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Multiple importations and transmission of colistin-resistant Klebsiella pneumoniae in a hospital in northern India

Published online by Cambridge University Press:  18 October 2019

Purva Mathur ,
Surbhi Khurana ,
Tom J.B. de Man ,
Neha Rastogi ,
Omika Katoch ,
Balaji Veeraraghavan ,
Ayyan Raj Neeravi ,
Manigandan Venkatesan ,
Subodh Kumar  and
Sushma Sagar
...Show all authors
Purva Mathur*
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Surbhi Khurana
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Tom J.B. de Man
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Neha Rastogi
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Omika Katoch
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Balaji Veeraraghavan
Affiliation:
Christian Medical College, Vellore, India
Ayyan Raj Neeravi
Affiliation:
Christian Medical College, Vellore, India
Manigandan Venkatesan
Affiliation:
Christian Medical College, Vellore, India
Subodh Kumar
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Sushma Sagar
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Amit Gupta
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Richa Aggarwal
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Kapil Dev Soni
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Rajesh Malhotra
Affiliation:
Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India
Anoop Velayudhan
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Valan Siromany
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Paul Malpiedi
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Joseph Lutgring
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA Emory University, Atlanta, Georgia, USA
Kayla Laserson
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Neil Gupta
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Padmini Srikantiah
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Aditya Sharma
Affiliation:
US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
*
Author for correspondence: Purva Mathur, Email: purvamathur@yahoo.co.in
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Abstract

Objective:

Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events.

Design:

Retrospective observational study.

Methods:

Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed.

Results:

Of 846 K. pneumoniae isolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%).

Conclusions:

Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 40 , Issue 12 , December 2019 , pp. 1387 - 1393
Copyright
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. 

