Antibiotics

1 pages, 130 KB

Open AccessRetraction

RETRACTED: Quazi et al. The Discovery of Novel Antimicrobial Agents Through the Application of Isocyanide-Based Multicomponent Reactions. Antibiotics 2023, 12, 849

by Sameer Quazi, Maliha Tabassum Rashid, Javid Ahmad Malik and Shreelaxmi Gavas

Antibiotics 2025, 14(9), 921; https://doi.org/10.3390/antibiotics14090921 - 12 Sep 2025

Abstract

The Antibiotics Editorial Office retracts the paper “The Discovery of Novel Antimicrobial Agents through the Application of Isocyanide-Based Multicomponent Reactions” [...] Full article

20 pages, 5032 KB

Open AccessCommunication

One Earth–One Health to Combat Antimicrobial Resistance Having a Dual Mutation Pattern, Based on the Robust Self-Regulation and Perpetual Reconstruction of Ecosystems

by Ganjun Yuan, Jianing Hu, Meifang Zhang, Xingguyue Chen and Yumei Luo

Antibiotics 2025, 14(9), 920; https://doi.org/10.3390/antibiotics14090920 - 11 Sep 2025

Abstract

Background/Objectives: Antimicrobial resistance (AMR) has emerged as a grave threat to human health, and a One Earth–One Health (OE-OH) concept was proposed for addressing this challenge in 2024. Here, this concept was systematically defined, clarified, and refined, for better understanding, interpreting related results, [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) has emerged as a grave threat to human health, and a One Earth–One Health (OE-OH) concept was proposed for addressing this challenge in 2024. Here, this concept was systematically defined, clarified, and refined, for better understanding, interpreting related results, and taking some measures to combat the crisis. Methods: Using logical reasoning and deductive methods, a dual mutation pattern was put forward for microbial resistance, adhering to the principle of parsimony and integrating Lamarckian, Darwinian, and Niche construction theories, and the evolutionary origins of current AMR were schematically presented. Subsequently, its theoretical foundation, together with a fundamental mathematical model, was defined and clarified based on the robust self-regulation and perpetual reconstruction of ecosystems, and then the generation, dissemination, and elimination of AMR and antibiotic resistance genes (ARGs) were sorted out and elucidated from abiotic and biotic factors. Finally, learning from the approach of problem management, some crucial measures are suggested for the research and development, application, and management of antibiotics, emphasizing the key role of simulating and utilizing the self-regulation of ecosystems. Results: A dual mutation pattern of microbial resistance and the evolutionary origins of current AMR was put forward. The theoretical foundation of the OE-OH concept, together with a fundamental mathematical model, was presented. Some unique perspectives, such as the emergence of AMR and ARGs 3.5 billion years ago and their ubiquity across the globe prior to antibiotic use, were clarified. Moreover, some crucial measures are proposed for addressing AMR. Conclusions: It is essential to implement the OH Joint Plan of Action from the OE-OH perspective, strongly emphasizing the key role of simulating and utilizing the self-regulation of ecosystems on addressing AMR. Full article

(This article belongs to the Special Issue The Spread of Antibiotic Resistance in Natural Environments)

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12 pages, 684 KB

Open AccessArticle

Incidence of Acute Kidney Injury in Autologous Hematopoietic Stem Cell Transplant Recipients According to the Administration of Empirical Amikacin: A Two-Centre Retrospective Cohort Study

by Sophie Schürch, Sarah Dräger, Michèle Hoffmann, Severin Bausch, Nicolas Gürtler, Cédric Hirzel, Jakob Passweg, Stefano Bassetti, Thomas Pabst, Parham Sendi and Michael Osthoff

Antibiotics 2025, 14(9), 919; https://doi.org/10.3390/antibiotics14090919 - 11 Sep 2025

Abstract

Background: The benefit of adjunctive aminoglycosides in the treatment of patients with febrile neutropenia (FN) is controversial. We investigated the incidence of acute kidney injury (AKI) in patients with FN or suspected infection according to empirical amikacin treatment. Methods: This two-centre, [...] Read more.

Background: The benefit of adjunctive aminoglycosides in the treatment of patients with febrile neutropenia (FN) is controversial. We investigated the incidence of acute kidney injury (AKI) in patients with FN or suspected infection according to empirical amikacin treatment. Methods: This two-centre, retrospective cohort study was conducted at the University Hospitals of Basel (amikacin group) and Bern (non-amikacin group), Switzerland, between 2016 and 2022. Adult patients requiring antibiotic treatment after autologous hematopoietic stem cell transplantation (HSCT) were included. All patients received empiric beta-lactam treatment combined with amikacin in the amikacin group (only University Hospital Basel). The primary endpoint was the incidence of AKI within seven days after the initiation of antibiotic treatment. Results: Overall, 250 patients were included. The majority was male (n = 163, 65.2%) and had a median age of 61 years (interquartile range (IQR) 55 to 67). The median baseline eGFR was similar in both groups (>90 mL/min/1.7 m²). There was no statistically significant difference in the incidence of AKI (4/125 vs. 5/125, p = 1.0). The maximum decline in eGFR from baseline within 7 days was significantly higher in the amikacin group (−4 mL/min/1.7 m² (IQR 8 to −12) vs. −2 mL/min/1.7 m² (IQR −7 to −1), p = 0.001). Two patients suffered from an infection with an extended spectrum beta-lactamase producing (ESBL) pathogen. Conclusions: Amikacin treatment did not significantly impact the incidence of AKI in patients undergoing autologous HSCT. The short-term administration of amikacin in patients with normal to high baseline eGFR is safe regarding renal function. However, in a low-resistance setting, the omission of empirical amikacin treatment should be considered. Full article

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

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21 pages, 888 KB

Open AccessArticle

Assessment of Factors Contributing to Multidrug Resistance in Urinary Tract Infections: Focus on Carbapenem Resistance

by Carina Alexandra Bandac, Constantin Ristescu, Pavel Onofrei, Ionela-Larisa Miftode, Rodica Radu, Vasile Lucian Boiculese, Ana-Maria Raluca Pauna, Theodor Florin Pantilimonescu, Andreea Luduşanu and Viorel Dragoș Radu

Antibiotics 2025, 14(9), 918; https://doi.org/10.3390/antibiotics14090918 - 11 Sep 2025

Abstract

Introduction: Urinary tract infections (UTIs) caused by carbapenem-resistant pathogens are increasingly common and pose serious treatment challenges due to limited antibiotic options and high complication rates. Identifying patients at risk is essential for guiding empirical therapy and improving outcomes. The primary objective of [...] Read more.

Introduction: Urinary tract infections (UTIs) caused by carbapenem-resistant pathogens are increasingly common and pose serious treatment challenges due to limited antibiotic options and high complication rates. Identifying patients at risk is essential for guiding empirical therapy and improving outcomes. The primary objective of this study was to identify risk factors associated with carbapenem-resistant (CR) UTIs by comparing them with carbapenem-susceptible (CS) UTIs. Secondary objectives included analyzing the types of microorganisms involved in both groups, their antibiotic susceptibility profiles, and the presence of carbapenemase enzymes among CR UTI cases. Method: We conducted a retrospective case-control study involving 127 hospitalized patients with UTIs caused by CR microorganisms and 91 patients with UTIs caused by multidrug-resistant (MDR) strains that retain susceptibility to carbapenems, admitted between 1 October 2023, and 31 March 2025. Results: In univariate analysis, CR UTI patients had significantly higher rates of neoplasia, neurological disorders, urosepsis at admission, septic shock, the presence of urinary catheters at diagnosis, permanent nephrostomy catheters, hospitalizations within the past 180 days, previous antibiotic exposure including carbapenems, and recent urological procedures. Multivariate analysis revealed four independent risk factors for CR UTIs: neoplasia (OR = 2.152; 95% CI: 1.044–4.436; p = 0.038), neurological disorders (OR = 7.427; 95% CI: 2.804–19.674; p < 0.0001), antibiotic use in the previous 180 days (OR = 2.792; 95% CI: 1.487–5.396; p = 0.001), and prior carbapenem treatment OR = 10.313; 95% CI: 1.277–83.248; p = 0.029). Most of the isolated organisms belonged to the Enterobacterales genus, with Klebsiella spp. and Pseudomonas aeruginosa being the most common pathogens in CR UTIs, accounting for over 90% of cases. Among patients tested for carbapenemase production, all but one tested positive for at least one carbapenemase. Conclusions: Neoplasia, neurological disorders, recent antibiotic therapy, and prior carbapenem use were significantly associated with increased risk of developing CR UTIs. Klebsiella spp. and Pseudomonas aeruginosa were the predominant causative organisms, with New Delhi metallo-β-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC) being the most frequently identified resistance mechanisms. Full article

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

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26 pages, 57341 KB

Open AccessArticle

AI-Powered Embedded System for Rapid Detection of Veterinary Antibiotic Residues in Food-Producing Animals

by Ximing Li, Lanqi Chen, Qianchao Wang, Mengting Zhou, Jingheng Long, Xi Chen, Jiangsan Zhao, Junjun Yu and Yubin Guo

Antibiotics 2025, 14(9), 917; https://doi.org/10.3390/antibiotics14090917 - 11 Sep 2025

Abstract

Background: Veterinary antibiotics are widely used in food-producing animals, raising public health concerns due to drug residues and the risk of antimicrobial resistance. Rapid and reliable detection systems are critical to ensure food safety and regulatory compliance. Colloidal gold immunoassay (CGIA)-based antigen–antibody test [...] Read more.

