Molecular mechanisms of β-lactam resistance in carbapenemase-producing Klebsiella pneumoniae from Sri Lanka

Abstract

Carbapenemases are increasingly important antimicrobial resistance determinants. Little is known about the carbapenem resistance mechanisms in Sri Lanka. We examined 22 carbapenemresistant Klebsiella pneumoniae from Sri Lanka to determine their b-lactam resistance mechanisms. The predominant resistance mechanisms we detected in this study were OXA-181, NDM-1 carbapenemases and extended-spectrum b-lactamase CTX-M-15. All isolates were then genotyped by pulsed-field gel electrophoresis, variable-number tandem repeat sequence analysis and multilocus sequence typing, and seven distinct genotypes were observed. Five OXA-181-positive Klebsiella pneumoniae isolates were genotypically related to an isolate of Indian origin. Multilocus sequence typing found that these related isolates belong to ST-14, which has been associated with dissemination of OXA-181 from the Indian subcontinent. Other genotypes we discovered were ST-147 and ST-340, also associated with intercontinental spread of carbapenemases of suspected subcontinental origin. The major porin genes ompK35 and ompK36 from these isolates had insertions, deletions and substitutions. Some of these were exclusive to strains within single pulsotypes. We detected one ompK36 variant, ins AA134-135GD, in six ST-14-and six ST-147, bla OXA-181 -positive isolates. This porin mutation was an independent predictor of high-level meropenem resistance in our entire Sri Lankan isolate collection (P50.0030). Analysis of the Sri Lankan ST-14 and ST-147 ins AA134-135GD-positive isolates found ST-14 was more resistant to meropenem than other isolates (mean MIC: 32±0 mg ml -1 and 20±9.47 mg ml -1 , respectively, P50.0277). The likely international transmission of these carbapenem resistance determinants highlights the need for regional collaboration and prospective surveillance of carbapenem-resistant Enterobacteriaceae.

Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia

“…In 2012, carbapenem-resistant K. pneumoniae was isolated from a teaching hospital in Colombo, Sri Lanka (111), although all Enterobacteriaceae previously isolated during the same seven-center study performed as part of the Antibiotic Resistance Surveillance Project in 2009 to 2010 were susceptible to carbapenems (107). The majority tested positive for OXA-181, with a minority carrying NDM-1 (111). NDM-positive Enterobacteriaceae have been exported from Sri Lanka via patients who had undergone treatment in that country's hospitals (112), similar to the case for other South Asian countries (6).…”

Evaluation of the In Vitro Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Meropenem-Resistant Pseudomonas aeruginosa Isolates

“…On the other hand, a sizeable majority of isolates exhibited oprD mutations. Avibactam restores the activity of ceftazidime against Gram-negative bacilli with resistance mediated through ESBLs, class A and some class D ␤-lactamases, and chromosomal and acquired AmpC class C enzymes (19)(20)(21)(22). It is reasonable to hypothesize that avibactam restores susceptibility to ceftazidime through inhibition of AmpC enzymes.…”

First Report of OXA-181-Producing Escherichia coli in China and Characterization of the Isolate Using Whole-Genome Sequencing

“…The only exception was in a Citrobacter freundii strain; bla NDM-1 was not detected on the plasmid carrying bla OXA-181 , suggesting that bla NDM-1 is likely located on a different plasmid. It would be interesting to explore whether bla NDM-1 was located on an IncX3 plasmid within those strains carrying bla NDM-1 and bla OXA-181 (9,10,12,(15)(16)(17)29). On the other hand, as WCHEC14828 has no bla NDM-1 , it may also be possible that an IncX3 plasmid carrying bla OXA-181 has replaced the IncX3 plasmid carrying bla NDM-1 due to plasmid incompatibility.…”