Antibiotics

16 pages, 1432 KiB

Open AccessArticle

Modulation of Antimicrobial Resistance in Listeria monocytogenes via Synergistic Interactions Between Thymbra capitata L. (Cav.) Essential Oil and Conventional Antibiotics

by Francesca Maggio, Francesco Buccioni, Stefania Garzoli, Antonello Paparella and Annalisa Serio

Antibiotics 2025, 14(6), 623; https://doi.org/10.3390/antibiotics14060623 - 19 Jun 2025

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Abstract

Background/Objectives: Antimicrobial resistance (AMR) poses a significant global health challenge, contributing to foodborne infections and diminishing the effectiveness of conventional antibiotics. In the quest for alternative strategies to mitigate resistance, this study has assessed the potential of T. capitata L. (Cav.) essential oil [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) poses a significant global health challenge, contributing to foodborne infections and diminishing the effectiveness of conventional antibiotics. In the quest for alternative strategies to mitigate resistance, this study has assessed the potential of T. capitata L. (Cav.) essential oil (TEO) to boost the antibiotic efficacy on L. monocytogenes. Methods: Five L. monocytogenes strains of different origins were tested with TEO alone and in combination with gentamicin, ampicillin, and penicillin G. Moreover, the cells were exposed to sublethal concentrations of TEO for 1 h to evaluate the effects on the antibiotic effectiveness. The antimicrobial activity was assessed by determining the Minimum Inhibitory (MICs) and Bactericidal Concentrations (MBCs), while potential interactions were evaluated using the Fractional Inhibitory Concentration Index and by studying the cell growth dynamics. Results: TEO demonstrated inhibitory activity against L. monocytogenes strains, both alone, in pre-exposure, and in combination with antibiotics, causing up to a seven-fold reduction in MIC and MBC values (from 8 to 1 µg/mL) and restoring susceptibility to the antimicrobial treatments. Positive interactions between TEO and antibiotics were observed, particularly for clinical isolates. Conclusions: TEO could be a promising antibiotic adjuvant in antimicrobial treatments, offering a natural and effective strategy to enhance antibiotic efficacy and to counteract resistance in L. monocytogenes. Full article

(This article belongs to the Special Issue The Search for Antimicrobial Agents from Natural Products)

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18 pages, 321 KiB

Open AccessReview

The Effect of Antibiotics on the Nervous System: Importance for Anesthesiology and Intensive Care

by Paweł Radkowski, Julia Oszytko, Kamil Sobolewski, Florian Trachte, Dariusz Onichimowski and Marta Majewska

Antibiotics 2025, 14(6), 622; https://doi.org/10.3390/antibiotics14060622 - 19 Jun 2025

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Abstract

Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the [...] Read more.

Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the current evidence on antibiotic-induced neurotoxicity, particularly in critical care settings. Methods: A comprehensive literature analysis was performed to assess the neurotoxic profiles, underlying mechanisms, and clinical manifestations associated with different antibiotic classes, including beta-lactams, fluoroquinolones, macrolides, aminoglycosides, and others. Results: Beta-lactam antibiotics (especially cephalosporins and carbapenems) are strongly associated with seizures, encephalopathy, and EEG abnormalities, mainly through GABAergic inhibition and mitochondrial dysfunction. Fluoroquinolones and macrolides can cause psychosis, insomnia, and neuropathy via NMDA activation and oxidative stress. Linezolid carries the risk of serotonin syndrome and optic neuropathy, while glycopeptides and aminoglycosides are primarily associated with ototoxicity. Risk factors include advanced age, renal or hepatic impairment, and high serum drug levels. Conclusions: The neurotoxic potential of antibiotics is a critical but under-recognised aspect of pharmacotherapy in intensive care. Improved awareness, pharmacovigilance, dose adjustment, and drug monitoring are crucial for mitigating adverse neurological effects. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship and Infection Prevention in Intensive Care Unit)

18 pages, 272 KiB

Open AccessReview

Livestock Antibiotics Use and Antimicrobial Resistance

by Elliot Enshaie, Sankalp Nigam, Shaan Patel and Vikrant Rai

Antibiotics 2025, 14(6), 621; https://doi.org/10.3390/antibiotics14060621 - 19 Jun 2025

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Abstract

Background/Objectives: Antibiotic resistance or antimicrobial resistance (AMR) in livestock is a growing global concern that threatens both human and animal health. The overuse and misuse of antibiotics in livestock production have led to an increased propensity for the development of AMR bacterial [...] Read more.

Background/Objectives: Antibiotic resistance or antimicrobial resistance (AMR) in livestock is a growing global concern that threatens both human and animal health. The overuse and misuse of antibiotics in livestock production have led to an increased propensity for the development of AMR bacterial strains in animals, which can be spread to humans through the consumption of contaminated animal products, direct contact, or environmental exposure. This review aims to summarize the development and transmission of AMR in livestock, explore its underlying mechanisms and impact on human and animal health, and discuss current practices and potential strategies for mitigation and prevention. Methods: For this narrative review, we searched articles on PubMed and Google Scholar using the terms antibiotic resistance, livestock, and environment, alone or in combination. Results: The history of antibiotic use in livestock and its link to increased AMR, along with the involved mechanisms, including the enzymatic breakdown of antibiotics, alterations in bacterial targets, horizontal gene transfer, and efflux pumps, are important. Antibiotics in livestock are used for growth promotion, disease prevention and control, and metaphylactic use. The role of livestock and the environment as reservoirs for resistant pathogens, their impact on human health, chronic infections, allergic reactions, toxicity, and the development of untreatable diseases is important to understand AMR. Conclusions: Given the widespread use of antibiotics and the potential consequences of AMR, collaborative global efforts, increased public awareness, coordinated regulations, and advancements in biological technology are required to mitigate the threat AMR poses to human and animal health. Regulatory solutions and the development of new therapeutic alternatives like antimicrobial peptides and bacteriophage therapy, and preventive measures such as DNA and mRNA vaccines, are future perspectives. Full article

(This article belongs to the Special Issue Livestock Antibiotic Use and Resistance)

14 pages, 1541 KiB

Open AccessArticle

First Report in the Americas of S. enterica Var. Enteritidis Carrying bla_NDM-1 in a Putatively New Sub-Lineage of IncC2 Plasmids

by Nicolás F. Cordeiro, Romina Papa-Ezdra, Germán Traglia, Inés Bado, Virginia García-Fulgueiras, María N. Cortinas, Leticia Caiata, Mariana López-Vega, Ana Otero, Martín López, Patricia Hitateguy, Cristina Mogdasy and Rafael Vignoli

Antibiotics 2025, 14(6), 620; https://doi.org/10.3390/antibiotics14060620 - 18 Jun 2025

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Abstract

Background: Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. Case report: We studied a patient who, after being discharged from an ICU, developed salmonellosis caused [...] Read more.

Background: Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. Case report: We studied a patient who, after being discharged from an ICU, developed salmonellosis caused by an antibiotic-susceptible S. enteritidis. After undergoing treatment with ciprofloxacin, the patient presented an episode of asymptomatic bacteriuria originated by a carbapenem and ciprofloxacin-resistant S. enteritidis. Results: Whole genome sequencing analysis revealed that both Salmonella isolates belonged to the same strain, and that isolate SEn_T2 acquired a plasmid carrying both bla_NDM-1 and qnrA1 genes (pIncCSEn) which was previously present in the patient’s gut in at least one Enterobacter cloacae isolate. Additionally, pIncCSEN was identified as a putatively new sub-lineage of IncC2 plasmids which lacked the first copy of the methyltransferase gene dcm and the rhs gene. The resistance genes bla_NDM-1 and qnrA1 were incorporated into a Tn21-derived transposon that included a complex class 1 integron whose genetic arrangement was: intI1- dfrA12- orfF- aadA2- qacEΔ1-sul1-ISCR1- trpF- ble- bla_NDM-1 (in reverse direction)- ISAba125-ISCR1- qnrA- cmlA1- qacEΔ1-sul1. Conclusions: Antimicrobial persistence and co-selection of antibiotic resistance play an important role in the dissemination of antimicrobial resistance genes; in this regard, a joint effort involving the infection control team, effective antibiotic stewardship, and genomic surveillance could help mitigate the spread of these multidrug resistant microorganisms. Full article

(This article belongs to the Special Issue Multidrug-Resistance Patterns in Infectious Pathogens)

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28 pages, 2556 KiB

Open AccessArticle

Evaluation of the Potential of Metal–Organic Compounds ZIF-8 and F300 in a Membrane Filtration–Adsorption Process for the Removal of Antibiotics from Water

by Daniel Polak, Szymon Kamocki and Maciej Szwast

Antibiotics 2025, 14(6), 619; https://doi.org/10.3390/antibiotics14060619 - 18 Jun 2025

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Abstract

Background/Objectives: Antibiotic contamination in water sources is a growing global concern, contributing to environmental degradation and the proliferation of antimicrobial resistance. Traditional treatment methods, such as advanced oxidation or high-pressure membrane processes, are often energy-intensive and economically unsustainable for large-scale or decentralized applications. [...] Read more.

