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Antibiotics
Volume 14
Issue 11
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Antibiotics, Volume 14, Issue 11 (November 2025) – 17 articles

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56 pages, 1847 KB  
Systematic Review
Existing Evidence from Economic Evaluations of Antimicrobial Resistance—A Systematic Literature Review
by Sajan Gunarathna, Yongha Hwang and Jung-Seok Lee
Antibiotics 2025, 14(11), 1072; https://doi.org/10.3390/antibiotics14111072 (registering DOI) - 24 Oct 2025
Abstract
Background/Objectives: Although antimicrobial resistance (AMR) is recognized as a critical global health threat across human, animal, and environmental domains, evidence from AMR economic evaluations remains limited. This study systematically reviewed available studies, emphasizing existing evidence and reported limitations in AMR-related economic evaluations. [...] Read more.
Background/Objectives: Although antimicrobial resistance (AMR) is recognized as a critical global health threat across human, animal, and environmental domains, evidence from AMR economic evaluations remains limited. This study systematically reviewed available studies, emphasizing existing evidence and reported limitations in AMR-related economic evaluations. Methods: A comprehensive review of peer-reviewed empirical studies was conducted, including publications up to July 2023 without temporal restrictions, but limited to English-language articles. Literature searches were undertaken in PubMed and Cochrane using a search strategy centered on the terms “economic evaluations” and “antimicrobial resistance.” Screening and data extraction were performed by two reviewers independently, with disagreements resolved through consensus or consultation with a third reviewer. Findings were synthesized narratively. Results: Of the 3682 records screened, 93 studies were included. Evidence gaps were identified across income and geographic regions, particularly in low- and middle-income countries (LMICs) and the African, Southeast Asian, and Eastern Mediterranean regions. Studies were comparatively more numerous in high-income countries (HICs) and the European and Americas regions. Substantial gaps also existed in one health approach and community-based evaluations. Nine major study limitations were identified, with many interlinked. The most frequent issues included limited generalizability primarily due to inadequate sampling approaches (n = 16), and single-center studies (n = 11), alongside errors in cost estimation (n = 4), and lack of consideration for essential features or information (n = 3). Conclusions: The review highlights persistent evidence gaps and recurring methodological shortcomings in AMR economic evaluations. Addressing these limitations, particularly in LMICs, will strengthen the evidence base and better inform policy implementation to combat AMR effectively. Full article
15 pages, 344 KB  
Article
Antibiotic Use in the Community in Spain: A National Surveillance System Within the Framework of the Spanish Action Plan on Antimicrobial Resistance
by Rocío Fernández-Urrusuno, Carmen Marina Meseguer-Barros, María García-Gil, Itxasne Lekue-Alkorta, María Belén Pina-Gadea, María Ana Prado-Prieto, Natalia Alzueta-Isturiz, Lucía Jamart-Sánchez, Laura Villar-Gómara and Antonio López-Navas
Antibiotics 2025, 14(11), 1071; https://doi.org/10.3390/antibiotics14111071 (registering DOI) - 24 Oct 2025
Abstract
Background: Antimicrobial resistance (AMR) remains a critical major public health challenge, largely driven by the inappropriate use of antibiotics in the community. In Spain, the National Action Plan on AMR (PRAN) emphasizes the need for robust surveillance systems based on standardized indicators [...] Read more.
Background: Antimicrobial resistance (AMR) remains a critical major public health challenge, largely driven by the inappropriate use of antibiotics in the community. In Spain, the National Action Plan on AMR (PRAN) emphasizes the need for robust surveillance systems based on standardized indicators and high-quality data sources. Objective: This study aimed to evaluate the feasibility of calculating PRAN prescribing indicators using the National Electronic Database for Pharmacoepidemiological Research in Primary Care (BIFAP) and to validate BIFAP as a data source for national antimicrobial prescribing surveillance. Methods: A population-based cross-sectional study was conducted using 2018 data from 9.4 million individuals. Results: Overall, 23.3% received at least one antibiotic prescription during the year, with an average of 1.8 treatments per patient. First-line recommended antibiotics represented 26.5% of total dispensed defined daily doses. Notable age-related variability in prescribing patterns was observed: children predominantly received first-line narrow-spectrum antibiotics, whereas older adults were more frequently prescribed broad-spectrum agents. Discusion: BIFAP-based indicators closely aligned with PRAN data while allowing for the calculation of additional metrics, such as prevalence of use, treatments per patient-year, and variations by age and sex. The findings underscore the importance of patient-level monitoring to identify demographic-age-specific priorities for targeted interventions aimed at optimizing antibiotic use in Primary Care. Conclusions: This study confirms the feasibility of using BIFAP to strengthen antibiotic consumption monitoring and policy evaluation efforts in Spain. Full article
(This article belongs to the Special Issue Antibiotic Stewardship in Ambulatory Care Settings)
21 pages, 844 KB  
Article
An Analysis of Primary Healthcare Antibiotic Prescription Rates Within Castile and Leon (Spain): 2013–2023
by Rocío Salvador Martín, María José Sierra-Medina, María Elena Sánchez-Gutiérrez, Bárbara Rodríguez Vázquez, Noelia Gallego-Ausín, Laura Azofra Casado, Mª Ángeles Machín Morón and Diego Serrano-Gómez
Antibiotics 2025, 14(11), 1070; https://doi.org/10.3390/antibiotics14111070 (registering DOI) - 24 Oct 2025
Abstract
Background/Objectives: According to the World Health Organization, more than one million deaths each year are attributable to bacterial resistance, making it one of today’s main public health threats that could cause up to 10 million deaths by 2050. In this study, antibiotic [...] Read more.
