TABLE 8.

Studies that primarily assessed combination therapy with colistin for the treatment of Acinetobacter baumannii infection

Reference and study typeStudy designCombination therapySynergy or greater efficacy with combination therapya
In vitro studies
    Yoon et al. (613)Checkerboard and time-kill studies with eight MDR A. baumannii strainsPolymyxin B + imipenem and/or rifampinSynergy with double and triple combinations
    Song et al. (518)Time-kill study with eight carbapenem-resistant A. baumannii strainsColistin + rifampinSynergy with combination compared to colistin alone
    Tan et al. (535)Time-kill and Etest-based methodColistin + minocyclineSynergy with combination shown with time-kill analyses only
    Kroeger et al. (302)Time-kill study using an in vitro pharmacodynamic modelColistin + continuously infused ceftazidimeCeftazidime prevented regrowth and development of colistin resistance
    Timurkaynak et al. (541)Checkerboard study with five MDR A. baumannii strainsColistin + rifampin, meropenem, azithromycin, or doxycyclineSynergy with all except doxycycline
    Wareham et al. (592)Combined Etest strip method with five OXA-23-carrying A. baumannii strainsPolymyxin B + imipenem, azithromycin, or rifampinMarked synergy not seen
    Giamarellos-Bourboulis et al. (194)Time-kill studies with 39 MDR A. baumannii strainsColistin + rifampinSynergy observed, most pronounced with colistin at 4× MIC
    Manikal et al. (351)Checkerboard study with 24 carbapenem-resistant A. baumannii strainsPolymyxin + meropenem, azithromycin, rifampin, or trimethoprim-sulfamethoxazoleSynergy observed with meropenem and azithromycin
    Tascini et al. (537)Checkerboard study with five strainsPolymyxin B + rifampin or ampicillin-sulbactamSynergy observed only with rifampin
    Hogg et al. (239)Checkerboard study with 13 MDR A. baumannii strainsColistin + rifampin (11 isolates were nonsusceptible to rifampin)Synergy observed in 11 isolates
Studies with animal models
    Montero et al. (373)Mouse pneumonia modelColistin + rifampin against one carbapenem- and rifampin-resistant A. baumannii isolateNo difference to rifampin alone but > 2 log reduction compared to colistin alone
    Pantopoulou et al. (415)Neutropenic rat thigh infection modelColistin + rifampin against one carbapenem- and rifampin-resistant A. baumannii isolateImprovement in 6-day survival with combination, tissue bacterial eradication similar to rifampin
Human studies
    Falagas et al. (161)Retrospective cohort studyColistin (n = 14) vs colistin-meropenem (n = 57)No synergy observed
    Motaouakkil et al. (374)Retrospective case series (noncomparative)Colistin + i.v. rifampin (n = 26) (16 received nebulized colistin, 9 received i.v. colistin, and 1 received intrathecal colistin)NA (favorable response in all)
    Petrosillo et al. (432)Retrospective case series (noncomparative)i.v. colistin + i.v. rifampin (n = 14) (five patients also received ampicillin-sulbactam)NA (mortality rate of 50%)
  • a NA, not assessed.