Antibiotics

14 pages, 228 KiB

Open AccessArticle

Stability of Nine Time-Dependent Antibiotics for Outpatient Parenteral Antimicrobial Therapy (OPAT) Use

by Elise d’Huart, Ibtissem Boutouha, Clara Berardi, Jean Vigneron, Béatrice Demore and Alexandre Charmillon

Antibiotics 2025, 14(5), 466; https://doi.org/10.3390/antibiotics14050466 (registering DOI) - 3 May 2025

Abstract

Background: The use of an elastomeric diffuser is favored to administer outpatient antibiotic therapy. A study published in 2022 highlighted the instability of several antibiotics in elastomeric devices at 37 °C. The objective was to evaluate the stability of nine time-dependent antibiotics that [...] Read more.

Background: The use of an elastomeric diffuser is favored to administer outpatient antibiotic therapy. A study published in 2022 highlighted the instability of several antibiotics in elastomeric devices at 37 °C. The objective was to evaluate the stability of nine time-dependent antibiotics that are unstable at 37 °C at lower concentrations and a reduced storage temperature of 32 °C. Methods: Chemical stability was assessed by pH measurement and high-performance liquid chromatography. Physical stability was evaluated by visual and subvisual inspection. The solutions were considered stable if the remaining drug percentage was ≥90%, the maximum variation in pH was less than 1, the particle count was within acceptable limits and the visual aspect remained unchanged after storage. Results: Solutions showing stability for 24 h are composed of 12.5 mg/mL cefiderocol in NS (normal saline) and 50–133 mg/mL piperacillin in NS-D5W (5% dextrose). Additionally, 12.5 mg/mL amoxicillin in NS; 12.5 mg/mL cefepime in NS-D5W; 12.5 mg/mL cefiderocol in D5W; 25 mg/mL cefiderocol in NS-D5W; 12.5 mg/mL cefotaxime in NS-D5W; 12.5 mg/mL cefoxitin in NS-D5W; 12.5 mg/mL ceftazidime in NS-D5W; 25 mg/mL ceftazidime in NS; 25 mg/mL cloxacillin in NS-D5W; and 25–50 mg/mL oxacillin in NS were shown to be stable for 12 h. Notably, 25 mg/mL amoxicillin in NS, 50 mg/mL cloxacillin in NS and 25 mg/mL oxacillin in D5W were shown to be stable for 8 h. Conclusions: These 12–24 h stability data indicate that these antibiotics can be administered by continuous infusion using only one–two elastomeric devices per day, facilitating outpatient parenteral antimicrobial therapy (OPAT). Full article

23 pages, 1575 KiB

Open AccessArticle

Mutation- and Transcription-Driven Omic Burden of Daptomycin/Dalbavancin-R and Glycopeptide-RS Fitness Costs in High-Risk MRSA: A Nexus in Antimicrobial Resistance Mechanisms—Genome Proneness—Compensatory Adaptations

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

Antibiotics 2025, 14(5), 465; https://doi.org/10.3390/antibiotics14050465 (registering DOI) - 2 May 2025

Abstract

Background: In Staphylococcus aureus, antimicrobial resistance (AMR) imposes significant fitness costs (FCs), including reduced growth rate, interbacterial competitiveness, and virulence. However, the FC molecular basis remains poorly understood. This study investigated the FC omic basis and compensatory adaptations in high-risk HA-, LA-, [...] Read more.

Background: In Staphylococcus aureus, antimicrobial resistance (AMR) imposes significant fitness costs (FCs), including reduced growth rate, interbacterial competitiveness, and virulence. However, the FC molecular basis remains poorly understood. This study investigated the FC omic basis and compensatory adaptations in high-risk HA-, LA-, and CA-MRSA, acquiring mono- or cross-resistance to second-line daptomycin (DAP) and dalbavancin (DAL), as well as reduced susceptibility (RS) to first-line glycopeptides, i.e., vancomycin and teicoplanin (GLYs, i.e., VAN, TEC), related to the specific mechanism of action (MOA)-related AMR-mechanisms and genomic backgrounds, paying increasing FCs. Methods: The FC omic basis associated with mono- or cross- DAP-/DAL-R and GLY-RS were investigated by integrated omics. This study focused on core-genome essential (EG) and accessory virulence gene (VG) SNPomics and transcriptomics by Illumina MiSeq whole-genome sequencing, RNA-seq, and bioinformatic analysis. Results: Moderate impact nsSNPs were identified in EGs related to vital cellular functions and VGs. Comparative EG transcriptomics revealed differential expressions and key dysregulations—via asRNAs—prevalently affecting the protein synthesis and cell-envelope EG clusters, as well as the VG cluster. Conclusions: Our data, firstly, underlined the EG and VG mutation- and transcription-driven omic-based FC burden and the compensatory adaptations associated with the emergence of mono-DAP-R, cross-DAP-R/hGISA, and DAP-R/DAL-R/GISA, linked to specific MOA-related AMR-mechanisms and genomic backgrounds in high-risk HA-, LA-, and CA-MRSA. Full article

(This article belongs to the Special Issue Molecular Characterization of Multidrug-Resistant Pathogens)

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33 pages, 3632 KiB

Open AccessArticle

Outcome of Bloodstream Infections Caused by Antibiotic-Resistant Bacteria: a 7-Year Retrospective Study at the University Hospital of Palermo, Italy

by Luca Pipitò, Eleonora Bono, Chiara Vincenza Mazzola, Raffaella Rubino, Antonio Anastasia, Salvatore Antonino Distefano, Alberto Firenze, Giovanni M. Giammanco, Celestino Bonura and Antonio Cascio

Antibiotics 2025, 14(5), 464; https://doi.org/10.3390/antibiotics14050464 - 1 May 2025

Abstract

Background: Bloodstream infections (BSIs) are both a primary cause and a severe complication of hospitalization. This retrospective study aims to analyze the epidemiology of BSIs at the University Hospital of Palermo from 2018 to 2024. Methods: We conducted a single-center, retrospective, observational study [...] Read more.

