The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneumoniae

Abstract

We tested two-drug combinations of doripenem, colistin, gentamicin, and doxycycline against 12 carbapenemase-producing Klebsiella pneumoniae (KPC) isolates by time-kill. The combination of doripenem and colistin reduced the starting inocula by 2 logs for each isolate (range, 2.02 to 6.01 log(10)) and was bactericidal and synergistic against 75 and 50%, respectively. Among colistin- and pan-drug-resistant isolates, synergy was identified in 60 and 67%, respectively. All other combinations were inferior. We are currently evaluating the combination of doripenem and colistin as a frontline therapy for KPC infection.

Fig 1

Representative area under the curve (AUC) for isolates alone and in combination for the following drug combinations: (a) colistin (dark gray) plus doripenem (light gray); (b) gentamicin (light gray) plus doxycycline (dark gray); and (c) doripenem (light gray) plus doxycycline (dark gray). Black shading represents the AUC for two-drug combinations.