Background/Objectives: According to the World Health Organization, more than one million deaths each year are attributable to bacterial resistance, making it one of today’s main public health threats that could cause up to 10 million deaths by 2050. In this study, antibiotic prescription rates at primary healthcare centers) within Castile and Leon are analyzed over the period 2013–2023, and some of the sociodemographic variables that might influence the prescription of antibiotics are determined. Methods: A descriptive, observational, ecological study was conducted based on data gathered by Concylia (pharmaceutical information system—Castile and Leon Health Service). Comparable variables (time of prescription and type of health center) and variables of results (Defined Daily Doses per 1000 health center card-holders per day and qualitative antibiotic selection variables) were analyzed. Results: During the first years under analysis, prescription rates increased, followed by a reduction at the start of 2015 that continued up until 2021. Another rise was then recorded, and prescriptions once again reached values in 2023 that were comparable to those observed in 2019 (17.62 and 17.45 Defined Daily Doses per 1000 health center card-holders per day). Throughout Castile and Leon as a whole, there were more prescriptions within urban areas; but when analyzed by provinces, prescriptions were mainly higher in rural areas within most provinces. The percentage of macrolides was higher in urban areas, whereas the percentage of fluoroquinolones was higher in rural areas. Conclusions: The variation was repeated throughout the period under study in a similar way in all the provinces of Castile and Leon and at a national level. Different prescription rates were observed by province within the autonomous region. Moreover, higher prescription rates were observed in the rural areas of most provinces. The data source did not allow linking prescriptions to diagnoses, limiting interpretation. Full article
(This article belongs to the Special Issue Antibiotic Use in the Communities—2nd Edition)
23 pages, 895 KB  
Review
From Tears to Toxins: Mapping Antibiotic Passage Through the Eye–Liver Axis
by Ivan Šoša
Antibiotics 2025, 14(11), 1069; https://doi.org/10.3390/antibiotics14111069 (registering DOI) - 24 Oct 2025
Abstract
Traditionally used to combat infections, systemic effects of antibiotics are increasingly recognized in the context of absorption through unconventional routes. One such as the ocular surface. This review tackles the bidirectional liver–eye axis, highlighting how trace antibiotic residues from environmental and therapeutic sources [...] Read more.
Traditionally used to combat infections, systemic effects of antibiotics are increasingly recognized in the context of absorption through unconventional routes. One such as the ocular surface. This review tackles the bidirectional liver–eye axis, highlighting how trace antibiotic residues from environmental and therapeutic sources affect the tear film, disturb ocular microbiota, and impact liver metabolism. It engages in anatomical pathways, microbial regulation, pharmacokinetics, and systemic immune responses. Additionally, this review discusses forensic uses and new therapeutic strategies, stressing the importance of integrated environmental monitoring and precision medicine to tackle nonmedicinal antibiotic exposure. Due to the absence of results from a systematic literature review, a narrative literature review was undertaken instead. More than 100 studies discussing mechanistic, clinical, and experimental insights were reviewed, with 98 of those studies being documented as source literature. The findings demonstrate that antibiotics may penetrate and be absorbed through the ocular surface, cause modifications of the hepatic first-pass metabolism, and change the activity of cytochrome P450. Correlations were documented between the various liver function biomarkers and the ocular tear film, as well as the thickness of the retinal pigment epithelium. The dysbiosis of eye microbiota may be an indicator of systemic inflammation associated with immune dysregulation. Restoring microbial homeostasis and addressing systemic dysregulation are novel therapeutic approaches, including the use of probiotics, nanoparticle scavengers, and CRISPR. The eye is a sensory organ and a metabolically active organ. Systemically, the eye can affect the liver through the ocular surface and the antibiotics through the liver–eye axis. To protect the systemic health of the individual and the lensed metabolically active eye, the eye and liver must be viewed as a sentinel of systemic balance. Novel therapies will be necessary with the added need for environmental monitoring. Full article
(This article belongs to the Special Issue Environmental Fate of Antibiotics: Monitoring, Toxicity, Resistance, and Removal Methods)
14 pages, 432 KB  
Review
Changing Antibiotic Prescribing Cultures: A Comprehensive Review of Social Factors in Outpatient Antimicrobial Stewardship and Lessons Learned from the Local Initiative AnTiB
by Janina Soler Wenglein, Reinhard Bornemann, Johannes Hartmann, Markus Hufnagel and Roland Tillmann
Antibiotics 2025, 14(11), 1068; https://doi.org/10.3390/antibiotics14111068 (registering DOI) - 24 Oct 2025
Abstract
Antimicrobial resistance (AMR) constitutes a major global health challenge, driven significantly by inappropriate antibiotic use in human medicine. Despite the existence of evidence-based guidelines, variability in antibiotic prescribing persists, influenced by psychosocial factors, diagnostic uncertainty, patient expectations, and local prescribing cultures. Outpatient care, [...] Read more.