Background: Bloodstream infections (BSIs) are both a primary cause and a severe complication of hospitalization. This retrospective study aims to analyze the epidemiology of BSIs at the University Hospital of Palermo from 2018 to 2024. Methods: We conducted a single-center, retrospective, observational study at the University Hospital Paolo Giaccone in Palermo, analyzing microbiological data from blood cultures collected between 1 January 2018 and 31 December 2024. Results: A total of 6345 blood culture isolates from 2967 patients were analyzed. Bacteremia-related mortality per 1000 patients rose from 5.1% in 2018 to 10.5% in 2024. The most isolated pathogens were non-aureus staphylococci (39.7%), followed by Klebsiella pneumoniae (12.1%) and Staphylococcus aureus (7.47%). Acinetobacter baumannii and Pseudomonas aeruginosa were more prevalent in ICUs. The number of K. pneumoniae, A. baumannii, S. aureus, and P. aeruginosa isolates per 1000 admitted patients increased significantly over time. Oxacillin resistance in S. aureus peaked at 49.0% in 2020 before declining, while among non-aureus staphylococci, it remained consistently high (>80%). Carbapenem-resistant K. pneumoniae peaked at 80% in 2022 before decreasing in 2024. Resistance to ceftazidime-avibactam and meropenem-vaborbactam was observed in 11.3% and 11.8% of K. pneumoniae, respectively. Multivariable analysis identified A. baumannii and K. pneumoniae BSIs as independent predictors of in-hospital mortality. Additionally, female sex, pneumonia, and central nervous system infections were significant risk factors for mortality. Conclusions: We observed an increasing trend in overall bacteremia-related mortality from 2018 to 2024. Microbiological data highlight the predominance of non-aureus staphylococci, K. pneumoniae, and S. aureus as leading pathogens of BSI, with A. baumannii emerging as a significant threat, particularly in ICUs. Rising antimicrobial resistance, especially among K. pneumoniae, underscores the urgent need for robust antimicrobial stewardship programs. K. pneumoniae and A. baumannii were associated with higher mortality. Full article

9 pages, 560 KiB

Open AccessArticle

Impact of Timing of Beta-Lactam Therapeutic Drug Monitoring and Therapy Adjustment in Critically Ill Patients

by Mohammad H. Alshaer, Nicole F. Maranchick, Kelly L. Maguigan, Bethany R. Shoulders, Mays J. Mousa, Melissa Murray, Jennifer Ashton, Kaitlin Alexander, Barbara A. Santevecchi, Kathryn DeSear, Veena Venugopalan, Kartikeya Cherabuddi and Charles A. Peloquin

Antibiotics 2025, 14(5), 463; https://doi.org/10.3390/antibiotics14050463 - 1 May 2025

Abstract

Purpose: To assess the impact of beta-lactam therapeutic drug monitoring (TDM) timing and therapy adjustment on clinical cure and 30-day mortality. Methods: This was a prospective study of critically ill patients admitted to the University of Florida Health Shands Hospital intensive care unit [...] Read more.

Purpose: To assess the impact of beta-lactam therapeutic drug monitoring (TDM) timing and therapy adjustment on clinical cure and 30-day mortality. Methods: This was a prospective study of critically ill patients admitted to the University of Florida Health Shands Hospital intensive care unit (ICU) between 2021 and 2022, ≥18 years old, and requiring beta-lactam therapy for a suspected or confirmed infection. Beta-lactam concentrations were measured per standard of care, pharmacokinetic/dynamic (PK/PD) target attainment was calculated, and therapy was adjusted if needed. Multiple regression and time-to-event (TTE) analyses were performed. Results: A total of 297 infection episodes from 268 patients were included. The mean (SD) age was 56 years (17), weight was 82 kg (32), and 14% received renal replacement therapy. The most common infection source was the lung, and the most common beta-lactam was cefepime. The most common infusion duration was 30 min. The median (IQR) time to first TDM was 2.7 days (1.7–4.7). Fifty-seven percent of patients required therapy adjustment. Increases in beta-lactam dose, frequency, or infusion duration were associated with lower 30-day mortality compared to continuing the same regimen (aOR 0.30, p = 0.015). Delay in performing TDM was associated with lower probability of clinical cure (aOR 0.92, p = 0.0023). Patients who had the regimen increased had shorter hospital stay compared to those who had it decreased. Timing of beta-lactam TDM in ICU patients was a significant predictor of clinical cure, while adjusting beta-lactam therapy to achieve higher exposure was a significant predictor of 30-day mortality. Full article

(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics of Antibacterial and Antivirulence Drugs, 2nd Edition)

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18 pages, 567 KiB

Open AccessArticle

First Report of CTX-M-32 and CTX-M-101 in Proteus mirabilis from Zagreb, Croatia

by Branka Bedenić, Josefa Luxner, Gernot Zarfel, Andrea Grisold, Mirela Dobrić, Branka Đuras-Cuculić, Mislav Kasalo, Vesna Bratić, Verena Dobretzberger and Ivan Barišić

Antibiotics 2025, 14(5), 462; https://doi.org/10.3390/antibiotics14050462 - 30 Apr 2025

Abstract

Background/Objectives: Proteus mirabilis is a frequent causative agent of urinary tract and wound infections in community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESC) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpC). Here, we report the [...] Read more.

