Genotype–Phenotype Links Between Aminoglycoside-Modifying Enzymes and Aminoglycoside MICs in Aminoglycoside-Resistant Klebsiella pneumoniae in a Southern Vietnam Tertiary Hospital

Aminoglycosides remain important components of combination therapy for complicated Klebsiella pneumoniae infections in Vietnam; however, gene-level evidence linking aminoglycoside-modifying enzymes (AMEs) with minimum inhibitory concentrations (MICs) and multidrug resistance is limited, particularly in tertiary-care settings in southern Vietnam. A cross-sectional analysis was conducted on 186 non-duplicate aminoglycoside-resistant Klebsiella pneumoniae clinical isolates collected in a tertiary-care hospital in Ho Chi Minh City. Species identity was reconfirmed using ZKIR qPCR. MICs for amikacin, gentamicin, and tobramycin were determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines, and 14 AME genes were detected using targeted qPCR. Associations between AME genes, aminoglycoside MICs or susceptibility categories, and co-resistance to major antibiotic classes were assessed using non-parametric and exact tests with Benjamini–Hochberg false discovery rate correction, with emphasis on effect direction and clinically interpretable genotype–phenotype patterns beyond statistical significance alone. AME genes were highly prevalent, with ant(2″)-Ia, aac(6′)-Ir, and aac(6′)-Ib detected in 97.3%, 91.9%, and 89.8% of isolates, respectively. The presence of aac(6′)-Ib and aac(6′)-Ih_v was associated with higher aminoglycoside MICs, resistance to amikacin and tobramycin, and broader multidrug resistance, including carbapenem resistance, whereas several other AMEs were linked to lower MICs. These findings indicate that specific AME profiles, particularly aac(6′)-Ib and aac(6′)-Ih_v, are associated with intensified aminoglycoside resistance in this setting and support the need for gene-informed surveillance to prioritise confirmatory MIC-based Antimicrobial Susceptibility Testing (AST) to guide local antimicrobial stewardship.