Antimicrobial resistance (AMR) constitutes a major global health challenge, driven significantly by inappropriate antibiotic use in human medicine. Despite the existence of evidence-based guidelines, variability in antibiotic prescribing persists, influenced by psychosocial factors, diagnostic uncertainty, patient expectations, and local prescribing cultures. Outpatient care, the setting in which most antibiotics are prescribed, is particularly affected by such challenges. Traditional top-down interventions, such as national guidelines, often fail to achieve sustained behavioral change among prescribers. In this comprehensive review, we provide an overview of the psychological and behavioral factors influencing antimicrobial stewardship (AMS) implementation, as well as describe a bottom-up project working to meet these challenges: the “Antibiotic Therapy in Bielefeld” (AnTiB) initiative. AnTiB employs a cross-sectoral strategy aimed at developing rational prescribing culture by means of locally developed consensus guidelines, interdisciplinary collaboration, and regularly held trainings. By addressing both the organizational and psychological aspects of prescribing practices, AnTiB has facilitated a harmonization of antibiotic use across specialties and care interfaces at the local level. The initiative’s success has led to its expansion within Germany, including through the creation of the AMS-Network Westphalia Lippe and the development of AnTiB-based national pediatric recommendations. These projects are all grounded in social structures designed to strengthen the long-term establishment of AMS measures. Our efforts underscore the importance of considering local social norms, professional network, and real-world practice conditions in AMS interventions. Integrating behavioral and social science approaches into outpatient antimicrobial stewardship—exemplified by the practitioner-led AnTiB model—improves acceptability and alignment with stewardship principles; wider adoption will require local adaptation, routine outpatient resistance surveillance, structured evaluation, and sustainable support. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship—from Projects to Standard of Care)
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24 pages, 6746 KB  
Article
Trends in Antimicrobial Resistance at a Greek Tertiary Hospital over a 7-Year Period, Including the COVID-19 Pandemic
by Eleni Mylona, Sofia Kostourou, Dimitroula Giankoula, Efthimia Spyrakou, Nektaria Michopanou, Chrysoula Kolokotroni, Maria Papagianni, Dimitris Kounatidis, Efstathia Perivolioti and Vasileios Papastamopoulos
Antibiotics 2025, 14(11), 1067; https://doi.org/10.3390/antibiotics14111067 (registering DOI) - 24 Oct 2025
Abstract
Background/Objectives: Antimicrobial resistance (AMR) remains a major global threat, with the COVID-19 pandemic influencing its dynamics, although its overall impact remains uncertain. This study analyzed seven-year AMR trends, including the pandemic period, in a tertiary care hospital in Greece that served as [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) remains a major global threat, with the COVID-19 pandemic influencing its dynamics, although its overall impact remains uncertain. This study analyzed seven-year AMR trends, including the pandemic period, in a tertiary care hospital in Greece that served as a COVID-19 referral center. Methods: Multiresistant bacteria isolated from all biological specimens of hospitalized patients between January 2018 and December 2024 were recorded and classified as multidrug- (MDR), extensively drug- (XDR), or pandrug-resistant (PDR). Overall AMR was defined as the sum of these categories. Annual incidences of overall AMR, its categories, and predominant Gram-negative (A. baumannii, K. pneumoniae, P. aeruginosa) and Gram-positive [methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE)] pathogens were analyzed for the entire hospital and by sector (medical, intensive care unit [ICU], surgical). Bloodstream infection (BSI) AMR was also evaluated. Trend analysis was performed using Joinpoint regression. Results: Overall AMR exhibited a transient peak around 2021 across the hospital, except in the surgical sector. A significant rise in average annual percentage change (AAPC) occurred only in the medical sector (p < 0.001). PDR incidence increased hospital-wide (p < 0.001). K. pneumoniae, P. aeruginosa, MRSA, and VRE rose significantly in the medical sector, whereas ICU incidences remained largely stable despite the 2021 peak. A. baumannii showed no significant change. BSI-related AMR increased in the medical sector (p < 0.001) but not in the ICU (p = 0.2). Conclusions: Although overall AMR did not rise uniformly, PDR organisms increased hospital-wide. These findings support updating empiric therapy guidelines, reinforcing infection prevention measures, and translating surveillance data into targeted stewardship actions to enhance patient care. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in the Era of Climate Change)
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21 pages, 2158 KB  
Article
Regulation of the Expression of nucS, a Key Component of the Mismatch Repair System in Mycobacteria
by Esmeralda Cebrián-Sastre, Ángel Ruiz-Enamorado, Alfredo Castañeda-García, Susanne Gola, Pablo García-Bravo, Leonor Kremer and Jesús Blázquez
Antibiotics 2025, 14(11), 1065; https://doi.org/10.3390/antibiotics14111065 - 24 Oct 2025
Abstract
Mismatch repair (MMR) system alterations can trigger transient hypermutation, promoting adaptive mutations under stress, such as antibiotic exposure. While most organisms use MutS and MutL protein families for MMR, many archaea and actinobacteria, including the major human pathogen Mycobacterium tuberculosis, lack these [...] Read more.
