Fosfomycin Susceptibility Patterns Among Uropathogens and Clinical Predictors of Resistance: A Cross-Sectional Study at a Tertiary Care Centre in Northern India

Introduction: Urinary tract infections (UTIs) represent a significant global health concern, with Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) as predominant uropathogens. Rising multidrug resistance, including extended-spectrum β-lactamase (ESBL)-producing strains, has renewed interest in fosfomycin as an oral therapeutic option. This study evaluated the fosfomycin susceptibility pattern among uropathogenic E. coli and K. pneumoniae in northern India. Method: This cross-sectional study was conducted at All India Institute of Medical Sciences (AIIMS), Rishikesh, from January to May 2025. Antimicrobial susceptibility testing (AST) of 407 culture-positive UTI isolates was performed using the VITEK-2 compact system (GN-235 cards) (bioMérieux SA, Marcy-l’Étoile, France), with results interpreted as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis identified independent predictors of fosfomycin resistance. Results: In this study, the participants were predominantly male, 242 (55.37%), with a median age of 50 years. E. coli accounted for 303 (69.3%) isolates and demonstrated high fosfomycin susceptibility, 302 (86%). On the other hand, K. pneumoniae, 104 (26%), exhibited alarmingly high resistance, 53 (98%). Bacterial species was the sole independent predictor of resistance, with K. pneumoniae being over 300 times more likely to be resistant than E. coli (OR = 322; 95% CI: 68.0-5765; p < 0.001). Age and sex were non-significant. The model showed excellent discrimination (AUC = 0.925). Conclusion: Fosfomycin showed excellent activity against E. coli, supporting its role as first-line therapy for uncomplicated UTI. However, the high resistance rate in K. pneumoniae strongly cautions against empirical fosfomycin use when this pathogen is suspected, reinforcing culture-guided prescribing practices.