy in the murine pneumonia model may reflect treatment time and challenges in standardizing in vivo conditions. These findings highlight the potential of ivacaftor as an adjunct to colistin therapy, warranting further investigation into its clinical applicability. Full article

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

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44 pages, 2549 KB

Open AccessReview

Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy

by Jessi M. Grossman and Dorothea K. Thompson

Antibiotics 2026, 15(4), 413; https://doi.org/10.3390/antibiotics15040413 - 18 Apr 2026

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Abstract

Carbapenems comprise a class of β-lactam antibiotics with broad-spectrum hydrolytic activity and are often reserved as last-line agents for the treatment of serious multidrug-resistant (MDR) bacterial infections. Clinically important nosocomial MDR Gram-negative bacteria (GNB) include Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter [...] Read more.

Carbapenems comprise a class of β-lactam antibiotics with broad-spectrum hydrolytic activity and are often reserved as last-line agents for the treatment of serious multidrug-resistant (MDR) bacterial infections. Clinically important nosocomial MDR Gram-negative bacteria (GNB) include Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Carbapenem resistance among these organisms is predominantly mediated by the production of β-lactamases called carbapenemases, such as K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and selected oxacillinase (OXA)-type carbapenemases. These enzymes degrade carbapenems, significantly compromising their clinical efficacy. To address escalating antimicrobial resistance, novel next-generation β-lactamase inhibitors (BLIs), partnered with established β-lactams (BLs), have been approved or are currently under development to inhibit carbapenemase activity. The present narrative review aims to synthesize the most current information on the major carbapenemases and discusses recently approved and investigational BL/BLI combination therapies in terms of their mechanisms of action, spectrum of activity, gaps in coverage, and available clinical and in vitro evidence. Development of resistance to novel BL/BLI combinations is also examined. Comparative analysis of inhibitory spectra and microbiological coverage indicates a continued need for metallo-β-lactamase inhibitors with direct pan-inhibitory activity, pathogen-specific BL/BLI regimens for carbapenem-resistant A. baumannii, and carbapenemase-targeted agents effective in the context of non-enzymatic resistance mechanisms. Treatment-emergent resistance to novel BL/BLIs and limitations in activity profiles underscore the critical need for continued innovation in pipeline development, vigilant global and local surveillance of carbapenemase epidemiology, and robust antimicrobial stewardship strategies to aid in preserving the efficacy of the antibacterial drug armamentarium. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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16 pages, 1365 KB

Open AccessArticle

Two Shorter Variants of the Proline-Rich Antimicrobial Peptide B7-005 Scaffold Active Against Clinical Isolates of Pseudomonas aeruginosa and Staphylococcus aureus

by Giacomo Cappella, Adriana Di Stasi, Clelia Cortese, Luisa Torrini, Agnese D’Amore, Virginia Niccolini, Luigi de Pascale, Bruno Casciaro, Mario Mardirossian, Alessandro Pini, Maria Luisa Mangoni and Marco Scocchi

Antibiotics 2026, 15(4), 412; https://doi.org/10.3390/antibiotics15040412 - 18 Apr 2026

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Abstract

Background/Objectives: Developing novel strategies to combat respiratory infections caused by multidrug-resistant “priority pathogens” like the ESKAPEE Pseudomonas aeruginosa and Staphylococcus aureus is an urgent priority. Methods: We investigated two shortened variants of the proline-rich antimicrobial peptide (PrAMP) B7-005, B7-006 (15-mer) and B7-007 (13-mer). [...] Read more.

Background/Objectives: Developing novel strategies to combat respiratory infections caused by multidrug-resistant “priority pathogens” like the ESKAPEE Pseudomonas aeruginosa and Staphylococcus aureus is an urgent priority. Methods: We investigated two shortened variants of the proline-rich antimicrobial peptide (PrAMP) B7-005, B7-006 (15-mer) and B7-007 (13-mer). Evaluation included MIC assays against laboratory and clinical multidrug-resistant isolates, mechanistic studies of membrane permeabilization, cytotoxicity testing on BEAS-2B bronchial epithelial cells, and proteolytic stability assays in human elastase and sputum. Results: Despite their reduced size, lower positive charge, and decreased proline content, both variants retained full antimicrobial activity against clinical pathogens with consistent MIC values ≤ 25 µM. These variants exhibit membrane permeabilization in P. aeruginosa but may also relay on a hybrid mode of action involving also intracellular targets. Notably, B7-006 and B7-007 displayed low cytotoxicity compared to the lytic peptide BMAP-18. While B7-007 showed greater susceptibility to proteolytic degradation than its parent B7-005, it preserved partial integrity during the initial hours of exposure. Conclusions: Overall, these findings demonstrate that the B7 scaffold tolerates substantial truncation while preserving potency and selectivity, identifying a minimal 13-amino-acid active core. This work provides critical insights into structure–activity relationships and supports the development of compact, mechanistically versatile antimicrobial peptides to address the growing threat of multidrug-resistant respiratory pathogens. Full article

(This article belongs to the Special Issue Resistance, Treatment and Prevention of ESKAPE Pathogens)

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24 pages, 2800 KB

Open AccessArticle

Genomic Epidemiology of ESBL and Non-ESBL-Producing Escherichia coli Across One Health Interfaces in Oman

by Hibatallah Sultan Al-Habsi, Zaaima Al Jabri, Amina Al-Jardani, Amira ElBaradei, Hafidha Al-Hattali, Faiza Syed, Zakariya Al Muharrmi, Wafa Al Alawi, Hatim Ali Eltahir and Meher Rizvi

Antibiotics 2026, 15(4), 411; https://doi.org/10.3390/antibiotics15040411 - 17 Apr 2026

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Abstract

Background: Antimicrobial resistance is a One Health problem driven by the intricate interactions across human, animal, and environmental interfaces that enable microbial exchange and movement of mobile genetic elements encoding resistance and virulence. This study investigated the genomic epidemiology of ESBL and [...] Read more.