Background/Objectives: Antibiotic contamination in water sources is a growing global concern, contributing to environmental degradation and the proliferation of antimicrobial resistance. Traditional treatment methods, such as advanced oxidation or high-pressure membrane processes, are often energy-intensive and economically unsustainable for large-scale or decentralized applications. This study explores the potential of two cost-effective, commercially available metal–organic frameworks (MOFs), ZIF-8 and F300, to improve the performance of membrane-based filtration–adsorption systems for removing tetracycline and sulfadiazine from water. Methods: Batch adsorption experiments were performed to evaluate the uptake capacities, kinetics, and isotherms of both MOFs toward the selected antibiotics. The membranes were modified using a low-cost silane-assisted deposition of MOF particles and tested in a microfiltration system. Removal efficiencies and water permeability were assessed and kinetic and isotherm models were applied to understand the adsorption mechanisms. Results: ZIF-8 showed superior adsorption performance, with maximum capacities of 442.2 mg/g for tetracycline and 219.3 mg/g for sulfadiazine. F300 was effective only for tetracycline. Membranes modified with ZIF-8 improved pharmaceutical removal by 187% (tetracycline) and 224% (sulfadiazine) compared to unmodified membranes. Although permeability decreased due to increased hydrophobicity, the materials and processes remained economically favorable. Conclusions: This study demonstrates that MOF-modified ceramic membranes, particularly those incorporating ZIF-8, offer a low-cost, scalable, and energy-efficient alternative for pharmaceutical removal from water. The approach combines strong environmental impact with economic viability, making it attractive for broader implementation in water treatment systems. Full article

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14 pages, 680 KiB

Open AccessArticle

Point-Prevalence Survey of Antimicrobial Use in Benin Hospitals: The Need for Antimicrobial Stewardship Programs

by Sarah Delfosse, Carine Laurence Yehouenou, Angèle Dohou, Dessièdé Ariane Fiogbe and Olivia Dalleur

Antibiotics 2025, 14(6), 618; https://doi.org/10.3390/antibiotics14060618 - 18 Jun 2025

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Abstract

Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for [...] Read more.

Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for use in two hospitals in Benin and included an analysis based on the 2021 WHO AWaRe classification. Results: Of the 450 patients enrolled, 148 received antimicrobials (AMs) (overall prevalence 32.9%), most of them orally (54.2%). Both hospitals had a high rate of Access and Watch antibiotics use, and both prescribed mainly metronidazole. In four prescriptions, hospital A used a non-recommended association of antibiotics, such as ceftriaxone + sulbactam and ofloxacin + ornidazole. While hospital A prescribed predominantly amoxicillin + clavulanic acid (19/92; 21%) and ceftriaxone (14/92; 15%), hospital B prescribed ampicillin (24/120; 20%) and cefuroxime (14/120; n = 12%). In hospital B, surgical antimicrobial prophylaxis (SAP) was suboptimal. While there were no single-dose prophylaxis prescriptions, all one-day prophylaxis (SP2) involved ampicillin for cesarean sections. In patients in intensive care units, prolonged prophylaxis (>1 day, SP3) accounted for all postoperative prescriptions. Conclusions: These findings highlight the critical need for implementing antimicrobial stewardship programs, expanding diagnostic laboratory capacity to minimize empirical prescribing, and strengthening medical student training to ensure quality and rational antibiotic use, thereby addressing the growing challenge of resistance in resource-limited settings. Full article

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

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15 pages, 635 KiB

Open AccessReview

Use of Daptomycin to Manage Severe MRSA Infections in Humans

by Marco Fiore, Aniello Alfieri, Daniela Fiore, Pasquale Iuliano, Francesco Giuseppe Spatola, Andrea Limone, Ilaria Pezone and Sebastiano Leone

Antibiotics 2025, 14(6), 617; https://doi.org/10.3390/antibiotics14060617 - 18 Jun 2025

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) represents a major therapeutic challenge due to its multidrug-resistance and the associated clinical burden. Daptomycin (DAP), a cyclic lipopeptide antibiotic, has become a key agent for the treatment of severe MRSA infections owing to its rapid bactericidal activity and [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a major therapeutic challenge due to its multidrug-resistance and the associated clinical burden. Daptomycin (DAP), a cyclic lipopeptide antibiotic, has become a key agent for the treatment of severe MRSA infections owing to its rapid bactericidal activity and favourable safety profile. In this narrative review, we examine studies published between 2010 and April 2025. The data suggest that treatment with high-dose (8–10 mg kg⁻¹) DAP shortened the time to blood-culture sterilisation by a median of 2 days compared with standard-dose vancomycin without increasing toxicity when model-informed area-under-the-curve monitoring was employed. Particular attention is given to the synergistic effects of DAP combined with fosfomycin or β-lactams, especially ceftaroline and ceftobiprole, in overcoming persistent and refractory MRSA infections; this approach results in a reduction in microbiological failure relative to monotherapy. Resistance remains uncommon (<2% of isolates), but recurrent mutations in mprF, liaFSR, and walK underscore the need for proactive genomic surveillance. Despite promising preclinical and clinical evidence supporting combination strategies, further randomized controlled trials are necessary to establish their definitive role in clinical practice, as are head-to-head cost-effectiveness evaluations. DAP remains a critical option in the evolving landscape of MRSA management, provided its use is integrated with precision dosing, resistance surveillance, and antimicrobial-stewardship frameworks. Full article

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

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20 pages, 2643 KiB

Open AccessArticle

Oxacillin-Supplemented Mueller-Hinton Agar for In Vitro Inhibition of Ambler Class C β-Lactamases in Enterobacterales

by Edgar-Costin Chelaru, Andrei-Alexandru Muntean, Mădălina-Maria Muntean, Mihai-Octav Hogea, Costin-Ștefan Caracoti, Bogdan-Florin Ciomaga, Thierry Naas and Mircea Ioan Popa

Antibiotics 2025, 14(6), 616; https://doi.org/10.3390/antibiotics14060616 - 18 Jun 2025

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Abstract

Background: The increasing incidence of infection with Gram-negative bacilli (GNB) producing broad-spectrum β-lactamases, such as extended-spectrum β-lactamases (ESBLs), cephalosporinases (AmpCs), and carbapenemases, has become a great clinical concern. AmpCs are found in many clinically relevant Enterobacterales, where they may compromise the effectiveness [...] Read more.