Background: Veterinary antibiotics are widely used in food-producing animals, raising public health concerns due to drug residues and the risk of antimicrobial resistance. Rapid and reliable detection systems are critical to ensure food safety and regulatory compliance. Colloidal gold immunoassay (CGIA)-based antigen–antibody test cards are widely used in food safety for the rapid screening of veterinary antibiotic residues. However, manual interpretation of test cards remains inefficient and inconsistent. Methods: To address this, we propose a complete AI-based detection system for veterinary antibiotic residues. The system is built on the Rockchip RK3568 platform and integrates a five-megapixel OV5640 autofocus USB camera (60° field of view) with a COB LED strip (6000 K, rated 5 W/m). It enables high-throughput, automated interpretation of colloidal gold test cards and can generate structured detection reports for regulatory documentation and quality control. The core challenge lies in achieving accurate and fast inference on resource-constrained embedded devices, where traditional detection networks often struggle to balance model size and performance. To this end, we propose VetStar, a lightweight detection algorithm specifically optimized for this task. VetStar integrates StarBlock, a shallow feature extractor, and Depthwise Separable-Reparameterization Detection Head (DR-head), a compact, partially decoupled detection head that accelerates inference while preserving accuracy. Results: Despite its compact size, with only 0.04 M parameters and 0.3 GFLOPs, VetStar maintains strong performance after distillation with the Bridging Cross-task Protocol Inconsistency Knowledge Distillation (BCKD) method. For our custom Veterinary Drug Residue Rapid Test Card (VDR-RTC) dataset, it achieves an mAP50 of 97.4 and anmAP50-95of 89.5. When deployed on the RK3568 device, it delivers results in just 5.4 s—substantially faster than comparable models. Conclusions: These results highlight the system’s strong potential for high-throughput, cost-effective, and rapid veterinary antibiotic residue screening, supporting food safety surveillance efforts. Full article

(This article belongs to the Special Issue Veterinary Antibiotics in Food-Producing Animals: Residue Detection, Risk Assessment and Regulatory Advances)

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19 pages, 338 KB

Open AccessReview

The Impact of COVID-19 on the Epidemiology of Carbapenem Resistance

by Aikaterini Sakagianni, Christina Koufopoulou, Petros Koufopoulos, Georgios Feretzakis and Vasiliki Koumaki

Antibiotics 2025, 14(9), 916; https://doi.org/10.3390/antibiotics14090916 - 11 Sep 2025

Abstract

Background: The global COVID-19 pandemic has significantly disrupted healthcare systems, inadvertently influencing the epidemiology of antimicrobial resistance (AMR). Among the most critical AMR threats are carbapenem-resistant organisms (CROs), which include carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. This review [...] Read more.

Background: The global COVID-19 pandemic has significantly disrupted healthcare systems, inadvertently influencing the epidemiology of antimicrobial resistance (AMR). Among the most critical AMR threats are carbapenem-resistant organisms (CROs), which include carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. This review explores the pandemic’s impact on carbapenem resistance patterns worldwide. Objectives: This study aimed to assess the effects of the COVID-19 pandemic on carbapenem resistance trends, identify key drivers, and discuss implications for clinical practice and public health policy. Methods: A comprehensive review of peer-reviewed literature, national surveillance reports, and WHO/ECDC data from 2019 to 2025 was conducted, with emphasis on hospital-acquired infections, antimicrobial use, and infection control practices during the pandemic. Results: The pandemic has led to increased use of broad-spectrum antibiotics, including carbapenems, often in the absence of confirmed bacterial co-infections. Overwhelmed healthcare systems and disruptions in infection prevention and control (IPC) measures have facilitated the spread of carbapenem-resistant organisms, particularly in intensive care settings. Surveillance data from multiple countries show a measurable increase in CRO prevalence during the pandemic period, with regional variations depending on healthcare capacity and stewardship infrastructure. Conclusions: COVID-19 has accelerated the emergence and dissemination of carbapenem resistance, underscoring the need for resilient antimicrobial stewardship and IPC programs even during public health emergencies. Integrating pandemic preparedness with AMR mitigation strategies is critical for preventing further escalation of resistance. Full article

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

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16 pages, 3955 KB

Open AccessArticle

Postβ-Lactamase-Inhibiting Effect of Sulbactam in Combination with Ceftriaxone on Extended-Spectrum-β-Lactamase-Producing Escherichia coli

by Ru Wang, Kun Mi, Aihua Lu, Chengyang Zhang, Lei Sun, Yuxiang Chen, Yuanhu Pan, Yanfei Tao and Lingli Huang

Antibiotics 2025, 14(9), 915; https://doi.org/10.3390/antibiotics14090915 - 11 Sep 2025

Abstract

Background/Objectives: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli poses a significant global health challenge, as it leads to antimicrobial treatment failure and is associated with elevated mortality rates. The use of β-lactam/β-lactamase inhibitor combinations offers an alternative approach for combating ESBL-producing bacteria. Ceftriaxone (CRO) [...] Read more.

Background/Objectives: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli poses a significant global health challenge, as it leads to antimicrobial treatment failure and is associated with elevated mortality rates. The use of β-lactam/β-lactamase inhibitor combinations offers an alternative approach for combating ESBL-producing bacteria. Ceftriaxone (CRO) and sulbactam have been coadministered in the clinical settings; however, discrepancies in their pharmacokinetics raise concerns regarding the rationality of this combination. Methods: This study was designed to investigate the postβ-lactamase inhibitor effect (PLIE) under both static and dynamic conditions, with the aim of supporting the clinical application of this combination. Results: The minimum inhibitory concentration (MIC) of CRO/SBT (2:1 ratio) against E. coli NCTC 13353 was determined to be 32/16 μg/mL. The PLIEs were determined to be −1.26, −0.57, and 0.37 h at CRO/SBT concentrations ranging from 1/2 MIC to 2 MIC, respectively. The results of CRO concentration, β-lactamase activity, bla_CTX-M-15 expression, and cell morphology collectively support that SBT exerts PLIEs and protects against the antibacterial activity of CRO. In the dynamic hollow-fiber infection model, CRO monotherapy showed no inhibitory effect on E. coli, whereas CRO/SBT combination therapy rapidly eliminated SBT, achieved comparable bactericidal effects, prolonged CRO exposure, and maintained low β-lactamase activity levels. Conclusions: In conclusion, CRO/SBT exerts an inhibitory effect on enzyme-producing strains by being able to produce PLIE to maintain the inhibition of β-lactamase. Full article

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

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22 pages, 790 KB

Open AccessArticle

Determinants of Implementation of Antimicrobial Stewardship Interventions for Managing Community Adult Acute Respiratory Infections: Qualitative Analysis from the OPTIMAS-GP Study Co-Design Phase

by Margaret Jordan, Mary Burns, Colin Cortie, Janette Radford, Christine Metusela, Judy Mullan, Simon Eckermann, Fiona Williams, Caitlin Keighley, Danielle Mazza, Indra Gajanayake, Stephen Barnett and Andrew Bonney

Antibiotics 2025, 14(9), 914; https://doi.org/10.3390/antibiotics14090914 - 11 Sep 2025

Abstract

Background/Objectives: Antimicrobial stewardship (AMS) interventions are critical to reducing inappropriate antibiotic prescribing for acute respiratory infections (ARIs) in primary care and mitigating antimicrobial resistance (AMR). While interventions are routinely employed in hospitals, implementation in general practice is nascent. This qualitative study, part of [...] Read more.

