Antibiotics

23 pages, 309 KB

Open AccessArticle

Knowledge, Attitudes and Practices Related to Antimicrobial Use and Resistance Among Livestock Sector Stakeholders in Seven Former Soviet Countries: A Multi-Country Regional Analysis

by Dora Kovacs, Eran Raizman, Anne Deckert, Chichak Aliyeva, Dragan Angelovski, Zaruhi Beglaryan, Duriya Charypkhan, Natalia Ciria, Tolibjon Khakimov, Maripa Kichinebatyrova, Elvira Maratova, Tamas Nagy, Anna Sargsyan, Oksana Yurchenko and Daniel Beltran-Alcrudo

Antibiotics 2026, 15(4), 384; https://doi.org/10.3390/antibiotics15040384 (registering DOI) - 9 Apr 2026

Abstract

Background/Objectives: Antimicrobial resistance (AMR) is one of the greatest health threats affecting humans, animals and the environment. Antimicrobial use (AMU) in the livestock sector contributes to the development and spread of AMR, highlighting the need to understand the current situation, to target knowledge [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) is one of the greatest health threats affecting humans, animals and the environment. Antimicrobial use (AMU) in the livestock sector contributes to the development and spread of AMR, highlighting the need to understand the current situation, to target knowledge gaps and non-prudent practices with tailored interventions, and improve antimicrobial stewardship. This is especially important in low- and middle-income countries (LMICs), where data on AMU and AMR are currently limited. This study assessed knowledge, attitudes and practices (KAP) among farmers, veterinarians, veterinary pharmacy personnel and feed mill personnel related to AMU (particularly considering the use of antibiotics) and AMR in seven former Soviet countries, Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Tajikistan and Ukraine. Methods: Face-to-face interviews were conducted between 2020 and 2025 with 3012 participants, with results analyzed using an aggregated regional approach. Results: The interviews revealed common regional knowledge gaps and practices among livestock sector stakeholders related to antimicrobials, AMR, antimicrobial residues, and prudent AMU. Non-prudent practices, such as the purchase of antimicrobials without a prescription, the use of antimicrobials as growth promoters, the inappropriate disposal of antimicrobials, and the frequent use of highest priority critically important antimicrobials (HPCIAs) were reported. Another factor that may hinder prudent AMU was the limited access of veterinarians to diagnostic laboratories. Conclusions: Despite significant global efforts to tackle AMR, there is an ongoing need to address knowledge gaps and non-prudent practices of livestock sector stakeholders in former Soviet countries. The findings highlight the importance of antimicrobial stewardship interventions that address system-level drivers of improper AMU beyond stakeholder trainings. Full article

26 pages, 1016 KB

Open AccessReview

Burn Infections and Sepsis: Challenges and Future Prospects of Antibacterial Therapy

by Ghazaleh Dadashizadeh, Margarita Elloso and Marc G. Jeschke

Antibiotics 2026, 15(4), 383; https://doi.org/10.3390/antibiotics15040383 (registering DOI) - 9 Apr 2026

Abstract

Infectious complications remain a principal determinant of late morbidity and mortality following major thermal injury, reflecting a convergence of barrier disruption, microbial adaptation, and host immune dysfunction. The post-burn environment creates a uniquely permissive niche for pathogen persistence, characterized by altered tissue perfusion, [...] Read more.

Infectious complications remain a principal determinant of late morbidity and mortality following major thermal injury, reflecting a convergence of barrier disruption, microbial adaptation, and host immune dysfunction. The post-burn environment creates a uniquely permissive niche for pathogen persistence, characterized by altered tissue perfusion, biofilm formation, and dynamic shifts in microbial ecology toward multidrug-resistant organisms. Concurrently, profound and evolving changes in host immunity and metabolism reshape both susceptibility to infection and response to therapy. This review integrates current evidence across pathophysiology, microbiology, diagnostics, and treatment, with a focus on challenges that limit effective infection control in burn patients. Particular attention is given to diagnostic uncertainty arising from overlap between sterile inflammation and true infection, the clinical implications of biofilm-associated tolerance, and the impact of burn-specific pharmacokinetic variability on antimicrobial efficacy. We further examine emerging diagnostic and therapeutic innovations, including host-response profiling, rapid molecular detection platforms, and next-generation anti-infective strategies targeting microbial virulence, biofilm structure, and host immune pathways. Despite substantial scientific advances, translation into clinical practice remains constrained by limited burn-specific trials, heterogeneous definitions, and systemic barriers to antimicrobial development. Collectively, these challenges underscore the need for integrated, precision-based approaches that combine early source control, individualized antimicrobial optimization, and advanced diagnostic frameworks. Future progress will depend on coordinated efforts to standardize definitions, generate high-quality multicenter data, and align innovation with clinical applicability across diverse healthcare settings. Full article

(This article belongs to the Topic Challenges and Future Prospects of Antibacterial Therapy, 2nd Edition)

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11 pages, 234 KB

Open AccessArticle

Clinical Characteristics, Infection Profiles, and Hospital Outcomes of Intensive Care Unit Patients Undergoing Antimicrobial Therapy with Ceftolozane/Tazobactam: A Multicentric Retrospective Analysis

by Pedro Kurtz, Pedro F. Del Peloso, Arthur M. Albuquerque, Bianca B. P. Antunes, Grazielle V. Ramos and Fernando A. Bozza

Antibiotics 2026, 15(4), 382; https://doi.org/10.3390/antibiotics15040382 (registering DOI) - 9 Apr 2026

Abstract

Introduction: Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor with potent activity against multidrug-resistant Gram-negative pathogens, notably Pseudomonas aeruginosa. Its use is vital in the management of severe infections in ICU patients, especially where resistance limits first-line antibiotic options. This study aimed to describe [...] Read more.

Introduction: Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor with potent activity against multidrug-resistant Gram-negative pathogens, notably Pseudomonas aeruginosa. Its use is vital in the management of severe infections in ICU patients, especially where resistance limits first-line antibiotic options. This study aimed to describe the clinical characteristics, infection profiles, antimicrobial therapies, and hospital outcomes of ICU patients in Brazil who were treated with ceftolozane/tazobactam. Methods: A multicenter retrospective analysis was conducted on ICU patients treated with ceftolozane/tazobactam across twelve private hospitals in Brazil admitted between July 2018 and February 2023. Data were extracted from electronic medical records, including demographics, comorbidities, infection characteristics, antimicrobial usage, and hospital outcomes. Additionally, microbiological data and treatment details were evaluated. Descriptive statistics were used for analysis. Results: The study included 104 patients, with a median age of 78 years (IQR 61, 87) and 43% of whom were female. Pneumonia (57%) and urinary tract infections (19%) were the primary indications for treatment. Mechanical ventilation was required in 62 patients (60%). Pathogens were isolated in 44 cases, with ESBL-producing Gram-negative bacteria (34%) and carbapenem-resistant strains (18%) being the most common. Empirical therapy was initiated in 57% of cases, with a median treatment duration of 10 days. Concomitant antibiotics were used in 64% of patients. Mechanically ventilated patients exhibited higher mortality (66% vs. 29%) and prolonged ICU stays (57 vs. 20 days) as compared to non-ventilated patients. Conclusions: Ceftolozane/tazobactam demonstrates efficacy and safety in managing multidrug-resistant Gram-negative infections in ICU settings. However, its empirical use, driven by high resistance rates, underscores the importance of microbiology-guided therapy. The observed high mortality and prolonged ICU stay highlight the critical need for optimized infection management strategies and continued antimicrobial stewardship in critically ill populations. Full article

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

18 pages, 2621 KB

Open AccessArticle

Genetic and Phenotypic Characterization of a Salmonella Enteritidis ST11 Clinical Isolate Carrying bla_NDM-13 in Jiaxing City, China

by Ping Li, Weiming Yang, Zhongwen Chen, Henghui Wang, Miaomiao Jia, Xuejuan Liu, Yong Yan and Guoying Zhu

Antibiotics 2026, 15(4), 381; https://doi.org/10.3390/antibiotics15040381 - 9 Apr 2026

Abstract

Background/Objectives: Multidrug-resistant Salmonella enterica serovar Enteritidis, especially those isolated from humans, remains a public concern. In the present study, S. Enteritidis strain 31404 was obtained clinically from a fecal sample of a fifteen-year-old girl, who was positive for bla_NDM-13. [...] Read more.

