Du Yingying, Liu Yan, Liu Tong, Pan Fen, Mu Shikui, Zhu Yunlou, Gao Hanlu, Jing Xin, Wang Xing, Liu Yuhao, Wang Sheng
Intensive Care Medical Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People's Republic of China.
Department of Critical Care Medicine, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, People's Republic of China.
Infect Drug Resist. 2024 Dec 23;17:5785-5794. doi: 10.2147/IDR.S473546. eCollection 2024.
This study aimed to evaluate the in vitro activity of omadacycline (OMC) and OMC-based combination therapy against carbapenem-resistant (CRKP).
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.
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.
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.
本研究旨在评估奥玛环素（OMC）及基于OMC的联合疗法对耐碳青霉烯类肺炎克雷伯菌（CRKP）的体外活性。
采用肉汤微量稀释法评估CRKP对OMC的体外敏感性。通过棋盘法评估OMC联合多黏菌素B（PB）、阿米卡星（AN）或美罗培南（MEM）对产KPC（A类）CRKP菌株的活性，以及OMC联合PB、氨曲南（ATM）、MEM或AN对B类及A类加B类CRKP菌株的活性。通过时间杀菌试验在产KPC的CRKP菌株中进一步评估OMC与PB的协同效应。
肉汤微量稀释法显示，产KPC的CRKP菌株与B类CRKP菌株之间的敏感性存在显著差异，MIC50/90分别为32/32 mg/L和0.5/8 mg/L。尽管产KPC的CRKP菌株对OMC耐药，但当OMC与PB联合使用时，在37.5%的产KPC的CRKP菌株中观察到协同效应。在9株产KPC的CRKP菌株中，时间杀菌试验发现，6株菌株（66.7%）在暴露于PB 2小时后的细胞密度与初始接种量相比降低了3.61±0.23 log CFU/mL。当这6株菌株暴露于OMC加PB时，细胞密度进一步平均降低了2.38±0.23 log CFU/mL，证实了它们强大的协同作用。
OMC单药治疗对产KPC的CRKP菌株无效，但OMC加PB对其有强大的协同作用，表明OMC加PB是体外抗产KPC的CRKP的首选联合治疗方案。