Background/Objectives: Antimicrobial stewardship (AMS) interventions are critical to reducing inappropriate antibiotic prescribing for acute respiratory infections (ARIs) in primary care and mitigating antimicrobial resistance (AMR). While interventions are routinely employed in hospitals, implementation in general practice is nascent. This qualitative study, part of the OPTIMAS-GP project, explored determinants influencing the implementation of evidence-based AMS strategies in Australian general practice. Methods: Using Experience-Based Co-Design, three rounds of online focus groups were conducted with ten healthcare professionals (GPs, pharmacists, microbiologist, practice staff) and ten adult patients who had experienced ARI management in primary care. Participants discussed the feasibility and acceptability of AMS interventions: shared decision-making (SDM) tools, delayed prescribing (DP) and point-of-care testing (PoCT) for C-reactive protein (CRP). Results: Thematic analysis of focus group transcriptions identified four interrelated themes: ‘Patient acceptance and engagement’, ‘Practising within a system’, ‘Prescribing stewardship’, and ‘Diagnostic stewardship’. Patient engagement was dependent upon expectations, trust, and personalised care, while systemic factors such as continuity of care, practice culture, and resource availability influenced implementation. DP was viewed as a pragmatic but potentially confusing strategy, requiring clear patient guidance and interprofessional collaboration. SDM tools were conceptually supported but challenged by time constraints and poor health literacy. PoCT-CRP was cautiously welcomed for selective use, with concerns expressed about workflow integration and overreliance on testing. Findings were mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) and Theoretical Domains Framework (TDF) to identify behavioural determinants and inform future implementation strategies. Recommendations include co-designing patient-centred AMS tools with clear instructions and red flags, enhancing GP-pharmacist collaboration, and addressing barriers to PoCT integration. Conclusions: These insights highlight the complexity of implementing AMS interventions in general practice and underscore the need for tailored, system-supported approaches to optimise antibiotic use and reduce AMR. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance, 2nd Edition)

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26 pages, 3530 KB

Open AccessArticle

Temporizin-1 Meets the Membranes: Probing Membrane Inser-Tion and Disruption Mechanisms

by Rosa Bellavita, Sara Palladino, Karyne Rangel, Guilherme Curty Lechuga, Lorenzo Emiliano Imbò, Lucia Falcigno, Gabriella D’Auria, Leonardo da Silva Lara, Mirian Cláudia de Souza Pereira, Salvatore Giovanni De-Simone, Stefania Galdiero and Annarita Falanga

Antibiotics 2025, 14(9), 913; https://doi.org/10.3390/antibiotics14090913 - 10 Sep 2025

Abstract

Background/Objectives: Temporizin-1, a hybrid antimicrobial peptide derived from the combination of Temporin A, Gramicidin peptide, and a poly-leu sequence, has strong trypanocide activity against Trypanosoma cruzi and moderate cytotoxicity towards mammalian cells. In this study, we investigated the mode of action of the [...] Read more.

Background/Objectives: Temporizin-1, a hybrid antimicrobial peptide derived from the combination of Temporin A, Gramicidin peptide, and a poly-leu sequence, has strong trypanocide activity against Trypanosoma cruzi and moderate cytotoxicity towards mammalian cells. In this study, we investigated the mode of action of the peptide upon interaction with protozoan and eukaryotic membranes. Methods: To this end, we conducted a series of biophysical assays using liposomes as biomimetic models, along with fluorescence-based experiments such as lipid mixing, membrane leakage, and assays involving Thioflavin and Laurdan. Results: Temporizin-1 displayed potent membranolytic activity on protozoan and eukaryotic membranes, causing significant membrane fusion and leakage with consequent pore formation. In addition, we also performed structural studies on liposome interaction, where we observed a helical structure that is conserved during membrane interaction. The NMR study confirms all the data obtained, providing both the structure of free Temporizin-1 in solution and the way it interacts with micelles. Moreover, Temporizin-1 demonstrated high selectivity against intracellular forms of T. cruzi and exhibited an additive effect when combined with benznidazole, highlighting its promising therapeutic activity. Conclusions: In conclusion, elucidating the mechanism of action of Temporizin-1 is essential for optimizing its structure and improving target selectivity, and driving the rational design of next-generation antimicrobial peptides by applying chemical strategies and delivery system’s conjugation. Full article

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

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22 pages, 2905 KB

Open AccessArticle

In Vitro and In Silico Analysis of Differential Antibacterial Activity of Pomegranate Polyphenols Against Gram-Positive and Gram-Negative Bacteria

by Relja Suručić, Maja Travar, Tatjana Kundaković Vasović, Jelena Radović Selgrad, Ljiljana Suručić, Milan Momčilović, Miloš P. Stojiljković and Ranko Škrbić

Antibiotics 2025, 14(9), 912; https://doi.org/10.3390/antibiotics14090912 - 10 Sep 2025

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Abstract

Background/Objectives: This study investigates the antimicrobial properties of pomegranate peel extract (PoPEx) and its major polyphenolic constituents against Gram-positive and Gram-negative bacteria, employing six clinical isolates of Staphylococcus aureus and five isolates of Escherichia coli. The study further aims to elucidate mechanisms [...] Read more.

Background/Objectives: This study investigates the antimicrobial properties of pomegranate peel extract (PoPEx) and its major polyphenolic constituents against Gram-positive and Gram-negative bacteria, employing six clinical isolates of Staphylococcus aureus and five isolates of Escherichia coli. The study further aims to elucidate mechanisms of action through molecular docking and transport studies. Methods: Chemical composition was analyzed using liquid chromatography–mass spectrometry (LC–MS). Antimicrobial activity was determined by the broth microdilution method. Molecular docking was performed with the AutoDock Vina algorithm, and transport studies through porin channels were carried out using Caver software. Results: PoPEx showed stronger activity against Gram-positive (MICs 15.62–500.00 μg/mL) than Gram-negative bacteria (MICs 125.00–500.00 μg/mL). Punicalagin was most active against S. aureus, while gallic acid was most effective against E. coli. Docking revealed high affinities of punicalagin and punicalin, whereas transport studies highlighted the advantage of smaller phenolics like gallic acid in crossing porins. Conclusions: Larger tannins exhibited strong target binding but limited porin permeability, reducing efficacy in Gram-negative bacteria. These findings provide insights into structure–activity relationships of pomegranate polyphenols and support their potential as natural antimicrobial agents. Full article

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

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13 pages, 215 KB

Open AccessArticle

Antibiotic Prescription Patterns in the Post-COVID-19 Era in Six European Countries: A Cross-Sectional Study

by Karel Kostev, Swati Upadhyaya, Oliver Utsch, Katarzyna Sosnowska, Marcel Konrad and Christian Tanislav

Antibiotics 2025, 14(9), 911; https://doi.org/10.3390/antibiotics14090911 - 10 Sep 2025

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Abstract

Background/Objective: After the relaxation of acute containment measures during the COVID-19 pandemic, Europe experienced a substantial rebound of non-COVID infections surpassing pre-pandemic levels and causing significant clinical burden. The aim of our study is to analyze outpatient prescription data in Germany, France, Italy, [...] Read more.

Background/Objective: After the relaxation of acute containment measures during the COVID-19 pandemic, Europe experienced a substantial rebound of non-COVID infections surpassing pre-pandemic levels and causing significant clinical burden. The aim of our study is to analyze outpatient prescription data in Germany, France, Italy, Belgium, the UK, and Poland in order to assess trends and disparities in the post-COVID landscape. Methods: The present cross-sectional study utilized data from six independently collected datasets containing details from longitudinal prescription (LRx) databases. We aimed to evaluate changes in the number of antibiotic prescriptions issued in 2022 (the first post-pandemic year) compared to 2021 (a pandemic year), as well as subsequent developments in 2023 and 2024. Analyses were stratified by age group and by sex. In addition, the most frequently prescribed antibiotics in each year and country were reported. Results: All countries experienced a marked increase in antibiotic use in 2022 compared to 2021. The year-on-year growth in 2022 ranged from +12.0% in France to a substantial +39.3% in Belgium. Germany, Poland, and the UK also showed strong increases of over 25%, while Italy rose by 21.5%. Growth slowed in 2023 and stabilized or declined in 2024, particularly in Poland, Italy, and Belgium. Pediatric antibiotic use surged in 2022, especially among children under 10 (+75% in the UK), then leveled off and even declined in some cases in 2024, while the number of antibiotic prescriptions in older adults either decreased or increased only slightly. Germany and the UK showed continued pediatric antibiotic use increases through 2023. Amoxicillin dominated prescriptions in most countries, but drug choice patterns varied widely by country. Conclusions: This study shows a clear increase in outpatient antibiotic prescriptions issued across Europe after the COVID-19 pandemic, particularly among children and teenagers. Although the overall trends are now starting to level out, some countries still show rising numbers. These findings underscore the importance of a renewed focus on antibiotic stewardship programs, particularly in outpatient and primary care settings. Full article

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

12 pages, 1411 KB

Open AccessArticle

Antimicrobial Resistance of Staphylococcus borealis Isolated from Pig Farms: High Prevalence of SCCmec Type V and Emergence of cfr-Positive Isolates

by Ji Hyun Lim, Ji Heon Park, Gi Yong Lee and Soo-Jin Yang

Antibiotics 2025, 14(9), 910; https://doi.org/10.3390/antibiotics14090910 - 9 Sep 2025

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Abstract

Background: The emergence of livestock-associated antimicrobial-resistant staphylococci, particularly non-aureus staphylococci, has become a major public health problem requiring immediate global attention. Methods: In this study, 92 Staphylococcus borealis isolates from 20 different pig farms in Korea were examined to determine the following: [...] Read more.