Background/Objectives: Multidrug-resistant Salmonella enterica serovar Enteritidis, especially those isolated from humans, remains a public concern. In the present study, S. Enteritidis strain 31404 was obtained clinically from a fecal sample of a fifteen-year-old girl, who was positive for bla_NDM-13. Methods: Antibiotic susceptibility testing and whole genome sequencing were performed. Core genome MLST and hierarchical clustering (HierCC) were performed using EnteroBase. Population structure analysis of 57 S. Enteritidis isolates collected between 2023 and 2025 in Jiaxing city was conducted. A comparative structure analysis of bla_NDM-13-positive plasmids was also performed. Results: S. Enteritidis strain 31404 was resistant to 13 antimicrobial agents. We found that strain 31404 belonged to ST11 and carried resistance genes, such as bla_NDM-13, bla_CTX-M-14, ble_MBL, fosA3, qnrS, and tet (A). bla_NDM-13 was located on an IncI1-I (α) plasmid designated as p31404-NDM13. S. Enteritidis isolate 31404 was closely related to PNUSAS514422, which was isolated from the United States in 2025. Comparative genetic environment related to bla_NDM-13-positive plasmids available in the NCBI database indicates that ΔTn125-mediated contexts were commonly associated with bla_NDM-13. IS1294 (IS91 family), which replaces ISAba125, is likely to mobilize bla_NDM-13. Conclusions: The findings in this study provide insights into the molecular characterization and diversification of bla_NDM-13. The identification of bla_NDM-13-containing transferable plasmids in different serotypes of Salmonella isolates (such as S. Rissen, S. Typhimurium, and S. Enteritidis) in different cities in China highlights the risk of the spread of carbapenem-resistant genes among Salmonella isolates. Full article

(This article belongs to the Special Issue Antibiotic Resistance Genes: Mechanisms, Evolution and Dissemination)

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13 pages, 647 KB

Open AccessArticle

Impact of Susceptibility Testing Methodology on the Positioning of Cefiderocol and Aztreonam-Avibactam Against Metallo-β-Lactamase-Producing Gram-Negative Bacteria

by Fernando del Nogal-Labrador, Beatriz González-Blanco, María Isabel Sanz, Raúl Recio, Patricia Brañas, Irene Muñoz-Gallego, Esther Viedma and Jennifer Villa

Antibiotics 2026, 15(4), 380; https://doi.org/10.3390/antibiotics15040380 - 9 Apr 2026

Abstract

Background/Objectives: The impact of antimicrobial susceptibility testing methodology on the categorization and positioning of cefiderocol and aztreonam-avibactam against metallo-β-lactamase (MBL)-producing Gram-negative bacilli remains unclear. This study aimed to evaluate the in vitro activity of cefiderocol and aztreonam-avibactam against clinical MBL-producing isolates and to [...] Read more.

Background/Objectives: The impact of antimicrobial susceptibility testing methodology on the categorization and positioning of cefiderocol and aztreonam-avibactam against metallo-β-lactamase (MBL)-producing Gram-negative bacilli remains unclear. This study aimed to evaluate the in vitro activity of cefiderocol and aztreonam-avibactam against clinical MBL-producing isolates and to assess the agreement between different cefiderocol susceptibility testing methods. Methods: A total of 299 non-duplicate clinical MBL-producing Gram-negative isolates were collected from clinical samples between 2022 and 2025. Antimicrobial susceptibility testing was performed using broth microdilution, disc diffusion, and gradient strip diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Carbapenemase genes were identified by immunochromatography and multiplex PCR. Categorical agreement and error rates between cefiderocol testing methods were analyzed. Results:Klebsiella pneumoniae was the predominant species, mainly producing NDM alone or in combination with OXA-48-like carbapenemases. Aztreonam-avibactam demonstrated complete activity against all Enterobacterales isolates (262/262, 100%) and high activity against Pseudomonas spp. (33/37, 89%). Cefiderocol susceptibility among Enterobacterales varied markedly depending on the testing method. Disc diffusion yielded 14% susceptibility (37/262), which increased to 52% (136/262) after ATU resolution, whereas broth microdilution showed 85% susceptibility (224/262). This resulted in low categorical agreement (42%) and a high rate of major errors (58%), with no very major errors detected. Cefiderocol activity did not differ substantially across carbapenemase types and was highest against VIM-producing Pseudomonas spp. Conclusions: Aztreonam-avibactam showed consistent in vitro activity against MBL-producing Enterobacterales, whereas cefiderocol activity was strongly influenced by the susceptibility testing methodology. Disc diffusion substantially underestimated cefiderocol susceptibility compared with broth microdilution. These findings highlight the critical impact of testing methodology on cefiderocol categorization and support the therapeutic role of last-line agents in the management of MBL-producing Gram-negative infections, with direct implications for clinical microbiology laboratories and antimicrobial stewardship programs. Full article

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

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20 pages, 2475 KB

Open AccessArticle

Occurrence and Characterization of Antimicrobial-Resistant and Virulent Enterococcus spp. in Dog Feces from Urban Green Spaces in Porto (Portugal)

by Jessica Ribeiro, Rui Lameiras, Vanessa Silva, Gilberto Igrejas, Francisco Cortez Nunes, Ana Isabel Ribeiro, Teresa Letra Mateus and Patrícia Poeta

Antibiotics 2026, 15(4), 379; https://doi.org/10.3390/antibiotics15040379 - 8 Apr 2026

Abstract

Background/Objectives: Enterococcus spp. are important indicators of AMR and potential opportunistic pathogens. Urban green spaces, frequented by dogs and humans, may serve as reservoirs for resistant bacteria. This study assessed the occurrence, AMR profiles, and virulence traits of Enterococcus spp. in dog [...] Read more.

Background/Objectives: Enterococcus spp. are important indicators of AMR and potential opportunistic pathogens. Urban green spaces, frequented by dogs and humans, may serve as reservoirs for resistant bacteria. This study assessed the occurrence, AMR profiles, and virulence traits of Enterococcus spp. in dog feces from urban green spaces in Porto (Portugal). Methods: In December 2023 and May 2024, 240 dog fecal samples were collected from 12 urban green spaces across Porto. Enterococcus spp. were isolated using selective culture, identified to species level, and tested for antimicrobial susceptibility following CLSI guidelines. PCR screening was performed for resistance genes (vanA, vanB, erm(A/B/C), vatD/E, tet(M/O/L/K)) and virulence genes (gelE, ace). Environmental and socioeconomic features, including vegetation density (NDVI), presence of water features, and neighborhood deprivation (EDI), were recorded to explore associations with bacterial occurrence and traits. Results: Thirty-two isolates were recovered, mainly E. faecium (n = 9) and E. faecalis (n = 7). High resistance rates were observed to tetracycline (56.3%) and quinupristin/dalfopristin (37.5%), with lower rates for vancomycin, teicoplanin, and ciprofloxacin (3.1%), and imipenem (6.3%). Tet(M) was the most prevalent resistance gene (40.6%), and gelE and ace were frequently detected, often co-occurring with resistance determinants. Distribution of resistance and virulence genes varied across green spaces, with widely used parks showing more isolates. Vegetation density and water features were not directly associated with bacterial recovery. Conclusions: Dog feces in urban green spaces contribute to localized AMR hotspots, acting as potential reservoirs of resistant and potentially pathogenic Enterococcus spp. These findings highlight the importance of One Health strategies for urban sanitation and AMR surveillance. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and One Health: Environmental Health, Food Safety, and Practice of Health Professionals)

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18 pages, 558 KB

Open AccessArticle

Effects of Prebiotic Gum Arabic Under Antibiotic-Containing Conditions in Atopic Dermatitis-Associated Bacteria: In Vitro Evaluation and Development of Semisolid Topical Carriers

by Derya Doğanay, Esra Mertoğlu, Ahmet Arif Kurt, Batuhan Cenk Özkan, Ertuğrul Osman Bursalıoğlu, Mustafa Eray Bozyel, Reyhan Aliusta, Özlem Türkoğlu, Halise Betül Gökçe, Emine Kızılay, Fatih Hacımustafaoğlu, Şaban Kalay, Rana Hamdemir, Ismail Bayır and Ismail Aslan

Antibiotics 2026, 15(4), 378; https://doi.org/10.3390/antibiotics15040378 - 8 Apr 2026

Abstract

Background/Objectives: Atopic dermatitis (AD) is associated with gut dysbiosis linked to early-life antibiotic use and Staphylococcus aureus colonization. Gum Arabic (GA), a prebiotic, may modulate this dysbiosis and influence AD-related microbial balance. This study evaluated whether GA could support AD-associated probiotics-Lactobacillus [...] Read more.

Background/Objectives: Atopic dermatitis (AD) is associated with gut dysbiosis linked to early-life antibiotic use and Staphylococcus aureus colonization. Gum Arabic (GA), a prebiotic, may modulate this dysbiosis and influence AD-related microbial balance. This study evaluated whether GA could support AD-associated probiotics-Lactobacillus casei, Bifidobacterium bifidum, and Bifidobacterium infantis-under amoxicillin- or azithromycin-containing conditions, examined the response of S. aureus under the same screening conditions, and developed GA-phospholipid-based semisolid carriers for topical application. Methods: Probiotic strains were cultured with 1–5% GA in the presence and absence of antibiotics, and viable cell counts were assessed. Sixteen topical formulations containing propylene glycol or isopropyl myristate in a hydrogenated phosphatidylcholine base were prepared and screened for rheological properties and galactose release using in vitro release testing (IVRT) and HPLC-UV. Results: GA at 1–2% concentrations promoted probiotic growth in antibiotic-free conditions. GA preserved B. infantis viability under azithromycin exposure in this in vitro screening model. For S. aureus, numerical CFU differences were observed between antibiotic-only and GA-containing conditions; however, the present screening design was not intended to determine antibiotic interaction outcomes. Formulations F14 (2% GA + 7% IPM) and F15 (3% GA + 7% IPM) exhibited optimal spreadability. IVRT showed that 6 h cumulative galactose release varied by formulation (F6 > F10 > F14 > F15). Conclusions: GA demonstrated dose-dependent prebiotic activity and preserved B. infantis viability under azithromycin exposure in this in vitro screening model. For S. aureus, the observed CFU differences between antibiotic-only and GA-containing conditions should be considered exploratory only and do not allow for conclusions regarding interference with antibiotic efficacy. Optimized GA-HPC systems with suitable rheological and release characteristics represent promising candidates for further preclinical investigation. Full article

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

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19 pages, 5567 KB

Open AccessArticle

Antibacterial Mechanism of Allicin E Against Aeromonas hydrophila and Therapeutic Effect in Carassius auratus gibelio

by Jinlong Li, Liushen Lu, Kai Chen, Ting Qin, Jun Xie, Ping Fang and Bingwen Xi

Antibiotics 2026, 15(4), 377; https://doi.org/10.3390/antibiotics15040377 - 8 Apr 2026

Abstract

Background/Objectives: The frequent use of antibiotics has led to increasing drug resistance in Aeromonas hydrophila; therefore, there is an urgent need to develop novel antimicrobial agents to prevent and control bacterial diseases in aquaculture. Allicin E (ALE) is derived from garlic [...] Read more.

