Rojas Laura J, Salim Madiha, Cober Eric, Richter Sandra S, Perez Federico, Salata Robert A, Kalayjian Robert C, Watkins Richard R, Marshall Steve, Rudin Susan D, Domitrovic T Nicholas, Hujer Andrea M, Hujer Kristine M, Doi Yohei, Kaye Keith S, Evans Scott, Fowler Vance G, Bonomo Robert A, van Duin David
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Clin Infect Dis. 2017 Mar 15;64(6):711-718. doi: 10.1093/cid/ciw805.
Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide.
A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014. Reference colistin resistance determination as performed by broth macrodilution was compared to results from clinical microbiology laboratories (Etest) and to polymyxin resistance testing. Each patient was included once, at the time of their first colistin-tested CRKp positive culture. Time to 30-day in-hospital all-cause mortality was evaluated by Kaplan-Meier curves and Cox proportional hazard modeling.
In 246 patients with CRKp, 13% possessed ColR CRKp. ColR was underestimated by Etest (very major error rate = 35%, major error rate = 0.4%). A variety of rep-PCR strain types were encountered in both the ColS and the ColR groups. Carbapenem resistance was mediated primarily by blaKPC-2 (46%) and blaKPC-3 (50%). ColR was associated with increased hazard for in-hospital mortality (aHR 3.48; 95% confidence interval, 1.73-6.57; P < .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp.
In this cohort, 13% of patients with CRKp presented with ColR CRKp. The apparent polyclonal nature of the isolates suggests de novo emergence of ColR in this cohort as the primary factor driving ColR. Importantly, mortality was increased in patients with ColR isolates.
包括黏菌素在内的多黏菌素是治疗耐碳青霉烯类肺炎克雷伯菌（CRKp）感染的重要“最后一线”疗法。黏菌素使用的增加导致对这种阳离子抗菌肽产生耐药性。
在耐肺炎克雷伯菌碳青霉烯类药物联盟（CRACKLE）中构建了一个队列，纳入在2011年12月至2014年10月研究期间感染或定植CRKp分离株并对黏菌素敏感性进行检测的患者。将肉汤稀释法进行的参考黏菌素耐药性测定结果与临床微生物实验室（Etest）的结果以及多黏菌素耐药性检测结果进行比较。每位患者在首次黏菌素检测CRKp阳性培养时仅纳入一次。通过Kaplan-Meier曲线和Cox比例风险模型评估30天院内全因死亡率。
在246例CRKp患者中，13% 携带ColR CRKp。Etest低估了ColR（极重大错误率 = 35%，重大错误率 = 0.4%）。在ColS组和ColR组中均遇到多种rep-PCR菌株类型。碳青霉烯类耐药主要由blaKPC-2（46%）和blaKPC-3（50%）介导。ColR与院内死亡风险增加相关（调整后风险比3.48；95%置信区间，1.73 - 6.57；P <.001）。在任何ColR CRKp中均未检测到质粒相关的ColR基因mcr-1和mcr-2。
在该队列中，13% 的CRKp患者存在ColR CRKp。分离株明显的多克隆性质表明该队列中ColR是作为驱动ColR的主要因素而重新出现的。重要的是，ColR分离株患者的死亡率增加。