Background: The emergence of livestock-associated antimicrobial-resistant staphylococci, particularly non-aureus staphylococci, has become a major public health problem requiring immediate global attention. Methods: In this study, 92 Staphylococcus borealis isolates from 20 different pig farms in Korea were examined to determine the following: (1) antimicrobial-resistance (AMR) profiles of the isolates, (2) prevalence of methicillin resistance and staphylococcal cassette chromosome methicillin resistance gene (SCCmec) types, (3) occurrence of chloramphenicol–florfenicol resistance gene (cfr)-mediated oxazolidinone resistance, and (4) genomic characteristics of cfr-positive methicillin-resistant S. borealis (MRSB) via whole-genome sequence (WGS) analysis. Results: The overall rate of S. borealis isolation was 9.1% (92 isolates/1009 swabs), and 34.8% (32/92) of the isolates were MRSB. Surprisingly, all 32 MRSB isolates carried SCCmec V for methicillin resistance, and 31/32 MRSB isolates displayed multidrug-resistance phenotypes. Although 22 cfr-positive S. borealis isolates (20 MRSB and two methicillin-susceptible S. borealis) were identified, most of the isolates were susceptible to linezolid because they carried the 35-bp insertion sequence in the cfr promoter. Moreover, WGS analyses suggested horizontal transmission of SCCmec V and cfr-containing plasmids among different staphylococci species, including Staphylococcus aureus, S. epidermidis, and S. borealis. Conclusions: To the best of our knowledge, this study is the first to describe the AMR characteristics of livestock-associated S. borealis isolates, particularly the high prevalence of SCCmec V and cfr. Collectively, these results suggest that S. borealis is a crucial reservoir of AMR genes on pig farms in Korea. Full article

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

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11 pages, 863 KB

Open AccessArticle

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

by Tomke Asendorf, Christine Wind and Andreas Vilcinskas

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

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Abstract

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

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

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16 pages, 3035 KB

Open AccessArticle

Co-Culturing Bacillus Strains for Enhanced Antimicrobial Activity

by Charlie Tran, Russell S. Addison, Ian E. Cock, Xiaojing Chen and Yunjiang Feng

Antibiotics 2025, 14(9), 908; https://doi.org/10.3390/antibiotics14090908 - 8 Sep 2025

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Abstract

Background/Objectives: Bacillus probiotic mixtures have been used as a novel source of antimicrobial production. However, there is a need to emphasize the potential of co-cultured Bacillus strains and to understand the underlying mechanisms involved in their combination formulation. Methods: Bacillus strains [...] Read more.

Background/Objectives: Bacillus probiotic mixtures have been used as a novel source of antimicrobial production. However, there is a need to emphasize the potential of co-cultured Bacillus strains and to understand the underlying mechanisms involved in their combination formulation. Methods: Bacillus strains BPR-11, BPR-16, and BPR-17, were cultured either as mono or multi-cultures. The bacterial growth and density were evaluated by measuring their optical density. The chemical profiles of their bioactive extracts were analysed by LC-MS, and their antimicrobial activity were tested against selected pathogens. Results: Our results reveal that co-cultured strains significantly increased bacterial growth, with an optical density level of, 2.67 which was significantly higher than the monocultures of BPR-11 (2.24), BPR-16 (2.32), and BPR-17 (2.22). Furthermore, the ethyl acetate extracts from these bacterial cultures showed that the combined co-culture (F1) exhibited the highest antimicrobial activity, with MICs of 25 µg/mL against C. perfringens, E. coli, and S. aureus, and 50 µg/mL against P. aeruginosa and S. enterica. In contrast, the monocultures BPR-16 and BPR-17 showed moderate activity with MICs of 50 µg/mL against C. perfringens, E. coli, and S. aureus, and 100 µg/mL against P. aeruginosa and S. enterica. BPR-11 had the lowest antimicrobial activity, with MICs of 100 µg/mL against C. perfringens, E. coli, and S. aureus, and no activity against P. aeruginosa and S. enterica. Metabolite profiling showed that the extract from the co-culture had a marked increase in the production of antimicrobial metabolites, including C₁₃-C₁₆ surfactin C. Lastly, the metabolism study of surfactin C analogues suggested that they were highly stable (99%) when incubated with cytochromes P450 over 120 min. Conclusions: Together, these findings highlight the potential for multi-strain co-culturing to develop new antimicrobials and provide valuable insights into the synergistic effects for antimicrobial production. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Prof. Dr. Rob Capon—Outstanding Contributions in the Field of Anti-Infectives)

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12 pages, 606 KB

Open AccessArticle

High Prevalence of Antimicrobial Resistance Genes in Rabbit Farms from Sumy Region, Ukraine

by Sara Gomes-Gonçalves, Jaqueline T. Bento, Ana Machado, Yevheniia Dudnyk, Oksana Shkromada, Halyna Rebenko, Adriano A. Bordalo and João R. Mesquita

Antibiotics 2025, 14(9), 907; https://doi.org/10.3390/antibiotics14090907 - 8 Sep 2025

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Abstract

Background/Objectives: Antimicrobial resistance (AMR) poses a significant threat to public health, food security, and sustainable livestock production. Despite increasing concern, AMR remains poorly studied in cuniculture, particularly in regions where rabbit farming is predominantly small-scale and household-based. This study aimed to assess [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) poses a significant threat to public health, food security, and sustainable livestock production. Despite increasing concern, AMR remains poorly studied in cuniculture, particularly in regions where rabbit farming is predominantly small-scale and household-based. This study aimed to assess the prevalence and diversity of antimicrobial resistance genes (ARGs) in rabbit farms in northeastern Ukraine. Methods: A total of 100 fecal samples were collected from clinically healthy rabbits housed in two farms and one vivarium. DNA was extracted and analyzed using real-time PCR targeting 21 ARGs associated with resistance to major antibiotic classes, including tetracyclines, sulfonamides, β-lactams, macrolides, quinolones, carbapenems, and multidrug efflux systems. Results: A diverse and widespread resistome was identified. The most prevalent genes included sul1 (96%), blaTEM (95%), tetM (94%), and ermB (93%). AcrB (78%) and qnrS/oqxB (approximately 67%) were also frequently detected. Carbapenemase genes (blaKPC, blaNDM, blaVIM) were identified in 6% of samples, despite limited veterinary use of carbapenems. Notably, 96% of samples harbored ARGs from three or more antibiotic classes, indicating a high potential for multidrug resistance. Conclusions: The findings demonstrate a high prevalence and diversity of ARGs in rabbit farming systems in northeastern Ukraine. The presence of clinically significant resistance genes, including those conferring carbapenem resistance, underscores the urgent need for targeted AMR surveillance and improved antibiotic stewardship in cuniculture, particularly in regions with minimal regulatory oversight of antimicrobial use. Full article

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

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17 pages, 2591 KB

Open AccessArticle

Comparative Analysis of Phenotypic and Genotypic Antibiotic Susceptibility of Pasteurella multocida Isolated from Various Host Species in France and Hungary

by Krisztina Pintér, Marianna Domán, Enikő Wehmann, Hubert Gantelet and Tibor Magyar

Antibiotics 2025, 14(9), 906; https://doi.org/10.3390/antibiotics14090906 - 8 Sep 2025

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Abstract

Background/Objectives: Pasteurella multocida is responsible for a wide variety of animal diseases worldwide, causing major economic losses. These infections are usually treated with antibiotics; however, the emergence of multidrug-resistant (MDR) strains is increasingly hindering. Understanding antibiotic resistance in P. multocida is important [...] Read more.