Background/Objectives: Proteus mirabilis is a frequent causative agent of urinary tract and wound infections in community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESC) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpC). Here, we report the characteristics of ESBLs and p-AmpC β-lactamases encountered among hospital and community isolates of P. mirabilis in two hospitals and the community settings in Zagreb, Croatia. Methods: Antibiotic susceptibility testing was performed using disk-diffusion and broth dilution methods. The double-disk-synergy test (DDST) and inhibitor-based test with clavulanic and cloxacillin were applied to screen for ESBLs and p-AmpC, respectively. PCR investigated the nature of ESBL, carbapenemases, and fluoroquinolone resistance determinants. Selected strains were subjected to molecular analysis of resistance traits by the Inter-Array CarbaResist Kit and whole-genome sequencing (WGS). Results: In total, 39 isolates were analyzed. Twenty-two isolates phenotypically tested positive for p-AmpC and seventeen for ESBLs. AmpC-producing organisms exhibited uniform resistance to amoxicillin-clavulanate, ESC, ciprofloxacin, and sulphamethoxazole-trimethoprim, and uniform susceptibility to carbapenems and piperacillin-tazobactam and all harbored bla_CMY-16genes. ESBL-positive isolates demonstrated resistance to amoxicillin-clavulanate, cefuroxime, cefotaxime, ceftriaxone, and ciprofloxacin but variable susceptibility to cefepime and aminoglycosides. They possessed bla_CTX-Mgenes that belong to cluster 1 (n = 5) or 9 (n = 12), with CTX-M-14 and CTX-M-65 as the dominant allelic variants. Conclusions: The study demonstrated the presence of CTX-M ESBL and CMY-16 p-AmpC among hospital and community-acquired isolates. AmpC-producing isolates showed uniform resistance patterns, whereas ESBL-positive strains had variable degrees of susceptibility/resistance to non-β-lactam antibiotics, resulting in more diverse susceptibility patterns. The study found an accumulation of various resistance determinants among hospital and outpatient isolates, mandating improvement in detecting β-lactamases during routine laboratory work. Full article

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

11 pages, 502 KiB

Open AccessArticle

Antimicrobial Lock Therapy: A Strategy for Managing Catheter-Related Bacteremia

by Firdevs Aksoy, Hanife Nur Karakoc Parlayan, Gulter Oncu Kurutas and Gurdal Yilmaz

Antibiotics 2025, 14(5), 461; https://doi.org/10.3390/antibiotics14050461 - 30 Apr 2025

Abstract

Objectives: This study aims to evaluate the use and efficacy of antibiotic-lock therapy (ALT) in the management of catheter-related bloodstream infections (CRBSIs), focusing on its impact on infection resolution, catheter retention, and clinical outcomes. Methods: Patients aged ≥18 years diagnosed with CRBSIs who [...] Read more.

Objectives: This study aims to evaluate the use and efficacy of antibiotic-lock therapy (ALT) in the management of catheter-related bloodstream infections (CRBSIs), focusing on its impact on infection resolution, catheter retention, and clinical outcomes. Methods: Patients aged ≥18 years diagnosed with CRBSIs who had long-term indwelling catheters and for whom catheter replacement posed clinical challenges were enrolled in the retrospective study from January 2019 to December 2024. Participants were divided into two groups based on treatment: Group 1 received intravenous (IV) antibiotics combined with antibiotic-lock therapy (ALT), while Group 2 received IV antibiotics alone. Patient demographics, pathogen distribution, administered antibiotic regimens, duration of treatment, laboratory parameters, clinical outcomes, and mortality rates were evaluated. Results: A total of 54 patients were included, of whom 42.6% were female, and the mean age was 66.3 ± 15.4 years. Group 1 comprised 50% of the study population. The median treatment duration was 14 days. The most common pathogen was Coagulase-negative staphylococci, and 33.3% of CRBSIs were caused by Gram-negative bacteria (GNB). Group 1 demonstrated lower C-reactive protein levels at treatment 48/72 h of treatment (p = 0.013) and a reduced frequency of catheter revision (p < 0.0001) compared to Group 2. Overall, ALT achieved a success rate of 88.9%, with success rates of 86% for GNB infections and 90% for Gram-positive bacterial infections. Among patients receiving daily ALT, the success rate was 86%, while those receiving the therapy every three days had a success rate of 90%. Conclusions: Antimicrobial lock therapy can be considered a treatment option for managing CRBSIs, particularly in cases where removal of the implantable catheter is not feasible, allowing for salvage. Full article

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

22 pages, 3567 KiB

Open AccessArticle

Chronic Heat Stress Can Induce Conjugation of a Novel ermB-Containing ICE_FZMF, Increasing Resistance to Erythromycin among Enterococcus Strains in Diverse Intestinal Segments in the Mouse Model

by Lingxian Yi, Zining Ren, Yu Feng, Yechun Zhang, Jianshuo Liu, Xiaowu Yuan, Qihong Kuang, Hui Deng, Bo Yang and Daojin Yu

Antibiotics 2025, 14(5), 460; https://doi.org/10.3390/antibiotics14050460 - 30 Apr 2025

Abstract

Background: The impact of heat stress on intestinal bacterial antimicrobial resistance (AMR) and its underlying mechanisms is not fully understood. This study aims to explore how heat stress influences AMR in the gut and the mechanisms involved. Methods: A Specific-Pathogen-Free (SPF) mouse model [...] Read more.

