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Treatment outcomes of colistin and carbapenem-resistant Acinetobacter baumannii infections: an exploratory subgroup analysis of a randomized clinical trial.

Background
We aimed to evaluate the association between mortality and colistin-resistance in infections caused by Acinetobacter baumannii and the interaction with antibiotic therapy.


Methods
This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant Gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) initially found to be colistin-susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed to be colistin-susceptible with those whose isolates were retrospectively found to be colistin-resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality.


Results
Data were available for 266 patients with CRAB; 214 colistin-susceptible and 52 colistin-resistant isolates. Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (p=0.174). After adjusting for variables associated with mortality, the mortality rate was significantly lower among patients with CoR isolates (OR 0.285, 95%CI 0.118-0.686). This difference was associated with treatment arm: mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination compared to colistin monotherapy (OR 3.065, 95%CI 1.021-9.202).


Conclusions
Colistin resistance as determined by BMD was associated with significantly lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy.