Antibiotics-Basel最新文献

Background/Objectives: Comparative analysis of antimicrobial resistomes in hospital and community wastewater can provide valuable insights into the diversity and distribution of antimicrobial resistance genes (ARGs), contributing to the advancement of the One Health approach. This study aimed to characterize and compare the resistome profiles of wastewater sources from a hospital and community. Methods: Longitudinal metagenomic analysis was conducted on wastewater samples collected from the National Center for Global Health and Medicine (hospital) and a shopping mall (community) in Tokyo, Japan, between December 2019 and September 2023. ARG abundance was quantified using reads per kilobase per million mapped reads (RPKM) values, and comparative analyses were performed to identify the significantly enriched ARGs in the two sources. Results: A total of 46 monthly wastewater samples from the hospital yielded 825 unique ARGs, with a mean RPKM of 2.5 across all detected genes. In contrast, 333 ARGs were identified in the three shopping mall wastewater samples, with a mean RPKM of 2.1. Among the ARGs significantly enriched in the hospital samples, 23, including genes conferring resistance to aminoglycosides (nine groups) and β-lactam antibiotics (eight groups), exhibited significantly high RPKM values. No ARGs were found to be significantly enriched in the community wastewater samples. Conclusions: This study highlights the higher diversity and abundance of ARGs, particularly those conferring resistance to aminoglycosides and β-lactam antibiotics including carbapenems, in hospital wastewater than in community wastewater. These findings underscore the importance of continuous resistome monitoring of hospital wastewater as part of the integrated One Health surveillance strategy.

Lipopeptides (LPs) have evolved from naturally occurring compounds to key therapeutic agents against multidrug-resistant (MDR) bacterial infections. However, their expanding clinical use has triggered emerging resistance mechanisms, posing serious challenges to anti-infective therapy. This systematic review outlines the development of LP resistance and highlights innovative strategies to counteract it. To overcome these evolving barriers, the field has transitioned from traditional empirical optimization to multidimensional rational design. Moving beyond conventional structure-activity relationship (SAR)-guided chemical synthesis, current approaches integrate diverse innovative methodologies. Based on these advances, this review provides the first systematic summary of contemporary strategies for developing novel LPs, offering new perspectives and methodological support to combat resistant bacterial infections and accelerate the development of next-generation LP-based therapeutics.

Background/objective: Inappropriate antibiotic use in paediatric populations is a leading driver of antimicrobial resistance. In the Murcia Region, Spain, the Purapi program promotes the rational use of antibiotics among children under 3 years of age. This study aimed to analyse antibiotic use in this age group during the pandemic period (2020-2023) and to assess the impact of the COVID-19 pandemic on the effectiveness of a multifaceted program promoting appropriate antibiotic use. Methods: A retrospective, multicentre, population-based study was conducted in primary care using data from 2019 to 2024. Systemic antibiotic use (ATC J01 group) among children under three years was measured as defined daily doses per 1000 inhabitants per day (DHD). Differences across years and healthcare areas were assessed using analysis of variance (ANOVA) with Bonferroni correction. Results: Antibiotic consumption decreased by 49% in 2020 compared to 2019, coinciding with the implementation of national COVID-19 containment measures. From 2021 onward, a gradual increase was observed; however, by 2024, levels remained 9% below pre-pandemic values. Penicillins account for 75% of prescriptions, mainly amoxicillin and amoxicillin-clavulanic acid. While variability across healthcare areas decreased during the pandemic, variability among primary care centres increased. Conclusions: The pandemic resulted in a temporary reduction in antibiotic use, followed by a partial rebound. Ongoing educational and stewardship interventions within the Purapi framework were instrumental in maintaining rational prescribing and may have contributed to maintaining reduced antibiotic consumption among children under three years of age during and after the pandemic. Strengthening and harmonising these initiatives is essential to ensure consistent paediatric antibiotic stewardship in primary care.

Background/Objectives:Staphylococcus aureus is a multifaceted pathogen responsible for diseases in humans and in several animal species, including dairy cows. This study aimed to characterize and compare the genetic diversity, lineage distribution, and antimicrobial resistance profiles of S. aureus isolates from bovine milk with human-derived reference genomes to investigate host adaptation and inter-species transmission. Methods: Genomic analyses were performed on S. aureus isolates from quarter milk samples of dairy cows together with human-derived sequences from public databases. Whole-genome sequencing and multi-locus sequence typing (MLST) were used to determine sequence type (ST) distribution, and the presence of key antibiotic resistance genes and mobile genetic elements (MGEs) was assessed. Comparative genomics was applied to evaluate gene content, phylogenetic relationships, and lineage-host associations. Results: The dataset encompassed bovine-adapted lineages (CC97, CC133, CC151) and human-associated lineages (CC1, CC5, CC8, CC30, CC45), as well as livestock-associated ST398 in bovine samples and human-adapted ST5 and ST6 in animals. ST8 was the only ST shared between animal and human isolates and showed differing resistance profiles, with animal ST8 carrying resistance determinants absent from human ST8. Bovine-adapted strains were characterized by recurrent loss of human-associated virulence genes and acquisition of bovine-associated mobile genetic elements, and blaZ and mecA were rarely detected in bovine-adapted CC97 but were frequently present in human CC5 and CC8. Overall, animal isolates carried fewer resistance genes than human isolates. Conclusions: S. aureus from dairy cows and humans displayed substantial genetic diversity, with evidence of host-associated lineages and dynamic changes in gene and mobile element content. These findings support the need for integrated One Health surveillance to track shared and host-adapted lineages and their antibiotic resistance determinants.