Background: Antimicrobial resistance is a One Health problem driven by the intricate interactions across human, animal, and environmental interfaces that enable microbial exchange and movement of mobile genetic elements encoding resistance and virulence. This study investigated the genomic epidemiology of ESBL and non-ESBL Escherichia coli across One Health interfaces in Oman. Methods: This prospective cross-sectional study analyzed 295 non-duplicate Escherichia coli isolates derived from 104 clinical, 173 animal [diseased (123) and healthy (50)], 14 sewage and four water sources. Antimicrobial susceptibility testing was performed phenotypically, and a representative subset of 50 ESBL and non-ESBL Escherichia coli from the three interfaces underwent whole genome sequencing to determine MLST, phylogroups, resistance genes, virulence determinants and plasmid replicons. Results: ESBL prevalence was highest in human isolates (73%), followed by sewage (28.6%) and animals (16.3% diseased; 8% healthy). blaCTX-M-15 predominated in humans, whereas blaCTX-M-55 dominated in animals and sewage, suggesting ecological partitioning with partial overlap. Quinolone resistance was lowest in the animal interface. Sewage isolates harbored the most complex resistome, including rmtB and plasmid-mediated quinolone resistance genes. MLST analysis revealed high diversity in human isolates, including globally recognized ExPEC lineages (ST10, ST38, ST73, ST127, ST131), while ST224 dominated in animals with evidence of possible spillover to humans. ST167 was confined to sewage, consistent with environmental maintenance of high-risk clones. Phylogroup structuring showed predominance of A, B2 and D among human isolates and A, B1, and E among animal and sewage isolates. Virulence profiling demonstrated broader virulome diversity in humans, but shared core determinants (fimH, sitA, traT) across all domains. IncFIB(AP001918) was the dominant plasmid replicon, particularly among ESBL isolates, underscoring its role in horizontal gene dissemination. Alarmingly, mutation in pmrB (V161G) was identified in a healthy animal isolate, pointing to a need for greater colistin restriction in animal husbandry. Conclusions: This study highlights plasmid-mediated resistance and shared virulence determinants linking reservoirs; although AMR profile was quite distinct across the three interfaces, human isolates demonstrated greater resistance than animal isolates, suggesting healthcare-driven AMR in Oman. Continued integrated genomic surveillance is essential to monitor gene flow and inform coordinated antimicrobial stewardship strategies. Full article

(This article belongs to the Special Issue Genomic Surveillance of Antimicrobial Resistance (AMR))

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26 pages, 2560 KB

Open AccessArticle

Albumin Nanoparticles Improve Colistin Performance Against Hetero- and Full-Resistant Clinical A. baumannii: A Mechanistic Study

by Sara Scutera, Viviana Cafiso, Giulia Vigna, Monica Argenziano, Eleonora Chines, Antonio Curtoni, Matteo Florio Furno, Giovanna Cristina Varese, Chiara Scarpa, Ilario Ferrocino, Stefania Raimondo, Gabriele Bianco, Roberta Cavalli and Tiziana Musso

Antibiotics 2026, 15(4), 410; https://doi.org/10.3390/antibiotics15040410 - 17 Apr 2026

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Abstract

Background: Colistin (Col) resistance and heteroresistance in extensively drug-resistant (XDR) Acinetobacter baumannii severely limit therapeutic options. We investigated the activity and mechanism of human albumin nanoparticles (haNPs) as colistin potentiators against genetically characterized clinical isolates. Methods: Sixteen clinical isolates were analyzed. Col MICs [...] Read more.

Background: Colistin (Col) resistance and heteroresistance in extensively drug-resistant (XDR) Acinetobacter baumannii severely limit therapeutic options. We investigated the activity and mechanism of human albumin nanoparticles (haNPs) as colistin potentiators against genetically characterized clinical isolates. Methods: Sixteen clinical isolates were analyzed. Col MICs were determined by broth microdilution, and heteroresistance by population analysis profiling. Potentiation of Col activity was assessed using both Col-loaded haNPs (Col/haNPs) and free Col co-administered with empty haNPs, alongside the proton motive force (PMF) uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Assays included checkerboard synergy (FICI), membrane potential analysis (DiOC₂(3)), intracellular Col quantification (UPLC–MS/MS), zeta potential measurements, transmission electron microscopy (TEM), protein leakage, and ROS detection. Results: Heteroresistance was detected in 9/16 isolates. Col/haNPs reduced Col MICs by 4–64-fold in resistant strains and shifted MICs to ≤2 mg/L in most heteroresistant isolates. Empty haNPs displayed no intrinsic antibacterial activity yet selectively potentiated Col, with strong synergy (FICI down to 0.035). Membrane depolarization and increased intracellular Col accumulation under haNP-treated conditions paralleled the effects of CCCP, indicating that haNPs elicit a CCCP-like functional response. These findings are compatible with perturbation of membrane energetics and possible downstream effects on PMF-dependent transport processes. TEM and surface charge analyses supported direct nanoparticle–envelope interaction and progressive membrane disruption. Conclusions: haNPs enhance Col activity across genetically diverse A. baumannii isolates, with particularly strong effects in heteroresistant strains. The combined effects of PMF modulation, increased intracellular drug availability, and envelope interaction provide a mechanistic rationale for the use of albumin-based nanoparticles, either as Col carriers or in combination with free drug, to overcome Col resistance and heteroresistance. Full article

(This article belongs to the Section Novel Antimicrobial Agents)

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28 pages, 1398 KB

Open AccessSystematic Review

Antibiotics and Other Drugs Removal by the CytoSorb^® Haemoadsorber: A Systematic Review of Available Evidence

by Sara Kenda, Jakob Gubenšek and Tomaž Vovk

Antibiotics 2026, 15(4), 409; https://doi.org/10.3390/antibiotics15040409 - 17 Apr 2026

Viewed by 619

Abstract

Background/Objectives: Haemoadsorption has recently emerged as an extracorporeal treatment option for sepsis, septic shock, intoxications, and cardiac surgery to modulate dysregulated inflammatory responses or remove a wide range of circulating molecules. To ensure appropriate clinical use of the CytoSorb^® haemoadsorber, it [...] Read more.

Background/Objectives: Haemoadsorption has recently emerged as an extracorporeal treatment option for sepsis, septic shock, intoxications, and cardiac surgery to modulate dysregulated inflammatory responses or remove a wide range of circulating molecules. To ensure appropriate clinical use of the CytoSorb^® haemoadsorber, it is essential to understand the extent to which specific drugs are adsorbed by the device. Methods: We conducted a systematic literature review using the PubMed and Ovid MEDLINE database to identify studies on drug binding to the CytoSorb^® haemoadsorber, including both in vivo and in vitro studies. Publications in English language, available up to 31 December 2025 that reported or enabled calculation of percentage of drug removal, CytoSorb^® clearance or half-life during CytoSorb^® therapy were included. Records were screened, eligibility and quality were assessed, and data were extracted independently by two reviewers. Results: We found that 26 studies reported on the binding of 56 drugs to CytoSorb^®, with most available information relating to antibiotics used in the treatment of sepsis and septic shock. CytoSorb^® appears to remove vancomycin and linezolid but not meropenem, although data for other antibiotics are insufficient to assess clinical relevance. Data on the removal of anticoagulant and antithrombotic drugs with CytoSorb^® before and during cardiac surgery indicate that using this procedure to reduce complications associated with apixaban and ticagrelor is feasible and safe. The available evidence on the use of CytoSorb^® for drug poisoning is of very low quality. Conclusions: Although the number of studies on drug binding to the CytoSorb^® is increasing, the review is limited by the marked heterogeneity among the included studies. It is advised to use therapeutic drug monitoring whenever possible during CytoSorb^® treatment. Research of binding of drugs to CytoSorb^® is crucial for its safe and effective clinical use, but adequate methodology is necessary. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients)

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39 pages, 3662 KB

Open AccessReview

Membrane-Focused Strategies Against Acinetobacter baumannii: The Therapeutic Potential of Functional Copolymers

by Barbara Cardoso Domingues, Marc Maresca, Jean-Michel Bolla and Véronique Sinou

Antibiotics 2026, 15(4), 408; https://doi.org/10.3390/antibiotics15040408 - 17 Apr 2026

Viewed by 341

Abstract

Antimicrobial resistance is a serious global public health concern, with Acinetobacter baumannii recognized as one of the most problematic multidrug-resistant (MDR) pathogens. This Gram-negative bacterium is highly persistent in the environment, possesses a remarkably adaptable cell envelope, and forms biofilms. As the effectiveness [...] Read more.