Mismatch repair (MMR) system alterations can trigger transient hypermutation, promoting adaptive mutations under stress, such as antibiotic exposure. While most organisms use MutS and MutL protein families for MMR, many archaea and actinobacteria, including the major human pathogen Mycobacterium tuberculosis, lack these components and instead rely on NucS, a structurally distinct enzyme driving a non-canonical MMR pathway. Given the role of MMR in mutation control, understanding how nucS expression is regulated could be essential for uncovering the molecular basis of antibiotic resistance development in mycobacteria. In this study, we characterized the nucS promoter and transcription start site in Mycobacterium smegmatis. We found that nucS expression declines during the stationary phase in both M. smegmatis and M. tuberculosis, paralleling replication activity and canonical MMR downregulation. Our data suggest that the alternative sigma factor σB may negatively regulate nucS expression during this phase. Additionally, we identified candidate compounds that may modulate nucS expression, underscoring its responsiveness to environmental cues. These findings enhance our understanding of mycobacterial stress responses and lay the groundwork for exploring antibiotic resistance mechanisms. Strikingly, our work reveals a case of double convergent evolution: both canonical (MutS/MutL) and non-canonical (NucS) pathways have independently evolved not only the same DNA repair function, but also similar regulatory frameworks for genome integrity preservation under stress conditions. Full article
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10 pages, 236 KB  
Article
Probiotics and Antibiotics Use for the Prevention of Travelers’ Diarrhea Among Polish Tourists—Results from an Online Survey: Why Is Education Needed?
by Martyna Biała, Michał Biały and Patrycja Leśnik
Antibiotics 2025, 14(11), 1064; https://doi.org/10.3390/antibiotics14111064 - 23 Oct 2025
Abstract
Background/Objectives: Traveler’s diarrhea (TD) is a pressing issue, affecting a significant portion of international travelers. Despite the guidelines discouraging routine use of antibiotics and the inconclusive evidence supporting probiotics for TD prevention, both remain popular prophylactic strategies. However, data on these practices [...] Read more.
Background/Objectives: Traveler’s diarrhea (TD) is a pressing issue, affecting a significant portion of international travelers. Despite the guidelines discouraging routine use of antibiotics and the inconclusive evidence supporting probiotics for TD prevention, both remain popular prophylactic strategies. However, data on these practices among Polish tourists are currently lacking. The objective of this study was to assess the prevalence of probiotic and antibiotic use as preventive measures against TD among Polish travelers. Methods: A cross-sectional survey was conducted between July and August 2025 among adults with at least one international trip per year. An anonymous online questionnaire collected demographic data, travel frequency, and the use of probiotics and/or antibiotics for TD prophylaxis. Results: Of 873 respondents, 848 completed the questionnaire (median age: 35 years; 62.5% female). Probiotic use for TD prevention was reported by 24% of respondents (7.4% during all travels, 11.9% during trips outside of Europe, and 4.7% occasionally). Probiotic use was significantly associated with higher travel frequency, female sex, and younger age. Antibiotic use for TD prophylaxis was declared by 5.3% of participants, more common among those without comorbidities, with no significant association with age, sex, or travel frequency. Additionally, 21.6% of respondents reported regular, daily use of probiotics, though only 10.9% were recommended by physicians. Conclusions: This study’s findings reveal that a significant proportion of Polish travelers used probiotics for TD prevention, despite limited evidence and expert guidelines. A small subset of respondents used an antibiotic as TD prophylaxis. As global antibiotic resistance continues to rise, emphasizing antimicrobial stewardship in travel medicine practice is crucial. The fact that many individuals self-administer probiotics without medical consultation underscores the need for greater public education on the risks, benefits, and limitations of these interventions. Full article
28 pages, 1388 KB  
Article
Antibiotic Resistance Patterns of Bacteria Involved in Colonization and/or Infection of Patients in Intensive Care Units in Northeastern Romania
by Alexandru Duhaniuc, Cristina Mihaela Sima, Georgiana Buruiană, Cătălina Luncă and Olivia Simona Dorneanu
Antibiotics 2025, 14(11), 1063; https://doi.org/10.3390/antibiotics14111063 (registering DOI) - 23 Oct 2025
Abstract
Background/Objectives: Healthcare-associated infections caused by multidrug-resistant (MDR) bacteria pose a significant and growing public health challenge, particularly in high-risk settings such as Intensive Care Units (ICUs). Colonization is often asymptomatic but can precede infection and contribute to hospital outbreaks, making early detection critical [...] Read more.