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References

Gupta, N, Limbago, BM, Patel, JB, Kallen, AJ. Carbapenem-resistant Enterobacteriaceae: epidemiology and prevention. Clin Infect Dis 2011;53:60–67.CrossRefGoogle Scholar
Paterson, DL. Resistance in gram-negative bacteria: enterobacteriaceae. Am J Med 2006;119:S20–S28; discussion S62–S70.CrossRefGoogle ScholarPubMed
Paterson, DL, Bonomo, RA. Extended-spectrum lactamases: a clinical update. Clin Microbiol Revs 2005;18:657–686.CrossRefGoogle ScholarPubMed
Wang, R, van Dorp, L, Shaw, LP, et al. The global distribution and spread of the mobilized colistin resistance gene mcr-1 . Nat Commun 2018;9:1179.CrossRefGoogle ScholarPubMed
Schwaber, MJ, Carmeli, Y. Mortality and delay in effective therapy associated with extended-spectrum lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 2007;60:913–920.CrossRefGoogle ScholarPubMed
Apisarnthanarak, A, Hsu, LY, Khawcharoenporn, T, Mundy, LM. Carbapenem-resistant gram-negative bacteria: how to prioritize infection prevention and control interventions in resource-limited settings? Expert Rev Anti Infect Ther 2013;11:147–157.CrossRefGoogle ScholarPubMed
Gandra, S, Mojica, N, Klein, EY, et al. Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis 2016;50:75–82.CrossRefGoogle Scholar
Laxminarayan, R, Chaudhury, RR. Antibiotic resistance in India: drivers and opportunities for action. PLoS Med 2016;13:e1001974.CrossRefGoogle ScholarPubMed
Pitout, JD, Nordmann, P, Laupland, KB, Poirel, L. Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother 2005;56:52–59.CrossRefGoogle Scholar
Benattar, YD, Zak-Doron, Y, Paul, M, et al. The effectiveness and safety of high-dose colistin: prospective cohort study. Clin Infect Dis 2016;63:1605–1612.CrossRefGoogle ScholarPubMed
Davies, M, Walsh, TR. A colistin crisis in India. Lancet Infect Dis 2018;18:256–257.CrossRefGoogle ScholarPubMed
Liu, YY, Wang, Y, Walsh, TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016;16:161–168.CrossRefGoogle ScholarPubMed
Recommendations for MIC determination of colistin (polymyxin E) as recommended by the joint CLSI-EUCAST Polymyxin Breakpoints Working Group. EUCAST website. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/General_documents/Recommendations_for_MIC_determination_of_colistin_March_2016.pdf. Published 2016. Accessed August 21, 2019.Google Scholar
Tan, TY, Ng, LS. Comparison of three standardized disc susceptibility testing methods for colistin. J Antimicrob Chemother 2006;58:864–867.CrossRefGoogle ScholarPubMed
Moskowitz, SM, Garber, E, Chen, Y, et al. Colistin susceptibility testing: evaluation of reliability for cystic fibrosis isolates of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. J Antimicrob Chemother 2010;65:1416–1423.CrossRefGoogle ScholarPubMed
Kaur, A, Gandra, S, Gupta, P, Mehta, Y, Laxminarayan, R, Sengupta, S. Clinical outcome of dual colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections: a single-center retrospective study of 75 cases in India. Am J Infect Control 2017;45:1289–1291.CrossRefGoogle ScholarPubMed
Pragasam, AK, Shankar, C, Veeraraghavan, B, et al. molecular mechanisms of colistin resistance in Klebsiella pneumoniae causing bacteremia from India—a first report. Front Microbiol 2016;7:2135.Google ScholarPubMed
Magiorakos, AP, Srinivasan, A, Carey, RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268–281.CrossRefGoogle ScholarPubMed
Clinical Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing, 28th Edition. Wayne, PA: CLSI; 2018.Google Scholar
Breakpoint tables for interpretation of MICs and zone diameters. Version 8.1. EUCAST website. http://www.eucast.org. Published 2018. Accessed August 21, 2019.Google Scholar
Clinical Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, 11th Edition. Wayne, PA: CLSI; 2018.Google Scholar
Clinical Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests, 13th Edition. Wayne, PA: CLSI; 2018.Google Scholar
Lo-Ten-Foe, JR, de Smet, AM, Diederen, BM, Kluytmans, JA, van Keulen, PH. Comparative evaluation of the VITEK 2, disk diffusion, etest, broth microdilution, and agar dilution susceptibility testing methods for colistin in clinical isolates, including heteroresistant Enterobacter cloacae and Acinetobacter baumannii strains. Antimicrob Agent Chemother 2007;51:3726–3730.CrossRefGoogle ScholarPubMed
Bankevich, A, Nurk, S, Antipov, D, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012;19:455–477.CrossRefGoogle ScholarPubMed
Li, H, Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics (Oxford, England) 2009;25:1754–1760.CrossRefGoogle ScholarPubMed
de Man, TJB, Limbago, BM. SSTAR, a stand-alone easy-to-use antimicrobial resistance gene predictor. mSphere 2016;1:e00050–15.CrossRefGoogle Scholar
Tamura, K, Stecher, G, Peterson, D, Filipski, A, Kumar, S. MEGA6: molecular evolutionary genetics analysis version 6.0. Molec Biol Evol 2013;30:2725–2729.CrossRefGoogle ScholarPubMed
Kaas, RS, Leekitcharoenphon, P, Aarestrup, FM, Lund, O. Solving the problem of comparing whole bacterial genomes across different sequencing platforms. PLoS One 2014;9:e104984.CrossRefGoogle ScholarPubMed
Gales, AC, Reis, AO, Jones, RN. Contemporary assessment of antimicrobial susceptibility testing methods for polymyxin B and colistin: review of available interpretative criteria and quality control guidelines. J Clin Microbiol 2001;39:183–190.CrossRefGoogle ScholarPubMed
Seale, AC, Gordon, NC, Islam, J, Peacock, SJ, Scott, JAG. AMR Surveillance in low and middle-income settings—a roadmap for participation in the Global Antimicrobial Surveillance System (GLASS). Wellcome Open Res 2017;2:92.CrossRefGoogle Scholar
Kanamori, H, Parobek, CM, Juliano, JJ, et al. A prolonged outbreak of KPC-3–producing Enterobacter cloacae and Klebsiella pneumoniae driven by multiple mechanisms of resistance transmission at a large academic burn center. Antimicrob Agent Chemother 2017;61(2). pii: e01516-16.Google Scholar
Snitkin, ES, Zelazny, AM, Thomas, PJ, et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 2012;4:148ra116.CrossRefGoogle ScholarPubMed
Aggarwal, R, Rastogi, N, Mathur, P, et al. Colistin-resistant Klebsiella pneumoniae in surgical polytrauma intensive care unit of level-1 trauma center: first case series from trauma patients in India. Ind J Crit Care Med 2018;22:103–106.Google ScholarPubMed
Smith, DL, Dushoff, J, Perencevich, EN, Harris, AD, Levin, SA. Persistent colonization and the spread of antibiotic resistance in nosocomial pathogens: resistance is a regional problem. Proc Nat Acad Sci U S A 2004;101:3709–3714.CrossRefGoogle ScholarPubMed
Ostrowsky, BE, Trick, WE, Sohn, AH, et al. Control of vancomycin-resistant Enterococcus in health care facilities in a region. New Engl J Med 2001;344:1427–1433.CrossRefGoogle ScholarPubMed
Schwaber, MJ, Carmeli, Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis 2014;58:697–703.CrossRefGoogle ScholarPubMed
French, CE, Coope, C, Conway, L, et al. Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute settings: an evidence review. J Hosp Infect 2017;95:3–45.CrossRefGoogle ScholarPubMed
Otter, JA, Yezli, S, Salkeld, JAG, French, GL. Evidence that contaminated surfaces contribute to the transmission of hospital pathogens and an overview of strategies to address contaminated surfaces in hospital settings. Am J Infect Control 2013;41:S6–S11.CrossRefGoogle ScholarPubMed
Dancer, SJ. Controlling hospital-acquired infection: focus on the role of the environment and new technologies for decontamination. Clin Microbiol Rev 2014;27:665–690.CrossRefGoogle ScholarPubMed
Chew, KL, La, MV, Lin, RTP, Teo, JWP. Colistin and polymyxin B susceptibility testing for carbapenem-resistant and mcr-positive Enterobacteriaceae: comparison of Sensititre, MicroScan, Vitek 2, and Etest with broth microdilution. J Clin Microbiol 2017;55:2609–2616.CrossRefGoogle ScholarPubMed