Five-Year Trends in ESBL-Associated Co-Resistance and Multidrug Resistance Among Clinical Escherichia coli Isolates, Galați, Romania

Extended-spectrum β-lactamase (ESBL) production in Escherichia coli often coexists with resistance to non-β-lactam agents. We assessed five-year resistance trends, ESBL-associated co-resistance and correlates of ESBL and multidrug resistance (MDR) in E. coli clinical isolates. A retrospective study of 834 E. coli isolates, including the first isolate per admission, from three departments of an infectious diseases hospital in Galați, Romania (2021–2025). Antimicrobial susceptibility testing results were interpreted according to CLSI (2021–2022) and EUCAST (2023–2025) criteria, ESBL production was detected phenotypically, and MDR was defined according to standard criteria. Analyses included logistic regression for trends, primary-panel stratified co-resistance comparisons with Holm correction, and multivariable models. Of 834 isolates (79.0% urinary), 108 (12.9%) were ESBL-positive and 132 (15.8%) MDR, without temporal trends. Resistance was highest to triole (28.9%) and ciprofloxacin (25.0%), and below 1% for nitrofurantoin, fosfomycin and meropenem. Gentamicin resistance rose from 9.6% in 2021 to 23.8% in 2025 (annual OR 1.43; 95% CI 1.20–1.70), mainly in ESBL-negative and urinary isolates. The increase occurred after 2023, under unchanged EUCAST breakpoints. ESBL producers were more often resistant to norfloxacin (58.5% vs. 12.1%), ciprofloxacin (57.9% vs. 15.2%), trimethoprim–sulfamethoxazole (52.8% vs. 25.4%) and gentamicin (33.6% vs. 9.4%), and 53.7% were resistant to at least two of these classes vs. 12.5% of ESBL-negative isolates. Male sex was independently associated with ESBL (adjusted OR 3.09; 95% CI 1.96–4.88) and MDR (2.55; 1.67–3.90). ESBL and MDR prevalence remained stable, but gentamicin resistance increased markedly, independently of ESBL status. ESBL production was associated with a broad co-resistance phenotype, whereas nitrofurantoin, fosfomycin and carbapenems remained highly active. Antibiotic-specific surveillance and review of aminoglycoside-containing empirical regimens are warranted.