Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospitalgrid.278247.c, Taipei, Taiwan.
Division of Infectious Diseases, Department of Paediatrics, Taipei Veterans General Hospitalgrid.278247.c, Taipei, Taiwan.
Microbiol Spectr. 2022 Jun 29;10(3):e0038122. doi: 10.1128/spectrum.00381-22. Epub 2022 Jun 2.
Colistin is one of the last-resort options for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections if novel antibiotics are unavailable, where the development of colistin resistance during treatment represents a major challenge for clinicians. We aimed to investigate the risk factors associated with the development of colistin resistance in patients with CRKP infections following colistin treatment. We conducted a retrospective case-control study of patients with CRKP strains available before and after colistin treatment at a medical center in Taiwan, between October 2016 and November 2020. Cases ( = 35) included patients with an initial colistin-susceptible CRKP (ColS-CRKP) strain and a subsequent colistin-resistant CRKP (ColR-CRKP) strain. Controls ( = 18) included patients with ColS-CRKP as both the initial and subsequent strains. The 30-day mortality rate after the subsequent CRKP isolation was not different between cases and controls (12/35 [34%] versus 5/18 [28%] [ = 0.631]). ( = 38) and ( = 11) accounted for the major mechanisms of carbapenem resistance. Alterations in were found in 18/35 (51%) ColR-CRKP strains, and was not detected in any of the strains. More patients received combination therapy in the control group than in the case group (17/18 versus 21/35 [ = 0.008]). The logistic regression model indicated that combination therapy with tigecycline was protective against the acquisition of colistin resistance (odds ratio, 0.17; 95% confidence interval, 0.05 to 0.62 [= 0.008]). We observed that the inclusion of tigecycline in colistin treatment mitigated the risk of acquiring colistin resistance. These results offer insight into using the combination of tigecycline and colistin for the treatment of CRKP infections in antimicrobial stewardship. Treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is challenging due to the limited options of antibiotics. Colistin is one of the last-resort antibiotics if novel antimicrobial agents are not available. It is crucial to identify modifiable clinical factors associated with the emergence of resistance during colistin treatment. Here, we found that the addition of tigecycline to colistin treatment prevented the acquisition of colistin resistance. Colistin-tigecycline combination therapy is therefore considered a hopeful option in antimicrobial stewardship to treat CRKP infections.
多黏菌素是治疗碳青霉烯类耐药肺炎克雷伯菌（CRKP）感染的最后手段之一，如果没有新型抗生素可用，治疗过程中多黏菌素耐药的发展对临床医生来说是一个重大挑战。我们旨在研究多黏菌素治疗后 CRKP 感染患者发生多黏菌素耐药的相关危险因素。我们对 2016 年 10 月至 2020 年 11 月在台湾一家医疗中心接受多黏菌素治疗前后的 CRKP 菌株患者进行了回顾性病例对照研究。病例组（n=35）包括初始多黏菌素敏感 CRKP（ColS-CRKP）菌株和随后多黏菌素耐药 CRKP（ColR-CRKP）菌株的患者。对照组（n=18）包括初始和随后菌株均为 ColS-CRKP 的患者。随后 CRKP 分离后 30 天死亡率在病例组和对照组之间无差异（12/35 [34%] 与 5/18 [28%] [=0.631]）。携带 blaNDM-1 （n=18）和 blaCTX-M-15 （n=11）的菌株分别占碳青霉烯类耐药的主要机制。18/35（51%）ColR-CRKP 菌株中发现了 基因的改变，而任何菌株中均未检测到 基因。对照组中接受联合治疗的患者多于病例组（17/18 与 21/35 [=0.008]）。逻辑回归模型表明，替加环素联合治疗可降低获得多黏菌素耐药的风险（比值比，0.17；95%置信区间，0.05 至 0.62 [=0.008]）。我们观察到，在多黏菌素治疗中加入替加环素可降低获得多黏菌素耐药的风险。这些结果为在抗菌药物管理中使用替加环素和多黏菌素联合治疗 CRKP 感染提供了参考。
由于抗生素选择有限，治疗碳青霉烯类耐药肺炎克雷伯菌（CRKP）感染具有挑战性。如果没有新型抗菌药物，多黏菌素是最后的抗生素之一。确定与多黏菌素治疗过程中耐药性出现相关的可改变的临床因素至关重要。在这里，我们发现替加环素联合多黏菌素治疗可预防多黏菌素耐药的发生。因此，多黏菌素-替加环素联合治疗被认为是抗菌药物管理中治疗 CRKP 感染的一个有希望的选择。