Background: The increasing incidence of infection with Gram-negative bacilli (GNB) producing broad-spectrum β-lactamases, such as extended-spectrum β-lactamases (ESBLs), cephalosporinases (AmpCs), and carbapenemases, has become a great clinical concern. AmpCs are found in many clinically relevant Enterobacterales, where they may compromise the effectiveness of most β-lactams, including carbapenems when associated with an impaired outer membrane. Detection and distinction between these resistance mechanisms are crucial for antimicrobial therapy and for implementation of proper infection control procedures to prevent further spread. Methods: The disk diffusion antibiogram using Mueller-Hinton agar (MHA) supplemented with cloxacillin (MHC), which inhibits AmpCs, was validated to identify AmpC-producing Enterobacterales (AmpC-PE). As cloxacillin is not available in several countries, we investigated the use of oxacillin as an alternative compound to inhibit AmpCs. The ability of MHA supplemented with oxacillin (MHO) to distinguish between carbapenem-resistant Enterobacterales (CREs) due to AmpC hyperproduction and the presence of a carbapenemase has particularly been investigated. Results: MHOs containing several concentrations of oxacillin were compared to MHA and MHC containing 250 mg/L cloxacillin (MHC250). A set of well-characterized Enterobacterales with different β-lactam resistance mechanisms were evaluated. MHO containing 300 mg/L of oxacillin (MHO300) gave similar results to MHC250. Conclusions: The use of MHO300 proved to be efficient in inhibiting AmpCs, allowing differentiation between AmpC hyperproducers and carbapenemase producers. In addition, the use of MHO300 allowed detection of resistance mechanisms hidden by AmpCs, such as ESBLs. Full article

(This article belongs to the Special Issue Epidemiology and Mechanism of Bacterial Resistance to Antibiotics)

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12 pages, 243 KiB

Open AccessArticle

Adherence to Staphylococcus aureus Bacteremia Management Recommendations Before, During, and After the COVID-19 Pandemic: Prognostic Implications

by Elizabeth Lorenzo-Hernández, Francisco Rivas-Ruiz, Jorge Fernández-Casañas, Vanesa Puerto-Romero, Maria Dolores Martín-Escalante and Alfonso Del Arco-Jiménez

Antibiotics 2025, 14(6), 615; https://doi.org/10.3390/antibiotics14060615 - 18 Jun 2025

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Abstract

Background/Objectives: This work aims to assess the evolution in the management of Staphylococcus aureus bacteremia (SAB) and the impact of the COVID-19 pandemic on it. SAB is associated with high morbidity and mortality, requiring structured management strategies. The COVID-19 pandemic led to major [...] Read more.

Background/Objectives: This work aims to assess the evolution in the management of Staphylococcus aureus bacteremia (SAB) and the impact of the COVID-19 pandemic on it. SAB is associated with high morbidity and mortality, requiring structured management strategies. The COVID-19 pandemic led to major changes in hospital workflows, potentially affecting the quality of SAB care. Methods: We conducted a retrospective per-protocol analysis of SAB episodes at Costa del Sol University Hospital (Marbella, Spain) across three periods: pre-pandemic, pandemic, and post-pandemic. Patients with early mortality or early transfer were excluded. Clinical variables, adherence to recommended management bundles, and outcomes were compared. Demographic characteristics were similar across the analyzed periods. Results: The incidence of SAB increased over time, with a notable rise post-pandemic. Key management indicators such as the identification of infection source and appropriate antibiotic therapy showed adherence rates of above 90%, while echocardiography exhibited an adherence rate of above 75% throughout the study. Adherence to the full management bundle was suboptimal, with no significant differences between periods. However, an appropriate treatment duration significantly improved in the post-pandemic group (p = 0.038). Mortality at 14 and 30 days was highest during the pandemic period (10.3% and 17.6%, respectively), although differences were not statistically significant. Complications and mortality were more frequent in patients with complete adherence to the bundle (p = 0.031). Conclusions: Despite stable or improved adherence to certain SAB management measures during the pandemic, mortality and complication rates did not significantly decrease, likely reflecting increased patient severity or healthcare system overload. These findings highlight the need for sustained, multidisciplinary, bedside-based approaches to SAB care, even during public health emergencies. Further research is needed to explore modifiable factors and enhance adherence to evidence-based recommendations. Full article

(This article belongs to the Special Issue Antibiotic Stewardship Implementation Strategies)

13 pages, 967 KiB

Open AccessReview

Interactions Between Iron Metabolism and the Endocannabinoid System in Bacterial Infections

by Kayle Brenna Dickson, Juan Zhou and Christian Lehmann

Antibiotics 2025, 14(6), 614; https://doi.org/10.3390/antibiotics14060614 - 18 Jun 2025

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Abstract

Iron is a key nutritional requirement for a variety of physiological functions, and its metabolism is tightly controlled under homeostatic conditions. The endocannabinoid system (ECS) represents an additional physiological system with a key role in maintaining homeostasis that is known for its role [...] Read more.

Iron is a key nutritional requirement for a variety of physiological functions, and its metabolism is tightly controlled under homeostatic conditions. The endocannabinoid system (ECS) represents an additional physiological system with a key role in maintaining homeostasis that is known for its role in modulating immune responses. Recent research has highlighted intriguing interactions between these systems, including the suppression of iron uptake by the ECS and alterations to the iron-catalyzed Fenton reaction. These interactions are particularly interesting in the context of bacterial infections. As iron is a vital nutrient for bacteria, modulating iron levels using the ECS may be able to control bacterial growth. This review aims to explore the current understanding of how the ECS affects iron homeostasis and its implications for bacterial pathogenesis. In this study, we provide an overview of both iron metabolism and the ECS, focusing on harnessing these systems to develop novel therapeutic strategies to modulate iron metabolism in bacterial infections. By elucidating these complex interactions, we hope to provide new insights into the development of novel treatments for bacterial infections. Full article

(This article belongs to the Special Issue Tackling Multidrug-Resistant Bacteria with New Antimicrobial Strategies)

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16 pages, 1919 KiB

Open AccessArticle

Development of a UHPLC-UV/Vis Method for Simultaneously Determining Six Beta-Lactam Antibiotics in Plasma: A Tool for the Clinical Implementation of Therapeutic Monitoring of Beta-Lactams

by Iria Varela-Rey, Marta Martínez-Guitián, Gonzalo Hermelo-Vidal, Enrique Bandín-Vilar, Ignacio Novo-Veleiro, Pablo Manuel Varela-García, Irene Zarra-Ferro, Miguel González-Barcia, Cristina Mondelo-García and Anxo Fernández-Ferreiro

Antibiotics 2025, 14(6), 613; https://doi.org/10.3390/antibiotics14060613 - 17 Jun 2025

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Abstract

Background/Introduction: Beta-lactam antibiotics are among the most frequently prescribed drugs in clinical practice, yet their therapeutic drug monitoring remains underutilized despite high interindividual pharmacokinetic variability, especially in critically ill patients. Methods: To address this, we developed and validated an ultra-high-performance liquid chromatography (UHPLC-UV/Vis) [...] Read more.

Background/Introduction: Beta-lactam antibiotics are among the most frequently prescribed drugs in clinical practice, yet their therapeutic drug monitoring remains underutilized despite high interindividual pharmacokinetic variability, especially in critically ill patients. Methods: To address this, we developed and validated an ultra-high-performance liquid chromatography (UHPLC-UV/Vis) method for the simultaneous quantification of six beta-lactams (cefepime, ceftolozane, ceftazidime, meropenem, ampicillin, and ertapenem) in plasma. Results: This method uses a single gradient mobile phase and a photodiode array detector, ensuring accurate separation, minimal interference, and robust analyte identification. Validation followed EMA bioanalytical guidelines, demonstrating selectivity, precision, accuracy, and linearity within clinically relevant ranges (1.0–50.0 mg/L). Stability tests showed that the analytes were stable in plasma for up to seven days at 4 °C and one month at −20 °C. Pilot clinical implementation in 35 patients revealed significant interindividual variability, supporting the need for routine beta-lactam monitoring. Approximately 26% of trough concentrations were below the minimal inhibitory concentration, while others exceeded thresholds associated with potential toxicity. Discussion: This study represents the first UHPLC-UV/Vis method for the simultaneous determination of these six beta-lactams, overcoming limitations of prior methods that required different mobile phases or excluded clinically relevant antibiotics. The method is universally applicable and easily transferable to routine clinical practice. Conclusions: These findings underline the importance of beta-lactam monitoring in optimizing treatment outcomes and combating antibiotic resistance in vulnerable populations. Further studies to assess free drug concentrations are warranted to enhance clinical applicability. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)

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22 pages, 3511 KiB

Open AccessArticle

Genomic Characterization and Safety Evaluation of Enterococcus lactis RB10 Isolated from Goat Feces

by Nattarika Chaichana, Sirikan Suwannasin, Jirasa Boonsan, Thunchanok Yaikhan, Chollachai Klaysubun, Kamonnut Singkhamanan, Monwadee Wonglapsuwan, Rattanaruji Pomwised, Siriwimon Konglue, Rusneeta Chema, Manaschanan Saivaew and Komwit Surachat

Antibiotics 2025, 14(6), 612; https://doi.org/10.3390/antibiotics14060612 - 16 Jun 2025

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Abstract

Background: The genus Enterococcus includes a diverse group of bacteria that are commonly found in the gastrointestinal tracts of humans and animals, as well as in various environmental habitats. Methods: In this study, Enterococcus lactis RB10, isolated from goat feces, was subjected to [...] Read more.

