Doripenem MICs and ompK36 porin genotypes of sequence type 258, KPC-producing Klebsiella pneumoniae may predict responses to carbapenem-colistin combination therapy among patients with bacteremia
Ryan K Shields, M Hong Nguyen, Brian A Potoski, Ellen G Press, Liang Chen, Barry N Kreiswirth, Lloyd G Clarke, Gregory A Eschenauer, Cornelius J Clancy, Ryan K Shields, M Hong Nguyen, Brian A Potoski, Ellen G Press, Liang Chen, Barry N Kreiswirth, Lloyd G Clarke, Gregory A Eschenauer, Cornelius J Clancy
Abstract
Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 μg/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo.
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Source: PubMed