Background: The impact of heat stress on intestinal bacterial antimicrobial resistance (AMR) and its underlying mechanisms is not fully understood. This study aims to explore how heat stress influences AMR in the gut and the mechanisms involved. Methods: A Specific-Pathogen-Free (SPF) mouse model was used, divided into a control group (maintained at 25 °C) and a heat stress group (exposed to 42 °C for 30 min twice daily for 55 days). The effectiveness of the model was verified by RT-qPCR and histopathological analysis. Antibiotic susceptibility testing and clonal analysis (ERIC-PCR) were performed. Colonization assays were conducted to determine the accumulation of resistant strains in the gut. Metagenomic sequencing was conducted to investigated microbial composition. Results: RT-qPCR and Histopathological analysis revealed intestinal damage and significant upregulation of genes related to stress response, intestinal barrier integrity and inflammation, indicating successful model establishment and physiological alterations. Antibiotic susceptibility testing revealed increased resistance to erythromycin, chloramphenicol, and tetracycline among Enterococcus strains. Clonal analysis demonstrated that these resistant strains were clonally unrelated. Sequencing identified a novel ermB-carrying integrative and conjugative element (ICE_FZMF) among four erythromycin-resistant strains. The rectum harbored a higher proportion of erythromycin-resistant Enterococcus strains with elevated minimum inhibitory concentrations (MICs) after 25 days of heat stress exposure. Colonization assays confirmed that heat stress led to the accumulation of erythromycin-resistant Enterococcus in the rectum. Metagenomic sequencing revealed significant changes in microbial composition, favoring anaerobic metabolism. Conclusions: This study suggests that chronic heat stress can promote the emergence of antibiotic-resistant strains through ICE transfer, providing insight for environmental safety. Full article

26 pages, 2519 KiB

Open AccessReview

Repurposing Anthelmintic Drugs for COVID-19 Treatment: A Comprehensive Meta-Analysis of Randomized Clinical Trials on Ivermectin and Mebendazole

by Shakta Mani Satyam, Mohamed El-Tanani, Mohamed Anas Patni, Abdul Rehman, Adil Farooq Wali, Imran Rashid Rangraze, Rasha Babiker, Syed Arman Rabbani, Yahia El-Tanani and Manfredi Rizzo

Antibiotics 2025, 14(5), 459; https://doi.org/10.3390/antibiotics14050459 - 30 Apr 2025

Abstract

Background: The COVID-19 pandemic necessitated the urgent exploration of therapeutic options, including drug repurposing. Anthelmintic drugs such as ivermectin and mebendazole have garnered interest due to their potential antiviral and immunomodulatory properties. However, conflicting evidence from randomized clinical trials (RCTs) necessitates a [...] Read more.

Background: The COVID-19 pandemic necessitated the urgent exploration of therapeutic options, including drug repurposing. Anthelmintic drugs such as ivermectin and mebendazole have garnered interest due to their potential antiviral and immunomodulatory properties. However, conflicting evidence from randomized clinical trials (RCTs) necessitates a comprehensive meta-analysis to determine their efficacy and safety in COVID-19 management. Objective: This meta-analysis evaluates the clinical efficacy of ivermectin and mebendazole in treating COVID-19 by analyzing their impact on viral clearance, symptom resolution, hospitalization duration, and safety profiles. Methods: A systematic search of Scopus, PubMed, Embase, and the Cochrane Library was conducted following PRISMA guidelines to identify RCTs published up to February 2025. Eligible studies included adult patients with confirmed COVID-19 who received ivermectin or mebendazole compared with a placebo or standard of care. Data extraction and risk of bias assessment were performed using the Cochrane Risk of Bias Tool. Statistical heterogeneity was evaluated using the I² statistic, and pooled effect sizes were calculated for primary clinical outcomes. Results: Twenty-three RCTs (n = 12,345) were included, with twenty-one studies on ivermectin and two on mebendazole. The pooled analysis suggested no statistically significant improvement in viral clearance (p = 0.39), hospitalization duration (p = 0.15), or symptom resolution (p = 0.08) with ivermectin or mebendazole. However, individual studies indicated potential benefits, particularly for mebendazole, in reducing viral load and inflammation. Both drugs exhibited favorable safety profiles, with no significant increase in adverse events. Conclusions: The promising propensities observed in selected studies underscore the potential of ivermectin and mebendazole as adjunct therapies for COVID-19. With well-established safety profiles, immunomodulatory effects, and affordability, these drugs present strong candidates for further exploration. Advancing research through well-designed, large-scale RCTs will help unlock their full therapeutic potential and expand treatment options in the fight against COVID-19. Full article

(This article belongs to the Special Issue Antimicrobials Agents: Latest Advances and Prospects)

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17 pages, 2801 KiB

Open AccessArticle

Isolation and Genomic Analysis of Escherichia coli Phage AUBRB02: Implications for Phage Therapy in Lebanon

by Tasnime A. Abdo Ahmad, Samar A. El Houjeiry, Antoine Abou Fayad, Souha S. Kanj, Ghassan M. Matar and Esber S. Saba

Antibiotics 2025, 14(5), 458; https://doi.org/10.3390/antibiotics14050458 - 30 Apr 2025

Abstract

Background/Objectives: Escherichia coli (E. coli), a prevalent Gram-negative bacterium, is a frequent cause of illness. The extensive use of antibiotics has led to the emergence of resistant strains, complicating antimicrobial therapy and emphasizing the need for natural alternatives such as phages. [...] Read more.

Background/Objectives: Escherichia coli (E. coli), a prevalent Gram-negative bacterium, is a frequent cause of illness. The extensive use of antibiotics has led to the emergence of resistant strains, complicating antimicrobial therapy and emphasizing the need for natural alternatives such as phages. Methods: In this study, a novel Escherichia coli phage, AUBRB02, was isolated from sewage and characterized through whole-genome sequencing, host range assays, and biofilm elimination assays. The phage’s stability and infectivity were assessed under various pH and temperature conditions, and different E. coli strains. Results: Phage AUBRB02 has an incubation period of 45 min, a lysis period of 10 min, and a burst size of 30 phages/infected cell. It is stable across pH 5.0–9.0 and temperatures from 4 °C to 60 °C. Treatment with AUBRB02 significantly reduced post-formation E. coli biofilms, as indicated by lower OD values compared with the positive control. The whole genome sequencing revealed a genome size of 166,871 base pairs with a G + C (Guanine and Cytosine content) content of 35.47%. AUBRB02 belongs to the Tequatrovirus genus, sharing 93% intergenomic similarity with its closest RefSeq relative, and encodes 262 coding sequences, including 10 tRNAs. Conclusions: AUBRB02 demonstrates high infectivity and stability under diverse conditions. Its genomic features and similarity to related phages highlight its potential for phage therapy, offering promising prospects for the targeted treatment of E. coli infections. Full article

