Clinical Microbiology and Antimicrobial Chemotherapy. 2025; 27(1):33-41
To study pharmacodynamics of meropenem alone and in combination with avibactam in an in vitro dynamic model; to evaluate effectiveness of meropenem against K. pneumoniae strains producing and not producing carbapenemases; to study impact of bacterial inoculum on meropenem activity and its effects.
K. pneumoniae producing KPC and OXA-48 carbapenemases and non-producing strains were exposed to meropenem or its combination with avibactam (carbapenemase-producing strains only) in a modified in vitro hollow-fiber infection model (pneumoniae) simulating human pharmacokinetics of drugs administrated thrice daily for 5 days. The antimicrobial effect against the total population of K. pneumoniae was evaluated at different starting bacterial inocula (106 and 108 CFU/ml) by plating the samples on the agar media.
In the hollow-fiber infection model, the effect of meropenem was bactericidal for carbapenemase non-producing K. pneumoniae with MICs 2–4 mg/L, while carbapenemase-producing strains with comparable MICs of meropenem predominantly demonstrated rapid regrowth at both high and low starting inocula. The addition of avibactam led to an increased effect of meropenem and a decrease in the number of bacterial cells of all three carbapenemase-producing K. pneumoniae at both starting inocula.
Based on meropenem susceptibility data of K. pneumoniae without checking the ability to carbapenemase production it is impossible to guarantee a successful outcome of carbapenem therapy with both low (imitation of mild infection) and high (imitation of severe infection) inocula. Addition of avibactam significantly enhanced the effect of meropenem on all carbapenemase-producing strains.