Resistance to Plazomicin: An Analysis of the Evidence from In Vitro Antimicrobial Susceptibility Studies

Introduction: Plazomicin, a novel, semi-synthetic aminoglycoside designed to overcome most aminoglycoside-modifying enzymes (AMEs), represents a therapeutic alternative to traditional aminoglycosides for complicated urinary-tract infections (cUTIs). In this review, we sought to evaluate the available data on drug resistance. Methods: We performed a thorough search across four databases (PubMed, Embase, Scopus, and Web of Science) from their inception to 4 November 2025 to identify relevant studies. The published Clinical and Laboratory Standards Institute (CLSI) antimicrobial susceptibility breakpoints for Enterobacterales were applied. Results: Fifty-five studies, out of a total of 905 records originally identified, were eligible for data extraction and analysis, yielding antimicrobial susceptibility data for 80,159 clinical isolates. The overall resistance of consecutive Enterobacterales isolates to plazomicin was 0–9.4%, and specifically for Escherichia coli and Klebsiella spp. isolates were up to 4.7% and 15.2%, respectively. Among selected isolates with specific resistance mechanisms, the resistance of carbapenem-resistant Enterobacterales (CRE) was 1.8–67.6%, and specifically for carbapenem-resistant E. coli and Klebsiella spp. isolates, 0–10% and 0.3–90%, respectively. Among multi-drug-resistant (MDR) isolates, up to 24.6% of MDR Klebsiella spp. isolates and up to 15% of MDR E. coli isolates were resistant to plazomicin. Among non-fermenting Gram-negative bacteria, the MIC90 values were consistently high. Conclusions: The demonstrated high activity of plazomicin against consecutive Enterobacterales isolates and the considerable, yet variable, activity against selected resistant isolates suggest its consideration as a valuable option in the treatment of complicated urinary-tract infections.