The in Vitro Activity of Omadacycline Alone and in Combination Against Carbapenem-Resistant

Overview

Journal Infect Drug Resist

Publisher Dove Medical Press

Date 2024 Dec 30

PMID 39734741

Authors

Yingying Du

Yan Liu

Tong Liu

Fen Pan

Shikui Mu

Yunlou Zhu

Hanlu Gao

Xin Jing

Xing Wang

Yuhao Liu

Sheng Wang

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to evaluate the in vitro activity of omadacycline (OMC) and OMC-based combination therapy against carbapenem-resistant (CRKP).

Methods: The broth microdilution assay assessed the in vitro susceptibility of CRKP to OMC. The checkerboard assay was performed to evaluate the activity of OMC combined with polymyxin B (PB), amikacin (AN), or meropenem (MEM) against KPC-producing (class A) CRKP strains, and OMC combined with PB, aztreonam (ATM), MEM, or AN against class B and class A plus class B CRKP strains. Synergistic effects of OMC and PB were further evaluated by time-kill assays in the KPC-producing CRKP strains.

Results: Broth microdilution assays revealed a notable variation in susceptibility between KPC-producing and class B CRKP strains, with MIC50/90 of 32/32 mg/L and 0.5/8 mg/L, respectively. Although KPC-producing CRKP strains were resistant to OMC, a synergistic effect was observed in 37.5% of KPC-producing CRKP strains when OMC was combined with PB. In the nine KPC-producing CRKP strains, time-kill assays found that cell densities of six strains (66.7%) decreased by 3.61 ± 0.23 log CFU/mL compared to the initial inoculum after 2 hours of PB exposure. The cell densities further decreased by an average of 2.38 ± 0.23 log CFU/mL when the six strains were exposed to OMC plus PB, confirming their potent synergism.

Conclusion: OMC monotherapy is ineffective against KPC-producing CRKP strains, but OMC plus PB has a potent synergistic effect on them, suggesting that OMC plus PB is the preferred combination therapy against KPC-producing CRKP in vitro.

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