Original Article Multiple importations and transmission of colistin-resistant Klebsiella pneumoniae in a hospital in northern India Purva Mathur MD 1 , Surbhi Khurana MSc 1 , Tom J.B. de Man MSc 2 , Neha Rastogi DM 1 , Omika Katoch MSc 1 , Balaji Veeraraghavan PhD 3 , Ayyan Raj Neeravi MSc 3 , Manigandan Venkatesan MSc 3 , Subodh Kumar MS 1 , Sushma Sagar MS 1 , Amit Gupta MS 1 , Richa Aggarwal MD 1 , Kapil Dev Soni MD 1 , Rajesh Malhotra MS 1 , Anoop Velayudhan MBBS 2 , Valan Siromany MBBS 2 , Paul Malpiedi MPH 2 , Joseph Lutgring PhD 2,4 , Kayla Laserson ScD 2 , Neil Gupta MD 2 , Padmini Srikantiah MD 2 and Aditya Sharma MD 2 1 Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India, 2 US Centers for Disease Control and Prevention, Atlanta, Georgia, USA, 3 Christian Medical College, Vellore, India and 4 Emory University, Atlanta, Georgia, USA 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 dif- fusion. 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. (Received 3 April 2019; accepted 18 August 2019) Invasive infections caused by gram-negative bacteria (GNB) are a frequent cause of morbidity and mortality in hospitalized patients. Globally, reports of resistance in GNB to critically important antibiotics, such as extended-spectrum cephalospor- ins, carbapenems, and colistin, are rising. 1–4 Due to the severity of illness and limited treatment options, invasive infections caused by antimicrobial-resistant (AR) GNB often result in higher mortality and longer duration of hospitalization com- pared to infections caused by GNB without extensive antimicro- bial resistance. 5 In middle-income countries such as India, infections caused by AR GNB also pose a challenge to infection control staff with limited resources to prevent transmission of these pathogens in healthcare facilities. 6 India has observed an increase in invasive infections caused by AR GNB. In particular, high proportions of carbapenem resistance in GNB isolates have been reported. 7 The cause of increasing re- sistance among GNB in India is not fully clear, but it appears to be facilitated by widespread use of antibiotics in humans and ani- mals, insufficient infection control in healthcare facilities, and lim- ited availability of safe water and sanitation facilities. 8 Though initially described mainly as a problem in healthcare facilities, AR GNB have also been detected in community-onset infections, heralding a wider dissemination of these pathogens into nonhospi- talized populations. 9 The high prevalence of carbapenem resistance in GNB in India has led to increasing use of a last resort antibiotic, colistin. Historically, colistin fell into disfavor for treatment of infections Author for correspondence: Purva Mathur, Email: purvamathur@yahoo.co.in Cite this article: Mathur P, et al. (2019). Multiple importations and transmission of colistin-resistant Klebsiella pneumoniae in a hospital in northern India. Infection Control & Hospital Epidemiology, https://doi.org/10.1017/ice.2019.252 © 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. Infection Control & Hospital Epidemiology (2019), 1–7 doi:10.1017/ice.2019.252