Microbiological and clinical impact of aminoglycosides on KPC-producing Klebsiella pneumoniae bacteraemia with aminoglycoside-modifying enzymes

Abstract

Background: Klebsiella pneumoniae (KPN) is a major pathogen associated with life-threatening infections. The global rise in carbapenem-resistant KPN, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing strains, presents a treatment challenge. The efficacy of aminoglycosides against KPC-producing KPN strains carrying aminoglycoside-modifying enzyme (AME) genes remains unclear. This study evaluated the clinical and microbiological effects of aminoglycoside therapy on AME gene-bearing KPC-producing KPN bacteraemia. Methods: We conducted a retrospective cohort study on adults with amikacin-susceptible KPC-producing KPN bacteraemia at a South Korean tertiary hospital (2022-2024). Antimicrobial susceptibility was assessed using VITEK 2 and disc diffusion per Clinical and Laboratory Standards Institute guidelines. The blaKPC gene was detected via immunochromatography, whereas whole-genome sequencing identified blaKPC subtypes and AME genes. Clinical and microbiological outcomes were analysed based on aminoglycoside use. Results: Among 136 patients (mean age: 63.6 years), 98 received aminoglycoside therapy, and 38 did not. Intraabdominal infections were the most common source. Microbiological clearance within one week was significantly lower in the aminoglycoside group (63.3 % vs. 84.2 %, (p = 0.005). Clinical improvement within three days was also lower (48% vs. 73.7 %). Mortality rates (28-d: 26.5% vs. 21.1 %, p = 0.660; in-hospital: 40.8% vs. 34.2 %, p = 0.559) did not differ significantly. Multivariable analysis found no significant association between aminoglycoside use and 28-d mortality (odds ratio 0.99; 95 % confidence interval: 0.33-3.13, p = 0.988). Conclusion: Aminoglycoside therapy did not improve clinical or microbiological outcomes in AME gene-bearing KPC-producing KPN bacteraemia, despite phenotypic susceptibility.