Research Article: Resistome of carbapenem- and colistin-resistant Klebsiella pneumoniae clinical isolates

Date Published: June 8, 2018

Publisher: Public Library of Science

Author(s): Sara Lomonaco, Matthew A. Crawford, Christine Lascols, Ruth E. Timme, Kevin Anderson, David R. Hodge, Debra J. Fisher, Segaran P. Pillai, Stephen A. Morse, Erum Khan, Molly A. Hughes, Marc W. Allard, Shashi K. Sharma, Yung-Fu Chang.


The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most β-lactam antibiotics, in Enterobacteriaceae is of increasing concern. The concurrent spread of resistance against colistin, an antibiotic of last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role in the rapid and accurate detection/characterization of existing and emergent resistance determinants, an essential aspect of public health surveillance and response activities to combat the spread of antimicrobial resistant bacteria. In the current study, WGS data was used to characterize the genomic content of antimicrobial resistance genes, including those encoding carbapenemases, in 10 multidrug-resistant Klebsiella pneumoniae isolates from Pakistan. These clinical isolates represented five sequence types: ST11 (n = 3 isolates), ST14 (n = 3), ST15 (n = 1), ST101 (n = 2), and ST307 (n = 1). Resistance profiles against 25 clinically-relevant antimicrobials were determined by broth microdilution; resistant phenotypes were observed for at least 15 of the 25 antibiotics tested in all isolates except one. Specifically, 8/10 isolates were carbapenem-resistant and 7/10 isolates were colistin-resistant. The blaNDM-1 and blaOXA-48 carbapenemase genes were present in 7/10 and 5/10 isolates, respectively; including 2 isolates carrying both genes. No plasmid-mediated determinants for colistin resistance (e.g. mcr) were detected, but disruptions and mutations in chromosomal loci (i.e. mgrB and pmrB) previously reported to confer colistin resistance were observed. A blaOXA-48-carrying IncL/M-type plasmid was found in all blaOXA-48-positive isolates. The application of WGS to molecular epidemiology and surveillance studies, as exemplified here, will provide both a more complete understanding of the global distribution of MDR isolates and a robust surveillance tool useful for detecting emerging threats to public health.

Partial Text

The Gram-negative bacterium Klebsiella pneumoniae is a clinically relevant pathogen that has a propensity to acquire multidrug resistance (MDR), thus limiting therapeutic options for treating community-acquired and nosocomial infections such as pneumonia, septicemia, wound, and urinary tract infections (UTIs) [1]. MDR and extensively drug-resistant (XDR) strains are defined as non-susceptible to at least one agent in three or more antimicrobial classes or non-susceptible to at least one agent in all but two or fewer antimicrobial classes, respectively [2]. The rapid worldwide spread of MDR K. pneumoniae, as well as other Enterobacteriaceae, poses a serious threat to global health [3]. K. pneumoniae, the most common Klebsiella species causing human infections, is one of the top three pathogens of international concern documented in the 2014 World Health Organization (WHO) Global Report on Surveillance of Antimicrobial Resistance [4].

WGS data for 10 MDR K. pneumoniae strains isolated between 2010 and 2013 in Pakistan were analyzed to provide a comparative genetic context for carbapenem and colistin resistance that will help inform infectious diseases epidemiology and the identification of antimicrobial resistance determinants. Knowledge of the genomic content of these historical isolates will also be useful for elucidating the spread of antimicrobial resistance in K. pneumoniae. The analyzed isolates represent a diverse population as indicated by the Kmer distance tree, assigned ST and capsular types, and the resistomes.

The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the U.S. Food & Drug Administration and U.S. Centers for Disease Control and Prevention. The mention of company names or products does not constitute endorsement by the FDA or CDC.




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