Background/Objectives.Lactiplantibacillus plantarum CRL681 has previously demonstrated a strong antagonistic effect against Escherichia coli O157:H7 in food matrices; however, the molecular mechanisms underlying this activity remain poorly understood. Since initial interactions between beneficial bacteria and pathogens occur mainly at the cell surface and in the extracellular environment, the characterization of the bacterial secretome is essential for elucidating these mechanisms. In this study, the secretome of L. plantarum CRL681 was comprehensively characterized using an integrated in silico and in vitro approach. Methods. The exoproteome and surfaceome were analyzed by LC-MS/MS under pure culture conditions and during co-culture with E. coli O157:H7. Identified proteins were functionally annotated, classified according to subcellular localization and secretion pathways, and evaluated through protein-protein interaction network analysis. Results. A total of 275 proteins were proposed as components of the CRL681 secretome, including proteins involved in cell surface remodeling, metabolism and nutrient transport, stress response, adhesion, and genetic information processing. Co-culture with EHEC induced significant changes in the expression of proteins associated with energy metabolism, transport systems, and redox homeostasis, indicating a metabolic and physiological adaptation of L. plantarum CRL681 under competitive conditions. Notably, several peptidoglycan hydrolases, ribosomal proteins with reported antimicrobial activity, and moonlighting proteins related to adhesion were identified. Conclusions. Overall, these findings suggest that the antagonistic activity of L. plantarum CRL681 against E. coli O157:H7 would be mediated by synergistic mechanisms involving metabolic adaptation, stress resistance, surface adhesion, and the production of non-bacteriocin antimicrobial proteins, supporting its potential application as a bioprotective and functional probiotic strain.

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Background/Objectives: Infections remain a leading cause of morbidity and mortality following liver transplantation, with bloodstream infections (BSIs) representing one of the most critical complications. This study aimed to identify factors associated with mortality in liver transplant recipients who developed BSIs over a 10-year period. Methods: This retrospective study was conducted at a tertiary university hospital between 1 April 2014 and 31 December 2024. A total of 467 adult patients underwent liver transplantation during the study period. Among 467 patients, a total of 210 bloodstream infection episodes occurring in 136 patients were included in the study. Results: BSIs occurred in 29.1% (136/467) of patients, with a total of 210 episodes. The median age was 55 years (IQR: 45-63). Most transplants (95.2%) were from living donors. Hepatitis B virus infection (27.1%) was the most common underlying etiology of cirrhosis. The majority of BSIs (61.2%) occurred within the first three months post-transplant. A total of 242 pathogens were isolated, with ESBL-producing Enterobacterales identified in 72.6% and carbapenem-resistant Enterobacterales (CRE) in 30.1% of cases. Notably, carbapenem resistance among Klebsiella spp. was high at 51.78%. The overall mortality rate was 14.28%. Multivariate analysis identified that a high Pitt Bacteremia Score (hazard ratio [HR] 1.502, 95% confidence interval [CI] 1.361-1.657, p < 0.001) and CRE infection (HR 3.644, 95% CI 1.380-9.620, p = 0.009) were independent predictors of mortality. Conclusions: BSIs are a significant post-transplant complication with high antimicrobial resistance. The Pitt bacteremia score is a strong predictor of mortality and may guide early risk stratification and clinical management in liver transplant recipients.

Background/Objectives: Infections due to multidrug-resistant (MDR) Acinetobacter baumannii represent a critical challenge in modern healthcare, with limited therapeutic options. Eravacycline, a novel fluorocycline antibiotic, demonstrates promising in vitro activity, but real-world clinical data for complex intra-abdominal infections (IAIs) are scarce. We present two cases of severe IAI caused by carbapenem-resistant A. baumannii (CRAB) successfully treated with eravacycline. Methods: We describe the clinical course, microbiological findings, and outcomes of two critically ill patients. Case 1 was a 75-year-old male with biliary peritonitis following an endoscopic procedure. Case 2 was a 64-year-old male with infected pancreatic walled-off necrosis. Both patients had cultures positive for CRAB and failed multiple prior antibiotic regimens. Results: In both cases, the initiation of intravenous eravacycline led to significant clinical improvement, including resolution of septic shock and defervescence. A marked reduction in inflammatory markers (C-reactive protein and procalcitonin) was observed, alongside microbiological clearance of CRAB. Eravacycline was well tolerated, with no significant adverse events. Conclusions: These case reports suggest that eravacycline can be an effective and safe salvage therapy for complex IAIs caused by CRAB, even in scenarios of partial source control. It represents a valuable addition to the antimicrobial armamentarium for managing infections caused by these extensively drug-resistant organisms.