Background/Objectives: Pasteurella multocida is responsible for a wide variety of animal diseases worldwide, causing major economic losses. These infections are usually treated with antibiotics; however, the emergence of multidrug-resistant (MDR) strains is increasingly hindering. Understanding antibiotic resistance in P. multocida is important for effective treatment strategies and public health, as it impacts both animal and human welfare. Methods: In this study, the antibiotic susceptibility of 80 P. multocida isolates was evaluated by phenotypic (disk diffusion and broth microdilution) and genotypic analysis via whole-genome sequencing, with particular attention to the occurrence of MDR strains. The strains were tested against antibiotics from nine antimicrobial classes (penicillins, cephalosporins, aminoglycosides, tetracyclines, macrolides, fluoroquinolones, lincosamides, phenicols, and sulfonamides). Antimicrobial resistance gene (ARG) sequences and single-nucleotide polymorphisms (SNPs) were evaluated in paired reads using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) and the Comprehensive Antibiotic Resistance Database (CARD) via Resistance Gene Identifier (RGI), respectively. Results: Phenotypic results indicated that cephalosporins and phenicols were the most effective drugs against P. multocida; however, the majority of strains were also susceptible to fluoroquinolones and tetracyclines. In contrast, high resistance rates were observed to sulfamethoxazole and clindamycin. The most prevalent resistance genes were strA, sul2, and tetH, while none of the strains harbored the bla-_TEM or erm (42) genes. Conclusions: Of the two phenotypic methods, MIC values showed a stronger positive correlation with genotypic results, making it a more suitable method for determining antibiotic susceptibility. The phenotypic results for phenicols, tetracyclines, and fluoroquinolones showed a strong correlation with the detected resistance genes. In contrast, resistance to sulfamethoxazole, β-lactams, and macrolides remained genetically unexplained, suggesting the existence of additional resistance mechanisms to be explored. Full article

(This article belongs to the Section Antibiotics in Animal Health)

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30 pages, 4428 KB

Open AccessSystematic Review

Prevalence and Antimicrobial Resistance of Enterobacteriaceae in Wild Birds Across Europe: A Systematic Review

by Daiana-Ionela Cocoș, Eugenia Dumitrescu, Florin Muselin, Diana Brezovan, János Degi, Oana-Maria Boldura and Romeo T. Cristina

Antibiotics 2025, 14(9), 905; https://doi.org/10.3390/antibiotics14090905 - 8 Sep 2025

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Abstract

Wild birds are increasingly recognized as reservoirs and vectors of antimicrobial-resistant (AMR) Enterobacteriaceae, but comprehensive assessments across Europe remain limited. AMR represents a growing threat to global health under the One Health framework. Background/Objectives: This review aimed to evaluate the occurrence, diversity, [...] Read more.

Wild birds are increasingly recognized as reservoirs and vectors of antimicrobial-resistant (AMR) Enterobacteriaceae, but comprehensive assessments across Europe remain limited. AMR represents a growing threat to global health under the One Health framework. Background/Objectives: This review aimed to evaluate the occurrence, diversity, and resistance patterns of Enterobacteriaceae in wild birds across Europe (1969–2025), and to identify ecological and methodological trends. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed and Web of Science until July 2025. Inclusion criteria targeted studies reporting Enterobacteriaceae isolation and/or AMR in free-living European birds. Data were synthesized thematically by bacterial species, avian order, resistance profile, and country. Risk of bias was assessed based on sampling, reporting, and diagnostic clarity. Results: Eighty studies met the inclusion criteria, covering over 18,000 wild birds from 25 countries. Escherichia coli and Salmonella enterica were most reported, often exhibiting resistance to β-lactams, fluoroquinolones, and tetracyclines. AMR was detected in birds from both urban and natural areas. Study designs varied widely, with inconsistent methods for bacterial identification and susceptibility testing. Conclusions: Wild birds in Europe carry resistant Enterobacteriaceae, including strains with clinically relevant resistance profiles. These findings support their inclusion in One Health AMR surveillance and highlight the need for harmonized protocols, expanded molecular tools, and ecological integration. Full article

(This article belongs to the Special Issue Challenges and Emerging Strategies to Tackle the Global Burden of Antimicrobial Resistance)

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3 pages, 140 KB

Open AccessEditorial

Antimicrobial Resistance and Therapy in the Intensive Care Unit

by Pablo Vidal-Cortés, Borja Suberviola-Cañas and David Andaluz-Ojeda

Antibiotics 2025, 14(9), 904; https://doi.org/10.3390/antibiotics14090904 - 8 Sep 2025

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Abstract

Antimicrobial resistance (AMR) has emerged as one of the greatest public health challenges in the last decades [...] Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Therapy in Intensive Care Unit)

11 pages, 1317 KB

Open AccessArticle

Purification and Characterization of Enterocins A, B, and a Novel High-Mass Bacteriocin from Enterococcus lactis-67 with Antilisterial Activity

by Ezequiel Hernandez-Mendoza, Miguel Ángel Martínez-Téllez, Humberto González-Ríos, Emmanuel Aispuro-Hernández, María de la Cruz Paredes-Aguilar, Alexa Rubí-Soberanes and Etna Aida Peña-Ramos

Antibiotics 2025, 14(9), 903; https://doi.org/10.3390/antibiotics14090903 - 6 Sep 2025

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Abstract

Background/Objectives: Listeria monocytogenes is a high-risk pathogen in the food industry involved in several outbreaks. Bacteriocins are natural-origin antimicrobial peptides or proteins that represent a good alternative to synthetic antimicrobials capable of inhibiting the growth of pathogens. This study aimed to purify [...] Read more.

Background/Objectives: Listeria monocytogenes is a high-risk pathogen in the food industry involved in several outbreaks. Bacteriocins are natural-origin antimicrobial peptides or proteins that represent a good alternative to synthetic antimicrobials capable of inhibiting the growth of pathogens. This study aimed to purify and identify bacteriocins from the cell-free supernatant of Enterococcus lactis-67, which exhibits antagonistic activity against L. monocytogenes. Methods: Protein purification was performed by precipitation with ammonium sulfate, dialysis, and fast protein liquid chromatography. Active protein fractions were analyzed by SDS-PAGE and identified by mass spectrometry. Results: In addition to enterocins A and B, a novel 47 kDa bacteriocin with LysM and NlpC/P60 domains, on the N- and C-terminal regions, respectively, was identified. This enterocin has not been described for Enterococcus before. Conclusions: This study contributes to the identification of new natural and effective strategies for ensuring food safety. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Bioactive Peptides and Their Derivatives)

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14 pages, 1394 KB

Open AccessArticle

Antifungal Susceptibility of Malassezia pachydermatis Isolates from Companion Animals and Genomic Insights into Resistance Mechanisms

by Marianna Domán, Dávid Első, Krisztina Pintér, Enikő Wehmann, Enikő Fehér and Tibor Magyar

Antibiotics 2025, 14(9), 902; https://doi.org/10.3390/antibiotics14090902 - 5 Sep 2025

Viewed by 387

Abstract

Background/Objectives: Malassezia pachydermatis is a lipophilic yeast frequently associated with otitis externa and dermatological disorders in companion animals. This study aimed to evaluate the antifungal susceptibility of M. pachydermatis isolates from dogs and cats and to investigate the genomic determinants of reduced [...] Read more.

Background/Objectives: Malassezia pachydermatis is a lipophilic yeast frequently associated with otitis externa and dermatological disorders in companion animals. This study aimed to evaluate the antifungal susceptibility of M. pachydermatis isolates from dogs and cats and to investigate the genomic determinants of reduced susceptibility. Methods: Susceptibility testing of 87 clinical isolates was performed using a modified CLSI broth microdilution method in Sabouraud dextrose broth supplemented with 1% Tween 80. The whole genome of ten representative isolates was sequenced and the genetic factors that are involved in drug resistance were investigated. Results: Ketoconazole, itraconazole, and terbinafine exhibited the highest efficacy, while miconazole and clotrimazole showed reduced activity. Whole genome sequencing revealed single nucleotide polymorphisms (SNPs) in genes that play a key role in the ergosterol biosynthesis pathway, particularly in ERG11 and ERG1. While some specific amino acid substitutions (e.g., K446R in ERG11) were found only in isolates with elevated MIC values, no direct correlation with resistance could be unequivocally established. Conclusions: Genomic analyses also uncovered chromosomal mutations and the heterozygosity of certain isolates, suggesting that complex, multifactorial mechanisms may drive the development of drug resistance. These findings highlight the importance of standardized susceptibility testing and further genomic investigations to promote effective antifungal therapy in veterinary medicine. Full article

(This article belongs to the Special Issue Companion Animals: Antimicrobial Resistance in Bacterial and Fungal Pathogens Associated with Skin and Ear Infections)

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13 pages, 602 KB

Open AccessArticle

Prophylactic Antibiotics in Vertebroplasty and Kyphoplasty: A Nationwide Analysis of Infection Rates and Antibiotic Use in South Korea

by Youngjin Kim, Young-Hoon Kim, Sukil Kim, Jun-Seok Lee, Sang-Il Kim, Joonghyun Ahn, So-Young Han and Hyung-Youl Park

Antibiotics 2025, 14(9), 901; https://doi.org/10.3390/antibiotics14090901 - 5 Sep 2025

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Abstract

Background/Objectives: Vertebroplasty (VP) and kyphoplasty (KP) are widely performed minimally invasive procedures for osteoporotic vertebral compression fractures and vertebral metastases. Although generally safe, postoperative surgical site infections (SSIs) can lead to severe complications. The true incidence of SSIs and optimal prophylactic antibiotic [...] Read more.