Antimicrobial resistance is a serious global public health concern, with Acinetobacter baumannii recognized as one of the most problematic multidrug-resistant (MDR) pathogens. This Gram-negative bacterium is highly persistent in the environment, possesses a remarkably adaptable cell envelope, and forms biofilms. As the effectiveness of conventional antibiotics declines, alternative strategies are being actively explored, particularly membrane-targeting approaches based on synthetic copolymers. These compounds mimic antimicrobial peptides, offer enhanced stability and structural tunability, and have a lower propensity to develop resistance. Recent advances in polymer chemistry have led to the design of antibacterial polymers with activity against MDR A. baumannii. Some of these act synergistically with existing antibiotics, restoring bacterial susceptibility or disrupting biofilms. However, their non-degradability remains a concern due to its potential implications for body/environment accumulation and related toxicity and/or selection of resistant strains. This review examines the biology of the A. baumannii cell envelope, its resistance mechanisms, and treatment limitations, while emphasizing the promise of membrane-active copolymers. By bridging materials science and microbiology, these approaches offer promising strategies for combating World Health Organization priority pathogens. Full article

(This article belongs to the Special Issue Advances in Antimicrobial Action and Resistance)

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16 pages, 1614 KB

Open AccessArticle

Catheter Duration Threshold and Risk Factors for Central Line-Associated Bloodstream Infections in a Tertiary ICU with Endemic Carbapenem Resistance: A Case–Control Study

by Enes Dalmanoğlu, Mehmet Özgür Özhan, Bülent Atik and Tülin Akarsu Ayazoğlu

Antibiotics 2026, 15(4), 407; https://doi.org/10.3390/antibiotics15040407 - 17 Apr 2026

Viewed by 381

Abstract

Background/Objectives: Central line-associated bloodstream infections (CLABSIs) remain a leading healthcare-associated infection in intensive care units (ICUs), yet independent risk factors and evidence-based catheter duration thresholds have not been defined through analytical study designs in settings with endemic multidrug-resistant organisms (MDROs). Methods: A retrospective [...] Read more.

Background/Objectives: Central line-associated bloodstream infections (CLABSIs) remain a leading healthcare-associated infection in intensive care units (ICUs), yet independent risk factors and evidence-based catheter duration thresholds have not been defined through analytical study designs in settings with endemic multidrug-resistant organisms (MDROs). Methods: A retrospective case–control study was conducted in the ICU of a tertiary teaching university hospital in western Türkiye (January 2019–December 2024). Cases (n = 74) were patients with confirmed CLABSIs per CDC/NHSN criteria; controls (n = 148) were randomly selected central venous catheter (CVC)-bearing patients without CLABSIs. A reduced multivariate logistic regression model (seven variables; events-per-variable ratio 10.6) identified independent risk factors. Results: In multivariate analysis, catheter duration (adjusted OR: 1.19 per day; 95% CI: 1.13–1.24; p < 0.001), renal replacement therapy (aOR: 3.66; 95% CI: 1.68–7.95; p = 0.001), vasopressor support (aOR: 3.04; 95% CI: 1.50–6.17; p = 0.002), APACHE-II score (aOR: 1.07 per point; 95% CI: 1.02–1.11; p = 0.002), lower Glasgow Coma Scale (aOR: 0.86 per point; 95% CI: 0.78–0.94; p = 0.002), mechanical ventilation (aOR: 2.48; 95% CI: 1.24–4.95; p = 0.010), and total parenteral nutrition (aOR: 2.33; 95% CI: 1.12–4.86; p = 0.024) were independently associated with CLABSI. The model demonstrated good discrimination (C-statistic: 0.864) and calibration (Hosmer–Lemeshow p = 0.425). Kaplan–Meier analysis showed CLABSI-free survival declining from 98.9% at day 7 to 42.9% at day 21 (log-rank p < 0.001); these within-study estimates reflect relative risk patterns given the artificial 1:2 case-to-control ratio. Receiver operating characteristic (ROC) analysis identified day 13 as an exploratory optimal cutoff (AUC: 0.818; 95% CI: 0.762–0.874; sensitivity: 77.0%; specificity: 74.3%). CLABSI-attributable ICU mortality was 20.3% (47.3% vs. 27.0%; p = 0.004). Late-onset CLABSIs (>10 days) were dominated by Gram-negative pathogens (68.3%) versus 35.7% in early-onset infections (Fisher’s exact p = 0.012), with Acinetobacter baumannii as the predominant organism (27.0%; 83.3% carbapenem-resistant). Conclusions: Each additional catheter-day is independently associated with a 19% increment in CLABSI odds, with an exploratory critical threshold at day 13 beyond which enhanced surveillance measures should be considered, pending external validation. Full article

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

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35 pages, 7317 KB

Open AccessArticle

Mechanistic Insights into the Anti-Virulence Effects of Viroelixir, a Phenolic Blend from Green Tea and Pomegranate, on Streptococcus mutans

by Manal Dahdah, Vijaykumar D. Nimbarte, Mahmoud Rouabhia, Yasmine Ettouil, Hawraa Issa, Latifa Koussih, Mikhlid H. Almutairi and Abdelhabib Semlali

Antibiotics 2026, 15(4), 406; https://doi.org/10.3390/antibiotics15040406 - 17 Apr 2026

Cited by 1 | Viewed by 437

Abstract

Background: Dental caries remains one of the most prevalent oral diseases worldwide, largely driven by the virulence of Streptococcus mutans. Although plant phenolics from green tea and pomegranate are known for their antimicrobial properties, their molecular mechanisms of action against key [...] Read more.