Background/Objectives: The frequent use of antibiotics has led to increasing drug resistance in Aeromonas hydrophila; therefore, there is an urgent need to develop novel antimicrobial agents to prevent and control bacterial diseases in aquaculture. Allicin E (ALE) is derived from garlic (Allium sativum L.), a plant extensively used in traditional medicine for treating infections. This study aimed to evaluate the potential of ALE against A. hydrophila, a major aquaculture pathogen, by investigating its antibacterial efficacy, mechanisms of action, and in vivo protective effects. Methods: The minimum inhibitory and bactericidal concentrations (MIC/MBC) were determined by broth microdilution. Antibacterial mechanisms were investigated through ROS detection, electron microscopy, fluorescent staining, and content leakage measurement. In vivo efficacy was evaluated in Carassius auratus gibelio by monitoring survival rates and bacterial loads, analyzing immune and antioxidant biomarkers, and histopathological analysis after A. hydrophila challenge. Results: ALE exhibited potent antibacterial activity (MIC = MBC = 8 μg/mL), achieving complete bacterial elimination within 1 h and showing a low resistance propensity. Mechanistically, ALE induced ROS accumulation, causing oxidative damage that disrupted membrane integrity and facilitated the leakage of cellular contents. In vivo, ALE significantly enhanced fish survival, reduced bacterial loads, modulated inflammatory cytokines, boosted antioxidant enzyme activities (SOD and CAT), and alleviated tissue damage. Conclusions: ALE possesses potent in vitro antibacterial activity and exerts an inhibitory effect on bacteria-induced inflammatory responses, effectively combating A. hydrophila through a multi-target mechanism and enhancing host resistance. Full article

(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents, 3rd Edition)

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20 pages, 798 KB

Open AccessArticle

Knowledge, Attitudes, and Antibiotic Prescribing Practices Among Physicians in Two High-Demand Healthcare Settings in Saudi Arabia

by Nahla H. Hariri, Hanin Mohammed Alsaedi, Bayan Fawaz Alzahrani, Thekra Abdulhafith Alwafi, Khalid Abdulrahman Basamih, Donia Jamaan Alghamdi, Hadeel Abdullah Alolowi, Hanin Mahmoud Qadah, Maryam Abdulrahim Jadw, Safaa M. Alsanosi, Maram H. Alshareef, Mohammed A. Garout, Nizar S. Bawahab, Saleh A. K. Saleh and Heba M. Adly

Antibiotics 2026, 15(4), 376; https://doi.org/10.3390/antibiotics15040376 - 7 Apr 2026

Abstract

Background: Antimicrobial resistance continues to threaten effective infection management worldwide and is driven largely by inappropriate prescribing practices. In Saudi Arabia, the cities of Makkah and Al-Madinah experience intense seasonal healthcare demand due to the annual pilgrimage, creating additional challenges for rational antibiotic [...] Read more.

Background: Antimicrobial resistance continues to threaten effective infection management worldwide and is driven largely by inappropriate prescribing practices. In Saudi Arabia, the cities of Makkah and Al-Madinah experience intense seasonal healthcare demand due to the annual pilgrimage, creating additional challenges for rational antibiotic use. This study aimed to evaluate physicians’ knowledge, attitudes, and prescribing behaviors related to antibiotics in these high-demand settings. Methods: A cross-sectional analytic study was conducted between June and August 2024 among physicians practicing in Makkah and Al-Madinah, including those participating in Hajj services. A previously validated, structured electronic questionnaire assessed knowledge of common pathogens, perceptions of antimicrobial resistance, prescribing influences, and counseling practices. The survey was distributed electronically to eligible physicians. Descriptive statistics were generated, and associations were examined using appropriate inferential tests with a 95% confidence level. Results: A total of 487 physicians participated. Most respondents (74%) correctly identified major bacterial causes of upper respiratory tract infections, and 90% acknowledged the association between prior antibiotic exposure and resistance. Nonetheless, misconceptions persisted regarding the benefit of antibiotics in viral conditions. Workload and patient expectations influenced prescribing behavior; 77% reported a greater likelihood of prescribing antibiotics during periods of high clinical pressure. While adherence to guideline-based practice was generally reported, variability existed in counseling practices and perceptions of stewardship policies. Conclusions: Although baseline knowledge was satisfactory, contextual and behavioral factors continue to influence prescribing decisions and may contribute to unnecessary antibiotic exposure, highlighting the need for strengthened antimicrobial stewardship strategies in high-demand healthcare environments. Full article

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10 pages, 458 KB

Open AccessArticle

In Vitro Antimicrobial Activity of Ceftobiprole and Comparator Agents Against Streptococcus pneumoniae Responsible for Lower Respiratory Tract Infections in the United States (2016–2020), Including Resistant Subsets and Select Serotypes

by Helio S. Sader, Mariana Castanheira, Mark E. Jones and Rodrigo E. Mendes

Antibiotics 2026, 15(4), 375; https://doi.org/10.3390/antibiotics15040375 - 7 Apr 2026

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Abstract

Background: Ceftobiprole is an advanced-generation cephalosporin approved in Europe in 2013 for various indications, and in the United States (US) in 2024 for community-acquired bacterial pneumonia (CABP), acute bacterial skin and skin structure infections, and Staphylococcus aureus bacteremia, including right-sided endocarditis. Methods [...] Read more.

Background: Ceftobiprole is an advanced-generation cephalosporin approved in Europe in 2013 for various indications, and in the United States (US) in 2024 for community-acquired bacterial pneumonia (CABP), acute bacterial skin and skin structure infections, and Staphylococcus aureus bacteremia, including right-sided endocarditis. Methods: The in vitro activity of ceftobiprole and comparators was evaluated against 2793 Streptococcus pneumoniae causing lower respiratory tract infections in 32 US sites (2016–2020), including against subsets from various geographic regions, resistance phenotypes and prevalent serotypes. Results: Ceftobiprole inhibited 99.5% of all S. pneumoniae at the MIC of ≤0.5 mg/L (MIC_50/90, 0.015/0.25 mg/L). Susceptibilities of 98.2% to 100% were observed for ceftobiprole against isolates originating from each surveyed year or each US Census Division. Ceftobiprole retained activity against isolates resistant to macrolides (98.8%), tetracycline (98.2%), oral penicillin (95.4%), against multidrug-resistant isolates (97.0%), and various serotypes (93.8–100%). Ceftriaxone (97.4%) and amoxicillin–clavulanate (95.1%) also showed elevated susceptibilities overall, but inconsistent results and lower than those observed for ceftobiprole were noted against isolates with elevated penicillin MIC or specific serotypes (i.e., 19A). Conclusions: These in vitro results, coupled with documented clinical efficacy, indicate that ceftobiprole is a valuable option to treat CABP caused by S. pneumoniae in the US. Full article

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

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40 pages, 19255 KB

Open AccessArticle

Integrated Phytochemical Profiling and Bioactivity Evaluation of Micromeria nervosa, with Emphasis on Antimicrobial and Antiviral Properties

by Ljuboš Ušjak, Krystyna Skalicka-Woźniak, Łukasz Kulinowski, Łukasz Świątek, Violeta Milutinović, Kinga Salwa, Anastazja Boguszewska, Izabela Korona-Glowniak, Katarzyna Suśniak, Marjan Niketić, Jelena Kukić Marković and Silvana Petrović

Antibiotics 2026, 15(4), 374; https://doi.org/10.3390/antibiotics15040374 - 6 Apr 2026

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Abstract

Background/Objectives: Lamiaceae species are valuable sources of bioactive natural products, often associated with anti-infective properties. This study investigated chemical composition and bioactivities of dry hydroethanolic extracts and essential oils from Micromeria nervosa (Desf.) Benth. aerial parts from two localities. Methods: Extracts [...] Read more.

Background/Objectives: Lamiaceae species are valuable sources of bioactive natural products, often associated with anti-infective properties. This study investigated chemical composition and bioactivities of dry hydroethanolic extracts and essential oils from Micromeria nervosa (Desf.) Benth. aerial parts from two localities. Methods: Extracts and essential oils were analyzed using LC-DAD-QTOF-MS/MS and GC-FID/MS, respectively. Antimicrobial activity was assessed against 14 strains (microdilution method), and antiviral activity against three viruses by determining cytopathic effects, viral titers (end-point dilution assay) and viral loads (qPCR/RT-qPCR). Cytotoxicity was evaluated on three cancer cell lines (MTT assay) and antioxidant potential using three colorimetric tests. Composition–activity correlation was statistically analyzed; in silico molecular docking/dynamics simulations were performed. Results: Thirty-five compounds were annotated in extracts, including 30 reported for the first time in this species, with rosmarinic acid as the main component. Essential oils contained 31 constituents, dominated by carvacrol. Newly detected phenolics included lithospermic acid and several salvianolic and clinopodic acids. Extracts and oils exhibited notable antibacterial activity, especially against five Gram-positive strains (MIC = 0.313–2.5 mg/mL), and oils showed marked anticandidal effects (MIC = 0.313–0.625 mg/mL) and enhanced cytotoxicity against colon, gastric and hypopharyngeal cancer cells (selectivity indices ≥ 1.66). Extracts displayed potent antiviral activity against human herpesvirus 1 (HHV-1) and adenovirus Ad5, reducing cytopathic effects and viral titers, with qPCR revealing decreased HHV-1 load. In silico analysis suggested HHV-1 glycoprotein D binding. Extracts also showed strong antioxidant potential. Conclusions: These findings demonstrate that M. nervosa is a rich source of compounds with antimicrobial/antiviral, cytotoxic and antioxidant activities, warranting further research. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Different Plant Extracts, Plant-Derived Compounds and Synthetic Derivatives of Natural Compounds on Pathogenic Microorganisms, 3rd Edition)

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24 pages, 3482 KB

Open AccessArticle

Antibiotic-Loaded PLA Composites for Local Prevention of Implant-Associated Infections: Comparative Evaluation Against Reference Strains and Clinical Isolates

by Anastassiya Khrustaleva, Azamat Yedrissov, Dmitriy Khrustalev, Irina Losseva, Alyona Lavrinenko, Artyom Savelyev, Vladimir Kazantsev, Marlen Kiikbayev, Polina Rusyaeva, Kristina Perepelitsyna and Aigerim Donenbaeva

Antibiotics 2026, 15(4), 373; https://doi.org/10.3390/antibiotics15040373 - 6 Apr 2026

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Abstract

Background/Objectives: Implant-associated infections remain among the most severe and clinically challenging complications in contemporary orthopedics, largely due to the formation of persistent bacterial biofilms and the limited penetration of systemically administered antibiotics into the tissue–implant interface. In this context, local antibacterial functionalization [...] Read more.

Background/Objectives: Implant-associated infections remain among the most severe and clinically challenging complications in contemporary orthopedics, largely due to the formation of persistent bacterial biofilms and the limited penetration of systemically administered antibiotics into the tissue–implant interface. In this context, local antibacterial functionalization of implantable materials represents a promising strategy for the prevention of early infectious complications. The objective of this study was to develop and comparatively evaluate the antimicrobial performance of PLA-based composites loaded with antibiotics from different pharmacological classes, with a view toward their potential application in individualized 3D-printed implants. Methods: Polylactic acid (PLA)-based composites incorporating gentamicin, ciprofloxacin, doxycycline, and vancomycin were fabricated using thermal processing under conditions compatible with extrusion and fused filament fabrication. Physicochemical characterization (FTIR, TGA, SEM) was performed to assess the structure and morphology of the composites, and in vitro antibiotic release studies were conducted. Antimicrobial activity was evaluated using an agar diffusion assay against ATCC reference strains and clinical isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa (n = 10 per species). The antibacterial performance of the composites was evaluated in comparison with standard commercial antibiotic disks used as qualitative reference controls. Results: Antibiotic-loaded PLA composites exhibited consistent and reproducible antibacterial activity, markedly exceeding that of neat PLA. The broadest activity spectrum was observed for PLA–ciprofloxacin (≈29–36 mm) and PLA–gentamicin (≈25–27 mm), which effectively inhibited both Gram-positive and Gram-negative clinical isolates, including MRSA and P. aeruginosa. PLA–vancomycin retained selective activity against staphylococci (≈14–15 mm), whereas PLA–doxycycline demonstrated limited efficacy against Gram-negative pathogens. Physicochemical analysis confirmed successful incorporation of antibiotics without detectable degradation of the polymer structure, while release studies demonstrated sustained antibiotic release from the composite materials. Importantly, the expected pharmacological activity profiles of the antibiotics were preserved after incorporation into the polymer matrix and subsequent high-temperature processing. Conclusions: The results demonstrate the feasibility of integrating clinically relevant antibiotics into a thermoplastic PLA matrix while preserving their selective antimicrobial activity following processing compatible with extrusion and additive manufacturing. The proposed PLA-based composites can be regarded as elements of a pharmacologically tunable antibacterial platform, offering a rationale for the development of context-dependent, biodegradable, 3D-printed implants for the local prevention of implant-associated infections in the setting of increasing antimicrobial resistance. Full article

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10 pages, 221 KB

Open AccessPerspective

Epidemiologic and Clinical Divergence of MRSA USA100 and USA300 in the United States

by Camille André and Michael S. Gilmore

Antibiotics 2026, 15(4), 372; https://doi.org/10.3390/antibiotics15040372 - 4 Apr 2026

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Abstract

Methicillin-resistant S. aureus (MRSA) is listed by the World Health Organization as a priority pathogen posing a major worldwide threat to public health. Two lineages of MRSA predominate as causes of human infections in the U.S.: USA300 and USA100. Although they are most [...] Read more.

Methicillin-resistant S. aureus (MRSA) is listed by the World Health Organization as a priority pathogen posing a major worldwide threat to public health. Two lineages of MRSA predominate as causes of human infections in the U.S.: USA300 and USA100. Although they are most often grouped together as MRSA, these two lineages differ in pathogenetic mechanisms in important ways. The epidemic spread of these two dominant lineages has been problematic because of the multidrug-resistant profile of USA100 and the virulence of USA300, as well as their ability to adapt to both community and hospital environments. In this perspective, we examine what is currently known about their distinctive biology and the consequent differences in infections caused by these two main MRSA epidemic clones. The purpose of this perspective is to provide critical insights to the clinical microbiology community to stimulate further research to inform the design of new prevention and management strategies for MRSA. Full article

(This article belongs to the Special Issue New Insights Toward the Development of Novel Inhibitors of S. aureus and P. aeruginosa Factors)

14 pages, 874 KB

Open AccessCommunication

Screening of 44 Baltic Sea Cyanobacterial Strains for Antibacterial and Quorum Sensing Inhibitory Potential: Selection of Promising Candidates

by Anna Toruńska-Sitarz, Robert Konkel, Agnieszka Ogrodnicka, Hanna Mazur-Marzec, Magdalena Socha and Donata Overlingė

Antibiotics 2026, 15(4), 371; https://doi.org/10.3390/antibiotics15040371 - 3 Apr 2026

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Abstract

Background/Objectives: Cyanobacteria represent a diverse group of microorganisms capable of synthesizing a broad array of biologically active metabolites. Some of these compounds, believed to contribute to the ecological and evolutionary success of cyanobacteria, are increasingly being investigated for potential biomedical and biotechnological applications. [...] Read more.

Background/Objectives: Cyanobacteria represent a diverse group of microorganisms capable of synthesizing a broad array of biologically active metabolites. Some of these compounds, believed to contribute to the ecological and evolutionary success of cyanobacteria, are increasingly being investigated for potential biomedical and biotechnological applications. They also hold promise in combating the growing threat of antimicrobial resistance (AMR). This screening study aimed to identify Baltic cyanobacterial strains with the potential to produce antibacterial compounds active against streptococci and mycobacteria, as well as quorum sensing inhibitors. Methods/Results: Extracts from forty-four cyanobacterial strains were tested using a broth microdilution assay. The most pronounced activity was observed for extracts derived from two Pseudanabaenaceae strains (KUCC C3 and C4), two Anabaena spp. strains (CCNP 1405 and CCNP 1406), and Aphanizomenon sp. KUCC C1. Inhibition of quorum sensing was the most frequently detected activity, with 30% of the tested extracts inhibiting violacein production in Chromobacterium violaceum ATCC 12472. Growth inhibition of Gram-positive bacteria was less common: 16% of cyanobacterial strains inhibited Streptococcus pyogenes ATCC 12344, and 11% inhibited Mycobacterium smegmatis ATCC 14468. Bioassay-guided fractionation of Aphanizomenon sp. KUCC C1, followed by LC–MS/MS analysis, revealed the presence of glycerolipids and glycolipids, including diacylglycerols (DAGs) and galactosyldiacylglycerols (MGDGs and DGDGs), as major constituents of fractions exhibiting quorum quenching activity. Conclusions: These findings highlight the potential of Baltic cyanobacteria as a source of natural compounds capable of disrupting bacterial communication and growth, offering prospects for the development of novel antimicrobial and anti-virulence agents. Full article

(This article belongs to the Special Issue Marine-Derived Antibiotics)

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10 pages, 1411 KB

Open AccessArticle

Inhibition of Biofilm Formation by Respiratory Bacterial Pathogens via Silver Nanoparticles and Functionalized HEPA Filters

by Mirella Llamosí, Bruno F. Gomes-Ribeiro, Mónica Echeverry-Rendón, Jose Yuste, Julio Sempere and Mirian Domenech

Antibiotics 2026, 15(4), 370; https://doi.org/10.3390/antibiotics15040370 - 3 Apr 2026

Viewed by 283

Abstract

Objective: The objective of this study is to evaluate the ability of silver oxide nanoparticle (Ag₂ONP)-functionalized high-efficiency particulate air (HEPA) filters and colloidal Ag₂ONP suspensions to inhibit biofilm formation by major respiratory pathogens causing infections at operating rooms. [...] Read more.

