Effect of Meropenem on Conjugative Plasmid Transfer in Klebsiella pneumoniae.

Abstract

Plasmid-mediated resistance is a major mechanism that contributes to the gradual decline in the effectiveness of antibiotics from different classes, including carbapenems. Antibiotics can significantly contribute to the efficiency of plasmid transfer between bacterial strains. To investigate the potential effect of an antibiotic on the efficacy of conjugative plasmid transfer, we conducted mating experiments with Klebsiella pneumoniae strains. Donor strains of K. pneumoniae that carry plasmids with bla_KPC or bla_OXA-48 carbapenemase genes and recipient plasmid-free K. pneumoniae strains were used in matings. Matings were conducted on the agar with or without meropenem at 1/8×, 1/4×, or 1/2×MIC against the respective recipients. In the second part of our study, we investigated the pharmacodynamic properties of meropenem against transconjugant strains of K. pneumoniae, which were obtained in the first part of this study. As a result, at a concentration equivalent to 1/8×MIC, meropenem primarily inhibited conjugation among K. pneumoniae strains, while at a concentration equal to 1/2×MIC, it facilitated conjugation. Transconjugants derived from K. pneumoniae with intermediate MICs failed to respond to simulated treatment with meropenem using prolonged infusion and a high-dose regimen. This finding suggests that such transconjugants may potentially pose a risk if involved in an infectious process.