Background: Dental caries remains one of the most prevalent oral diseases worldwide, largely driven by the virulence of Streptococcus mutans. Although plant phenolics from green tea and pomegranate are known for their antimicrobial properties, their molecular mechanisms of action against key S. mutans virulence targets remain insufficiently characterized. Aim: This study investigated the antibacterial and anti-virulence properties of Viroelixir, a phenolic-rich formulation derived from green tea (Camellia sinensis) and pomegranate (Punica granatum), against S. mutans, with particular emphasis on predictive molecular docking interactions with critical virulence-associated proteins. Methods: Viroelixir phytochemical composition was characterized by LC–MS using a C18 reverse-phase column and negative electrospray ionization mode. Antibacterial activity was evaluated using growth kinetics, agar plating, and crystal violet assays. Acidogenicity, hemolytic activity, and biofilm formation were assessed using pH modulation, hemolysis assays, SEM, and biofilm biomass quantification. Virulence gene expression was analyzed by RT-qPCR. In silico molecular docking was performed to explore potential interactions between major LC–MS-supported phenolic constituents and S. mutans virulence proteins, including glucosyltransferase B (GtfB), LuxS, and SpaP. Biocompatibility was evaluated in human gingival epithelial cells. Results: The LC-MS analysis revealed a complex mixture of phenolic compounds consistent with catechins and ellagitannins. Compound identification was considered tentative and based on mass spectral range and chromatographic behavior. Viroelixir significantly inhibited S. mutans growth, acid production, hemolytic activity, and biofilm formation in a concentration-dependent manner. Key virulence genes were markedly downregulated. Docking analyses suggested stable binding of selected phenolics—particularly punicalagin, catechin, and epigallocatechin—within the active sites of GtfB, LuxS, and SpaP. Importantly, Viroelixir showed no cytotoxic effects on gingival epithelial cells. Conclusions: Viroelixir exerts potent antibacterial and anti-virulence effects against S. mutans through a multi-target mechanism combining transcriptional suppression and predictive molecular inhibition of virulence proteins, supporting its potential as a safe, natural therapeutic for caries prevention. Full article

(This article belongs to the Section Antibiofilm Strategies)

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21 pages, 7924 KB

Open AccessArticle

Genomic and GWAS-Based Insights into Antimicrobial Resistance in Shewanella algae Isolated from Penaeus monodon

by Ponsit Sathapondecha, Wichai Pornthanakasem, Timpika Thepsuwan, Pacharaporn Angthong, Wiyada Chumpol, Kamonwan Lunha, Suganya Yongkiettrakul and Wanilada Rungrassamee

Antibiotics 2026, 15(4), 405; https://doi.org/10.3390/antibiotics15040405 - 16 Apr 2026

Viewed by 614

Abstract

Background/Objectives: The emergence of antimicrobial-resistant (AMR) pathogens in aquaculture ecosystems poses a significant risk to both food security and human health. Shewanella species are recognized as significant AMR reservoirs, yet their prevalence and resistance mechanisms within a shrimp-related ecosystem remain poorly characterized. This [...] Read more.

Background/Objectives: The emergence of antimicrobial-resistant (AMR) pathogens in aquaculture ecosystems poses a significant risk to both food security and human health. Shewanella species are recognized as significant AMR reservoirs, yet their prevalence and resistance mechanisms within a shrimp-related ecosystem remain poorly characterized. This study aimed to perform a genotypic and phenotypic characterization of S. algae VK101, isolated from wild-caught black tiger shrimp (Penaeus monodon) broodstock. Methods: A complete 5.21 Mb genome was generated using a hybrid Illumina and Oxford Nanopore sequencing approach. Antimicrobial susceptibility was evaluated for 21 antibiotics via Minimum Inhibitory Concentration (MIC) testing. Comparative pangenomics and genome-wide association studies (GWAS) across 125 S. algae genomes were conducted to identify novel resistance determinants. Results: MIC analysis revealed that VK101 was resistant to ampicillin (>16 µg/mL) and colistin (8 µg/mL), while showing intermediate susceptibility to imipenem and ciprofloxacin. In silico analysis identified 205 antimicrobial resistance genes (ARGs), including a perfect hit for the fluoroquinolone resistance gene qnrA3. Notably, no mcr genes were detected. Although VK101 exhibited moderate resistance (8 µg/mL), GWAS across the broader S. algae population linked a specific lptA mutation (K140N) to high-level resistance (64 µg/mL). Other GWAS-identified genes (e.g., czcA, ampC, and oprM) likely represent indirect associations driven by genetic linkage or clade-specific markers rather than direct causal factors. Conclusions: These findings highlighted the presence of multidrug-resistant S. algae in wild-caught P. monodon broodstock, reflecting the occurrence of antimicrobial resistance in aquatic environments. Colistin resistance in these isolates was primarily mediated by chromosomal variants rather than mobile mcr elements, indicating the need for integrated genomic surveillance within the aquaculture value chain. Full article

(This article belongs to the Special Issue Antibiotics and Antimicrobial Resistance in Aquaculture: Alternative and Complementary Treatment Methods)

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10 pages, 469 KB

Open AccessArticle

A Performance Evaluation of the Vitek^®2 AST-N440 Card for Colistin Susceptibility Testing of Carbapenem-Resistant Acinetobacter baumannii Complex Isolates Using Broth Microdilution as the Reference Method

by Dimitra Petropoulou, Anastasios Ioannidis, Christina Kaminioti, Christina Mparka, Evgenia Mitropoulou, Georgia Petropoulou, Polyxeni Karakosta, Georgios Alexandros Baziotis and Spyros Pournaras

Antibiotics 2026, 15(4), 404; https://doi.org/10.3390/antibiotics15040404 - 16 Apr 2026

Viewed by 344

Abstract

Background/Objectives: Accurate determination of colistin (COL) in vitro activity against carbapenem-resistant Acinetobacter baumannii complex (CRAB) isolates remains challenging, as the reference broth microdilution (BMD) method is labor-intensive and not routinely implemented in most clinical laboratories. Semi-automated susceptibility methods for colistin in the clinical [...] Read more.

Background/Objectives: Accurate determination of colistin (COL) in vitro activity against carbapenem-resistant Acinetobacter baumannii complex (CRAB) isolates remains challenging, as the reference broth microdilution (BMD) method is labor-intensive and not routinely implemented in most clinical laboratories. Semi-automated susceptibility methods for colistin in the clinical laboratory require validation. The present study evaluated the performance characteristics of the recently introduced Vitek^®2 card AST-N440 for COL antimicrobial susceptibility testing (AST) on CRAB isolates compared with a BMD-based reference method (ComASP Colistin). Methods: A total of 176 single-patient CRAB isolates from two distinct tertiary Greek hospitals between 2024 and 2025 were included. COL susceptibility testing was performed using Vitek^®2 AST-N440 and compared with BMD. Minimum inhibitory concentrations (MICs) were interpreted according to EUCAST breakpoints. Method performance was evaluated by calculating categorical (CA) and essential agreement (EA), sensitivity, specificity, positive and negative predictive values (PPV/NPV), and major (ME) and very major error rates (VME) according to ISO 20776-2. Results: Compared with BMD, AST-N440 showed a sensitivity of 89.6% and a specificity of 62.3%, with a PPV and NPV of 81.7% and 76.0%, respectively. The CA (80.1%) and the EA (46.0%) were below ISO acceptance criteria. The VME rate was 10.4%, and the ME rate 37.7%. Identical MIC values were observed in 25.0% of the isolates, while Vitek^®2 reported lower and higher MIC values than BMD in 46.6% and 28.4% of isolates, respectively. Conclusions: The Vitek^®2 AST-N440 card performed suboptimally for COL susceptibility testing in CRAB isolates. Further validation of automated systems for COL AST is needed. Full article

(This article belongs to the Special Issue Recent Developments in Antimicrobial Resistance Epidemiology and Antimicrobial Therapy for Clinically Relevant Bacteria)

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15 pages, 530 KB

Open AccessArticle

Antibiotic Adjuvant Potential of Selected Essential Oil Components Against Respiratory Pathogens: From Planktonic Synergy to Early-Stage Biofilm Inhibition

by Viktória Lilla Balázs, Rita Filep, Edit Ormai, Lilla Radványi, Béla Kocsis, Erika Kerekes and Marianna Kocsis

Antibiotics 2026, 15(4), 403; https://doi.org/10.3390/antibiotics15040403 - 16 Apr 2026

Viewed by 487

Abstract

Background: Respiratory tract infections remain among the most common indications for antibiotic therapy and represent a major driver of antimicrobial resistance. The ability of respiratory pathogens to form biofilms further contributes to treatment failure and recurrence. This study aimed to evaluate the antibiotic [...] Read more.