Background: The genus Enterococcus includes a diverse group of bacteria that are commonly found in the gastrointestinal tracts of humans and animals, as well as in various environmental habitats. Methods: In this study, Enterococcus lactis RB10, isolated from goat feces, was subjected to comprehensive genomic and functional analysis to assess its safety and potential as a probiotic strain. Results: The genome of E. lactis RB10, with a size of 2,713,772 bp and a GC content of 38.3%, was assembled using Oxford Nanopore Technologies (ONT). Genome annotation revealed 3375 coding sequences (CDSs) and highlighted key metabolic pathways involved in carbohydrate, protein, and amino acid metabolism. The strain was susceptible to important antibiotics, including ampicillin, chloramphenicol, tetracycline, and vancomycin, but exhibited resistance to aminoglycosides, a common trait in Enterococcus species with non-hemolytic activity. Genomic analysis further identified two intrinsic antimicrobial resistance genes (ARGs). The strain also demonstrated antimicrobial activity against Bacillus cereus DMST 11098 and Salmonella Typhi DMST 22842, indicating pathogen-specific effects. Key genes for adhesion, biofilm formation, and stress tolerance were also identified, suggesting that RB10 could potentially colonize the gut and compete with pathogens. Moreover, the presence of bacteriocin and secondary metabolite biosynthetic gene clusters suggests its potential for further evaluation as a biocontrol agent and gut health promoter. Conclusions: However, it is important to note that E. lactis RB10 was isolated from goat feces, a source that may harbor both commensal and opportunistic bacteria, and therefore additional safety assessments are necessary. While further validation is needed, E. lactis RB10 exhibits promising probiotic properties with low pathogenic risk, supporting its potential use in food and health applications. Full article

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13 pages, 2150 KiB

Open AccessArticle

Investigation of Therapeutic Efficacy of Intravesical Tigecycline Administration in Rats with Cystitis Induced by Extensively Drug-Resistant (XDR), Tigecycline-Sensitive Acinetobacter baumannii Strain

by Cihan Yüksel, Işıl D. Alıravcı, Murat Koşan, Sinem Esen, Sevinç Yenice Aktaş, Neslihan Kaya Terzi, Ahmet Ali Berber, Sevil Alkan and Selçuk Kaya

Antibiotics 2025, 14(6), 611; https://doi.org/10.3390/antibiotics14060611 - 16 Jun 2025

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Abstract

Background: This study aimed to evaluate the therapeutic efficacy of intravesical tigecycline administration in a rat model of cystitis induced by a tigecycline-sensitive, extensively drug-resistant (XDR) Acinetobacter baumannii strain. Methods: Thirty-six female Wistar albino rats were inoculated intravesically with XDR A. baumannii to [...] Read more.

Background: This study aimed to evaluate the therapeutic efficacy of intravesical tigecycline administration in a rat model of cystitis induced by a tigecycline-sensitive, extensively drug-resistant (XDR) Acinetobacter baumannii strain. Methods: Thirty-six female Wistar albino rats were inoculated intravesically with XDR A. baumannii to induce cystitis. Twenty-four rats that developed infection were divided into four groups: untreated control, saline irrigation, low-dose tigecycline (6.25 mg/kg), and high-dose tigecycline (25 mg/kg). Microbiological clearance was assessed via urine cultures on days 3 and 5. Bladder tissues were analyzed histopathologically and for genotoxicity using the Comet assay. Results: On day 5, microbiological clearance was significantly higher in tigecycline-treated groups compared to controls (p = 0.028). Histopathology revealed significantly more inflammation in the high-dose tigecycline group (p = 0.029). Genotoxicity was observed in both tigecycline groups, independent of dose (p < 0.05). Conclusions: Intravesical tigecycline demonstrated microbiological efficacy against XDR A. baumannii-induced cystitis. However, its inflammatory and genotoxic potential necessitates further preclinical evaluation. Full article

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11 pages, 337 KiB

Open AccessArticle

Early Administration of Rifampicin Does Not Induce Increased Resistance in Septic Two-Stage Revision Knee and Hip Arthroplasty

by Leonard Grünwald, Benedikt Paul Blersch and Bernd Fink

Antibiotics 2025, 14(6), 610; https://doi.org/10.3390/antibiotics14060610 - 16 Jun 2025

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Abstract

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication that follows arthroplasty and occurs in approximately 2% of all cases. One of several cornerstones of therapy is an optimized antibiotic regimen. Early administration of rifampicin—together with a combination of an antibiotic to [...] Read more.

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication that follows arthroplasty and occurs in approximately 2% of all cases. One of several cornerstones of therapy is an optimized antibiotic regimen. Early administration of rifampicin—together with a combination of an antibiotic to which the specific microorganism is susceptible—accompanying a two-stage revision surgery, remained controversial due to the potential risk of emerging resistance. However, the exact time to start rifampicin treatment often remains unclear and might be crucial in the treatment regimen. Methods: In a retrospective study design, a total of 212 patients receiving a two-stage revision surgery after a diagnosis of PJI (60.8% THA, 39.2% TKA) received an individual rifampicin combination therapy after initial debridement and removal of all foreign material, starting rifampicin on the second day postoperatively. Results: At the time of spacer explantation, two patients had developed rifampicin resistance (0.9%). At follow-up (M = 55.4 ± 21.8 months) after reimplantation, three patients had developed rifampicin resistance (1.4%). Concerning the development of reinfection, in general, in the study group and the necessity for further treatment, a total of 25 patients showed signs of reinfection (11.8%). Conclusions: Only 0.9% after the first stage and 1.4% at follow-up after the second stage of all 212 patients with accompanying long-term rifampicin combination therapy developed a rifampicin resistance. Therefore, rifampicin administration could be started on the second postoperative day when sufficient concentrations of the accompanying antibiotics can be expected. Full article

(This article belongs to the Special Issue Advances in the Field of Biofilm-Associated Musculoskeletal Infections)

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15 pages, 292 KiB

Open AccessReview

Is Osteoarthritis a State of Joint Dysbiosis?

by Mincong He, Frank Kolhoff, Michael A. Mont and Javad Parvizi

Antibiotics 2025, 14(6), 609; https://doi.org/10.3390/antibiotics14060609 - 15 Jun 2025

Viewed by 391

Abstract

Osteoarthritis (OA) has traditionally been defined as a degenerative joint disease driven by mechanical wear, aging, and metabolic disturbances. However, emerging evidence suggests that joint dysbiosis, a dysregulation in the joint microbiome, may play an important role in OA pathogenesis. This review explores [...] Read more.

Osteoarthritis (OA) has traditionally been defined as a degenerative joint disease driven by mechanical wear, aging, and metabolic disturbances. However, emerging evidence suggests that joint dysbiosis, a dysregulation in the joint microbiome, may play an important role in OA pathogenesis. This review explores the mechanisms linking dysbiosis to OA. We examine the presence and origin of joint dysbiosis, also highlighting the gut–joint and oral–joint axes as potential routes for microbial translocation. However, challenges remain in distinguishing causation from correlation and addressing microbial contaminants in microbiome studies. Future research should prioritize longitudinal studies and multiomics integration to elucidate the complex interplay between microbial communities and joint health. 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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30 pages, 2650 KiB

Open AccessReview

The Role of Livestock Antibiotic Use in Microbiota Dysbiosis and Neuroinflammation

by Serena Silvestro, Carmelo Biondo, Angelina Midiri, Borrello Lucia and Giuseppe Mancuso

Antibiotics 2025, 14(6), 608; https://doi.org/10.3390/antibiotics14060608 - 15 Jun 2025

Viewed by 446

Abstract

Antibiotic overuse in livestock is a major concern, as it contributes to the emergence of antibiotic resistance and may adversely affect both animal and human health. One important consequence is its impact on the gut microbiota, a complex microbial ecosystem essential for maintaining [...] Read more.