Objective: The objective of this study is to evaluate the ability of silver oxide nanoparticle (Ag₂ONP)-functionalized high-efficiency particulate air (HEPA) filters and colloidal Ag₂ONP suspensions to inhibit biofilm formation by major respiratory pathogens causing infections at operating rooms. Background: Respiratory infections caused by bacterial pathogens such as Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus species are often associated with the formation of biofilms, which confer increased resistance to antibiotics and host immune responses. Effective strategies to prevent biofilm formation on biological surfaces and in air filtration systems are urgently needed in clinical settings. Methods: The biofilm-forming ability of each bacterial strain was assessed by crystal violet microplate assay, viable count or confocal microscopy after prior incubation of the culture medium with Ag₂ONP-coated HEPA filter material or colloidal Ag₂ONP suspension. Results: Both silver-functionalized filters and silver nanoparticle suspensions significantly inhibited biofilm formation by S. pneumoniae and P. aeruginosa, with near-complete suppression observed. In the case of S. aureus and S. epidermidis, the silver nanoparticle suspension showed partial inhibition of biofilm development. Conclusions: Ag₂ONP-functionalized HEPA filters and colloidal Ag₂ONP suspensions effectively prevent biofilm formation by major respiratory pathogens, for both Gram-negative and Gram-positive bacteria. These materials show promise for integration with air filtration and surface coating systems to reduce microbial load and transmission in healthcare environments such as operating room facilities. Full article

(This article belongs to the Topic Antimicrobial Agents and Nanomaterials—2nd Edition)

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15 pages, 1600 KB

Open AccessArticle

A Prospective Multicenter Randomized Study to Assess the Impact of a Novel Catheter Coating on Clinical Bacteriuria

by Mark Rochester, Catherine Rennie, Clare Hayes, Jean O’Driscoll and Maurizio Belci

Antibiotics 2026, 15(4), 369; https://doi.org/10.3390/antibiotics15040369 - 3 Apr 2026

Viewed by 216

Abstract

Background: Catheter-associated urinary tract infections (CAUTIs) are a common source of morbidity and antibiotic use. Camstent Ltd. surface coated catheters aim to reduce bacterial colonization and infection. This study compares outcomes with Camstent Coated Catheters (CCC) versus standard uncoated catheters, Standard Care (SC). [...] Read more.

Background: Catheter-associated urinary tract infections (CAUTIs) are a common source of morbidity and antibiotic use. Camstent Ltd. surface coated catheters aim to reduce bacterial colonization and infection. This study compares outcomes with Camstent Coated Catheters (CCC) versus standard uncoated catheters, Standard Care (SC). Objectives: The aim of the study was to investigate the reduction in bacteriuria in CCC versus SC, uncoated catheters. Methods: This is a prospective, UK, multi-center, randomized study including an Intention to Treat (ITT) population and a Per Protocol (PP) population of 200 and 188 subjects respectively. The PP population was sub-divided into primary and secondary cohorts with 107 and 81 subjects considered for study randomization receiving either a CCC or SC respectively. The primary endpoints including time to infection, number of days of infection and incidence of infection, and secondary endpoints including time to symptoms, UTI antibiotic use, patient reported outcomes like patient discomfort and catheter blockage were evaluated at days 0, 3, 5, 7, 10, 14, 21 and 28. For statistical analysis, Hodges–Lehmann and Fisher’s exact test were used. Results: The primary end points: Colonization-free rates at day 7 were higher in the CCC group than in the SC group (79% versus 46%) and the difference persisted on day 14 (69% versus 39%) (p = 0.016); the mean number of days infected during the first 14 days was lower in the CCC group than the SC group (3 versus 4.6 days) (two-sided; p = 0.0117); the infection rates at day 14 were lower in the CCC group than SC group (33% versus 50%). This trend continued at days 21 and 28, with consistently lower infection rates in the CCC group than SC group but did not reach statistical significance (p > 0.05). The secondary endpoint is in the secondary cohort: Time to the development of symptoms defined as a UTI requiring antibiotics showed that zero cases occurred in the CCC compared with the SC group (0% versus 20%) at p = 0.0054; median time to symptoms in the SC group was 9.0 days; and expanding this endpoint to include the primary cohort revealed that symptomatic infections occurred at 4% in the CCC group and 20% in the SC group (p = 0.0007) with a longer median time to symptoms in the CCC group than SC (13.5 versus 7 days); UTI antibiotic use was significantly lower in the CCC group than the SC group (4% vs. 21%). Conclusions: Compared with SC, CCCs were associated with substantial reductions in bacterial colonization, symptomatic CAUTI, and antibiotic use, supporting their adoption within strategies to prevent CAUTIs and promote antimicrobial stewardship. Trial registration: This study was registered prospectively in the Clinical Trials Registry (NCT04461262; Study Details|NCT04461262|The Impact Of A Catheter Coating On Clinical Bacteriuria|r). Full article

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30 pages, 1286 KB

Open AccessArticle

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

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

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

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Abstract

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

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

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

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16 pages, 1097 KB

Open AccessArticle

Inferred Mobility-Resolved Resistome Architecture Suggests Recurrent Co-Resistance Modules on a Conserved Chromosomal Backbone in Multidrug-Resistant Escherichia coli from Intensive Swine Production in Hungary

by Ádám Kerek, Balázs Nagyházi, Gergely Álmos Tornyos, Levente Hunor Husz, Máté Hetyésy, Eszter Kaszab, Enikő Fehér, Patrik Mag and Ákos Jerzsele

Antibiotics 2026, 15(4), 367; https://doi.org/10.3390/antibiotics15040367 - 2 Apr 2026

Viewed by 266

Abstract

Background: Multidrug-resistant (MDR) Escherichia coli in intensive pig production represents a persistent animal health and One Health concern. Here, we integrated quantitative phenotypic susceptibility data with whole-genome sequencing (WGS) to characterize the resistome and its inferred genomic context (chromosomal vs. plasmid-predicted contigs and [...] Read more.

Background: Multidrug-resistant (MDR) Escherichia coli in intensive pig production represents a persistent animal health and One Health concern. Here, we integrated quantitative phenotypic susceptibility data with whole-genome sequencing (WGS) to characterize the resistome and its inferred genomic context (chromosomal vs. plasmid-predicted contigs and mobile genetic element (MGE)-proximal regions) in swine-associated MDR E. coli from Hungary. Methods: A total of 203 E. coli isolates from large-scale pig farms were tested by broth microdilution. Based on resistance-oriented screening from an extended-spectrum β-lactamase (ESBL)-screen-positive pool, 116 isolates were subjected to whole-genome sequencing (WGS) as a resistance-enriched subset. Resistance determinants were annotated using the Comprehensive Antibiotic Resistance Database (CARD). Results: Resistance-oriented screening indicated frequent β-lactamase activity and ESBL screening positivity (110/203 and 127/203 isolates, respectively), consistent with strong antimicrobial selection pressure in the source population. Across the full phenotypic panel, 78/203 isolates (38.4%) met the MDR definition (non-susceptible to ≥3 antimicrobial classes), with marked between-farm variation (p < 0.001) but no age-group effect (p = 0.75). Non-β-lactam minimum inhibitory concentration (MIC) distributions showed pronounced, site-dependent high-MIC “tails”, most notably for tetracyclines, trimethoprim–sulfamethoxazole, fluoroquinolones, and colistin. In the WGS cohort (n = 116), we detected 82 distinct resistance determinants (5433 total occurrences), featuring a conserved chromosomal backbone enriched for intrinsic multidrug resistance components and lipid A modification pathways, alongside common plasmid- and MGE-associated acquired ARG modules involving tetracycline (tetA/tetB), sulfonamide/trimethoprim (sul/dfrA), aminoglycoside-modifying enzymes, and phenicol determinants (floR/cat). High-priority mobile determinants were rare but present, including mcr-1 (3/116; plasmid-associated) and plasmid-mediated quinolone resistance qnrB5 (2/116). Conclusions: Importantly, mobility/context inferences are restricted to this ESBL-screen-enriched WGS subset. Swine-associated E. coli from Hungarian large-scale farms harbors complex resistance architectures shaped by co-selection of mobile ARG modules on top of a pervasive chromosomal resistance backbone. Mobility-aware surveillance and stewardship are warranted to mitigate dissemination risks at the animal–environment–human interface. Full article

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

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17 pages, 6518 KB

Open AccessArticle

3-Amidinophenylalanine-Derived Inhibitors’ Antiviral Effect Against H1N1 Influenza A Virus

by Lilla Tóth, András Marosi, Luna C. Schmacke, Torsten Steinmetzer, Anita Rácz, Dávid Bajusz, Ákos Jerzsele, Sándor Kunsági-Máté, Miklós Poór and Erzsébet Pászti-Gere

Antibiotics 2026, 15(4), 366; https://doi.org/10.3390/antibiotics15040366 - 2 Apr 2026

Viewed by 255

Abstract

Background/Objectives: Transmembrane serine proteases such as TMPRSS2 and matriptase have been identified as pivotal host factors in the influenza A infection due to their capacity to cleave the hemagglutinin and thereby facilitate viral activation. The inhibition of these enzymes has the potential to [...] Read more.

