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Published on: March 24, 2023
Effect of Meropenem on Conjugative Plasmid Transfer in Klebsiella pneumoniae
Daria A Kondratieva1, Julia R Savelieva1, Maria V Golikova1
1Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics, 11 Bolshaya Pirogovskaya Street, 119021 Moscow, Russia.
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 blaKPC or blaOXA-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.
Insights
Meropenem
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Plasmid-mediated resistance is a significant driver of antibiotic ineffectiveness.
- Carbapenem antibiotics face declining efficacy due to resistance mechanisms.
- Antibiotics can influence the transfer of plasmids between bacteria.
Purpose of the Study:
- To examine the impact of meropenem on the conjugative transfer of carbapenemase-encoding plasmids in Klebsiella pneumoniae.
- To evaluate the pharmacodynamic properties of meropenem against K. pneumoniae transconjugants.
Main Methods:
- Conjugation experiments using K. pneumoniae strains carrying blaKPC or blaOXA-48 genes.
- Exposure to varying sub-inhibitory concentrations of meropenem (1/8×, 1/4×, 1/2× MIC).
- Pharmacodynamic testing of meropenem against resulting transconjugant strains.
Main Results:
- Meropenem at 1/8× MIC inhibited plasmid conjugation, while 1/2× MIC facilitated it.
- Transconjugants with intermediate meropenem resistance showed poor response to simulated high-dose, prolonged treatment.
- The study highlights a dual role of meropenem in modulating plasmid transfer.
Conclusions:
- Sub-inhibitory meropenem concentrations can paradoxically promote carbapenemase gene transfer in K. pneumoniae.
- Transconjugants with intermediate resistance pose a potential clinical risk due to treatment failure.
- Understanding antibiotic effects on plasmid transfer is crucial for combating antimicrobial resistance.