Antibiotic overuse in livestock is a major concern, as it contributes to the emergence of antibiotic resistance and may adversely affect both animal and human health. One important consequence is its impact on the gut microbiota, a complex microbial ecosystem essential for maintaining host health. A growing body of research highlights the critical role of a balanced gut microbiota in maintaining the integrity of the gut-microbiota–brain axis, a bidirectional communication network between the gastrointestinal tract and the central nervous system (CNS). Antibiotics introduced through the food chain and the environment can disrupt microbial balance, leading to dysbiosis and systemic inflammation. In this context, the concept of “One Health” is emphasized, which recognizes the deep interconnection between the health of humans, animals, and the environment to address the global problem of antibiotic resistance. Several animal studies highlight how dysbiosis can induce neuroinflammation and potentially damage the gut–brain barrier. This review explores the mechanisms by which antibiotic use in livestock alters the gut microbiota and compromises the gut-microbiota–brain axis integrity, outlining the implications for public health and the possible link with neurodegenerative conditions. Full article

(This article belongs to the Special Issue Livestock Antibiotic Use and Resistance)

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13 pages, 950 KiB

Open AccessArticle

Surveillance of Multidrug-Resistant Genes in Clinically Significant Gram-Negative Bacteria Isolated from Hospital Wastewater

by Shriya C. Shetty, Lakshya S. Gowda, Ankeeta Menona Jacob, Kalidas Shetty and A. Veena Shetty

Antibiotics 2025, 14(6), 607; https://doi.org/10.3390/antibiotics14060607 - 15 Jun 2025

Viewed by 439

Abstract

Background/Objectives: Antimicrobial resistance (AMR) has become a serious public health threat worldwide. Among the various surveillance domains, hospital wastewater (HWW) has been overlooked, and it is the major reason for the threats posed by AMR. Therefore, the HWW domain is of paramount importance [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) has become a serious public health threat worldwide. Among the various surveillance domains, hospital wastewater (HWW) has been overlooked, and it is the major reason for the threats posed by AMR. Therefore, the HWW domain is of paramount importance for tackling the AMR. In this regard, the present study investigated the occurrence of Gram-negative bacteria from HWW and evaluated the isolates’ multi-drug-resistant (MDR) pattern in the study environment. Methods: This descriptive study involves HWW samples (n = 24) consecutively collected across 6 months. The samples were cultured for bacteria, identified, and subjected to antimicrobial susceptibility testing via Kirby–Bauer. PCR confirmed the presence of drug-resistance genes in Gram-negative bacterial isolates. Results: High rates of Enterobacterales resistant to carbapenems and cephalosporins observed in isolates from final treated effluent. The molecular screening showed tetD, tetE, tetG, catA1, catA2, bla_NDM-1, quinolones, qnrA, qnrB, qnrS, and qepa. Conclusions: Overall, our results suggest that microbiological surveillance and identification of resistance genes of clinically important pathogens in HWW can be a general screening method for early determination of under-detected antimicrobial resistance profiles in hospitals and early warning of outbreaks and difficult-to-treat infections. Full article

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

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33 pages, 1374 KiB

Open AccessReview

Antimicrobials in Livestock Farming and Resistance: Public Health Implications

by Marilena Trinchera, Silvia De Gaetano, Elenoire Sole, Angelina Midiri, Serena Silvestro, Giuseppe Mancuso, Teresa Catalano and Carmelo Biondo

Antibiotics 2025, 14(6), 606; https://doi.org/10.3390/antibiotics14060606 - 14 Jun 2025

Viewed by 841

Abstract

The accelerated spread of bacterial resistance has been demonstrated to reduce the effectiveness of antibiotic treatments for infections, resulting in higher morbidity and mortality rates, as well as increased costs for livestock producers. It is expected that the majority of future antimicrobial use [...] Read more.

The accelerated spread of bacterial resistance has been demonstrated to reduce the effectiveness of antibiotic treatments for infections, resulting in higher morbidity and mortality rates, as well as increased costs for livestock producers. It is expected that the majority of future antimicrobial use will be in animal production. The management of antimicrobial resistance (AMR) in the livestock sector poses significant challenges due to the multifaceted nature of the problem. In order to identify appropriate solutions to the rise of antimicrobial resistance, it is imperative that we have a comprehensive understanding of the disease dynamics underpinning the ways in which antimicrobial resistance is transmitted between humans and animals. Furthermore, in consideration of the anticipated requirement to satisfy the global demand for food, it is imperative that we guarantee that resistance is not transmitted or propagated during the treatment and disposal of animal waste, particularly from intensive farming. It is also crucial to formulate a research agenda to investigate how antibiotic resistance in animal faeces from livestock farming is affected by intensified farming activities. The review analyses the environment’s role in the transmission resistance chain and reviews methodologies for disrupting the link. A particular focus is placed on the limitations of the applied methodologies to reduce antimicrobial resistance in global animal production. Full article

(This article belongs to the Special Issue Livestock Antibiotic Use and Resistance)

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10 pages, 1559 KiB

Open AccessArticle

Is It Possible to Optimize the Elaboration and Preservation of a Vancomycin Catheter Lock Solution?

by Marta Díaz-Navarro, David Samitier, Félix García-Moreno, María Sanjurjo, Patricia Muñoz, Beatriz Torroba and María Guembe

Antibiotics 2025, 14(6), 605; https://doi.org/10.3390/antibiotics14060605 - 14 Jun 2025

Viewed by 347

Abstract

Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration [...] Read more.

Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration (MIBC) of a frozen V lock solution. Methods: Two V-2 mg/mL solutions were tested: (1) V + heparin 100 IU/mL and (2) V + citrate 2%. Solutions were frozen at −20 °C, followed by 48 h refrigeration, and analyses were performed at baseline and after 2, 4, 8, and 12 weeks (experiment 1). In addition, after the 12-week freezing period, solution 1 was also preserved for 1 and 2 weeks at both 4 °C and room temperature (experiment 2). V concentration was assessed by HPLC-DAD at 205 nm and validated with forced degradation tests. A <10% variation indicated significant change. MBIC was determined by XTT staining of 24 h biofilms exposed to decreasing concentrations of each solution. Microorganisms tested included methicillin-susceptible and -resistant Staphylococcus aureus (MSSA, MRSA), Staphylococcus epidermidis ATCC35984 (SE), and a highly biofilm-forming clinical S. epidermidis strain (SEclin). MIBC was defined as ≥50% reduction in metabolic activity. Results: In experiment 1, while V concentration remained stable over time, MIBC values varied, notably increasing from 8 weeks for all strains. Moreover, in experiment 2, significant reductions in both V concentration and MIBC were detected in the 2-week period. Conclusions: V lock solution appears to be able to be 12-weeks frozen followed by up to 1 week at refrigeration or room temperature. This facilitates the optimization of vial preparation in hospital pharmacy laboratories. Full article

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

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14 pages, 1400 KiB

Open AccessArticle

From Farm to Slaughter: Tracing Antimicrobial Resistance in a Poultry Short Food Chain

by Andrea Laconi, Roberta Tolosi, Claudia Chirollo, Cristiana Penon, Giacomo Berto, Francesco Galuppo and Alessandra Piccirillo

Antibiotics 2025, 14(6), 604; https://doi.org/10.3390/antibiotics14060604 - 13 Jun 2025

Viewed by 475

Abstract

Background: Short food supply chains are commonly perceived as more sustainable and safer alternatives to conventional production systems, often linked to organic, free-range livestock practices. Materials and methods: This study investigates, for the first time, the distribution of antimicrobial resistance genes [...] Read more.