Background: Respiratory tract infections remain among the most common indications for antibiotic therapy and represent a major driver of antimicrobial resistance. The ability of respiratory pathogens to form biofilms further contributes to treatment failure and recurrence. This study aimed to evaluate the antibiotic adjuvant potential of selected essential oil components against clinically relevant respiratory bacteria and to determine whether planktonic synergistic interactions translate into early-stage antibiofilm efficacy. Thymol, eugenol, trans-cinnamaldehyde, and terpinen-4-ol were tested against Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. Methods: Minimum inhibitory concentrations were determined by broth microdilution. Synergistic interactions with clinically relevant antibiotics were assessed using the checkerboard method and fractional inhibitory concentration index (FICI) analysis. Selected combinations were further evaluated in a 6 h crystal violet-based early-stage biofilm model. Gram-positive strains generally exhibited higher susceptibility to the tested components than Gram-negative bacteria. Results: Synergistic interactions (FICI ≤ 0.5) were most frequently observed between β-lactam antibiotics and phenolic components, particularly thymol and trans-cinnamaldehyde. Strong synergy was detected for vancomycin-eugenol against MRSA and for amoxicillin/clavulanic acid–cinnamaldehyde against M. catarrhalis. Importantly, synergistic combinations translated into significantly enhanced inhibition of early biofilm formation, increasing inhibition rates by 15–40% compared to antibiotic monotherapy (p < 0.05). Selected essential oil components enhanced the antibacterial activity of clinically relevant antibiotics and effectively potentiated early-stage biofilm inhibition. Conclusions: These findings support further investigation of phytochemical-antibiotic combinations as potential adjunct strategies in respiratory infection management. Full article

(This article belongs to the Special Issue Alternative Approaches to Treating Antimicrobial Resistant Infections, 4th Edition)

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16 pages, 1637 KB

Open AccessArticle

In Vitro Antifungal Activity of Essential Oils and Nanoemulsions of Zingiber cassumunar and Cymbopogon citratus Against Planktonic and Biofilm Forms of Malassezia pachydermatis

by Sirikorn Promcham, Orawan Limsivilai, Theerawat Kritsadasima, Suttiwee Chermprapai, Natthasit Tansakul, Pareeya Udomkusonsri and Chompoonek Yurayart

Antibiotics 2026, 15(4), 402; https://doi.org/10.3390/antibiotics15040402 - 16 Apr 2026

Viewed by 445

Abstract

Malassezia pachydermatis is a yeast pathogen associated with recurrent skin and ear infections in dogs, often complicated by biofilm formation and reduced antifungal susceptibility. We aimed to evaluate the in vitro antifungal activity of essential oils and nanoemulsions of Zingiber cassumunar and Cymbopogon [...] Read more.

Malassezia pachydermatis is a yeast pathogen associated with recurrent skin and ear infections in dogs, often complicated by biofilm formation and reduced antifungal susceptibility. We aimed to evaluate the in vitro antifungal activity of essential oils and nanoemulsions of Zingiber cassumunar and Cymbopogon citratus compared with conventional antifungal agents against planktonic and biofilm forms of M. pachydermatis. Preliminary screening of six plant extracts was performed using 12 clinical isolates identified Z. cassumunar and C. citratus for nanoemulsion formulation. Antifungal susceptibility testing of conventional antifungal agents and nanoemulsions was subsequently conducted using 31 clinical isolates, and nanoemulsions were prepared by high-pressure homogenization. Both essential oils exhibited antifungal activity, and nanoemulsion formulations showed enhanced inhibitory effects compared with the crude oils. Biofilm-associated cells demonstrated reduced susceptibility, particularly to conventional antifungal agents. Terbinafine was the most potent agent against planktonic cells but showed reduced efficacy in biofilms. Nanoemulsions of Z. cassumunar and C. citratus exhibited improved activity against both forms. These findings suggest that nanoemulsification may enhance the in vitro antifungal performance of essential oils against M. pachydermatis biofilms. However, further studies, including mechanistic investigations and in vivo evaluations, are required to confirm their therapeutic potential and safety. Full article

(This article belongs to the Special Issue Evaluation of Antibacterial and Antibiofilm Activities of Plant Essential Oils Against Pathogenic Microorganisms)

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16 pages, 457 KB

Open AccessArticle

Antibiotic Use in the Emergency Department: A Retrospective Study in Indonesia

by Ikhwan Yuda Kusuma, Ria Benkő, Erika Piroska Papfalvi, Ni Made Amelia Ratnata Dewi, Fiqih Nurkholis, Róbert Nacsa, Dezső Csupor and Mária Matuz

Antibiotics 2026, 15(4), 401; https://doi.org/10.3390/antibiotics15040401 - 15 Apr 2026

Viewed by 603

Abstract

Background: Antimicrobial resistance (AMR) is a global health threat arising from inappropriate antibiotic use. Data on the prescription of antibiotics in emergency departments (EDs), critical care points for infection management, are limited. Objective: This study aimed to assess systemic antibiotic use in an [...] Read more.

Background: Antimicrobial resistance (AMR) is a global health threat arising from inappropriate antibiotic use. Data on the prescription of antibiotics in emergency departments (EDs), critical care points for infection management, are limited. Objective: This study aimed to assess systemic antibiotic use in an Indonesian ED. Methods: This retrospective observational study was conducted in the Cilacap Teaching Hospital ED in 2022. Data, including patient demographics and systemic antibiotic prescription details (World Health Organization Anatomical Therapeutic Chemical (WHO ATC): J01) were extracted from electronic medical records. Antibiotic use was analyzed according to age groups (children [0–14 years], adults [15–64 years], and the elderly [≥65 years]), administration route, and the World Health Organization Access, Watch, and Reserve classification. Results: Among all ED visits during the study period, 52.1% (14,396/27,640) received systemic antibiotics, and adults comprised 68.5% (9861/14,396) of antibiotic-exposed cases. Cephalosporins were the most frequently prescribed antibiotics in all age groups (42.4–50.9%). Penicillins were more frequently prescribed in children (29.9%) than in adults (10.0%) and the elderly (6.6%), whereas fluoroquinolones were more commonly prescribed in the elderly (21.1%) than in adults (16.2%) and children (3.8%). Watch-class antibiotics, comprising 63.9% of all prescriptions, were commonly prescribed in the elderly (71.9%). Oral route was the predominant form (65.8%), particularly in children (76.5%). The most frequently prescribed antibiotics differed across age groups, with amoxicillin followed by cefixime in children, and cefixime followed by ceftriaxone in both adults and the elderly. Conclusions: This study showed high antibiotic exposure and identified age-related differences in antibiotic prescribing, and patterns that warrant further evaluation within antimicrobial stewardship frameworks, to optimize antibiotic use and mitigate AMR. Full article