(This article belongs to the Section Bacteriophages)

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30 pages, 4645 KiB

Open AccessReview

New Perspectives in the Fight Against Multidrug-Resistant Bacteria: The Potential of Endolysin Biocomposites

by Carlos E. Camacho-González, Cesar S. Cardona-Felix, Alejandro Pérez-Larios, Víctor M. Zamora-Gasga, Sonia G. Sáyago-Ayerdi and Jorge A. Sánchez-Burgos

Antibiotics 2025, 14(5), 457; https://doi.org/10.3390/antibiotics14050457 - 30 Apr 2025

Abstract

The growing threat of multidrug-resistant bacteria requires innovative therapies beyond traditional antibiotics. This review highlights the potential of endolysin biocomposites using alginate oligosaccharides (AOSs) and modified cellulose (CL) as stabilizers. AOSs could enhance endolysin stability and potentially support colonic fermentation, producing short-chain fatty [...] Read more.

The growing threat of multidrug-resistant bacteria requires innovative therapies beyond traditional antibiotics. This review highlights the potential of endolysin biocomposites using alginate oligosaccharides (AOSs) and modified cellulose (CL) as stabilizers. AOSs could enhance endolysin stability and potentially support colonic fermentation, producing short-chain fatty acids that may synergize with endolysins to combat pathogens and improve gut health. KZ144 and LysPA26 are proposed as optimal candidates for their broad pH range, divalent cation tolerance, and potential effectiveness against Gram-positive and Gram-negative pathogens. Integrating AOSs and CL into biocomposites could offer a novel dual-action strategy against gastrointestinal diseases while potentially reducing antibiotic dependence. Full article

(This article belongs to the Special Issue Beyond Phages: Exploring Endolysins as Key Players in the Future of Antibacterial Therapeutics)

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10 pages, 895 KiB

Open AccessArticle

Correlation Between Blood Culture Time to Positivity and Vegetation Size in Staphylococcus aureus Infective Endocarditis

by Sebastian D. Santos-Patarroyo, Juan A. Quintero-Martinez, Brian D. Lahr, Supavit Chesdachai, Omar Abu Saleh, Hector I. Michelena, Hector R. Villarraga, Daniel C. DeSimone and Larry M. Baddour

Antibiotics 2025, 14(5), 456; https://doi.org/10.3390/antibiotics14050456 - 30 Apr 2025

Abstract

Background: The relationship between vegetation characteristics in Staphylococcus aureus infective endocarditis (IE) and blood culture time to positivity (TTP) has not been investigated. This study evaluates the correlation between vegetation length and TTP in patients with S. aureus IE. Methods: A retrospective cohort study [...] Read more.

Background: The relationship between vegetation characteristics in Staphylococcus aureus infective endocarditis (IE) and blood culture time to positivity (TTP) has not been investigated. This study evaluates the correlation between vegetation length and TTP in patients with S. aureus IE. Methods: A retrospective cohort study was conducted that included 164 definite cases S. aureus IE. Vegetation length was determined by transesophageal echocardiography (TEE), and TTP was measured in hours from the initial time of blood culture incubation to positivity. Correlations between vegetation characteristics and TTP were analyzed using Spearman’s rank correlation coefficient. Results: A modest but statistically significant negative correlation was observed between vegetation length and TTP (Spearman ρ = −0.18, p = 0.020), suggesting that larger vegetations were associated with shorter TTP. No significant correlations were found for other vegetation characteristics (e.g., vegetation mobility, location, or number) and TTP. Conclusions: Larger vegetation size in S. aureus IE was associated with shorter TTP. These findings highlight the importance of vegetation size in the pathophysiology of S. aureus IE and its role in bacteremia dynamics. Full article

(This article belongs to the Special Issue Advances in Infective Endocarditis Research: From Bench to Bedside)

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29 pages, 16106 KiB

Open AccessArticle

Development of Chrome-Doped Hydroxyapatite in a PVA Matrix Enriched with Amoxicillin for Biomedical Applications

by Steluta Carmen Ciobanu, Daniela Predoi, Simona Liliana Iconaru, Krzysztof Rokosz, Steinar Raaen, Coralia Bleotu and Mihai Valentin Predoi

Antibiotics 2025, 14(5), 455; https://doi.org/10.3390/antibiotics14050455 - 30 Apr 2025

Abstract

Background/Objectives: In this paper, we report the development of the first chrome-doped hydroxyapatite in a poly (vinyl alcohol) (PVA) matrix enriched with amoxicillin for biomedical applications. The development of chromium-doped hydroxyapatite coatings in a PVA matrix enriched with amoxicillin aims to provide [...] Read more.

Background/Objectives: In this paper, we report the development of the first chrome-doped hydroxyapatite in a poly (vinyl alcohol) (PVA) matrix enriched with amoxicillin for biomedical applications. The development of chromium-doped hydroxyapatite coatings in a PVA matrix enriched with amoxicillin aims to provide new biomaterials with improved physico-chemical and biological properties, making them promising candidates for biomedical applications. Methods: Through ultrasound studies, we obtained valuable information on the stability of the samples. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, metallographic microscopy (MM), and atomic force microscopy (AFM) were employed for the characterization of the samples. The biocompatibility of the CrHApAPV and CrHApAPV-Ax coatings was assessed using the MG63 human osteoblast-like cell line. To evaluate the cytotoxic potential of these coatings, the cell viability was quantified using the MTT assay after 24 h of incubation. The antibacterial activity of the coatings was evaluated with the aid of the reference strain Pseudomonas aeruginosa ATCC 27853 (P. aeruginosa). Results: The XRD patterns of CrHApAPV and CrHApAPV-Ax samples were examined to evaluate the effects of PVA and amoxicillin on the lattice parameters, unit cell volume, and average crystallite sizes. The results of the in vitro antibacterial assay demonstrated that both the CrHApAPV and CrHApAPV-Ax coatings exhibited very good antibacterial properties for all the tested time intervals. Conclusions: Our results underline the stability of the analyzed samples. Moreover, our physico-chemical and biological studies highlight that CrHApAPV and CrHApAPV-Ax coatings could be considered promising materials for biomedical uses. Full article

