ANTIBACTERIAL ACTIVITY OF CYTIDINE ANALOG AGAINST DRUG-RESISTANT Enterobacter cloacae COMPLEX

Abstract

Antimicrobial resistance is a major global public health concern, particularly among gram-negative bacteria such as the Enterobacter cloacae complex, a common hospital-associated pathogen. Resistance to multiple antimicrobial agents severely limits available treatment options. Therefore, this study aims to identify alternative therapeutic agents from nucleoside analog compounds capable of inhibiting the growth of ceftazidime- and colistin-resistant E. cloacae complex. A total of 290 nucleoside analogs were screened for antimicrobial activity. Among them, B2 – a cytidine analog – inhibited the growth of drug-resistant E. cloacae complex by more than 75% at a concentration of 8 µM (2 µg/mL). The minimum inhibitory concentration was subsequently determined using the broth microdilution method, revealing MIC values ranging from 1–2 µg/mL and demonstrating dose-dependent antibacterial activity. In addition, B2 exhibited enhanced activity when combined with the standard treatment meropenem, showing an additive effect with a fractional inhibitory concentration index (FICI) of 0.75. Our findings suggest that this cytidine analog has potential for development as a novel alternative therapeutic agent against drug-resistant E. cloacae complex infections and may contribute to reducing reliance on, and resistance to, currently used antimicrobial agents.