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

Laura J. Rojas, Madiha Salim, Eric Cober, Sandra S. Richter, Federico Perez, Robert A. Salata, Robert C. Kalayjian, Richard R. Watkins, Steve Marshall, Susan D. Rudin, T. Nicholas Domitrovic, Andrea M. Hujer, Kristine M. Hujer, Yohei Doi, Keith S. Kaye, Scott Evans, Vance G. Fowler, Robert A. Bonomo, David Van Duin

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155 Citations (Scopus)


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 <. 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.

Original languageEnglish
Pages (from-to)711-718
Number of pages8
JournalClinical Infectious Diseases
Issue number6
Publication statusPublished - 15-03-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases


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