Comparative evaluation of intratracheal colistimethate sodium, imipenem, and meropenem in BALB/c mice with carbapenem-resistant Acinetobacter baumannii pneumonia

SummaryObjectiveThe identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB).MethodsA murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 107 colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4 h the infected BALB/c mice were treated intratracheally with 25 μl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20 mg/kg, meropenem group), every 8 h. The therapeutic efficacy of these agents was examined.ResultsA. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p < 0.001 vs. the control and CMS groups, p = 0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs.ConclusionsAdministration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.