Background/Objectives: Transmembrane serine proteases such as TMPRSS2 and matriptase have been identified as pivotal host factors in the influenza A infection due to their capacity to cleave the hemagglutinin and thereby facilitate viral activation. The inhibition of these enzymes has the potential to serve as an effective therapeutic strategy against numerous seasonal influenza strains. In our study, four 3-amidinophenylalanine-derived inhibitors were used to elucidate their antiviral efficacy, pharmacokinetic properties and affinities toward certain related trypsin-like serine proteases. Methods: K_i values for TMPRSS2, matriptase, thrombin and factor Xa were determined using enzyme kinetic measurements. Cytochrome P450 3A (CYP3A) inhibitory activity was investigated using human liver microsomes, and protein binding was evaluated with human serum albumin and α₁-acid glycoprotein. In vitro antiviral efficacy and cytotoxicity were determined in MDCK-II cells. Results: All compounds were non-cytotoxic and exhibited a relatively high affinity toward matriptase and bovine thrombin in the 10–30 nM concentration range. Among the inhibitors, MI-441 displayed the lowest K_i value for TMPRSS2 (~60 nM). The weakest CYP3A inhibitory activity was observed for compounds MI-447 and MI-448. In addition, three of the four compounds (MI-441, MI-443 and MI-447) demonstrated significant antiviral activity. Conclusions: This study demonstrates that the investigated inhibitors exhibit a favorable safety profile, low binding to human serum albumin and pronounced antiviral activity against H1N1. Full article

(This article belongs to the Special Issue Current Advances and Innovations in Anti-Infective Agents Discovery)

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18 pages, 3946 KB

Open AccessArticle

Isolation and Characterization of a Klebsiella Phage H33IIK Targeting Multidrug-Resistant Klebsiella pneumoniae in Peru

by Elsa Aguilar-Ancori, Marishani Marin-Carrasco, Duly Nuñez-Carazas, Abraham Espinoza-Culupú, Pablo Ramirez and Enrique Mamani-Zapana

Antibiotics 2026, 15(4), 365; https://doi.org/10.3390/antibiotics15040365 - 1 Apr 2026

Viewed by 451

Abstract

Background: The global rise in multidrug-resistant (MDR) Gram-negative bacteria (GNB) poses an urgent challenge for infection control and antibiotic stewardship. Among these, Klebsiella pneumoniae is a major cause of hospital-acquired infections and is listed as a critical priority pathogen by the World [...] Read more.

Background: The global rise in multidrug-resistant (MDR) Gram-negative bacteria (GNB) poses an urgent challenge for infection control and antibiotic stewardship. Among these, Klebsiella pneumoniae is a major cause of hospital-acquired infections and is listed as a critical priority pathogen by the World Health Organization. Peru reports an exceptionally high prevalence of MDR K. pneumoniae, underscoring the need for innovative antimicrobial approaches. Methods: Here, we describe the isolation and characterization of lytic Klebsiella bacteriophage from sewage samples collected from the Huatanay River (Cusco, Peru) in 2023. Phages were isolated using the reference strain MDR K. pneumoniae ATCC BAA-2814. Then, they were screened against 50 clinical MDR K. pneumoniae strains. Results: The phage H33IIK demonstrated effective antibacterial capability, showing strict host specificity for K. pneumoniae, thermal stability, moderate pH tolerance, and high burst size. Whole-genome sequencing analysis classified it within the class Caudoviricetes, family Ackermannviridae, and genus Taipeivirus. The genomic analysis confirmed the absence of lysogeny-related, antimicrobial resistance, and virulence genes, supporting its suitability and safety for potential biotechnological applications. Conclusions: These findings highlight phage H33IIK as a lytic agent effective against MDR K. pneumoniae. It could contribute to the development of phage-based approaches to combat MDR GNB. Full article

(This article belongs to the Special Issue Combating Antimicrobial Resistance Spread in Food and Drinks Using Bacteriophage Technologies)

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15 pages, 3335 KB

Open AccessArticle

Genomic Insight into the Mobility of Antibiotic Resistance Genes in Multidrug-Resistant Escherichia coli Isolated from Dewatered Sludge Cakes

by Taeun Kim, Yeojin Han, Seohyeon Je, Minwoo Kim and Hokyung Song

Antibiotics 2026, 15(4), 364; https://doi.org/10.3390/antibiotics15040364 - 1 Apr 2026

Viewed by 295

Abstract

Background/Objectives: Municipal wastewater treatment plants (WWTPs) act as reservoirs for antibiotic-resistant bacteria, which pose a threat to global public health. In this study, we used whole-genome sequencing (WGS) to characterize antibiotic resistance genes (ARGs) and their association with mobile genetic elements (MGEs) [...] Read more.

Background/Objectives: Municipal wastewater treatment plants (WWTPs) act as reservoirs for antibiotic-resistant bacteria, which pose a threat to global public health. In this study, we used whole-genome sequencing (WGS) to characterize antibiotic resistance genes (ARGs) and their association with mobile genetic elements (MGEs) in five multidrug-resistant (MDR) Escherichia coli isolates from dewatered sludge cake samples collected from a municipal WWTP in Cheongju, Republic of Korea. Methods: Susceptibility to nine antibiotics was evaluated via disk diffusion assay. Among the isolates exhibiting multidrug resistance (MDR) to three or more antibiotic classes, five isolates were randomly selected for whole-genome sequencing using the Illumina NovaSeqX platform. Additionally, we compared the genomic structures of five WWTP isolates with 35 environmental E. coli isolates from South Korea deposited in the NCBI pathogen database. ARGs and MGEs, including plasmids, integrons, and insertion sequences (ISs), were detected in the genome assemblies. Results: ARGs were differentially distributed between chromosomal and plasmid-derived contigs. Efflux pump-related genes were predominantly located on the chromosome across all isolates, whereas several beta-lactamase genes (e.g., bla_TEM-30 and bla_TEM-33), fluoroquinolone, and tetracycline resistance genes were localized on putative plasmid contigs. Furthermore, we characterized specific MGEs associated with these ARGs, including a class 1 integron gene cassette (dfrA17–aadA5–qacEΔ1–sul1) and an IS-mediated module (mph(A)–mrx–IS6100). Core-genome multilocus sequence typing (cgMLST) revealed that these MDR isolates represented diverse genetic lineages rather than a single clonal cluster. Conclusions: The results from this study highlight the necessity of enhanced post-treatment management of wastewater byproducts and WGS-based surveillance to mitigate the environmental spread of MDR bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Resistance Genes: Spread and Evolution, 2nd Edition)

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14 pages, 432 KB

Open AccessArticle

A Cross-Sectional Analysis of Clinical and Biological Characteristics of Inpatients with Complicated Acute Pyelonephritis

by Marius-Costin Chițu, Carmen-Marina Pălimariu, Teodor Salmen, Tudor-Petru Nicodin, Delia Reurean-Pintilei, Dan-Arsenie Spînu, Viorel Jinga, Anca Pantea Stoian and Dan Liviu Dorel Mischianu

Antibiotics 2026, 15(4), 363; https://doi.org/10.3390/antibiotics15040363 - 1 Apr 2026

Viewed by 300

Abstract

Background: Complicated acute pyelonephritis (AP) is a severe upper urinary tract infection associated with systemic inflammation, organ dysfunction, and the risk of sepsis. The increasing prevalence of antimicrobial-resistant (AMR) organisms can alter clinical management. This study aimed to characterize the biological profile [...] Read more.

Background: Complicated acute pyelonephritis (AP) is a severe upper urinary tract infection associated with systemic inflammation, organ dysfunction, and the risk of sepsis. The increasing prevalence of antimicrobial-resistant (AMR) organisms can alter clinical management. This study aimed to characterize the biological profile of inpatients with complicated AP and to eventually identify laboratory markers associated with risks of sepsis and AMR infections. Material and Methods: A retrospective observational analysis on 553 adult inpatients diagnosed with complicated AP between 2021 and 2025 was conducted in a tertiary center. Demographic, clinical, and biological parameters were analyzed, including inflammatory markers and renal and hepatic markers. Results: Group characteristics included a mean age of 63.82 ± 15.67 years, and 63% were female. At admission, inflammatory markers were raised, with leukocytosis (15.6 ± 5.8 × 10³/µL), neutrophilia (10.1 ± 4.7 × 10³/µL), and elevated C-reactive protein (CRP) (median 43.2 mg/dL). Coagulation activation was significant with elevated fibrinogen of 747 ± 145 mg/dL and D-dimer with a median level of 1249 ng/mL, of which 58% exceeded 1000 ng/mL. Mild to moderate renal impairment was frequently observed (creatinine 1.69 ± 0.76 mg/dL). In multivariate analysis, no biological parameter proved to be an independent predictor of AMR status among organisms. Discussion and Conclusions: Inpatients with complicated AP showed a pronounced inflammatory and procoagulant biological profile that did not vary between AMR pathogen and non-AMR pathogen infections. This suggests that the clinical value of biomarkers, such as leukocyte and neutrophile, CRP, D-dimer, fibrinogen, procalcitonin, urea, and creatinine, lies primarily in assessing disease severity rather than predicting antimicrobial resistance. The microbiological profile was dominated by Gram-negative pathogens, particularly Escherichia coli, although a heterogeneous spectrum of microorganisms was identified. Full article

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

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15 pages, 2606 KB

Open AccessArticle

Antibiotic Resistance and Genomic Diversity of Methicillin-Resistant Staphylococcus aureus Clonal Complex 45 Isolates in Kuwait Hospitals

by Samar S. Boswihi, Tina Verghese and Edet E. Udo

Antibiotics 2026, 15(4), 362; https://doi.org/10.3390/antibiotics15040362 - 1 Apr 2026

