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

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dc.citation.issue2
dc.citation.volume90
dc.contributor.authorZavascki, Alexandre P.
dc.contributor.authorGirardello, Raquel [UNIFESP]
dc.contributor.authorMagagnin, Cibele M.
dc.contributor.authorAntochevis, Laura C.
dc.contributor.authorMaciel, Rafael A.
dc.contributor.authorPalmeiro, Jussara K. [UNIFESP]
dc.contributor.authorGales, Ana C. [UNIFESP]
dc.coverageNew York
dc.date.accessioned2020-07-08T13:09:49Z
dc.date.available2020-07-08T13:09:49Z
dc.date.issued2018
dc.description.abstractThe 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.en
dc.description.affiliationUniv Fed Rio Grande do Sul, Med Sch, Dept Internal Med, Porto Alegre, RS, Brazil
dc.description.affiliationUniv Fed Sao Paulo, EPM, Dept Internal Med, Lab Alerta,Div Infect Dis,UNIFESP, Sao Paulo, Brazil
dc.description.affiliationHosp Clin Porto Alegre, Ctr Pesquisa Expt, Lab Pesquisa Resistencia Bacteriana LABRESIS, Porto Alegre, RS, Brazil
dc.description.affiliationFac Med, Programa Pos Grad Ciencias Med, Porto Alegre, RS, Brazil
dc.description.affiliationUniv Sao Paulo, LIM03, Div Lab Cent, Hosp Clin,Fac Med, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Parana, Lab Bacteriol, Unidade Lab Anal Clin, Complexo Hosp Clin, Curitiba, Parana, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, EPM, Dept Internal Med, Lab Alerta,Div Infect Dis,UNIFESP, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundo de Incentivo a Pesquisa e Eventos do Hospital de Clinicas de Porto Alegre
dc.description.sponsorshipNational Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil
dc.format.extent134-138
dc.identifierhttp://dx.doi.org/10.1016/j.diagmicrobio.2017.10.006
dc.identifier.citationDiagnostic Microbiology And Infectious Disease. New York, v. 90, n. 2, p. 134-138, 2018.
dc.identifier.doi10.1016/j.diagmicrobio.2017.10.006
dc.identifier.issn0732-8893
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54222
dc.identifier.wosWOS:000423255800015
dc.language.isoeng
dc.publisherElsevier Science Inc
dc.relation.ispartofDiagnostic Microbiology And Infectious Disease
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectPolymyxinsen
dc.subjectColistinen
dc.subjectResistanceen
dc.subjectGram-negative bacillien
dc.subjectKlebsiella pneumoniae carbapenemaseen
dc.subjectTherapyen
dc.subjectHetero-resistanceen
dc.titleEmergence of polymyxin B resistance in a polymyxin B-susceptible KPC-producing Klebsiella pneumoniae causing bloodstream infection in a neutropenic patient during polymyxin B therapyen
dc.typeinfo:eu-repo/semantics/article
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