4.7 Article

Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations

Journal

JOURNAL OF CLINICAL MEDICINE
Volume 8, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/jcm8091444

Keywords

Klebsiella pneumoniae; colistin; heteroresistance; population analysis profiles; PmrAB; PhoPQ

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [2018R1D1A1B07049433]
  2. National Research Foundation of Korea [2018R1D1A1B07049433] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Heteroresistance may pose a threat to the prognosis of patients following colistin treatment. We investigated colistin heteroresistance in Klebsiella pneumoniae isolates from South Korea. Among 252 K. pneumoniae blood isolates, 231 were susceptible to polymyxins. Heteroresistance to colistin was determined using population analysis profiles, disk diffusion assays, and E-test strip tests for the susceptible isolates. As a result, we identified three colistin-heteroresistant K. pneumoniae isolates belonging to separate clones (ST11, ST461, and ST3217) by multilocus sequence typing analysis. Two colistin-resistant subpopulations were selected from each heteroresistant isolate in either disk diffusion testing or E-testing. Two resistant subpopulations from the same isolate exhibited different amino acid substitutions in the two-component regulatory systems PmrAB and PhoPQ. An in vitro time-kill assay showed that meropenem combined with colistin had a 1x minimum inhibitory concentration bactericidal effect against a multidrug-resistant, colistin-heteroresistant isolate.

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