Viewed by 275

Abstract

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. MRSA is a highly diverse strain that includes several epidemic clones, including CC45. A previous study conducted among MRSA isolates in Kuwait identified CC45 in two isolates in the early 2000s. This study [...] Read more.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. MRSA is a highly diverse strain that includes several epidemic clones, including CC45. A previous study conducted among MRSA isolates in Kuwait identified CC45 in two isolates in the early 2000s. This study provides an update on the prevalence and molecular characteristics of CC45 among MRSA isolates in Kuwait hospitals, during 2016–2022. Methods: A total of 13,276 MRSA isolates were collected during 2016–2022 and typed using antibiogram, DNA microarray, Staphylococcal protein A (spa) typing, pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing (MLST). Results: CC45 was detected in 87 (0.65%) of the 13,276 MRSA isolates. The isolates were resistant to fusidic acid (n = 71), erythromycin (n = 16), and inducible clindamycin resistance (n = 15). Twenty-one isolates were resistant to multiple antibiotics. Spa typing identified 19 types, with t362 (n = 35) and t132 (n = 27) as the dominant types. DNA microarray identified seven genotypes with CC45-MRSA-[IV + fus] (n = 36) and CC45-MRSA-[VI + fus] (n = 30) as the dominant types. MLST identified six sequence types (STs): ST7119, ST508, ST45, ST46, ST9548, and ST10699. PFGE clustered the isolates into two major types, A and B, with type A being the major type (n = 83), mostly consisting of CC45-MRSA-[IV + fus] isolates. The CC45-MRSA-[IV + fus] and CC45-MRSA-[VI + fus] genotypes were detected throughout the study period (2016–2022), whereas the other genotypes were detected less frequently. Conclusions: The CC45-MRSA circulating in Kuwait hospitals comprises genetically diverse isolates that may have originated from different sources. The emergence of multidrug resistance among the isolates poses challenges for therapy and infection prevention. Full article

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

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11 pages, 699 KB

Open AccessArticle

Antimicrobial Susceptibility of Pseudomonas aeruginosa from Elderly Patients in Intensive Care Units of United States Medical Centers (2021–2025)

by Helio S. Sader, Rodrigo E. Mendes, Timothy B. Doyle, Marisa L. Winkler and Mariana Castanheira

Antibiotics 2026, 15(4), 361; https://doi.org/10.3390/antibiotics15040361 - 1 Apr 2026

Viewed by 295

Abstract

Objectives: The primary objective was to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa causing infection in elderly (≥65 years old) patients hospitalized in intensive care units (ICUs) of United States medical centers. Susceptibility results from isolates of elderly patients in ICUs were [...] Read more.

Objectives: The primary objective was to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa causing infection in elderly (≥65 years old) patients hospitalized in intensive care units (ICUs) of United States medical centers. Susceptibility results from isolates of elderly patients in ICUs were compared to isolates from elderly patients not in ICUs (elderly non-ICU) and adult ICU patients (18 to 64 years old; adult ICU). Methods: P. aeruginosa isolates were consecutively collected from 74 US medical centers in 2021–2025 and susceptibility tested by reference broth microdilution in the monitoring laboratory (Element Iowa City [JMI Laboratories]). The organism collection included 999 isolates from elderly ICU, 2027 isolates from elderly non-ICU, and 1022 isolates from adult ICU patients. Results: The most active agents against P. aeruginosa from all three patient groups were ceftazidime-avibactam (95.8% to 97.3% susceptible), ceftolozane-tazobactam (96.0% to 98.3% susceptible), imipenem-relebactam (97.6% to 98.7% susceptible), and tobramycin (91.4% to 94.7% susceptible). Susceptibility to piperacillin-tazobactam, ceftazidime, cefepime, meropenem, and imipenem were markedly lower among isolates from elderly and adult ICU patients compared to elderly non-ICU patients. Susceptibility to levofloxacin and tobramycin were lower among isolates from adult ICU patients compared to elderly ICU and non-ICU patients. Moreover, the frequency of multidrug-resistant (MDR) isolates was markedly higher among elderly (18.4%) and adult (22.4%) ICU patients compared to elderly non-ICU (11.0%) patients. An annual analysis of susceptibility to selected β-lactams showed a slight variation in susceptibility rates without a clear trend. Conclusions: Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam were highly active and exhibited similar coverage against a large contemporary collection of P. aeruginosa isolates from ICU elderly, non-ICU elderly, and ICU adult patients. Cross-resistance among these β-lactamase inhibitor combinations (BLICs) varied markedly, indicating that all three should be tested in the clinical laboratory and available for clinical use. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Hospital-Acquired Infections)

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9 pages, 536 KB

Open AccessArticle

Detecting erm-Mediated Inducible Macrolide–Lincosamide–Streptogramin B Resistance in Anaerobic Clinical Isolates

by Fabio Daniel Thalmann, Claudio Neidhöfer, Pascal Schläpfer, Christopher Field, Karoline Leuzinger, Claudia Lang and Peter M. Keller

Antibiotics 2026, 15(4), 360; https://doi.org/10.3390/antibiotics15040360 - 1 Apr 2026

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Abstract

Background: Inducible macrolide–lincosamide–streptogramin B (iMLSB) resistance is well defined in Gram-positive aerobes but remains poorly characterized in anaerobes, where standardized detection strategies are lacking. Following withdrawal of EUCAST guidance to infer clindamycin resistance from erythromycin resistance in Peptostreptococcus and Bacteroides spp. because [...] Read more.

Background: Inducible macrolide–lincosamide–streptogramin B (iMLSB) resistance is well defined in Gram-positive aerobes but remains poorly characterized in anaerobes, where standardized detection strategies are lacking. Following withdrawal of EUCAST guidance to infer clindamycin resistance from erythromycin resistance in Peptostreptococcus and Bacteroides spp. because of inconsistent species-specific performance, a diagnostic gap persists. Methods: We therefore assessed the accuracy of the D-test for detecting iMLSB resistance in anaerobes by correlating phenotypic results with whole-genome sequencing data. Fifty clinical anaerobic isolates, including Finegoldia magna, Peptostreptococcus anaerobius, and Bacteroides spp., were included in the analysis. Antimicrobial susceptibility testing was performed using gradient diffusion to determine minimum inhibitory concentrations of erythromycin and clindamycin, complemented by D-test analysis for phenotypic detection of inducible resistance. Whole-genome sequencing was undertaken to identify erm genes encoding ribosomal methyltransferases associated with the iMLSB phenotype. Results: Among the 50 isolates, erm genes were detected in 16 strains (32.0%). The prevalence of erm positivity was highest among Gram-positive cocci (50%), followed by Gram-positive rods (35.3%) and Gram-negative rods (11.8%). Five erm-positive isolates exhibited a characteristic D-shaped growth pattern, with high erythromycin MICs (>256 mg/L) and low clindamycin MICs (≤2 mg/L), consistent with an inducible iMLSB phenotype, whereas the remaining eleven demonstrated constitutive resistance. Conclusions: The D-test accurately identified inducible iMLSB resistance among Gram-positive anaerobic cocci and, if confirmed in larger studies, could form the basis of an accessible and pragmatic screening strategy for this subgroup. Integration of molecular analyses seems essential for the evidence-based refinement of diagnostic algorithms, particularly in the absence of robust, species-specific guidance. Full article

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

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40 pages, 1018 KB

Open AccessReview

Carbapenem-Resistant Serratia marcescens: Genomic Plasticity, Virulence Architecture, and the Expanding Threat of Multidrug Resistance

by Theodoros Karampatakis, Katerina Tsergouli and Payam Behzadi

Antibiotics 2026, 15(4), 359; https://doi.org/10.3390/antibiotics15040359 - 1 Apr 2026

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Abstract

Serratia marcescens is a highly adaptable Gammaproteobacterium with broad ecological distribution and growing clinical importance. Advances in whole-genome sequencing (WGS) and pangenome analysis reveal extensive genomic plasticity, driven by mobile genetic elements (MGEs) such as plasmids, transposons, integrons, prophages, and extracellular vesicles, which [...] Read more.

Serratia marcescens is a highly adaptable Gammaproteobacterium with broad ecological distribution and growing clinical importance. Advances in whole-genome sequencing (WGS) and pangenome analysis reveal extensive genomic plasticity, driven by mobile genetic elements (MGEs) such as plasmids, transposons, integrons, prophages, and extracellular vesicles, which collectively accelerate virulence and antimicrobial resistance (AMR) evolution. S. marcescens displays a dynamic accessory genome enriched in resistance and virulence determinants, supporting persistence in diverse environments, including hospital water systems. Clinically, S. marcescens is an emerging opportunistic pathogen associated with severe healthcare-associated infections, ICU outbreaks, and multidrug-resistant “superbug” phenotypes. Its resistome includes intrinsic AmpC β-lactamase, broad efflux systems, and chromosomal determinants conferring resistance to β-lactams, polymyxins, and multiple additional drug classes, while acquired ESBLs and carbapenemases urther limit therapeutic options. Integrating genomic, evolutionary, and clinical insights underscores the urgent need for improved surveillance, mechanistic understanding, and targeted interventions against carbapenem-resistant S. marcescens (CRSM). Full article

(This article belongs to the Special Issue Molecular Characterization of Gram-Negative Bacteria: Antimicrobial Resistance, Virulence and Epidemiology, 2nd Edition)

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21 pages, 4066 KB

Open AccessArticle

Phenotypic and Genomic Analysis of Antimicrobial Resistance in Escherichia coli Isolated from Food-Transport Containers Used in Institutional Catering

by Levente Hunor Husz, Gergely Álmos Tornyos, Eszter Kaszab, Enikő Fehér, András Bittsánszky, András József Tóth, Miklós Süth, Ákos Jerzsele and Ádám Kerek

Antibiotics 2026, 15(4), 358; https://doi.org/10.3390/antibiotics15040358 - 30 Mar 2026

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Abstract

Background: Public catering is an underexplored One Health interface where structurally complex food-transport equipment may sustain reservoirs of antimicrobial-resistant bacteria. We investigated Escherichia coli from reusable institutional catering food-transport containers, focusing on a difficult-to-clean pressure-relief/ventilation valve compartment. Our objectives were to quantify [...] Read more.

