Doripenem, Gentamicin, and Colistin, Alone and in Combinations, against Gentamicin-Susceptible, KPC-Producing Klebsiella pneumoniae Strains with VariousompK36Genotypes

Abstract

ABSTRACTGentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producingKlebsiella pneumoniaestrains. 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/minorompK36mutants (n= 5). An algorithm incorporatingompK36genotypes and susceptibility to gentamicin and doripenem may predict antimicrobial activity against KPC-producingK. pneumoniae.