Background/Objectives: Healthcare-associated infections caused by multidrug-resistant (MDR) bacteria pose a significant and growing public health challenge, particularly in high-risk settings such as Intensive Care Units (ICUs). Colonization is often asymptomatic but can precede infection and contribute to hospital outbreaks, making early detection critical for infection control and containment. The aim of the study is to evaluate the antibiotic susceptibility patterns of MDR bacteria involved in colonization and/or infection among patients admitted to the ICU at a tertiary care hospital in Northeastern Romania and to investigate the relationship between MDR bacterial colonization and subsequent infection. Methods: A total of 118 patients from ICU were included in this study and a total of 609 bacterial strains were isolated, involved in both colonization and infection, with multiple isolates per patient included if obtained from different sites or time points. Results: A predominance of Gram-negative bacilli was found to be involved in both colonization and infection in the ICU, with Acinetobacter baumannii (n = 146; 26.64%), Klebsiella pneumoniae (n = 146; 26.64%), Escherichia coli (n = 60; 10.95%), and Pseudomonas aeruginosa (n = 56; 10.22%) as the main bacteria involved in colonization, and A. baumannii (n = 23; 37.7%), K. pneumoniae (n = 19; 31.1%), and P. aeruginosa (n = 15; 24.6%) as the main bacteria involved in infections. The study revealed a high diversity of antibiotypes among K. pneumoniae (43 distinct antibiotypes), E. coli (35 distinct antibiotypes) and P. aeruginosa (27 distinct antibiotypes). In contrast, only 6 antibiotypes were identified for A. baumannii, with most strains belonging to a single dominant antibiotype. For K. pneumoniae, E. coli and A. baumannii, infections mainly involved the same antibiotype as that found in colonization, while infections with P. aeruginosa were often linked to different antibiotypes than those involved in colonization. Conclusions: This study demonstrates a high colonization-to-infection link among ICU patients in a Northeastern Romanian tertiary care hospital, and these findings underscore the importance of systematic colonization screening to identify patients at high risk in ICU settings. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Hospital-Acquired Infections)
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16 pages, 2966 KB  
Article
Assessment of Polymyxin B with Sodium Deoxycholate Sulfate Micelles in a Rat Model to Combat Polymyxin Nephrotoxicity
by Muhammad Ali Khumaini Mudhar Bintang, Jongdee Nopparat and Teerapol Srichana
Antibiotics 2025, 14(11), 1062; https://doi.org/10.3390/antibiotics14111062 - 23 Oct 2025
Abstract
Background/Objectives: Polymyxin B (PMB) was incorporated into a sodium deoxycholate sulfate (SDCS) micelle formulation to mitigate polymyxin-induced nephrotoxicity. This study examined the effect of the formulation on nephrotoxicity and biodistribution in a rat model. Methods: Four groups of rats were subcutaneously administered [...] Read more.
Background/Objectives: Polymyxin B (PMB) was incorporated into a sodium deoxycholate sulfate (SDCS) micelle formulation to mitigate polymyxin-induced nephrotoxicity. This study examined the effect of the formulation on nephrotoxicity and biodistribution in a rat model. Methods: Four groups of rats were subcutaneously administered one of the following: normal saline, SDCS, PMB, or a PMB-SDCS formulation. After treatment, the weight changes were recorded, and the rats were euthanized to collect blood for serum biochemistry measurements. The histopathological damage to organs was examined. Two additional groups of rats received the same dose of PMB and the PMB-SDCS formulation subcutaneously; however, their serum PMB was measured at predetermined time points, and the PMB concentrations in the organs were measured. Molecular docking for PMB and formulation with human serum albumin was also performed. Results: The PMB-SDCS formulations showed improvement in serum biomarker measurements. Several abnormalities were observed in the kidney, liver, lung, and spleen tissues following PMB treatment, which indicated evidence of toxicity. The docking showed SDCS reduces PMB binding affinity on HSA. The PMB-SDCS formulations were associated with less acute toxicity and less nephrotoxic damage compared with the PMB group. The results were supported by less PMB accumulation in the kidneys in the formulation group. Conclusions: The study indicates that SDCS has the potential to mitigate PMB-induced nephrotoxicity in rat models, suggesting a promising strategy for safer use that warrants further investigation. Full article
(This article belongs to the Special Issue Nanotechnology-Based Antimicrobials and Drug Delivery Systems)
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31 pages, 1016 KB  
Review
Long-Term Macrolides in Chronic Respiratory Diseases: Dusk or a New Dawn? A Narrative Review
by Daniele Previtero, Gioele Castelli, Ylenia Padrin, Virginia Santello, Daniele Mengato, Davide Biondini, Graziella Turato, Mariaenrica Tiné, Paolo Spagnolo and Umberto Semenzato
Antibiotics 2025, 14(11), 1061; https://doi.org/10.3390/antibiotics14111061 - 23 Oct 2025
Abstract
Macrolides—especially azithromycin—have been increasingly investigated in chronic respiratory diseases for their combined antimicrobial, anti-inflammatory, and immunomodulatory properties. Randomized controlled trials have demonstrated significant reductions in exacerbation frequency in selected patient populations with bronchiectasis, COPD, and asthma, although benefits on lung function and quality [...] Read more.