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

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16 pages, 1227 KB

Open AccessArticle

Antimicrobial Resistance Profiles of Gram-Negative Bacteria Isolated from Saker Falcons (Falco cherrug) in Western Romania

by Daiana-Ionela Cocoș, Oana-Maria Boldura, Eugenia Dumitrescu, Răzvan-Tudor Pătrînjan, Florin Muselin, Diana Brezovan, Janos Degi and Romeo Teodor Cristina

Antibiotics 2026, 15(4), 400; https://doi.org/10.3390/antibiotics15040400 - 15 Apr 2026

Viewed by 382

Abstract

Background/Objectives: The Saker Falcon (Falco cherrug) is an endangered raptor species of ecological and conservation relevance. Despite its status, data regarding its microbiota and the prevalence of antimicrobial resistance (AMR) remain scarce, especially in Eastern Europe. This single-facility study aims [...] Read more.

Background/Objectives: The Saker Falcon (Falco cherrug) is an endangered raptor species of ecological and conservation relevance. Despite its status, data regarding its microbiota and the prevalence of antimicrobial resistance (AMR) remain scarce, especially in Eastern Europe. This single-facility study aims to investigate the phenotypic and genotypic AMR profiles of Gram-negative bacteria isolated from captive Saker Falcons in Western Romania. Methods: Freshly voided fecal droppings were collected non-invasively from 40 clinically healthy Saker Falcons. Bacterial identification was performed using selective media and the VITEK^® 2 system. Antimicrobial susceptibility testing (AST) was conducted on a representative subset of 12 isolates. Selected resistance-associated genes were screened by conventional PCR. Results: Escherichia coli was the most prevalent 60% (n = 24/40), followed by Hafnia alvei 10% (n = 4/40) and Pseudomonas spp. 10% (n = 4/40). AST revealed phenotypic resistance among Enterobacteriaceae primarily to ampicillin 20% (n = 2/10), tetracycline 20% (n = 2/10), fluoroquinolones and sulfonamides 10% (n = 1/10), while susceptibility to imipenem 90% (n = 9/10) and gentamicin 90% (n = 9/10) remained high. The targeted resistance-associated genes were detected in selected phenotypically resistant isolates. PCR screening detected blaZ and ampC in 62.5% (n = 5/8) of tested isolates, blaOXA-61 in 37.5% (n = 3/8), blaOXA-51 in 25% (n = 2/8), tetK in 37.5% (n = 3/8), and gyrA in 12.5% (n = 1/8). The isolate used as the negative control, pansusceptible in AST, was confirmed negative for all targeted genes. Conclusions: This single-facility study provides baseline data on AMR traits in Gram-negative bacteria associated with Saker Falcons in Western Romania. Given the limited scale and isolate-based design of the study, the findings should be interpreted cautiously, but they support further investigation of wildlife-associated AMR within a One Health context. Full article

(This article belongs to the Special Issue Antibiotic Resistance in a One Health Context: Bridging Environmental, Agricultural, Nutritional, Veterinary, and Clinical Perspectives)

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11 pages, 420 KB

Open AccessArticle

Penicillin Allergy, Really?—A Cross-Sectional Mixed-Methods Study in Baden-Württemberg, Germany, to Explore General Practitioner Perspectives on Delabeling Potential in Primary Care

by Regina Poß-Doering, Nicola A. Litke, Elham Khatamzas and Attila Altiner

Antibiotics 2026, 15(4), 399; https://doi.org/10.3390/antibiotics15040399 - 15 Apr 2026

Viewed by 390

Abstract

Background: Most penicillin allergy labels are documented in early childhood and result from events of low risk for allergy. In Germany, evidence-based strategies to evaluate the likelihood of a true penicillin allergy are still lacking. As general practitioner input is indispensable regarding required [...] Read more.

Background: Most penicillin allergy labels are documented in early childhood and result from events of low risk for allergy. In Germany, evidence-based strategies to evaluate the likelihood of a true penicillin allergy are still lacking. As general practitioner input is indispensable regarding required resources for the implementation of successful delabeling strategies in outpatient care, a mixed-methods study in Baden-Württemberg, Germany explored untapped delabeling potential and conditions for successful initiatives based on their experiences, to support preservation of penicillin as a treatment option and prevent resistance development. Methods: A cross-sectional convergent mixed-methods study was conducted with an online survey and semi-structured interviews. The survey link and invitation to participate in an interview was sent to randomly selected publicly available e-mail addresses. Survey data were analyzed descriptively. Qualitative data were analyzed inductively based on thematic analysis. Results: n = 101 survey questionnaires and n = 15 interviews were analyzed regarding relevance, experiences, framework conditions, and potential approaches to delabeling. All participants with limited recollection of the index reaction. Most participants considered delabeling a highly relevant topic in general practice. Delabeling efforts were discouraged by lack of time, expertise, and remuneration, and uncertainty due to missing guidelines. Taking a sufficient medical history and, if necessary, subsequent testing were seen as one approach to delabeling. For a standardized approach in primary care, patient and care provider education, precise guideline recommendations, and delabeling expert teams were suggested. Conclusions: The findings mirror aspects already identified in international research. A nationwide survey with general practitioners could confirm that addressing necessary resources and systemic adjustments would support effective penicillin allergy delabeling in outpatient care. Full article

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

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3 pages, 137 KB

Open AccessEditorial

Editorial for the Special Issue “Staphylococcal Biology and Pathogenesis”

by Richard A. Proctor

Antibiotics 2026, 15(4), 398; https://doi.org/10.3390/antibiotics15040398 - 15 Apr 2026

Viewed by 250

Abstract

This Special Issue of Antibiotics contains a series of articles that discuss the best approaches to the study of the pathogenesis, immune response, and therapeutics of Staphylococcus aureus infections [...] Full article

(This article belongs to the Special Issue Staphylococcal Biology and Pathogenesis)

35 pages, 5348 KB

Open AccessReview

Targeting Bacterial Infections in Periodontal Disease: From Conventional Antibiotics to Next-Generation Therapeutics

by Nada Tawfig Hashim, Rasha Babiker, Muhammed Mustahsen Rahman, Riham Mohammed, Vivek Padmanabhan, Md Sofiqul Islam, Mariam Elsheikh, Salma Musa Adam Abduljalil, Ghiath Mahmoud, Nallan C. S. K. Chaitanya, Bogahawatte Samarakoon Mudiyanselage Samadarani Siriwardena, Ayman Ahmed and Bakri Gobara Gismalla

Antibiotics 2026, 15(4), 397; https://doi.org/10.3390/antibiotics15040397 - 14 Apr 2026

Viewed by 569

Abstract

Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, [...] Read more.

Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, pharmacokinetic constraints, and disruption of the commensal microbiome, leading to inconsistent outcomes and disease recurrence. This review highlights the mechanistic limitations of conventional antibiotic therapies in periodontitis and critically examines emerging next-generation therapeutic strategies aimed at overcoming these challenges. Specifically, it explores antimicrobial peptides, quorum sensing inhibitors, nanotechnology-based drug delivery systems, host modulation approaches, and microbiome-targeted therapies, with emphasis on their molecular mechanisms, clinical relevance, and translational potential. By integrating microbial, host, and pharmacological perspectives, this review provides a comprehensive framework for advancing precision-guided periodontal therapy and supports the shift toward targeted, sustainable, and personalized treatment strategies. Full article

(This article belongs to the Special Issue Strategies to Combat Antibiotic Resistance and Microbial Biofilms)

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42 pages, 2137 KB

Open AccessReview

Detection to Disruption: A Comprehensive Review of Bacterial Biofilms and Therapeutic Advances

by Pranay Amruth Maroju, Angad S. Sidhu, Amogh R. Motaganahalli, Robert E. Minto, Fatih Zor, Christine Kelley-Patteson, Rahim Rahimi, Aladdin H. Hassanein and Mithun Sinha

Antibiotics 2026, 15(4), 396; https://doi.org/10.3390/antibiotics15040396 - 13 Apr 2026

Viewed by 1446

Abstract

Bacterial biofilms are structured microbial communities enclosed within a self-produced extracellular polymeric substance matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This matrix promotes adhesion, structural stability, and the development of heterogeneous microenvironments that restrict antimicrobial penetration and shield bacteria from host [...] Read more.

Bacterial biofilms are structured microbial communities enclosed within a self-produced extracellular polymeric substance matrix composed of polysaccharides, proteins, extracellular DNA, and lipids. This matrix promotes adhesion, structural stability, and the development of heterogeneous microenvironments that restrict antimicrobial penetration and shield bacteria from host immune responses. As a result, biofilms are major contributors to chronic, recurrent, device-related, and difficult-to-treat infections, posing a major challenge for clinical management and antimicrobial stewardship. This review summarizes current understandings of biofilm biology, its clinical relevance, including the stages of biofilm development, the composition and protective roles of the matrix, and the physiological heterogeneity that arises during maturation. It also examines key mechanisms underlying biofilm tolerance and resistance, such as limited antibiotic diffusion, and sequestration, enzymatic inactivation, efflux pump upregulation, persister cell formation, and horizontal gene transfer. In addition, it highlights important clinical settings in which biofilms are implicated, including cystic fibrosis, chronic wounds, osteomyelitis, implant- or device-associated infections, and breast implant illness, in which persistent implant-associated biofilms and the resulting chronic inflammatory milieu have been hypothesized to contribute to local and systemic manifestations in a subset of patients. The review further discusses conventional and emerging approaches for biofilm detection alongwith real-time monitoring. Biofilm-associated infections remain difficult to eradicate because persistence is driven by multiple interconnected protective mechanisms. Effective management therefore requires integrated strategies that combine accurate detection with multifaceted therapies, including antibiotics alongside matrix-disrupting enzymes, quorum-sensing inhibitors, bacteriophages, metabolic reactivators, and nanotechnology-based delivery systems. Advances in multi-omics and system-level modeling will be essential for developing next-generation strategies to prevent, monitor, and treat biofilm-associated disease. Full article

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

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21 pages, 1442 KB

Open AccessArticle

Open-Label Prospective Randomized Comparative Study of the Efficacy and Safety of Gentamicin in Comparison to Other Antibiotics in the Management of Acute Appendicitis in Surgically Treated Patients

by Nika Obolnar, Žan Čebron, Gregor Norčič, Darko Černe, Aleš Jerin, Urška Čegovnik Primožič, Gaj Vidmar, Tadeja Pintar Kaliterna and Bojana Beović

Antibiotics 2026, 15(4), 395; https://doi.org/10.3390/antibiotics15040395 - 13 Apr 2026

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Abstract

Background: Antimicrobial resistance coupled with the lack of new antibiotics calls for the responsible use of antibiotics, including old antimicrobials. Aminoglycosides are effective against bacteria in acute appendicitis, a common intra-abdominal infection. Their use has been discouraged recently, but their place in therapy [...] Read more.

Background: Antimicrobial resistance coupled with the lack of new antibiotics calls for the responsible use of antibiotics, including old antimicrobials. Aminoglycosides are effective against bacteria in acute appendicitis, a common intra-abdominal infection. Their use has been discouraged recently, but their place in therapy is based on studies performed in the era of lower resistance rates, and with multiple dosing regimens. Methods: In a prospective randomized open-label study, we compared the efficacy and safety of gentamicin in one daily dose and metronidazole (GTM+MZ) to ertapenem (ETP) and to cefuroxime with metronidazole (CXM+MZ) in adult patients surgically treated for acute appendicitis. Efficacy was assessed via the duration of antibiotic treatment and hospital stay, c-reactive protein (CRP) dynamics, and post-operative complications. Nephrotoxicity was assessed with urine biomarkers. Statistical analysis comprised mixed-model analysis of variance (ANOVA) with the missing-data-imputation method and linear mixed model (LMM). Results: One hundred-and-sixty-six patients were included in this study. There were no significant differences among the three groups in the durations of treatment and lengths of stay (p = 0.093, p = 0.222). CRP level was the lowest (p = 0.003) in the ETP group. There were five complications during hospitalization, with two of them classified as infectious. Both occurred in the GTM+MZ group; however, the difference was not statistically significant (p = 0.330). No difference was found in complications in the month following the operation (p = 0.763). Biomarkers indicating kidney injury showed the same trend in all three groups. Conclusions: Our results suggest the use of once-daily dose of gentamicin following an appendectomy for acute appendicitis. Gentamicin may be used to decrease selective pressure of other antimicrobials. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Surgical Infection)

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11 pages, 243 KB

Open AccessArticle

Correlation Between Surgical Ward Stay and High Gentamicin Resistance of Enterococcus faecalis: A Retrospective Study

by Luiza Sannikova, Agnieszka Misiewska-Kaczur, Michał Dyaczyński, Bartosz Socha, Georgii Gogichev and Marcin Basiak

Antibiotics 2026, 15(4), 394; https://doi.org/10.3390/antibiotics15040394 - 13 Apr 2026

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Abstract

Background: The increasing antimicrobial resistance of Enterococcus faecalis, particularly high-level aminoglycoside resistance, represents a growing challenge in the management of hospital-acquired infections. Surgical wards are considered potential environments for the dissemination of resistant strains due to frequent antibiotic exposure and invasive procedures. [...] Read more.