(This article belongs to the Special Issue Nanotechnology-Based Antimicrobials and Drug Delivery Systems)

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12 pages, 585 KiB

Open AccessArticle

Antimicrobial Resistance Profile and Biofilm Formation of Listeria monocytogenes Isolated from Meat

by Joana Paiva, Vanessa Silva, Patrícia Poeta and Cristina Saraiva

Antibiotics 2025, 14(5), 454; https://doi.org/10.3390/antibiotics14050454 - 30 Apr 2025

Abstract

Introduction: Listeria monocytogenes is the causative agent of listeriosis, a serious infectious disease with one of the highest case fatality rates among foodborne diseases affecting humans. Objectives: This study investigated the prevalence, antimicrobial resistance pattern and biofilm production capacity of L. monocytogenes isolated [...] Read more.

Introduction: Listeria monocytogenes is the causative agent of listeriosis, a serious infectious disease with one of the highest case fatality rates among foodborne diseases affecting humans. Objectives: This study investigated the prevalence, antimicrobial resistance pattern and biofilm production capacity of L. monocytogenes isolated in meats. Materials: A total of 75 samples were analyzed, including fresh meats and meat preparations, in Northern Portugal. Methods: The strains were identified using morphological and molecular methods. Antimicrobial resistance was determined using the Kirby–Bauer disk diffusion method, against a panel of 12 antibiotics and the presence of the respective antimicrobial resistance genes was investigated by polymerase chain reaction (PCR). The ability to form biofilms was evaluated by the microtiter biofilm assay. Results: The overall prevalence of L. monocytogenes among screened samples was 17.33%. The isolates were resistant to trimethoprim-sulfamethoxazole (85.71%), ciprofloxacin (38.10%), meropenem (33.33%), tetracycline and erythromycin (28.57%), rifampicin (23.81%), and kanamycin (14.29%). Six isolates (28.57%) exhibited a multidrug-resistance profile. All strains showed positive result for the virulence gene specific to listeriolysin O (hlyA). In the genotypic resistance analysis of the strains, the genes identified were tetK (23.81%), aadA, tetL, bla_OXA-48 (14.29%), ermC, and msr(A/B) (4.76%). All isolates had the ability to form biofilms, with no significant differences in biofilm biomass production at 24 h and 48 h. Some of these strains showed a high capacity for biofilm production. Conclusions: These findings raise public health concerns due to resistance to first-line antibiotics and the biofilm-forming capacity of these isolates, which pose risks to the food industry. Enhanced monitoring and surveillance are essential to guide public health strategies in order to mitigate the threat posed by L. monocytogenes in food. Full article

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

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16 pages, 1402 KiB

Open AccessArticle

Prevalence, Antimicrobial Resistance, and Virulence Potential of Staphylococcus aureus in Donkeys from Nigeria

by Onyinye Josephine Okorie-Kanu, Madubuike Umunna Anyanwu, Obichukwu Chisom Nwobi, Regina Yaya Tambe-Ebot, Nkechi Harriet Ikenna-Ezeh, Chukwuemeka Calistus Okolo, Lynda Onyinyechi Obodoechi, Patience Chinasa Ugwu, Ifeyinwa Riona Okosi, Ishmael Festus Jaja and James Wabwire Oguttu

Antibiotics 2025, 14(5), 453; https://doi.org/10.3390/antibiotics14050453 - 29 Apr 2025

Abstract

Background: Animal-associated antimicrobial-resistant staphylococci pose a One Health concern, as they can spread into the environment and cause serious infections. Yet, donkeys in Nigeria have been largely overlooked as potential reservoirs of these pathogens. Aim/Objectives: To isolate Staphylococcus aureus from donkeys in Obollo-Afor, [...] Read more.

Background: Animal-associated antimicrobial-resistant staphylococci pose a One Health concern, as they can spread into the environment and cause serious infections. Yet, donkeys in Nigeria have been largely overlooked as potential reservoirs of these pathogens. Aim/Objectives: To isolate Staphylococcus aureus from donkeys in Obollo-Afor, southeast Nigeria, assess their antimicrobial resistance profiles, and evaluate their virulence potential. Materials and Methods: Staphylococci were isolated from the nasal swabs of 250 donkeys, using mannitol salt agar, confirmed biochemically, with Staphylococcus aureus identified via a latex agglutination test and mass spectrometry. The resistance profiles of the isolates, including in regard to methicillin, inducible clindamycin, and β-lactamase production, were determined using disc diffusion, while vancomycin resistance was assessed through the use of agar dilution. The virulence factors were evaluated phenotypically. Results: Of the 250 samples, 11 (4.4%) contained S. aureus and 239 (95.6%) grew other Staphylococcus species. The resistance rates of the 11 S. aureus isolates to gentamicin, penicillin, tigecycline, cefoxitin, linezolid, and chloramphenicol were 45.5%, 66.7%, 54.5%, 27.3%, 36.4%, and 18.1%, respectively. The phenotypic methicillin-resistant S. aureus prevalence was 1.2%. Additionally, 23.5% of the S. aureus isolates were multidrug resistant, with a mean antibiotic resistance index of 0.25. All the S. aureus isolates exhibited virulence factors like clumping factor expression, catalase, caseinase, lecithinase, and gelatinase activity, while the occurrence of haemagglutinin, biofilm, pellicle, and hemolysin occurred in 27.3%, 54.5%, 36.4%, 72.2%, respectively. Conclusion: Although a small percentage of donkeys in Nigeria may harbor S. aureus, these animals are potentially spreading antimicrobial resistance, including multidrug and methicillin resistance, to humans and the environment. Full article