Macrolides—especially azithromycin—have been increasingly investigated in chronic respiratory diseases for their combined antimicrobial, anti-inflammatory, and immunomodulatory properties. Randomized controlled trials have demonstrated significant reductions in exacerbation frequency in selected patient populations with bronchiectasis, COPD, and asthma, although benefits on lung function and quality of life are variable. Beyond these advantages, concerns remain regarding antimicrobial resistance and uncertainties about long-term safety. Different guidelines across various diseases therefore recommend cautious and selective use of macrolides, with attention to phenotype selection, while alternative or emerging options such as biologics and novel anti-inflammatory agents are reshaping the therapeutic landscape. In this narrative review, we analyze the evidence for macrolide therapy across major chronic respiratory diseases, highlighting both the enduring clinical relevance and the limitations of long-term macrolide therapy, and discussing whether these drugs are approaching their therapeutic dusk or could still open a new dawn for selected patients. To this end we researched EMBASE and PubMed for articles published in English between 2000 and 2020 with restrictions to original articles, and freely between 2021 and 2025. Full article
(This article belongs to the Special Issue Antibiotics and Infectious Respiratory Diseases, 2nd Edition)
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37 pages, 8061 KB  
Review
Chemical Diversity and Ecological Origins of Anti-MRSA Metabolites from Actinomycetota
by Sayoane Pessoa Fernandes, Luana Layse Câmara de Almeida, Thalisson Amorim de Souza, Genil Dantas de Oliveira, Marcelly da Silveira Silva, Valnês da Silva Rodrigues-Junior, Harley da Silva Alves and Samuel Paulo Cibulski
Antibiotics 2025, 14(11), 1060; https://doi.org/10.3390/antibiotics14111060 - 23 Oct 2025
Abstract
Antimicrobial resistance (AMR) poses a major global threat to human health. Among multidrug-resistant pathogens, MRSA is a leading cause of severe nosocomial infections, urgently demanding the discovery of novel antimicrobial agents. Nature, particularly Actinomycetota, remains a prolific source of potent bioactive compounds [...] Read more.
Antimicrobial resistance (AMR) poses a major global threat to human health. Among multidrug-resistant pathogens, MRSA is a leading cause of severe nosocomial infections, urgently demanding the discovery of novel antimicrobial agents. Nature, particularly Actinomycetota, remains a prolific source of potent bioactive compounds to combat pathogens. This review analyzes recent advancements in anti-MRSA compounds from Actinomycetota. We highlight the most promising bioactive metabolites, their sources, mechanisms of action, and current limitations. Our analysis identified numerous compounds with potent activity against MRSA, including chromomycins, actinomycins, diperamycin, lunaemycin A, lactoquinomycin A, and weddellamycin, which exhibit submicromolar minimal inhibitory concentrations (MICs). The renewed interest in exploring Actinomycetota de novo is directly driven by the AMR crisis. Furthermore, bioprospecting efforts in underexplored ecological niches, such as mangroves and marine sediments, have proven highly promising, as these habitats often harbour unique microbial communities producing novel metabolites. These findings underscore the critical importance of ecology-driven drug discovery in expanding the antimicrobial arsenal and effectively addressing the global health challenge of MRSA and other resistant pathogens. Full article
(This article belongs to the Special Issue Current Advances and Innovations in Anti-Infective Agents Discovery)
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19 pages, 1558 KB  
Article
Genomic Characterization and Antimicrobial Resistance Profile of Streptococcus uberis Strains Isolated from Cows with Mastitis from Northwestern Spain
by Emiliano J. Quinto, Paz Redondo del Río, Beatriz de Mateo Silleras, Alberto Prieto, Gonzalo López-Lorenzo, Carlos M. Franco and Beatriz I. Vázquez
Antibiotics 2025, 14(11), 1059; https://doi.org/10.3390/antibiotics14111059 - 23 Oct 2025
Abstract
Background/Objectives: Streptococcus uberis is a Gram-positive bacterium and a major cause of bovine mastitis. The use of antimicrobial treatments raises concerns about resistance. This study aimed to characterize S. uberis isolates from one of the ten largest milk-producing regions in Europe. Methods [...] Read more.
Background/Objectives: Streptococcus uberis is a Gram-positive bacterium and a major cause of bovine mastitis. The use of antimicrobial treatments raises concerns about resistance. This study aimed to characterize S. uberis isolates from one of the ten largest milk-producing regions in Europe. Methods: Thirty-six isolates from 36 cows with mastitis were identified using MALDI-TOF and VITEK®MS. Susceptibility to 9 antibiotics (penicillin G, ampicillin, tetracycline, erythromycin, clindamycin, cefotaxime, ceftriaxone, levofloxacin, and moxifloxacin) was determined with VITEK®2. Whole-genome sequencing was performed using MinION Mk1C. Results: Alleles were identified for 7 loci: arcC, ddl, gki, recP, tdk, tpi, and yqiL. Only 10 isolates had alleles for all the loci. The loci with the highest number of alleles were ddl and tdk (33/36 strains), while arcC had the fewest (19/36). Four isolates were assigned to known sequence types (ST6, ST307, and ST184), and novel alleles were detected in 32 of the 36 isolates. Twelve isolates showed phenotypic resistance to one or more of the following antibiotics: tetracycline, erythromycin, clindamycin, and ceftriaxone. The lnu was the most frequently detected resistance gene (27 out of 102 total gene appearances). A total of 19 virulence factors were identified. All strains were predicted to be capable of infecting human hosts. Conclusions: Streptococcus uberis is a potential reservoir of antimicrobial resistance genes. The use of antimicrobials to treat bovine mastitis has reduced the susceptibility of this microorganism to several antibiotics, underscoring the importance of monitoring antimicrobial use in veterinary practice. The results also highlight the high genetic diversity of the isolates, suggesting a strong capacity to adapt to different environmental conditions. Full article
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15 pages, 748 KB  
Article
City or Suburb, Resistance Flows: Wastewater-Borne ESKAPE and AMR Genes in Malaysian Hospitals
by Sophia Karen Bakon, Nur Fatihah Sholehah Zakaria, Mohd Azerulazree Jamilan, Hazimah Hashim and Zuraifah Asrah Mohamad
Antibiotics 2025, 14(11), 1058; https://doi.org/10.3390/antibiotics14111058 - 23 Oct 2025
Abstract
Background/Objectives: Hospital wastewater has become a major hotspot for the spread of antimicrobial resistance and the accumulation of antibiotic-resistant genes. We focused on ESKAPE pathogens isolated from hospital wastewater and their antibiotic profiles, which are known to cause nosocomial infections in hospitals. Screening [...] Read more.