Background: Short food supply chains are commonly perceived as more sustainable and safer alternatives to conventional production systems, often linked to organic, free-range livestock practices. Materials and methods: This study investigates, for the first time, the distribution of antimicrobial resistance genes (ARGs) and characterizes the microbial communities’ composition, using 16S rRNA sequencing and real-time PCR, respectively. Eleven fecal, 76 slaughterhouse surface, 11 cecal, and 11 carcass samples, from 11 poultry farms belonging to the same short food chain, were analyzed in the study. Results: While cleaning and disinfection procedures appeared to reduce the bacterial load on slaughterhouse surfaces, diverse and potentially resistant bacteria, including genera such as Staphylococcus and Streptococcus, persisted both before and after slaughter. ARGs conferring resistance to high-priority critically important antimicrobials (HPCIAs), such as fluoroquinolones and third-generation cephalosporins, were frequently detected on carcasses, with qnrS (76.15%, 95%CI 68.02-84.28%) and bla_CMY2 (57.8%, 95%CI 48.38-67.22%) being the most prevalent. The slaughtering process emerged as a critical step for ARG dissemination via intestinal bacteria, such as genus Lactobacillus. Additionally, the detection of mcr genes and bla_NDM on carcasses but not in the bird gut samples suggests possible anthropogenic contamination. Discussion: These findings highlight that the evisceration process, slaughterhouse environment, and personnel are all contributing factors in ARG spread and underscore the need for enhanced hygiene protocols and reduced gut ARG carriage in domestic birds to mitigate the risk for the consumer. Full article

(This article belongs to the Special Issue Livestock Antibiotic Use and Resistance)

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13 pages, 776 KiB

Open AccessArticle

In Vitro Activity of Cefaclor/Beta-Lactamases Inhibitors (Clavulanic Acid and Sulbactam) Combination Against Extended-Spectrum Beta-Lactamase Producing Uropathogenic E. coli

by Ali Atoom, Bayan Alzubi, Dana Barakat, Rana Abu-Gheyab, Dalia Ismail-Agha, Awatef Al-Kaabneh and Nawfal Numan

Antibiotics 2025, 14(6), 603; https://doi.org/10.3390/antibiotics14060603 - 13 Jun 2025

Viewed by 635

Abstract

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been [...] Read more.

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been introduced in recent years. While these agents have shown efficacy, their clinical utility is constrained by high cost, limited availability, and emerging resistance mechanisms. The rational of this study was to test the in vitro activity of a cost-effective alternative to currently available BL–BLI combinations against ESBL-producing E. coli isolated from urinary tract infections (UTIs). Objective: This study investigates the in vitro antimicrobial activity of cefaclor (CFC), both as monotherapy and in combination with the β-lactamase inhibitors clavulanic acid (CA) and sulbactam (SUL), against 52 ESBL-producing E. coli isolates derived from urine cultures of patients diagnosed with UTIs. Methods: The susceptibility ranges were measured by disk diffusion and minimal inhibitory concentration (MIC) methods. In addition, the Time kill assay and disk approximation method were performed to measure the synergistic and bactericidal activity of the approached combination. Results: The MIC50 and MIC90 for CFC were improved from more than 128 µg/mL to 8/4 µg/mL when CFC was combined with either CA or SUL. The triple combination format of CFC/CA/SUL showed MIC50 and MIC90 values at 8/4/4 µg/mL and 64/32/32 µg/mL, respectively. The recovered susceptibility percentages were 54%, 54%, and 58% for CFC/CA, CFC/SUL, and CFC/CA/SUL combinations, respectively. Disk approximation and time–kill assay results revealed synergy and bactericidal effects when CFC combined with CA or SUL for isolates that showed susceptibility restorations of CFC when coupled with CA or SUL by the disk diffusion and MIC method. Conclusions: This study proposes a cost-effective combination that could mitigate resistance development and offer a sparing option to last resort treatment choices including carbapenems. However, testing efficacy in a clinical setting is crucial. Full article

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15 pages, 1157 KiB

Open AccessArticle

Antifungal Activity of Selected Naphthoquinones and Their Synergistic Combination with Amphotericin B Against Cryptococcus neoformans H99

by Naira Sulany Oliveira de Sousa, Juan Diego Ribeiro de Almeida, Linnek Silva da Rocha, Izabela de Mesquita Bárcia Moreira, Flávia da Silva Fernandes, Ani Beatriz Jackisch Matsuura, Kátia Santana Cruz, Emersom Silva Lima, Érica Simplício de Souza, Hagen Frickmann and João Vicente Braga de Souza

Antibiotics 2025, 14(6), 602; https://doi.org/10.3390/antibiotics14060602 - 13 Jun 2025

Viewed by 613

Abstract

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising [...] Read more.

Background/Objectives: Cryptococcosis, caused by Cryptococcus neoformans and Cryptococcus gattii species complexes, remains a significant health concern, particularly among immunocompromised patients. The emergence of antifungal resistance and toxicity of conventional treatment underscore the urgent need for novel therapeutic approaches. Combination therapies represent a promising strategy to enhance efficacy and overcome resistance. This study investigated the antifungal activity of five naphthoquinones against nine isolates of Cryptococcus spp. and assessed their synergistic effects with amphotericin B (AmB). Methods: In this study, five selected naphthoquinones were evaluated for their antifungal activity against Cryptococcus spp. isolates using broth microdilution assays to determine minimum inhibitory concentrations (MICs), according to CLSI guidelines. The potential synergistic effect with AmB was assessed using checkerboard assays, with synergy interpreted based on the fractional inhibitory concentration index (FICI). Cytotoxicity was evaluated in MRC-5 human lung fibroblast cells using the MTT assay. Results: Among the compounds tested, 2-methoxynaphthalene-1,4-dione (2-MNQ) demonstrated antifungal activity, with MIC values ranging from 3.12 to 12.5 µg/mL. Checkerboard assays revealed a synergistic interaction between 2-MNQ and AmB, with a fractional inhibitory concentration index (FICI) of 0.27. The combination reduced the MIC of AmB by 4.17-fold. These findings highlight the potential of synthetic naphthoquinones, particularly 2-MNQ, as effective antifungal agents with synergistic properties when combined with AmB. The observed synergy suggests complementary mechanisms, including increased fungal membrane permeability and oxidative stress induction. Conclusions: This study highlights the potential of 2-MNQ and 2,3-DBNQ as antifungal candidates against Cryptococcus spp., with emphasis on the synergistic interaction observed between 2-MNQ and amphotericin B. The findings reinforce the importance of structural modifications in naphthoquinones to enhance antifungal activity and support the need for further preclinical studies investigating combination therapies aimed at improving treatment efficacy in patients with cryptococcosis. Full article

(This article belongs to the Special Issue Fungal Metabolites and Synthetic Derivatives: Antimicrobial Properties Toward Microbial Pathogens)

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18 pages, 1231 KiB

Open AccessArticle

The Genetic Background and Culture Medium Only Marginally Affect the In Vitro Evolution of Pseudomonas aeruginosa Toward Colistin Resistance

by Matteo Cervoni, Antonio Maria Ferriero, Alessandra Lo Sciuto, Francesca Guidi, Naida Babić Jordamović, Silvano Piazza, Olivier Jousson, Alfonso Esposito and Francesco Imperi

Antibiotics 2025, 14(6), 601; https://doi.org/10.3390/antibiotics14060601 - 13 Jun 2025

Viewed by 930

Abstract

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to [...] Read more.