(This article belongs to the Collection Staphylococcus— Molecular Pathogenesis, Virulence Regulation and Antibiotics Resistance)

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16 pages, 558 KiB

Open AccessArticle

The Influence of the Seasonal Variability of Candida spp. Bloodstream Infections and Antifungal Treatment: A Mediterranean Pilot Study

by Paola Di Carlo, Nicola Serra, Ornella Collotta, Claudia Colomba, Alberto Firenze, Luigi Aprea, Salvatore Antonino Distefano, Andrea Cortegiani, Giovanni Giammanco, Teresa Maria Assunta Fasciana, Roberta Virruso, Angela Capuano, Consolato M. Sergi and Antonio Cascio

Antibiotics 2025, 14(5), 452; https://doi.org/10.3390/antibiotics14050452 - 29 Apr 2025

Abstract

Background/Objectives: Various factors associated with seasonality, including temperature, humidity, geographical composition, and seasonal fluctuations, can influence the trends of microbes responsible for hospital infections, such as Candida spp. This study evaluates the seasonal variability of Candida spp. bloodstream infections and antifungal resistance [...] Read more.

Background/Objectives: Various factors associated with seasonality, including temperature, humidity, geographical composition, and seasonal fluctuations, can influence the trends of microbes responsible for hospital infections, such as Candida spp. This study evaluates the seasonal variability of Candida spp. bloodstream infections and antifungal resistance in hospitalized patients in Sicily. Methods: We retrospectively analyzed the demographic and epidemiological characteristics of 175 patients with blood cultures positive for Candida spp. Who were hospitalized at University Hospital Paolo Giaccone (A.U.O.P.), University of Palermo, Italy, from 1 January 2022 to 31 December 2024. Data on Candida species and antifungal resistance were also collected from the hospital’s database system to prevent and control hospital infections in A.U.O.P. Results: A total of 175 patients, 57.7% males, with a mean age of 68.3 years, were included in this study. Candida parapsilosis, Candida albicans, and Candida glabrata were more frequent in ICU (54.5%, p = 0.0001), medical (72.5%, p = 0.0003), and surgical settings (24%, p = 0.0161), respectively. C. parapsilosis was more frequent in dead patients (53.2%, p = 0.005). Among the seasons, we observed a significantly higher presence of C. glabrata in Autumn (20%, p = 0.0436). From the analysis of the seasons, C. parapsilosis and C. albicans were more frequent for each season, except in Spring, where the most frequent isolates were C. glabrata (5.1%, p = 0.0237) and C. parapsilosis (9.7%, p < 0.0001). The antifungal with the most resistance to Candida spp. was fluconazole in all seasons. Conclusions: Our study highlights the seasonal trends in Candida spp. and antifungal resistance, emphasizing climate change’s challenges on fungal diseases. These findings may contribute to improving prevention and treatment strategies for candidemia. Full article

(This article belongs to the Special Issue Climate Change and Antibiotic Resistance)

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33 pages, 634 KiB

Open AccessReview

Delivery of Outpatient Parenteral Antimicrobial Therapy (OPAT) in an Ever-Changing National Health Service (UK): Benefits, Barriers, and Opportunities

by Oyewole Christopher Durojaiye, Charlotte Fiori and Katharine Cartwright

Antibiotics 2025, 14(5), 451; https://doi.org/10.3390/antibiotics14050451 - 29 Apr 2025

Abstract

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to manage a broad range of infections, enabling patients to receive intravenous antibiotics safely outside inpatient settings. In this review, we examine the current landscape of OPAT practice across the United Kingdom (UK), assessing its [...] Read more.

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to manage a broad range of infections, enabling patients to receive intravenous antibiotics safely outside inpatient settings. In this review, we examine the current landscape of OPAT practice across the United Kingdom (UK), assessing its clinical, economic, and operational impact. The benefits of OPAT for patients and the National Health Service (NHS), as well as its associated risks, are discussed. Additionally, we explore the challenges hindering its broader implementation within the UK. Finally, we highlight recent innovations and emerging applications of OPAT relevant to the NHS, underscoring key considerations for its future expansion and emphasising the need for a nationally coordinated strategy to realise its full potential. Full article

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19 pages, 3856 KiB

Open AccessArticle

Antimicrobial Susceptibility Profiles of Escherichia coli Isolates from Clinical Cases of Geese in Hungary Between 2022 and 2023

by Ádám Kerek, Ábel Szabó and Ákos Jerzsele

Antibiotics 2025, 14(5), 450; https://doi.org/10.3390/antibiotics14050450 - 29 Apr 2025

Abstract

Background: Antimicrobial resistance (AMR) poses an increasing threat to animal health and food safety. In the poultry sector, particularly in waterfowl farming, the widespread use of antibiotics may contribute to the dissemination of resistant Escherichia coli strains. This study aims to map the [...] Read more.