Background: The increasing antimicrobial resistance of Enterococcus faecalis, particularly high-level aminoglycoside resistance, represents a growing challenge in the management of hospital-acquired infections. Surgical wards are considered potential environments for the dissemination of resistant strains due to frequent antibiotic exposure and invasive procedures. Methods: The aim of this study was to evaluate the association between hospitalization in a general surgery ward and the detection of Enterococcus faecalis isolates with high-level gentamicin resistance (HLGR). A retrospective observational study was conducted using microbiological and clinical data from a single medical center in Poland between 2022 and 2024. Only the first isolate per patient was included in the analysis. HLGR was detected using gentamicin at a screening concentration of 500 µg/mL. Associations between clinical variables and HLGR were assessed using univariate analysis and multivariable logistic regression, including hospitalization in a general surgery ward, age, prior hospitalization, and antibiotic therapy within 90 days. Results: HLGR was identified in a substantial proportion of Enterococcus faecalis isolates. Hospitalization in a general surgery ward was significantly associated with HLGR detection. In multivariable analysis, surgical ward hospitalization remained independently associated with HLGR after adjustment for other variables. Prior antibiotic exposure demonstrated the strongest association with HLGR. Conclusions: Hospitalization in a general surgery ward was associated with an increased likelihood of detecting Enterococcus faecalis isolates with high-level gentamicin resistance. These findings support the importance of antimicrobial stewardship and infection control strategies in surgical settings to limit the spread of resistant enterococcal strains. Full article

(This article belongs to the Special Issue Current Challenges in Antimicrobial Stewardship)

19 pages, 5186 KB

Open AccessArticle

Exploratory Insights on Epidemiology, Genomic Features and Pangenome Analysis of NDM-1-Positive Carbapenem-Resistant Acinetobacter baumannii Isolates from Costa Rica

by Jose Arturo Molina-Mora, Daniel Cascante-Serrano, Leana Quirós-Rojas, Gian Carlo González-Carballo, Xavier Araya, Elvira Segura-Retana, Heylin Estrada-Murillo, Stefany Lozada-Alvarado, Mariela Alvarado-Rodríguez, Javier Alfaro-Camacho and Fernando García-Santamaría

Antibiotics 2026, 15(4), 393; https://doi.org/10.3390/antibiotics15040393 - 12 Apr 2026

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Abstract

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical pathogen associated with severe hospital infections and high antimicrobial resistance. Despite the global significance of A. baumannii, there are limited data from Costa Rica regarding the resistance rate and genomic characteristics of CRAB. Methods [...] Read more.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical pathogen associated with severe hospital infections and high antimicrobial resistance. Despite the global significance of A. baumannii, there are limited data from Costa Rica regarding the resistance rate and genomic characteristics of CRAB. Methods: This study aimed to provide initial and exploratory epidemiological data on infections caused by A. baumannii and CRAB isolated in Costa Rica and to gain insights on the genome of selected strains, focusing on their resistance determinants and phylogenetic relationships. Results: Based on data from five main hospitals in Costa Rica, resistance rate to carbapenems was estimated at 9.8% to imipenem and 6.1% to meropenem. From 190 carbapenem-resistant clinical isolates available in a local collection, seven A. baumannii strains were identified, all showing resistance to carbapenems and carrying the bla_NDM-1 gene. Whole-genome sequencing of two strains yielded two distinct MLST profiles (Pasteur scheme: ST-150 for strain IPAT15 and ST-250 for IPAT72), as well as variations in the number and identity of plasmids, genomic islands, and other elements of the mobilome. Both isolates carried ten antimicrobial resistance genes, which are predicted to be harbored in plasmids for IPAT15, unlike the chromosomal determinants in IPAT72. A pangenome analysis of 878 genomes from a public database identified over 51,000 genes, with only 1338 (2.6%) forming the core genome. Phylogenetic analysis and assignation of international clones (ICs) showed predominance of IC2. Isolates from Costa Rica clustered near IC9 and shared some resistance determinants, but they were not directly assigned to an IC. Conclusions: Overall, this study provides exploratory insights regarding the occurrence of CRAB in Costa Rica using epidemiological and genomic data, with profiles that are comparable to other regions in Latin America and diverse genomic resistance determinants. While this study does not show the whole landscape of CRAB in Costa Rica, these data constitute an initial approach for improving clinical management and public health responses to CRAB infections, to ultimately improve outcomes for patients affected by this pathogen. Full article

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

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12 pages, 2734 KB

Open AccessArticle

Synergistic Effect of the Mucosa-Friendly Agents Berberine and Tea Tree Oil on Mucosal Protection Against Neisseria gonorrhoeae in an In Vitro T84 Cell Mucosa Model

by Mon-Der Cho, Shang-Yu Chou, Jung-Sheng Chen, Yu-Ming Hsu, Chi-Ying Li, Yi-Hong Tsai and Fang-Rong Chang

Antibiotics 2026, 15(4), 392; https://doi.org/10.3390/antibiotics15040392 - 12 Apr 2026

Viewed by 573

Abstract

Introduction: Neisseria gonorrhoeae, a bacterium responsible for gonorrhea, can spread through oral sex, causing pharyngeal gonorrhea, which is also a leading cause of urethritis in outpatient clinics. This study investigated whether tea tree oil (TTO) alone or in combination with other [...] Read more.

Introduction: Neisseria gonorrhoeae, a bacterium responsible for gonorrhea, can spread through oral sex, causing pharyngeal gonorrhea, which is also a leading cause of urethritis in outpatient clinics. This study investigated whether tea tree oil (TTO) alone or in combination with other natural products could serve as an effective alternative to chlorhexidine in preventing the spread of oral gonorrhea. Methods: An in vitro model was developed using T84 epithelial cells as a mucosal layer and Neisseria gonorrhoeae strain MS11. The study assessed the minimal inhibitory concentration (MIC), bacterial adherence, invasion, and transmigration across the mucosal barrier. Berberine (BB), a major and bioactive alkaloid derived from Coptis chinensis, was tested with and without TTO in MIC assays and epithelial cell viability tests. Ceftriaxone was used as a positive control. Results: The MIC values for TTO, BB, and ceftriaxone against the MS11 strain were determined to be 0.2%, 5 μg/mL, and 0.0125 μg/mL, respectively. Notably, the combination of TTO with BB demonstrated a synergistic effect, reducing the MIC to 0.000625% TTO + 1.25 μg/mL BB. This combination provided the strongest protective effect. No cytotoxicity was observed in the epithelial cell viability tests for 0.2% diluted TTO, 5 μg/mL BB, or the combination of 0.000625% TTO + 1.25 μg/mL BB. Conclusions: BB, when combined with TTO, exhibited a synergistic antimicrobial effect against Neisseria gonorrhoeae strain MS11 in the T84 mucosal model. These findings highlight the potential of this combination as a natural alternative to chlorhexidine gluconate for managing oral gonorrhea. Full article

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Antibiotics, Volume 15, Issue 4 (April 2026) – 97 articles

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