Background/Objectives: Hospital wastewater has become a major hotspot for the spread of antimicrobial resistance and the accumulation of antibiotic-resistant genes. We focused on ESKAPE pathogens isolated from hospital wastewater and their antibiotic profiles, which are known to cause nosocomial infections in hospitals. Screening for antibiotic resistant genes in isolates and quantifying antibiotic residues in hospital wastewaters, which may reflect the amount of usage of antibiotics in Klang Valley city hospitals in Malaysia. Methods: Hospital wastewater treatment plants from Klang Valley city were selected based on the study criteria. ESKAPE pathogens were isolated and identified using 16S rRNA PCR, and antibiotic sensitivity testing was performed. Antibiotic resistant gene screenings were performed using quantitative PCR, and quantification of antibiotic residues in the effluent samples was performed using liquid chromatography-mass spectrometry (LC-MS). Results: Klebsiella pneumoniae with Multiple Antibiotics Resistance Index (MARi) ranging from low (0.29) to very high resistance (0.71) dominantly isolated among ESKAPE pathogens followed by Enterococcus faecium ranging from low (0.29) to critical resistance (1.0) from hospital wastewater in Klang Valley city. The ermB gene was the predominant antibiotic resistance gene identified in Klang Valley city hospitals and suburban hospitals, representing 45.5% of isolated E. faecium from suburban hospitals and 69% from city hospitals. Although the detection of antibiotic residues was minimal, vancomycin and ciprofloxacin were detected from the wastewater. Conclusions: These findings call for improved wastewater management and antibiotic stewardship to mitigate the spread of resistant pathogens from healthcare facilities into the environment. Full article
(This article belongs to the Special Issue Environmental Fate of Antibiotics: Monitoring, Toxicity, Resistance, and Removal Methods)
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9 pages, 365 KB  
Article
Cefiderocol Comparative Resistance and Clinical Predictors in CRE-BSI: Data from an OXA-48–Endemic Region with Rising OXA-48/NDM Coproducers
by Rıdvan Dumlu and Ali Mert
Antibiotics 2025, 14(11), 1057; https://doi.org/10.3390/antibiotics14111057 - 22 Oct 2025
Abstract
Background/Objectives: Bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacterales (CREs) are a growing public health threat due to limited therapeutic options and high mortality. In Turkey, oxacillinase-48 (OXA-48) producers predominate, while OXA-48/New Delhi metallo-β-lactamase (NDM) co-producers are increasingly detected. Although ceftazidime–avibactam (CAZ-AVI) is [...] Read more.
Background/Objectives: Bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacterales (CREs) are a growing public health threat due to limited therapeutic options and high mortality. In Turkey, oxacillinase-48 (OXA-48) producers predominate, while OXA-48/New Delhi metallo-β-lactamase (NDM) co-producers are increasingly detected. Although ceftazidime–avibactam (CAZ-AVI) is effective against OXA-48, treating NDM-positive isolates remains challenging. Cefiderocol, a novel siderophore cephalosporin active against both serine- and metallo-β-lactamases, is not yet available in Turkey. Establishing baseline susceptibility rates and identifying clinical predictors of resistance are, therefore, crucial before its introduction. Methods: This retrospective study included adult patients with CRE-BSIs diagnosed at a tertiary university hospital in Istanbul between January and December 2023. Demographic, clinical, and microbiological data were collected from electronic medical records. Susceptibility to cefiderocol, CAZ-AVI, and colistin was determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 criteria. Risk factors for cefiderocol resistance were analyzed. Results: Among 202 isolates, cefiderocol showed the highest susceptibility (94%, n = 190), followed by CAZ-AVI (82%, n = 166) and colistin (70%, n = 141), with all pairwise differences being statistically significant (p < 0.001). Cefiderocol resistance (6%, n = 12) was significantly associated with hematologic malignancy, hematopoietic stem cell transplantation, prior CAZ-AVI or polymyxin exposure, prolonged hospitalization, and repeated admissions. Conclusions: Cefiderocol demonstrated potent in vitro activity against CRE-BSI isolates, with resistance confined to distinct high-risk clinical settings. This pre-implementation study provides baseline microbiological and epidemiological data from an OXA-48 endemic region with rising NDM prevalence, underscoring the importance of early surveillance and stewardship strategies before cefiderocol becomes clinically available. Full article
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15 pages, 2926 KB  
Article
Identification of the Genetic Basis of Phage Resistance in Sequentially Generated Phage-Resistant Klebsiella pneumoniae Using an Established Phage Library
by Wenbo Zhao, Congyang Du, Zheng Chen, Yunze Zhao, Stefan Schwarz, Hong Yao, Chenglong Li, Chunyan Xu and Xiang-Dang Du
Antibiotics 2025, 14(11), 1056; https://doi.org/10.3390/antibiotics14111056 - 22 Oct 2025
Viewed by 139
Abstract
Objectives: To explore the genetic basis of phage resistance in sequentially generated capsular mutants of phage-resistant Klebsiella pneumoniae using an established phage library. Methods: Sequential induction strategies were employed to obtain phage-resistant K. pneumoniae capsular mutants by exposing ST11-K64 K. pneumoniae Kp2325 to [...] Read more.
