Doripenem, gentamicin, and colistin, alone and in combinations, against gentamicin-susceptible, KPC-producing Klebsiella pneumoniae strains with various ompK36 genotypes

Abstract

Gentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producing Klebsiella pneumoniae strains. Treatment with the combination of doripenem (8 μg/ml) plus colistin (2 μg/ml) was inferior to treatment with gentamicin (2 μg/ml), doripenem-gentamicin, gentamicin-colistin, and doripenem-gentamicin-colistin against strains with glycine and aspartic acid insertions in OpmK36 porin at amino acid (aa) positions 134 and 135 (n = 9). Doripenem-colistin was comparable to other 2- or 3-drug regimens and superior to single drugs against wild-type/minor ompK36 mutants (n = 5). An algorithm incorporating ompK36 genotypes and susceptibility to gentamicin and doripenem may predict antimicrobial activity against KPC-producing K. pneumoniae.