Background/Objectives: Colistin is a last-resort treatment for Pseudomonas aeruginosa multidrug-resistant infections, but resistance to it is emerging. While colistin resistance in P. aeruginosa is typically associated with chromosomal mutations inducing lipopolysaccharide (LPS) aminoarabinosylation, other mutations unrelated to LPS modifications have been proposed to influence the extent of colistin resistance. Here, we examined whether the genetic background and culture conditions affect the evolution of high-level colistin resistance in this bacterium. Methods: We performed in vitro evolution experiments in the presence or absence of increasing colistin concentrations with two phylogenetically distant reference strains in a standard laboratory medium and in two media mimicking P. aeruginosa growth during lung or systemic infections. Resistance-associated mutations were identified by comparative genomics, and the role of selected mutated genes was validated by allele replacement, deletion, or conditional mutagenesis. Results: Most colistin-resistant mutants carried mutations in genes belonging to four functional groups: two-component systems controlling LPS aminoarabinosylation (PmrAB, PhoPQ), LPS biosynthesis, the production of the polyamine norspermidine, and fatty acid metabolism. No mutation was exclusively and invariably associated with a specific strain or medium. We demonstrated that norspermidine is detrimental to the acquisition of colistin resistance upon PmrAB activation and that impaired fatty acid biosynthesis can promote colistin resistance, even if it increases susceptibility to other antibiotics. Conclusions: The evolution of colistin resistance in P. aeruginosa appeared to be only marginally affected by the genetic background and culture conditions. Notably, mutations in fatty acid biosynthetic genes represent a newly identified genetic determinant of P. aeruginosa colistin resistance, warranting further investigation in clinical isolates. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Virulence Mechanisms in Gram-Negative Bacteria: An Alliance for Success)

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12 pages, 814 KiB

Open AccessArticle

Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series

by Laura Doménech-Moral, Sonia García-García, Alba Pau-Parra, Manuel Sosa, Adrian Puertas Sanjuan, Camilo Bonilla, Elisabeth Gallart, Laura Castellote, Patricia Faixó, Jessica Guevara, Albert Vilanova, María Martínez-Pla, Aldair Conto, Xavier Nuvials, Pilar Lalueza, Ricard Ferrer, Maria Queralt Gorgas and Jordi Riera

Antibiotics 2025, 14(6), 600; https://doi.org/10.3390/antibiotics14060600 - 12 Jun 2025

Viewed by 409

Abstract

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in [...] Read more.

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO. Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters—Area Under Curve (AUC_0–24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T_1/2), volume of distribution (Vd), and clearance (CL)—were estimated and compared with published data in non-ECMO populations. Results: Five patients were included. The median AUC_0–24 was 227.3 µg·h/mL (IQR 182.4–311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727–832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5–3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure. Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing. Full article

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

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11 pages, 644 KiB

Open AccessArticle

Antibiotic Resistance Awareness in Kosovo: Insights from the WHO Antibiotic Resistance: Multi-Country Public Awareness Survey

by Flaka Pasha, Valon Krasniqi, Adelina Ismaili, Shaip Krasniqi, Elton Bahtiri, Hasime Qorraj Bytyqi, Valmira Kolshi Krasniqi and Blana Krasniqi

Antibiotics 2025, 14(6), 599; https://doi.org/10.3390/antibiotics14060599 - 12 Jun 2025

Viewed by 489

Abstract

Background/Objectives: Antimicrobial resistance (AMR) poses a critical global health threat, rendering common bacterial infections increasingly difficult to treat and placing considerable strain on healthcare systems. This study assesses public awareness, perceptions, and behaviors related to antibiotic use and AMR in Kosovo, a country [...] Read more.

Background/Objectives: Antimicrobial resistance (AMR) poses a critical global health threat, rendering common bacterial infections increasingly difficult to treat and placing considerable strain on healthcare systems. This study assesses public awareness, perceptions, and behaviors related to antibiotic use and AMR in Kosovo, a country with limited existing data on the topic. Methods: Using a cross-sectional survey design, 568 participants from diverse demographic backgrounds provided insights into their knowledge and practices concerning antibiotic use and antibiotic resistance. Results: The results revealed that although 75% of participants had heard of antibiotic resistance, only a limited proportion understood key terms. Knowledge of appropriate antibiotic use varied, with 67% of respondents correctly recognizing the need to complete a prescribed antibiotic course, while 29% believed it was acceptable to stop treatment once they felt better. Gender and educational level emerged as significant factors, with women and more educated individuals demonstrating greater awareness of proper antibiotic use and the risks of misuse. While 71% of respondents considered it unacceptable to use antibiotics prescribed to others, 41% believed it was acceptable to reuse previously effective antibiotics. Most participants (96%) reported obtaining antibiotics through prescriptions. Public awareness of AMR was generally high, but conceptual understanding remained limited, with misconceptions about the origins of resistance, incorrectly attributing it to the human body rather than bacteria. Conclusions: Targeted public health campaigns, guided by the One Health approach, integrating human, animal, and environmental health, are needed. A multifaceted strategy, including education, policy reforms, and international collaboration, is essential to mitigate AMR and preserve the efficacy of antibiotics for future generations. Full article

(This article belongs to the Special Issue Antibiotic Use in the Communities—2nd Edition)

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26 pages, 2125 KiB

Open AccessReview

Antibiotic Resistance in Aquaculture: Challenges, Trends Analysis, and Alternative Approaches

by Elshafia Ali Hamid Mohammed, Béla Kovács, Ronald Kuunya, Eltayeb Omaima Awad Mustafa, Azza Siddig Hussien Abbo and Károly Pál

Antibiotics 2025, 14(6), 598; https://doi.org/10.3390/antibiotics14060598 - 11 Jun 2025

Viewed by 1317

Abstract

Antibiotic resistance in aquaculture has emerged as a global crisis, representing a serious threat to the health of aquatic animals, environment, and human. The extensive use of antibiotics in aquaculture has led to rapid development of resistant bacterial strains, resulting in environmental contamination [...] Read more.

Antibiotic resistance in aquaculture has emerged as a global crisis, representing a serious threat to the health of aquatic animals, environment, and human. The extensive use of antibiotics in aquaculture has led to rapid development of resistant bacterial strains, resulting in environmental contamination and the dissemination of resistant genes. Understanding of the research trends, key contributors, and thematic evolution of this field is essential for guiding future studies and policy interventions. The study aimed to conduct a bibliometric analysis of research on antibiotic resistance development in aquaculture, identifying key areas of research, leading contributors, emerging challenges, and alternative solutions. Data were extracted from the Web of Science (WoS) database covering the period from 2000 to 2025. A systematic search strategy was employed, utilizing terms including “antibiotic resistance” AND “bacteria,” AND “aquaculture”. Relevant publications were extracted from the WoS using these keywords. R-tool was then used to analyze the obtained metadata including keywords, citation patterns, and co-authored country. The analysis revealed a remarkable increase in publications over the past 25 years, with key contributions from China, India, and the USA. The most significant articles focused on the presence of multidrug resistant bacteria in the aquatic environments and, antibiotic-resistant genes, and horizontal gene transfer. Probiotics are the alternative solution to overcome the antibiotic resistance and enhance aquaculture sustainability. Future research should focus on the interdisciplinary collaboration, novel antimicrobial alternatives, and global monitoring approaches. Full article

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12 pages, 1167 KiB

Open AccessArticle

Ability of Linezolid to Combat Staphylococcus aureus and Pseudomonas aeruginosa Isolated from Polymicrobial Wound Infections

by Samar A. Ahmed, Vy T. Luu, Teresa C. Oyono Nsuga, Steven E. Burgos, Eugene Kreys, Jered Arquiette and Justin R. Lenhard

Antibiotics 2025, 14(6), 597; https://doi.org/10.3390/antibiotics14060597 - 11 Jun 2025

Viewed by 420

Abstract

Background/Objectives: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of Staphylococcus aureus and Pseudomonas aeruginosa. Methods: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing [...] Read more.

