Resistant bacterial pathogens are significantly jeopardizing the successful treatment of serious infections. MDR Klebsiella pneumoniae isolates are highly challenging. While AGS antibiotics play a critical role against this pathogen, their intracellular accumulation is poorly known. Therefore, we aimed to characterize the intracellular accumulation and washout kinetics of three AGS in MDR K. pneumonia.
Our ultra-sensitive UPLC-MS/MS assay allowed us to characterize intracellular AGS kinetics for the first time. The AGS showed extensive uptake and a prolonged residence time in K. pneumoniae. Accumulation was most extensive for plazomicin and tobramycin. This study provides important, mechanistic insights for the design of optimal AGS combination dosage regimens to combat MDR K. pneumoniae.
Learning Objectives:
Mechanisms of resistance to aminoglycoside antibiotics.
Intracellular accumulation and washout kinetics of aminoglycosides (AGS) in multidrug-resistant (MDR) Klebsiella pneumoniae.
How UPLC-MS/MS contribute to measuring the concentration of intracellular aminoglycosides (AGS).