Background/Objectives: Vertebroplasty (VP) and kyphoplasty (KP) are widely performed minimally invasive procedures for osteoporotic vertebral compression fractures and vertebral metastases. Although generally safe, postoperative surgical site infections (SSIs) can lead to severe complications. The true incidence of SSIs and optimal prophylactic antibiotic strategies remains unclear. This study evaluated SSI incidence and the impact of antibiotic timing and type using a nationwide quality assessment (QA) database in South Korea. Methods: We analyzed data from the 7th to 9th QA waves of the Health Insurance Review and Assessment (HIRA) Service, including 23,868 patients who underwent VP or KP. SSI incidence was compared across antibiotic timing groups (preoperative-only, postoperative-only, and combined) and antibiotic types. Multivariate logistic regression identified independent risk factors for SSIs. Results: SSI occurred in 47 patients (0.20% of 23,868 procedures). No infections were observed in the preoperative-only group, compared with 0.36% in the postoperative-only group and 0.19% in the pre- and postoperative group. The lowest incidence (0.16%) was seen with first- or second-generation cephalosporins. Multivariate analysis found no significant difference between the preoperative-only and the combined regimens, nor between first-/second-generation cephalosporins and broad-spectrum antibiotics. However, surgery at a tertiary hospital (aOR: 3.566) and malnutrition (aOR: 2.915) were independently associated with increased SSI risk. Conclusions: This nationwide study, the largest to date on VP and KP, demonstrated that SSIs are rare (0.2%). A single preoperative dose of first- or second-generation cephalosporins was as effective as combined or broader-spectrum regimens. Targeted preventive measures may be warranted for high-risk groups such as patients with malnutrition or those treated in tertiary hospitals. Full article

(This article belongs to the Special Issue Orthopedic Infections: Epidemiology and Antimicrobial Treatment)

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14 pages, 2212 KB

Open AccessArticle

Comparison of Cost Savings of Methods of Prevention of Orthopedic Implant-Associated Infection in Arthroplasty and Closed Fracture Surgery Patients

by Pedro Augusto Maciel Moreira, Thiago de Carvalho Gontijo, Gabriel Costa Colen, Ana Carolina Morganti, Felipe Ismael Ulloa Gómez, Pedro Assis Mourão, Gabrielle Adriane Rodrigues Mota, Braulio R. G. M. Couto, Patrícia Almeida de Vasconcellos Rocha, Laila Gonçalves Machado, Raquel Bandeira da Silva and Mauro José Salles

Antibiotics 2025, 14(9), 900; https://doi.org/10.3390/antibiotics14090900 - 5 Sep 2025

Viewed by 384

Abstract

Background/Objectives: Surgical site infections (SSIs) are serious complications in orthopedic implant-associated procedures, increasing morbidity, mortality, and hospital costs. The purpose of this study was to evaluate the impact of a structured infection prevention and control (IPC) service on SSI incidence and cost [...] Read more.

Background/Objectives: Surgical site infections (SSIs) are serious complications in orthopedic implant-associated procedures, increasing morbidity, mortality, and hospital costs. The purpose of this study was to evaluate the impact of a structured infection prevention and control (IPC) service on SSI incidence and cost savings across hip arthroplasty (HA), knee arthroplasty (KA), and open reduction and internal fixation (ORIF). Methods: A retrospective analysis included 6930 patients treated between 2019 and 2024, divided into pre-intervention (2019–2022) and post-intervention (2023–2024) cohorts. Preventive methods (PMs) comprised enhanced antibiotic prophylaxis, Staphylococcus aureus screening, chlorhexidine bathing, intraoperative audits, and behavioral interventions. Economic evaluation used literature-based costs, standardized to 2024 US dollars (USD 2024), with sensitivity analyses performed. Results: SSI incidence decreased from 5.6% to 1.1% overall (p < 0.001), with consistent reductions across procedures: ORIF (5.2%→1.0%), HA (9.2%→2.4%), and KA (4.8%→1.2%). In 2023, approximately 31 SSIs and one infection-related death were prevented, avoiding 308 hospital days. Cost savings ranged from USD 209,188 to USD 376,898, with cost saving confirmed in 93% of simulations. Conclusions: Comprehensive infection-prevention protocols, delivered through a structured IPC service, significantly reduced SSIs and generated substantial cost savings. These findings support wider use of these PMs in orthopedic surgery. Full article

(This article belongs to the Special Issue Bone and Joint Infections: The Challenges of Prevention, Diagnosis and Treatment and Opportunities for Future Research)

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18 pages, 1880 KB

Open AccessArticle

Antimicrobial Resistance Profiles of Clinically Relevant Enterobacteriaceae Isolates: A Retrospective Study at a Southern Italian Hospital

by Giorgia Stornelli, Beatrice Marinacci, Valentina Puca, Benedetta Pellegrini, Roberta Zita Marulli, Ivana Cataldo, Francesca Sisto, Vittoria Perrotti, Arianna Pompilio, Mattia Mori, Pamela Di Giovanni and Rossella Grande

Antibiotics 2025, 14(9), 899; https://doi.org/10.3390/antibiotics14090899 - 5 Sep 2025

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Abstract

Background: The Enterobacteriaceae family is the most heterogeneous group of Gram-negative bacilli, with both environmental and clinical relevance. Although many of these species are part of the normal intestinal microbiota, species such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are [...] Read more.

Background: The Enterobacteriaceae family is the most heterogeneous group of Gram-negative bacilli, with both environmental and clinical relevance. Although many of these species are part of the normal intestinal microbiota, species such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis are among the most common opportunistic pathogens, frequently responsible for nosocomial infections, including urinary tract infections, bacteraemia, and pneumonia. Based on these concerns, these species are increasingly being studied for their ability to develop antimicrobial resistance, often mediated by extended spectrum β-lactamase or carbapenemase production. The present study aims to analyse the antimicrobial resistance profiles of Enterobacteriaceae isolated from a southern Italian hospital focusing on the species of major clinical importance. Methods: A retrospective analysis was carried out on biological samples collected between 2019 and 2023 at the Microbiology Laboratory of the San Pio Hospital, Vasto (Italy). Eight hundred ninety patients were included, with an average age of 73 years. Bacterial identification was carried out using bacterial culture and biochemical methods, while antimicrobial sensitivity was assessed by using the automated Walk Away System. Results: The most frequently isolated species were Escherichia coli (63.2%), Klebsiella spp. (21.9%), and Proteus spp. (8.8%). All isolates showed resistance to at least one antimicrobial and most to more than four. The highest resistance rates were observed for Cefotaxime (16.0%), followed by Ampicillin (15.6%) and Ciprofloxacin (13.2%). Conclusions: The high prevalence of antimicrobial resistance among clinically relevant Enterobacteriaceae species is a growing clinical challenge. The results of this study, which describe the trend of resistance among Enterobacteriaceae in a local hospital, could help to raise awareness highlighting the urgent need for more advanced diagnostic tools and new therapeutic strategies to treat infections caused by multi-resistant microorganisms. Full article

(This article belongs to the Special Issue Multidrug-Resistant Gram-Negative Bacteria Infections: Current Epidemiology, Prognosis and Treatment Options)

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12 pages, 571 KB

Open AccessArticle

Epidemiological Trends of Carbapenemase-Producing Pseudomonas aeruginosa in a Tertiary Care Hospital in Athens, Greece, During 2020–2023

by Vasiliki Koumaki, Eleni Voudanta, Aikaterini Michelaki, Maria Orfanidou, Eleni Vagiakou, Georgia Vrioni and Athanasios Tsakris

Antibiotics 2025, 14(9), 898; https://doi.org/10.3390/antibiotics14090898 - 5 Sep 2025

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Abstract

Background: Infections caused by carbapenemase-producing Pseudomonas aeruginosa (CPPA) isolates have become a worldwide clinical challenge for clinicians due to the limited treatment options. This study provides epidemiological data on CPPA clinical isolates recovered from one of the largest tertiary care hospitals in Athens, [...] Read more.