Background/Objectives: The optimal therapy for polymicrobial wound infections is poorly defined. We sought to characterize the ability of linezolid to combat mixed cultures of Staphylococcus aureus and Pseudomonas aeruginosa. Methods: The antistaphylococcal activity of linezolid was assessed in 24-h time-killing experiments that used S. aureus and P. aeruginosa isolated from polymicrobial wound infections. Clindamycin was also evaluated as a comparator. A Hill-type mathematical model was used to assess the maximum killing of S. aureus (E_max). The ability of linezolid to potentiate the activity of host defense peptides against P. aeruginosa was evaluated using LL-37. Results: In the presence of P. aeruginosa, the E_max of linezolid decreased in 5/9 co-culture experiments and increased in 4/9 co-culture experiments in comparison to linezolid against S. aureus alone. The potency of linezolid was not significantly impacted by the presence of P. aeruginosa. In comparison, the maximal S. aureus killing achieved by clindamycin decreased in eight out of nine experiments, and somewhat paradoxically, the potency increased in nine out of nine experiments. In the host defense peptide assay, the supratherapeutic linezolid concentration of 64 mg/L did not significantly enhance the killing of the LL-37 peptides (p ≥ 0.121), but the concentration of linezolid was significantly associated with the killing of one of three P. aeruginosa isolates (p = 0.005). Conclusions: P. aeruginosa had a minimal impact on the antistaphylococcal activity of linezolid in comparison to clindamycin. Linezolid did not exert a consistent ability to enhance the antipseudomonal activity of host defense peptides. These data may help inform antimicrobial selection during polymicrobial wound infections. Full article

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11 pages, 1844 KiB

Open AccessBrief Report

The Co-Existence of mcr-1.1 and mcr-3.5 in Escherichia coli Isolated from Clinical Samples in Thailand

by Panida Nobthai, Sirigade Ruekit, Dutsadee Peerapongpaisarn, Prawet Sukhchat, Brett E. Swierczewski, Nattaya Ruamsap and Paphavee Lertsethtakarn

Antibiotics 2025, 14(6), 596; https://doi.org/10.3390/antibiotics14060596 - 10 Jun 2025

Viewed by 433

Abstract

The emergence of colistin resistance poses a significant threat to its efficacy as a last-line treatment against multidrug-resistant Gram-negative bacterial infections. In this study, 178 multi-drug resistant (MDR) Escherichia coli isolates collected from clinical samples at Queen Sirikit Naval Hospital, Chonburi, Thailand, were [...] Read more.

The emergence of colistin resistance poses a significant threat to its efficacy as a last-line treatment against multidrug-resistant Gram-negative bacterial infections. In this study, 178 multi-drug resistant (MDR) Escherichia coli isolates collected from clinical samples at Queen Sirikit Naval Hospital, Chonburi, Thailand, were evaluated for colistin resistance. Of these, six were identified as mcr gene carriers, mediating colistin resistance. Specifically, mcr-1 was detected in three E. coli isolates, mcr-3 was detected in one E. coli isolate, and mcr-1 and mcr-3 were detected in two E. coli isolates, designated AMR-0220 and AMR-0361. Whole-genome sequencing and bioinformatics analysis revealed that AMR-0220 and AMR-0361 belonged to ST410 and ST617 lineages, respectively. Both isolates carried multiple plasmids, with mcr-1.1 located on an IncX4-type plasmid that is closely related to previously reported mcr-1.1-carrying IncX4 plasmids. In contrast, mcr-3.5 was identified on distinct plasmid backbones: an IncFIB-type plasmid in AMR-0220 and an IncFII-type plasmid in AMR-0361. Overall, our findings demonstrate that the mcr genes found in E. coli isolates in this region are located on different mobile genetic elements, indicating the potential for a widespread dissemination of colistin resistance among Gram-negative bacteria throughout Thailand’s healthcare system. Full article

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24 pages, 4082 KiB

Open AccessArticle

Epoxy-Functionalized Isatin Derivative: Synthesis, Computational Evaluation, and Antibacterial Analysis

by Deepanjali Shukla, Iqbal Azad, Mohd Arsh Khan, Ziaul Husain, Azhar Kamal, Sabahat Yasmeen Sheikh, Ibrahim Alotibi, Varish Ahmad and Firoj Hassan

Antibiotics 2025, 14(6), 595; https://doi.org/10.3390/antibiotics14060595 - 9 Jun 2025

Viewed by 1677

Abstract

Background/Objectives: The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant Klebsiella pneumoniae. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. [...] Read more.

Background/Objectives: The current need for new antibacterial compounds that target non-classical pathways is highlighted by the emergence of multidrug-resistant Klebsiella pneumoniae. In the development of antibiotics, DNA adenine methyltransferase (Dam), a key regulator of bacterial gene expression and pathogenicity, is still underutilized. Epoxy-functionalized analogues of isatin derivatives have not been adequately investigated for their antibacterial activity, particularly as Dam inhibitors. In the pursuit of antimicrobial agents, this study synthesized an epoxy-functionalized isatin derivative (L3) using a one-pot reaction. The compound was characterized using FT-IR, ¹H-NMR, ¹³C-NMR, HR-MS, and UV–Vis spectroscopy. Methods: In silico evaluation performed by using ADMETlab3 and SwissADME. While molecular docking studies were achieved by AutoDock and Vina to find L3’s interaction with potential antibacterial target (Dam protein in K. pneumoniae). In addition, the antibacterial potential of L3 was evaluated using minimum inhibitory concentration (MIC) assays against Bacillus cereus, Bacillus pumilus, Escherichia coli, and K. pneumoniae. Results: Among these, L3 exhibited potential inhibitory activity against K. pneumoniae, with a MIC value of 93.75 μg/mL. In silico evaluations confirmed L3’s favorable drug-like properties, including potential oral bioavailability, blood–brain barrier (BBB) permeability, and low plasma protein binding (PPB). The compound satisfied Lipinski’s and other drug-likeness rules as well as getting a quantitative estimate of drug-likeness (QED) score of 0.52. Here, a homology model of Dam protein in K. pneumoniae was generated using the SWISS-MODEL server and validated using computational tools. Targeted docking analysis revealed that L3 exhibited significant potential binding affinity against Dam protein, with binding energies of −6.4 kcal/mol and −4.85 kcal/mol, as determined by Vina and AutoDock, respectively. The associated inhibition constant was calculated as 280.35 µM. Further interaction analysis identified the formation of hydrogen bonds with TRP7 and PHE32, along with Van der Waals’ interactions involving GLY9, ASP51, and ASP179. Conclusions: These findings highlight L3 as a promising scaffold for antimicrobial drug development, particularly in targeting Dam protein in K. pneumoniae. Furthermore, the ADMET profiling and physicochemical properties of L3 support its potential as a drug-like candidate. Full article

(This article belongs to the Special Issue Discovery and Synthesis of Antimicrobial Compounds Against Multidrug Resistance)

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Open AccessArticle

Does Empirical Antibiotic Use Improve Outcomes in Ventilated Patients with Pandemic Viral Infection? A Multicentre Retrospective Study

by Elisabeth Papiol, Julen Berrueta, Juan Carlos Ruíz-Rodríguez, Ricard Ferrer, Sara Manrique, Laura Claverias, Alejandro García-Martínez, Pau Orts, Emili Díaz, Rafael Zaragoza, Marco Marotta, María Bodí, Sandra Trefler, Josep Gómez, Ignacio Martín-Loeches and Alejandro Rodríguez

Antibiotics 2025, 14(6), 594; https://doi.org/10.3390/antibiotics14060594 - 8 Jun 2025

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Abstract

Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To [...] Read more.

Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To evaluate whether EAT at ICU admission reduces ventilator-associated pneumonia (VAP) incidence or ICU mortality in critically ill patients with pandemic viral pneumonia, stratified by presence of COI. Methods: This retrospective analysis combined two national multicentre ICU registries in Spain, including 4197 adult patients requiring invasive mechanical ventilation for influenza A(H1N1) or COVID-19 between 2009 and 2021. Primary outcomes were ICU mortality and VAP incidence. Analyses were stratified by microbiologically confirmed bacterial COI. Propensity score matching, Cox regression, General Linear (GLM), and random forest models were applied. Results: Among patients without COI (n = 3543), EAT was not associated with lower ICU mortality (OR = 1.02, 95%CI 0.81–1.28, p = 0.87) or VAP (OR = 1.02, 95%CI 0.79–1.39, p = 0.89). In patients with confirmed COI (n = 654), appropriate EAT was associated with reduced VAP (17.4% vs. 36.3%, p < 0.001) and ICU mortality (38.4% vs. 49.6%, OR = 1.89, 95%CI 1.13–3.14, p = 0.03) compared to inappropriate EAT. Conclusions: EAT was not associated with a lower incidence of VAP or higher survival rates and could be harmful if administered incorrectly. These findings support a more targeted approach to antibiotic use, guided by microbiology, biomarkers and stewardship principles. Full article

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

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Antibiotics, Volume 14, Issue 6 (June 2025) – 95 articles

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