Background: Libya, a conflict-affected North African country, has a fragile health system and poor surveillance, leaving it largely underrepresented in global estimates. Earlier Libyan reviews were descriptive, lacking breakpoint standardization, isolate-level pooling, or AMR-attributable mortality and DALY estimates. To our knowledge, this study represents the first comprehensive report that integrates phenotypic and genotypic data to estimate deaths and DALYs attributable to AMR-induced mortality and morbidity, describe spatiotemporal patterns, and model future trajectories. Methods: We performed a meta-analysis according to the PRISMA 2020 guideline of Libyan studies reporting phenotypic or genotypic resistance among clinical bacterial isolates (1970-2024), combined with microbiology records from hospitals and national surveillance systems (preregistered in PROSPERO ID: CRD420251066018). Susceptibility results were standardized to CLSI/EUCAST and deduplicated using WHO GLASS first-isolate rules. We used random-effects meta-regression to estimate pooled resistance, and the counterfactual approach of Global Burden of Disease (GBD) was applied to estimate AMR-attributable DALYs. Molecular data on resistance genes, sequence types, and tuberculosis mutations were systematically collected. Results: We included 62 eligible studies together with national and facility-level surveillance datasets, providing isolate-level susceptibility data for 31,439 clinical isolates from Libya. In 2024, we estimated 2183 deaths (95% UI 1752-2614) attributable to AMR, representing 9.7% (95% UI 7.8-11.6) of total deaths with a mortality rate of 15.2 per 100,000 (12.2-18.2). DALYs attributable to AMR increased from 14,628 (95% UI 11,702-17,554) in 1970 to 96,715 (95% UI 77,372-116,058). The highest pooled resistance involved carbapenem-resistant/MDR A. baumannii, third-generation cephalosporin- and fluoroquinolone-resistant Enterobacterales, and carbapenem-resistant P. aeruginosa. Molecular data showed widespread ESBLs, OXA-/NDM-type carbapenemases, plasmid-mediated colistin resistance, high-risk E. coli ST131 and K. pneumoniae ST147 lineages, and canonical drug-resistant M. tuberculosis mutations. Conclusions: Combined with global and regional evidence, our findings suggest a high and increasing burden of AMR in Libya. These findings emphasize the need for rapid expansion of data collection systems, GLASS-aligned surveillance, diagnostic capacities, and infection control measures.

Background: Antibiotic overuse in Neonatal Intensive Care Units (NICUs) is a major contributor to antimicrobial resistance and adverse neonatal outcomes. This study aims to evaluate baseline antibiotic utilization (AU), identify factors influencing variability, and assess the impact of neonatal characteristics and sepsis incidence. Methods: A multicenter retrospective analysis examined AU in seven NICUs from 2019 to 2023, involving 25,532 neonatal admissions during national antibiotic stewardship program implementation. Data encompassed neonatal clinical parameters, sepsis incidence, and AU metrics, including days of therapy (DOT) per 1000 patient-days. Statistical analyses included correlation assessments and multivariate regression to identify determinants of antibiotic use. Results: Overall, 43.8% of neonates received antimicrobials, with individual NICUs ranging from 24% to 73% (p < 0.001). Antimicrobial-exposed neonates had a mean gestational age of 35.1 weeks [SD ± 4.4] and a mean birth weight of 2360 g [SD ± 970]. Antimicrobial-exposed neonates were generally more premature [35.1 (±4.4) weeks vs. 37.5 (±2.5) weeks (p < 0.001)] and had lower mean birth weight [2360 g (±971) vs. 2817 g (±686) (p < 0.001)] compared to those not exposed to antimicrobials. Total antimicrobial days varied markedly (8761 to 37,683 days), with DOT per 1000 patient-days ranging from 322 to 1031. Antimicrobial use for culture-negative sepsis varied widely among centers, from 23% to 73%. Antimicrobial-exposed neonates had higher all-cause mortality compared to those who did not [(7.5% vs. 3.2%), (p < 0.001)]. Multivariate analysis revealed individual NICU practice patterns remained significant predictors after adjusting for neonatal characteristics. Conclusions: Neonatal antimicrobial use varied significantly among NICUs, driven primarily by institutional practices rather than neonatal demographics. These findings provide nationally representative baseline data to inform neonatal antimicrobial stewardship interventions and offer transferable lessons for other countries seeking to optimize antibiotic use in NICUs amid rising global antimicrobial resistance.