Objectives: Linezolid resistance among Enterococcus species poses a growing clinical and public health concern, especially due to the dissemination of transferable resistance genes, such as optrA. This study aimed to evaluate the prevalence of linezolid resistance and to characterize the molecular epidemiology and genetic contexts of optrA-positive linezolid-resistant Enterococcus (LRE) isolates from clinical and animal sources in South Korea. Methods: A total of 2156 Enterococcus isolates, collected through nationwide surveillance from hospitalized patients and healthy livestock (pigs, cattle, and chickens) between 2017 and 2019, were retrospectively analyzed. Phenotypic susceptibility testing, optrA gene screening, and whole-genome sequencing were performed to investigate genetic environments and phylogenetic relationships. Results: The prevalence of linezolid resistance was 0.2% in clinical isolates, 3.3% in pigs, 4.3% in cattle, and 1.4% in chickens. optrA-positive linezolid-resistant isolates were less frequent, with rates of 0.1%, 1.4%, 0.9%, and 1.0%, respectively. Multilocus sequence typing identified sequence types (STs) 330 and ST476 in E. faecalis from humans, with no shared STs between human and livestock isolates. The optrA gene was located either chromosomally, frequently associated with transposon Tn6674, or on multidrug resistance plasmids. Notably, optrA variants exhibited host-specific distribution patterns. Phylogenetic analysis demonstrated considerable genomic diversity, and Korean ST476 isolates were genetically related to international strains reported from livestock, poultry products, and wild birds, suggesting potential global dissemination. Conclusions: This study provides a comprehensive, nationally representative assessment of linezolid resistance in South Korea. The findings highlight the zoonotic potential and possible international dissemination of optrA-carrying ST476 lineages, underscoring the need for integrated One Health surveillance to monitor and control the spread of transferable resistance genes.

Background: Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales are an increasing cause of complicated urinary tract infections (UTIs). Reliance on carbapenems to treat these infections accelerates resistance, underscoring the urgent need for effective oral transition options to preserve last-line agents and lessen healthcare burden. Methods: We conducted a multicenter, open-label, randomized, noninferiority trial at four tertiary hospitals in South Korea (November 2022–June 2025). Adults hospitalized with complicated UTIs due to ESBL-producing Enterobacterales who improved after 3–7 days of intravenous antibiotics were randomized (1:1) to either continue intravenous carbapenem or β-lactam/β-lactamase inhibitor therapy or switch to oral fosfomycin trometamol (3 g once daily). The primary outcome was clinical cure, defined as resolution of urinary tract infection–related symptoms and signs within 4 days after completion of treatment. Secondary outcomes included microbiological cure, readmission, adverse events, and 30-day recurrence. Results: Of the 344 screened patients, 299 were randomized (152 oral fosfomycin; 147 intravenous therapy). Clinical cure occurred in 92.8% of the oral fosfomycin group and 95.2% of the intravenous group (risk difference, −2.47%; 95% CI −7.84 to 2.89), confirming noninferiority. Microbiological cure was similarly high in both groups: urine (98.0% vs 96.6%) and blood (97.3% vs 97.5%). Safety profiles and 30-day outcomes were also comparable. Conclusions: Oral fosfomycin was noninferior to continued intravenous therapy when used as oral transition therapy for complicated UTIs caused by ESBL-producing Enterobacterales. These findings provide evidence to support oral fosfomycin transition as a carbapenem-sparing antibiotic stewardship strategy for patients with complicated UTIs caused by ESBL-producing Enterobacterales. Clinical Trials Registration: KCT0007669.

Background/Objective: Acinetobacter baumannii is an opportunistic pathogen responsible for various healthcare-associated infections, particularly in critically ill patients. The emergence and rapid spread of multidrug- and extensively drug-resistant strains, notably carbapenem-resistant A. baumannii (CRAB), threaten global health. We aimed to investigate the clonal distribution, antimicrobial resistance profiles, and resistance determinants of CRAB bloodstream isolates in Korean hospitals to identify emerging high-risk clones and their potential clinical impact. Methods: Sequence types (STs) were determined using the Oxford multilocus sequence typing scheme, and antimicrobial susceptibility profiles and resistance determinants were evaluated. Results: We analyzed 812 CRAB bloodstream isolates collected from nine South Korean tertiary hospitals between 2016 and 2020. The isolates were classified into 39 STs, with ST191 (n = 245) and ST369 (n = 192) being the most prevalent. Between 2016 and 2020, ST369 increased from 2.6% to 37.9%, while ST195, first detected in 2018 (0.5%), increased to 19.0%; however, ST191 declined from 45.2% to 19.0%. Most CRAB infections were hospital-acquired (91.6%, 744 of 812), predominantly affecting men aged ≥51 years, particularly the 71–80-year-olds. Resistance rates were ≥80% for ampicillin-sulbactam and ciprofloxacin. bla_OXA-23 was detected in 807 isolates, confirming its central role in carbapenem resistance. ST195 exhibited higher resistance to minocycline (29.4%) than did the other STs. Conclusions: Dynamic clonal shifts and high antimicrobial resistance exist among CRAB isolates in Korean hospitals, with the rapid emergence of ST195 and ST369 increasing clinical challenges. Continuous epidemiological surveillance and targeted infection control measures are essential to control the spread of high-risk CRAB clones.