Background: Antimicrobial resistance (AMR) poses an increasing threat to animal health and food safety. In the poultry sector, particularly in waterfowl farming, the widespread use of antibiotics may contribute to the dissemination of resistant Escherichia coli strains. This study aims to map the antibiotic resistance profiles of E. coli isolates from geese in Hungary, determine the prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, and analyze resistance patterns and co-resistance relationships. Methods: E. coli isolates from clinical cases between 2022 and 2023 were examined using minimum inhibitory concentration (MIC) determination. Susceptibility results were evaluated based on the Clinical Laboratory Standard Institute (CLSI) breakpoints. Cluster analysis and principal component analysis (PCA) were applied to identify resistance patterns. Co-resistance relationships were examined through network analysis, while Monte Carlo simulations were used to estimate the expected prevalence of MDR strains. Results: Among the examined isolates, neomycin resistance was particularly high (86.8%), while florfenicol (73.6%) and amoxicillin (65.9%) resistance levels were also significant. The prevalence of MDR strains was 86.8%, and XDR strains accounted for 38.5%. Co-resistance analysis revealed a strong correlation between neomycin and spectinomycin resistance, as well as amoxicillin and doxycycline resistance. Monte Carlo simulations estimated that the expected range of MDR strain prevalence could vary between 80.2% and 92.3%. Conclusions: The high prevalence of MDR and XDR strains highlights the urgent need to reassess antibiotic usage strategies in goose farming. These findings underscore the importance of targeted antibiotic use, continuous microbiological surveillance, and the exploration of alternative therapeutic approaches to mitigate AMR. Full article

(This article belongs to the Special Issue Detection of Bacteria and Antibiotics Surveillance in Livestock)

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12 pages, 1201 KiB

Open AccessArticle

Genetic Variation in the blaZ Gene Leading to the BORSA Phenotype in Staphylococcus aureus

by Mia Aarris, Frederik Boëtius Hertz, Karen Leth Nielsen, Alexander Sato, Helle Krogh Johansen, Henrik Westh, Michael Kemp, Svend Ellermann-Eriksen, Anders Løbner-Olesen, Niels Frimodt-Møller and Godefroid Charbon

Antibiotics 2025, 14(5), 449; https://doi.org/10.3390/antibiotics14050449 - 29 Apr 2025

Abstract

Background/Objectives: Staphylococcus aureus is a leading cause of bacteraemia in Danish hospitals. Approximately 70% of clinical S. aureus isolates are penicillin-resistant, which is predominantly due to blaZ-mediated β-lactamase production. Methods: A collection of 489 S. aureus strains derived from bacteraemia were cultured [...] Read more.

Background/Objectives: Staphylococcus aureus is a leading cause of bacteraemia in Danish hospitals. Approximately 70% of clinical S. aureus isolates are penicillin-resistant, which is predominantly due to blaZ-mediated β-lactamase production. Methods: A collection of 489 S. aureus strains derived from bacteraemia were cultured and their genomes sequenced. Results: From this collection, 71% of isolates were methicillin-susceptible S. aureus (MSSA) harbouring blaZ. While most isolates contained the blaZ gene belonging to the well-characterised A, B, C and D variants, three strains (1%) produced a BlaZ protein characterised by having threonine residues on both positions 128 and 216 and, therefore, belonged to neither of the established blaZ variants. We named this variant, variant F. We report that clinical isolates expressing blaZ variant F were resistant to oxacillin. The β-lactamase production phenotype in isolates carrying either of the A, B, C or D variants was only weakly discernible on MIC gradient strip and disk diffusion tests. When the β-lactamases were expressed either from a T7 promoter or from their endogenous promoters in Escherichia coli, variant F was significantly better at degrading ampicillin than variant A. We also showed that variant F conferred oxacillin resistance when expressed in an isogenic S. aureus strain, while variant A did not. Finally, we demonstrated that the F variant threonine 216 played a role in the enzyme’s superior activity. Conclusions: Our findings demonstrate that the new F variant of BlaZ is sufficient to render S. aureus a BORSA strain, which is superior in the degradation of common anti-staphylococcal β-lactam antibiotics, such as benzylpenicillin, cloxacillin, and oxacillin. It is sensitive to β-lactamase inhibitors and rapidly degrades nitrocefin. We provide a genetic explanation for the borderline oxacillin-resistant S. aureus (BORSA) phenotype. Full article

(This article belongs to the Section Genetic and Biochemical Studies of Antibiotic Activity and Resistance)

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21 pages, 1743 KiB

Open AccessArticle

Bacterivorous Ciliate Tetrahymena pyriformis Facilitates vanA Antibiotic Resistance Gene Transfer in Enterococcus faecalis

by Temilola O. Olanrewaju, James S. G. Dooley, Heather M. Coleman, Chris McGonigle and Joerg Arnscheidt

Antibiotics 2025, 14(5), 448; https://doi.org/10.3390/antibiotics14050448 - 28 Apr 2025

Abstract

Background: Wastewater treatment plants (WWTPs) are hotspots for the emergence and spread of antibiotic resistance genes (ARGs). In activated sludge treatment systems, bacterivorous protozoa play a crucial role in biological processes, yet their impact on the horizontal gene transfer in Gram-positive enteric bacteria [...] Read more.

Background: Wastewater treatment plants (WWTPs) are hotspots for the emergence and spread of antibiotic resistance genes (ARGs). In activated sludge treatment systems, bacterivorous protozoa play a crucial role in biological processes, yet their impact on the horizontal gene transfer in Gram-positive enteric bacteria remains largely unexplored. This study investigated whether the ciliate Tetrahymena pyriformis facilitates the transfer of antibiotic resistance genes between Enterococcus faecalis strains. Methods: Conjugation assays were conducted under laboratory conditions using a vanA-carrying donor and a rifampicin-resistant recipient at an initial bacterial concentration of 10⁹ CFU/mL and ciliate density of 10⁵ N/mL. Results: Transconjugant numbers peaked at 2 h when experiments started with recipient bacteria harvested in the exponential growth phase, and at 24 h when bacteria were in the stationary phase. In both cases, vanA gene transfer frequency was highest at 24 h (10⁻⁴–10⁻⁵ CFU/mL), and the presence of energy sources increased gene transfer frequency by one order of magnitude. Conclusions: These findings suggest that ciliate grazing may contribute to vanA gene transfer in WWTP effluents, potentially facilitating its dissemination among permissive bacteria. Given the ecological and public health risks associated with vanA gene persistence in wastewater systems, understanding protozoan-mediated gene transfer is crucial for mitigating the spread of antibiotic resistance in aquatic environments. Full article

(This article belongs to the Special Issue Tracking Reservoirs of Antimicrobial Resistance Genes in Environment)

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