Background: Infections caused by carbapenemase-producing Pseudomonas aeruginosa (CPPA) isolates have become a worldwide clinical challenge for clinicians due to the limited treatment options. This study provides epidemiological data on CPPA clinical isolates recovered from one of the largest tertiary care hospitals in Athens, Greece, serving a diverse patient population during and after the COVID-19 pandemic. Materials and Methods: The study included all consecutive single-patient CPPA clinical isolates identified from January 2020 to December 2023 in the clinical laboratory. Identification and antimicrobial susceptibility testing were performed using the VITEK-2 automated system. A lateral flow immunoassay and the FilmArray system for blood cultures only were used for the detection of the five most prevalent carbapenemases. Their epidemiological and antimicrobial susceptibility trends were retrospectively analyzed. Results: During the study period, a total of 628 single-patient CPPA were identified among 902 carbapenem-resistant P. aeruginosa clinical isolates. An increasing number of CPPA was revealed during the survey, especially in the post-COVID period (rising from n = 102 in 2020, n = 105 in 2021, and n = 123 in 2022 to n = 298 in 2023; p < 0.05). Regarding the type of carbapenemase, VIM metallo-beta-lactamase was the only carbapenemase identified during the first two years of the study (2020 to 2021). In 2022, VIM- and NDM-producing isolates split almost evenly at proportions of 57% and 43%, respectively. In 2023, NDM-producing isolates seem to have surpassed VIM producers with rates of 54.4% and 45.6%, respectively. As far as antimicrobial resistance profiles, high rates of resistance were observed for most of the antipseudomonal drugs, exceeding 90% across all study years, with little significant variation. However, aztreonam exhibited moderate activity and colistin exhibited excellent activity, remaining the most viable drugs in this setting. Conclusions: Following the COVID-19 pandemic, an increase in CPPA pathogens was identified, while an epidemiological shift was also observed, with the carbapenemase NDM dominating over VIM since 2023. Continuous surveillance is required to track resistance patterns and guide empirical therapy. In this context, new antimicrobials and antimicrobial combinations are also urgently needed. Full article

(This article belongs to the Special Issue Microbial Resistance to Carbapenems: Epidemiology, Detection and Treatment Options)

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14 pages, 1199 KB

Open AccessArticle

Biotransformation of Antibiotics by Coriolopsis gallica: Degradation of Compounds Does Not Always Eliminate Their Toxicity

by Bouthaina Ghariani, Héla Zouari-Mechichi, Abdulrahman H. Alessa, Hussain Alqahtani, Ahmad A. Alsaigh and Tahar Mechichi

Antibiotics 2025, 14(9), 897; https://doi.org/10.3390/antibiotics14090897 - 5 Sep 2025

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Abstract

Background/Objectives: Wastewaters containing antibiotics pose risks to human health and soil ecosystems. In this study, the white-rot fungus Coriolopsis gallica (a basidiomycete exhibiting high laccase production) was used for the biotransformation of three antibiotics (50 mg L⁻¹): tetracycline, chloramphenicol, and sulfanilamide. [...] Read more.

Background/Objectives: Wastewaters containing antibiotics pose risks to human health and soil ecosystems. In this study, the white-rot fungus Coriolopsis gallica (a basidiomycete exhibiting high laccase production) was used for the biotransformation of three antibiotics (50 mg L⁻¹): tetracycline, chloramphenicol, and sulfanilamide. Methods: The biotransformation process was investigated in liquid and solid media using high-performance liquid chromatography (HPLC) and the bacterial growth inhibition agar well diffusion method, respectively. Results: Among the three antibiotics tested, tetracycline showed the highest biotransformation efficiency, achieving a 100% removal rate in the liquid medium and a 100% decrease in the growth inhibition of Escherichia coli in the solid medium. Chloramphenicol and sulfanilamide were partially removed (20% and 16%, respectively) after 12 days of treatment in more than one step without the loss of their antibacterial activities. The presence of these antibiotics in the culture medium of C. gallica enhanced laccase activity, indicating that this ligninolytic enzyme might participate in the biotransformation process. Conclusions: Thus, the results reported in this article extend our knowledge of the catalytic potential of C. gallica and give further perspectives for its application in the biodegradation of antibiotics. To the best of our knowledge, this is the first study wherein C. gallica was used for the treatment of tetracycline, chloramphenicol, and sulfanilamide. Full article

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29 pages, 1619 KB

Open AccessReview

Combined Toxicity of Microplastics and Antimicrobials on Animals: A Review

by Kuok Ho Daniel Tang

Antibiotics 2025, 14(9), 896; https://doi.org/10.3390/antibiotics14090896 - 5 Sep 2025

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Abstract

Background/Objectives: Microplastics are ubiquitous pollutants that pose physical toxicity and serve as vectors for antimicrobial agents, altering their bioavailability and toxicity. Unlike previous reviews that focus solely on antibiotics and terrestrial or aquatic ecosystems, this review integrates recent findings on the combined [...] Read more.

Background/Objectives: Microplastics are ubiquitous pollutants that pose physical toxicity and serve as vectors for antimicrobial agents, altering their bioavailability and toxicity. Unlike previous reviews that focus solely on antibiotics and terrestrial or aquatic ecosystems, this review integrates recent findings on the combined impacts of microplastics and antimicrobials on both aquatic and terrestrial animals, highlighting their biological responses. Methods: Recent experimental studies involving aquatic and terrestrial animals published in peer-reviewed journals were reviewed. These studies employed co-exposure designs using microplastics of different sizes, aging conditions, and surface chemistries in combination with antimicrobial compounds. Results: Microplastics combined with antimicrobials cause species-specific and often synergistic toxicity in aquatic organisms, affecting reproduction, immunity, oxidative stress, gene expression, and microbiota, with co-exposure often amplifying adverse physiological and developmental effects. Similarly, co-exposure to microplastics and antimicrobials in rodents, amphibians, birds, and soil invertebrates frequently leads to synergistic toxicity, oxidative stress, disrupted gut microbiota, and enhanced accumulation and bioavailability of pollutants, promoting inflammation, neurotoxicity, metabolic dysfunction, and increased antibiotic resistance gene propagation. Particle size, aging, and antimicrobial type influence toxicity severity. Certain microplastic-antimicrobial combinations can exhibit antagonistic effects, though less frequently reported. Conclusions: The interactions between microplastics and antimicrobials pose heightened risks to the health of organisms and ecological stability. These findings underscore the need to revise current risk assessment protocols to consider pollutant mixtures and microplastics-mediated transport. Future research should focus on environmentally relevant exposures, mechanistic studies using omics tools, and long-term ecological impacts. Integrated regulatory strategies are essential to address the compounded effects of microplastics and chemical contaminants. Full article

(This article belongs to the Special Issue Environmental Fate and Effects of Antibiotics and Antibiotic Resistance Genes, 2nd Edition)

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14 pages, 1307 KB

Open AccessArticle

Impact of Obesity on Serum Concentrations of Vancomycin Administered as Continuous Infusion and on Clinical Outcomes in Critically Ill Patients—A Retrospective Observational Study

by Stefanie Nothofer, Rico Angeli, Manfred Weiss, Christian Dumps, Felix Berger, Josephin Eckert, Felix Girrbach, Nadin Scheidt, Susan Menzel, Mirko Lange, Hermann Wrigge and Philipp Simon

Antibiotics 2025, 14(9), 895; https://doi.org/10.3390/antibiotics14090895 - 4 Sep 2025

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Abstract

Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such [...] Read more.