Objectives: To explore the genetic basis of phage resistance in sequentially generated capsular mutants of phage-resistant Klebsiella pneumoniae using an established phage library. Methods: Sequential induction strategies were employed to obtain phage-resistant K. pneumoniae capsular mutants by exposing ST11-K64 K. pneumoniae Kp2325 to different single phages. Whole genome sequencing and bioinformatic analysis were used to elucidate the capsular-related genetic changes in phage-resistant mutants. Phenotypic changes were assessed through gene complementation, growth assays, phage cleavage spectrum analysis, TEM for phage morphology, CPS analysis, biofilm formation, and virulence assays. Results: Three sequentially generated phage-resistant K. pneumoniae capsular mutants were obtained, designated R1, R2 and R3. The narrowing of the phage cleavage spectrum and the evolutionary trade-offs of biological phenotypes were observed. Key genetic changes included: (1) ISKpn26 insertion disrupting wcaJ in R1; (2) combined wcaJ insertion and 9-bp deletion in waaH in R2; and (3) CPS gene cluster deletion in R3 were identified as key mechanisms of phage resistance in K. pneumoniae mutants R1, R2 and R3, respectively. Conclusions: Sequential exposure to different single phages led to rapid evolution of phage resistance in K. pneumoniae via genetic mutations that disrupt capsular synthesis. These findings highlight the critical role of bacterial capsule in phage–host interactions and emphasize the need to use phage cocktails targeting different types of receptors to counteract the evolution of bacterial defense mechanisms in phage therapy. Full article
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13 pages, 1184 KB  
Article
Tourism and the Global Vectoring of Antimicrobial-Resistant Disease: What Countries Are Most Impacted?
by Peter Collignon and John J. Beggs
Antibiotics 2025, 14(11), 1055; https://doi.org/10.3390/antibiotics14111055 - 22 Oct 2025
Viewed by 152
Abstract
Background: Tourists returning home and visitors from abroad often carry antimicrobial-resistant (AMR) bacteria. Many of these resistant bacteria are acquired from, or were spread via, the environment (especially water). Understanding the impact from acquiring resistant bacteria via tourism upon global antimicrobial resistance is [...] Read more.
Background: Tourists returning home and visitors from abroad often carry antimicrobial-resistant (AMR) bacteria. Many of these resistant bacteria are acquired from, or were spread via, the environment (especially water). Understanding the impact from acquiring resistant bacteria via tourism upon global antimicrobial resistance is limited. Methods: Traveller transmission of AMR bacteria can be estimated from combining the numbers of travellers with AMR bacteria rates in different regions and the prevalence of communicable diseases. We used resistance data (WHO and contemporary publications) to measure the prevalence of E.coli resistance to third-generation cephalosporins. The study uses data from 2019, the year with the most complete dataset that also predates disruptions to travel caused by the COVID-19 pandemic. We then used the global burden of disease study and travel data from the World Travel and Tourism to create regional and country level indices measuring the impact of AMR bacteria for 241 countries. Estimates of global travel patterns were obtained using a gravity-style trip distribution model. Findings: Regions with the highest impact of AMR bacteria from returning travellers were Northern Europe and Western Europe. The region with the highest impact of AMR bacteria from visiting travellers was the Caribbean where small island countries receive large numbers of visitors. For countries/administrative regions with populations greater than 5 million, the AMR bacterial travel impacts measured in decreasing risk order from the highest were Hong Kong, Denmark, New Zealand, Hungary, Norway and Sweden. Interpretation: For some countries the incidence of AMR infection among both visitors and returning travellers is much higher than in the domestic population. This impact and how these bacteria are acquired from the environment, must be factored into public health policies for containing global spread of AMR bacteria and as part of a One Health approach. Full article
(This article belongs to the Special Issue The One Health Action Plan Against Antimicrobial Resistance)
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