Emergence of polymyxin B resistance in a polymyxin B-susceptible KPC-producing Klebsiella pneumoniae causing bloodstream infection in a neutropenic patient during polymyxin B therapy

Emergence of polymyxin B resistance in a polymyxin B-susceptible KPC-producing Klebsiella pneumoniae causing bloodstream infection in a neutropenic patient during polymyxin B therapy

Author Zavascki, Alexandre P. Google Scholar
Girardello, Raquel Autor UNIFESP Google Scholar
Magagnin, Cibele M. Google Scholar
Antochevis, Laura C. Google Scholar
Maciel, Rafael A. Google Scholar
Palmeiro, Jussara K. Autor UNIFESP Google Scholar
Gales, Ana C. Autor UNIFESP Google Scholar
Abstract The emergence of resistance to polymyxins in KPC-producing Klebsiella pneumoniae isolates has been a major clinical problem. This study evaluated the molecular mechanisms associated with polymyxin B (PMB) resistance that emerged in a previously PMB-susceptible KPC-2-producing K. pneumoniae during PMB therapy for a bloodstream infection in a neutropenic patient. The first isolate (PMB-susceptible) was obtained while the patient was receiving meropenem and other isolates were recovered from 2 sets of blood cultures in different dates while the patient was receiving PMB therapy (4 of 6 blood cultures bottles yielded isolates with full PMB resistance). The population analysis profile of the first isolate revealed the growth of resistant subpopulations with PFGE profile distinct from the parental isolate but undistinguishable from those obtained in subsequent days under PMB exposure. Resistant subpopulations were obtained from all parental PMB-susceptible and in one PMB-resistant isolate recovered from the patient. The molecular mechanism observed in the hetero-resistant subpopulations (IS1-like in mgrB-promoter region, increased rstB transcription with no mutation and non-identified mechanism) differed from those found in the PMB-resistant isolates, in which no mutation or transcriptional alterations were detected. This study showed that the mechanism of resistance to PMB that emerged during PMB therapy was not related to those observed in subpopulations selected in vitro from PMB-susceptible isolates recovered from the patient. The absence of mutations in the former isolates may be due to adaptive resistance occurred because of sub-optimal PMB levels as well as amikacin and meropenem used in combination. (C) 2017 Elsevier Inc. All rights reserved.
Keywords Polymyxins
Colistin
Resistance
Gram-negative bacilli
Klebsiella pneumoniae carbapenemase
Therapy
Hetero-resistance
xmlui.dri2xhtml.METS-1.0.item-coverage New York
Language English
Sponsor Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clinicas de Porto Alegre
National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil
Date 2018
Published in Diagnostic Microbiology And Infectious Disease. New York, v. 90, n. 2, p. 134-138, 2018.
ISSN 0732-8893 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Inc
Extent 134-138
Origin http://dx.doi.org/10.1016/j.diagmicrobio.2017.10.006
Access rights Closed access
Type Article
Web of Science ID WOS:000423255800015
URI https://repositorio.unifesp.br/handle/11600/54222

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