Background: Public catering is an underexplored One Health interface where structurally complex food-transport equipment may sustain reservoirs of antimicrobial-resistant bacteria. We investigated Escherichia coli from reusable institutional catering food-transport containers, focusing on a difficult-to-clean pressure-relief/ventilation valve compartment. Our objectives were to quantify phenotypic resistance using applied clinical breakpoints, assess inhibitor-synergy outcomes in ESBL confirmatory testing, and contextualize inhibitor-positive isolates by whole-genome sequencing (WGS). Methods: E. coli was isolated from containers sourced from 17 institutions and three central kitchens using ISO 16649-2. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Extended-spectrum β-lactamase (ESBL) confirmatory testing used cefotaxime/ceftazidime ± clavulanate; inhibitor positivity was defined as a ≥3 two-fold MIC decrease in the presence of clavulanate in isolates meeting CLSI screening thresholds. Inhibitor-positive isolates underwent WGS and CARD-based resistome profiling. Results: Resistance was most frequent to colistin (10, 10.8%), followed by doxycycline (8, 8.6%), florfenicol (7, 7.5%), enrofloxacin (4, 4.3%), and gentamicin (3, 3.2%). Third-generation cephalosporin resistance by clinical breakpoints was uncommon (cefotaxime: 2, 2.2%; ceftazidime: 1, 1.1%). Inhibitor-positive ESBL confirmatory phenotypes occurred in 30 isolates (32.3%), which were sequenced. WGS identified 45 resistance-associated genes across inhibitor-positive isolates but detected no classical ESBL genes; all carried chromosomal ampC/ampH alongside ubiquitous efflux-associated determinants. All WGS isolates belonged to phylogroup A, with serotype O154:H9 (20, 66.7%) and ST5549 (17, 56.7%) predominating. Conclusions: Institutional catering food-transport containers can harbor AMR E. coli, with colistin as the most frequent resistance phenotype and frequent inhibitor-positive ESBL confirmatory profiles that, in this set, were not explained by classical ESBL gene carriage. Integrating phenotype, WGS resistomics, and lineage structure supports targeted hygiene surveillance and risk-informed One Health monitoring in mass catering systems. Full article

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

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31 pages, 685 KB

Open AccessReview

When Disinfection Fails: Biocide Tolerance as a Driver of Campylobacter Persistence and Resistance

by Inês M. Fonseca, Inês Martins, Mónica Oleastro and Susana Ferreira

Antibiotics 2026, 15(4), 357; https://doi.org/10.3390/antibiotics15040357 - 30 Mar 2026

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Abstract

Campylobacter spp. constitutes a significant global public health hazard as it is a leading cause of reported foodborne diseases. Human infection is predominantly acquired through the ingestion of contaminated food, unpasteurized milk and untreated water, prompting the widespread implementation of chemical disinfection across [...] Read more.

Campylobacter spp. constitutes a significant global public health hazard as it is a leading cause of reported foodborne diseases. Human infection is predominantly acquired through the ingestion of contaminated food, unpasteurized milk and untreated water, prompting the widespread implementation of chemical disinfection across several sectors, from healthcare, domestic environments, and food-processing to animal husbandry. While these biocidal agents encompass multiples classes with different modes of action and efficacy, growing evidence suggests that their extensive and repeated use may unintentionally promote bacterial persistence, tolerance and adaptive responses. Although biocide resistance has been documented in several foodborne pathogens, data on biocide tolerance in Campylobacter spp. remain limited. Available studies report variable degrees of reduced susceptibility to commonly used biocides among isolates originating from poultry production, food-processing environments, and water systems. Importantly, while biocide-induced adaptive responses in Campylobacter spp. may potentially overlap with antimicrobial resistance mechanisms, the extent to which these agents drive co-selection, persistence, or dissemination requires further elucidation. Evidence remains limited on the effects of long-term and repeated exposure under realistic processing conditions, the interplay between stress-induced gene regulation and stable genetic changes, and the contribution of mobile genetic elements, biofilm formation, and microbial communities in shaping antimicrobial resistance evolution. In light of the global health burden imposed by campylobacteriosis and the rising challenge of antimicrobial-resistant Campylobacter, this review brings together current evidence on the role of biocides in shaping bacterial survival, adaptation, and resistance mechanisms. Full article

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28 pages, 1456 KB

Open AccessSystematic Review

The Role of Combination Antibiotic Therapy in Combatting Drug-Resistant Acinetobacter baumannii Infections: A Systematic Review of Randomised Control Trials

by Anteneh Assefa Gezmu, Abel Workalemahu Tesfaye and Anthony R. M. Coates

Antibiotics 2026, 15(4), 356; https://doi.org/10.3390/antibiotics15040356 - 30 Mar 2026

Viewed by 786

Abstract

Background: Acinetobacter baumannii is a major global health threat due to its rapid acquisition of multidrug resistance, particularly to carbapenems. Combination antibiotic therapy has been proposed to enhance antimicrobial activity and suppress resistance; however, evidence from randomized trials remains inconclusive. Methods: A systematic [...] Read more.

Background: Acinetobacter baumannii is a major global health threat due to its rapid acquisition of multidrug resistance, particularly to carbapenems. Combination antibiotic therapy has been proposed to enhance antimicrobial activity and suppress resistance; however, evidence from randomized trials remains inconclusive. Methods: A systematic review of randomized controlled trials (RCTs) was conducted following PRISMA guidelines to evaluate the efficacy and safety of antibiotic combination therapy versus monotherapy for drug-resistant A. baumannii infections. Searches across MEDLINE, Embase, Global Health, and Cochrane Central (January 2010–June 2025) identified eligible RCTs reporting clinical outcomes. Data on clinical cure, mortality, microbiological eradication, adverse events, and resistance emergence are described narratively. Results: Eight RCTs enrolling 324 participants were included. Most trials investigated colistin-based combinations (e.g., colistin plus rifampicin, meropenem, fosfomycin, or sitafloxacin); one assessed tigecycline plus cefoperazone–sulbactam. No regimen demonstrated a significant mortality or clinical cure benefit over monotherapy, despite some combinations showing earlier or higher microbiological clearance, most notably colistin–fosfomycin and colistin–rifampicin, without corresponding improvement in clinical outcomes. Adverse events, predominantly nephrotoxicity, were common but comparable across groups. Heterogeneity in trial size, infection severity, and resistance mechanisms limited cross-study comparability. Conclusions: Current RCT evidence does not support routine use of combination therapy over monotherapy for drug-resistant A. baumannii infections, particularly in septic ICU populations where host factors dominate outcomes. Future trials should focus on early-stage or non-sepsis infections, incorporate molecular resistance profiling, and evaluate emerging agents such as sulbactam–durlobactam to guide precision therapy. Full article

(This article belongs to the Special Issue Evaluation of Emerging Antimicrobials, 2nd Edition)

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11 pages, 1016 KB

Open AccessArticle

Real-World Evidence on Different Amoxicillin-Containing Regimens for Helicobacter pylori Treatment in Elderly Patients: Analysis of Efficacy, Safety, and Virulence Gene Association

by Xue-Liang Chen, Wen Gao, Hui Ye, Zi-Cheng Wang, Hong Cheng and Xue-Zhi Zhang

Antibiotics 2026, 15(4), 355; https://doi.org/10.3390/antibiotics15040355 - 30 Mar 2026

Viewed by 371

Abstract

Background: Helicobacter pylori (H. pylori) infection is an established risk factor for gastric cancer. However, treatment efficacy and the underlying mechanisms in elderly patients with H. pylori infection remain incompletely characterised. This study aimed to compare the eradication efficacy and [...] Read more.

Background: Helicobacter pylori (H. pylori) infection is an established risk factor for gastric cancer. However, treatment efficacy and the underlying mechanisms in elderly patients with H. pylori infection remain incompletely characterised. This study aimed to compare the eradication efficacy and safety of four amoxicillin-containing regimens for H. pylori infection in elderly patients. Methods: Elderly patients (age ≥ 60 years) with Helicobacter pylori infection treated at five hospitals in Beijing between January 2018 and June 2025 were enrolled. Participants were stratified into four groups according to the prescribed regimen: vonoprazan–amoxicillin (VA) dual therapy, rabeprazole–amoxicillin (RA) dual therapy, rabeprazole–Jinghua Weikang (a Chinese herbal medicine, granules)–amoxicillin–furazolidone (RJAF) quadruple therapy, and rabeprazole–bismuth–amoxicillin–furazolidone (RBAF) quadruple therapy. The primary endpoint was the eradication rate for each regimen. Secondary outcomes included the incidence of adverse events (AEs) and data on comorbidities. In addition, serological testing for H. pylori virulence-associated antibodies (CagA, VacA, UreA, and UreB) was performed in 32 patients at baseline, prior to treatment initiation. Results: A total of 312 patients were screened. The eradication rates with VA, RA, RJAF, and RBAF were 96.3%, 94.0%, 86.8%, and 86.6%, respectively (χ² = 6.92, p = 0.075). The incidence of AEs was 13.8%, 15.5%, 17.9%, and 19.1% in the VA, RA, RJAF, and RBAF groups, respectively (p = 0.391). Conclusions: In elderly patients with Helicobacter pylori infection, dual therapy demonstrates non-inferior efficacy compared with triple therapy and conventional quadruple therapy. More complex regimens do not confer additional clinical benefit. Among the two dual-therapy regimens, VA dual therapy shows superior overall performance and is therefore recommended as the first-line treatment of choice. Full article

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Antibiotics, Volume 15, Issue 4 (April 2026) – 60 articles

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