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

Antibacterial Resistance Leadership Group

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

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.

Original languageEnglish
Pages (from-to)711-718
Number of pages8
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume64
Issue number6
DOIs
Publication statusPublished - 15-03-2017
Externally publishedYes

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Colistin
Carbapenems
Klebsiella pneumoniae
Mortality
Disk Diffusion Antimicrobial Tests
Polymyxins
Antimicrobial Cationic Peptides
Hospital Mortality
Microbiology
Infection
Plasmids
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

@article{f955d5116aeb4026a158ffe6ad384bf9,
title = "Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality",
abstract = "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.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.",
author = "{Antibacterial Resistance Leadership Group} and Rojas, {Laura J.} and Madiha Salim and Eric Cober and Richter, {Sandra S.} and Federico Perez and Salata, {Robert A.} and Kalayjian, {Robert C.} and Watkins, {Richard R.} and Steve Marshall and Rudin, {Susan D.} and Domitrovic, {T. Nicholas} and Hujer, {Andrea M.} and Hujer, {Kristine M.} and Yohei Doi and Kaye, {Keith S.} and Scott Evans and Fowler, {Vance G.} and Bonomo, {Robert A.} and {van Duin}, David",
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doi = "10.1093/cid/ciw805",
language = "English",
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Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae : Laboratory Detection and Impact on Mortality. / Antibacterial Resistance Leadership Group.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 64, No. 6, 15.03.2017, p. 711-718.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae

T2 - Laboratory Detection and Impact on Mortality

AU - Antibacterial Resistance Leadership Group

AU - Rojas, Laura J.

AU - Salim, Madiha

AU - Cober, Eric

AU - Richter, Sandra S.

AU - Perez, Federico

AU - Salata, Robert A.

AU - Kalayjian, Robert C.

AU - Watkins, Richard R.

AU - Marshall, Steve

AU - Rudin, Susan D.

AU - Domitrovic, T. Nicholas

AU - Hujer, Andrea M.

AU - Hujer, Kristine M.

AU - Doi, Yohei

AU - Kaye, Keith S.

AU - Evans, Scott

AU - Fowler, Vance G.

AU - Bonomo, Robert A.

AU - van Duin, David

PY - 2017/3/15

Y1 - 2017/3/15

N2 - 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.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.

AB - 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.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.

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U2 - 10.1093/cid/ciw805

DO - 10.1093/cid/ciw805

M3 - Article

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JO - Clinical Infectious Diseases

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SN - 1058-4838

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