Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality.

Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality.

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 Jr; Bonomo Robert A; van Duin David

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2017

2017-03

Background: 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. Methods: 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. Results: 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 \textless .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp. Conclusions: 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.

*beta-Lactam Resistance; *carbapenem-resistant Enterobacteriaceae; *colistin; *Klebsiella pneumoniae; *mortality; *ST258; Aged; Anti-Bacterial Agents/pharmacology/*therapeutic use; beta-Lactamases/genetics; Carbapenems/pharmacology/therapeutic use; Colistin/pharmacology/*therapeutic use; Comorbidity; Female; Humans; Kaplan-Meier Estimate; Klebsiella Infections/diagnosis/*drug therapy/*microbiology/mortality; Klebsiella pneumoniae/classification/*drug effects/genetics; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Proportional Hazards Models

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