Background/Objectives: Vancomycin is a commonly used antibiotic in critically ill patients with severe methicillin-resistant Staphylococcus aureus infections. Due to its narrow therapeutic window, under- or overdosing is likely to result in adverse effects, especially in patients with conditions associated with altered pharmacokinetics such as obesity. The objective of this study was to investigate the impact of obesity on serum concentrations of vancomycin in critically ill patients receiving intravenous vancomycin by continuous infusion based on ideal body weight (IBW). Methods: This retrospective observational study performed at the University Hospital of Leipzig, Germany, included all patients admitted to the intensive care unit (ICU) between January 2009 and December 2015 who received guideline-based vancomycin therapy based on IBW. Serum concentrations were obtained through routinely performed therapeutic drug monitoring (TDM). Results: A total of 1066 patients with a median age of 62 years were included in this study. The median (25%; 75% quantile) vancomycin treatment duration was 4 (2; 7) days and the median time to reach target concentrations of 20–25 mg L⁻¹ was 3 (2; 4) days without a significant difference between BMI groups. Overall, only 25.9% of patients were in the therapeutic range of 20–25 mg L⁻¹ in the entire treatment interval. 47.8% of vancomycin concentrations obtained from TDM were below the desired target range with no differences between the BMI groups (p = 0.077). 26.3% of measurements exceeded the target range, with a significant increase in the morbidly obese group (p < 0.001). A higher BMI was associated with an increased ICU, in-hospital, 28- and 90-day mortality in morbidly obese patients (p < 0.05). Age, BMI and high SAPS-II and SOFA scores were significant predictors of an increased risk of death. Conclusions: Our preliminary findings suggest that IBW-based dosing may help reduce the risk of supratherapeutic concentrations in morbidly obese patients. The high rates of sub- and supratherapeutic vancomycin serum concentrations across all patients highlight the need for close TDM and dose adjustments, particularly in morbidly obese patients with the highest rates of supratherapeutic vancomycin serum concentrations and of RRT. Full article

(This article belongs to the Special Issue Epidemiology and Antimicrobial Dosing Regimens in Intensive Care Units)

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12 pages, 265 KB

Open AccessReview

Antibiotics for the Treatment of Patients with Metallo-β-Lactamase (MBL)-Producing Gram-Negative Bacterial Infections

by Matthew E. Falagas, Dimitrios S. Kontogiannis, Dimitrios Ragias and Stylianos A. Kakoullis

Antibiotics 2025, 14(9), 894; https://doi.org/10.3390/antibiotics14090894 - 4 Sep 2025

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Abstract

Infections caused by MBL-producing Gram-negative bacterial pathogens have disseminated worldwide and are associated with considerable morbidity and mortality. We evaluated the published clinical evidence on the use of various antibiotics for the treatment of patients with such infections. The available data suggest the [...] Read more.

Infections caused by MBL-producing Gram-negative bacterial pathogens have disseminated worldwide and are associated with considerable morbidity and mortality. We evaluated the published clinical evidence on the use of various antibiotics for the treatment of patients with such infections. The available data suggest the consideration of the new antibiotics cefiderocol and aztreonam-avibactam for the treatment of patients with infections caused by MBL-producing Gram-negative bacterial pathogens. However, their considerable cost and limited availability hinder their use. Also, the combination of ceftazidime-avibactam and aztreonam has been occasionally used, especially when there was an unavailability of aztreonam-avibactam. Additionally, old antibiotics such as colistin and fosfomycin, especially in combination antimicrobial therapy, may be considered for the treatment of patients with such infections. The relevant clinical data on the use of tigecycline and aminoglycosides for infections caused by MBL-producing pathogens are limited. Thus, the evaluation of the published evidence suggests the best treatment options for the treatment of patients with such infections at present. Also, the limited available data highlight the need for dissemination of the already acquired clinical experience and the conduct of new studies examining currently available antibiotics, as well as investigational antimicrobial agents for the treatment of patients with infections caused by MBL-producing Gram-negative bacterial pathogens. Full article

(This article belongs to the Special Issue Gram-Negative Multidrug-Resistant Pathogens and Their Treatment, 2nd Edition)

9 pages, 215 KB

Open AccessCommunication

Rapid Emergence of Cefiderocol Resistance Associated with Mutation of EnvZ Gene in a VIM-Producing ST307 Klebsiella pneumoniae Strain

by Simone Ambretti, Benedetta Secci, Raul Cetatean, Milo Gatti, Pierluigi Viale, Federico Pea and Claudio Foschi

Antibiotics 2025, 14(9), 893; https://doi.org/10.3390/antibiotics14090893 - 4 Sep 2025

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Abstract

Infections caused by carbapenem-resistant Enterobacterales (CRE), particularly those harboring metallo-β-lactamases (MBLs) such as VIM, constitute a significant public health threat due to the paucity of effective therapeutic options. Cefiderocol (CFD), a novel siderophore-conjugated cephalosporin, exhibits potent activity against CRE by exploiting bacterial iron [...] Read more.

Infections caused by carbapenem-resistant Enterobacterales (CRE), particularly those harboring metallo-β-lactamases (MBLs) such as VIM, constitute a significant public health threat due to the paucity of effective therapeutic options. Cefiderocol (CFD), a novel siderophore-conjugated cephalosporin, exhibits potent activity against CRE by exploiting bacterial iron uptake systems. Nevertheless, the emergence of CFD resistance has been recently documented. This study aimed to characterize the development of CFD resistance in a VIM-producing Klebsiella pneumoniae isolate during antimicrobial treatment. Antimicrobial susceptibility was assessed by broth microdilution using iron-depleted medium according to EUCAST guidelines. Whole-genome sequencing and comparative genomic analyses focused on mutations in genes related to iron transport and CFD resistance, using Illumina MiSeq. Initial isolates (RS, BA1) were susceptible to CFD (MIC 2 mg/L), whereas the isolate recovered after 9 days of CFD therapy (BA2) was resistant (MIC 8 mg/L). In conclusion, this study illustrates for the first time the rapid emergence of CFD resistance in a VIM-producing ST307 K. pneumoniae isolate linked to a missense variant in envZ gene, arising after a 9-day CFD treatment. Full article

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

20 pages, 1867 KB

Open AccessArticle

Serratia marcescens Isolates from Bovine Mastitic Milk: Antimicrobial Resistance and Virulence Features

by Guilherme Moreira, Luís Pinho, João R. Mesquita and Eliane Silva

Antibiotics 2025, 14(9), 892; https://doi.org/10.3390/antibiotics14090892 - 3 Sep 2025

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Abstract

Background: Bovine mastitis (BM) is a major disease affecting dairy herds (DHs), with Serratia marcescens (S. marcescens) being increasingly implicated as a causative agent. The growing concern over antimicrobial resistance (AMR) extends to BM-associated S. marcescens isolates, where resistance patterns [...] Read more.

Background: Bovine mastitis (BM) is a major disease affecting dairy herds (DHs), with Serratia marcescens (S. marcescens) being increasingly implicated as a causative agent. The growing concern over antimicrobial resistance (AMR) extends to BM-associated S. marcescens isolates, where resistance patterns are emerging. Methods: Here, four BM Gram-negative isolates were investigated: 1-DH1, 2-DH1, 3-DH2, and 4-DH3. Phenotypic characterization was performed using the Neg-Urine-Combo98 panel on a MicroScan WalkAway Plus system. Whole-genome sequencing (WGS) was performed to characterize and identify AMR and virulence factors (VF) genes and plasmids in isolates 1-DH1, 3-DH2, and 4-DH3, and phylogenomic analyses were conducted for a visual comparison of the genomes. Results: Phenotypically, isolates 1-DH1, 2-DH1, and 4-DH3 were identified as S. marcescens, and 3-DH2 as Serratia odorifera (confirmed as S. marcescens by WGS). A 28.00% (n = 25) prevalence of phenotypic AMR for isolates 1-DH1, 2-DH1, and 4-DH3 against Aug-E, AM, To, Cfx, Crm, Cl, and Fd was shown, and 24.00% (n = 25) for isolate 3-DH2 against Aug-E, AM, To, Crm, Cl, and Fd. The AMR genes AAC(6′)-Ic, aac(6′)-Ic_1, aac(6′)-Ial, H-NS, SRT-2, oqxB, oqxB_1, oqxB25, mexI, CRP, and blaSST-1, and flgH, fliP, fliM, and fliG VF genes were identified in the whole genome of the S. marcescens sequenced isolates 1-DH1, 2-DH1, and 4-DH3. In addition, a phylogenomic analysis of these three isolates revealed that WGS genomes are more closely related to S. marcescens prevenient from environmental sources. Conclusions: This study reports, for the first time, AMR resistance to tobramycin, cefuroxime, colistin, and nitrofurantoin in BM S. marcescens isolates. Genomic analysis revealed the presence of multiple AMR and VF genes, further highlighting the pathogenic potential of these isolates. Phylogenomic analysis revealed that the genome of the three BM S. marcescens isolates is more closely related to environmental S. marcescens strains. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence in Bacterial Isolates: A Genomic Perspective from Human and Animal Sources)

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Antibiotics, Volume 14, Issue 9 (September 2025) – 73 articles

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