Colistin Monotherapy Versus Colistin/rifampicin Combination Therapy in Pneumonia Caused by Colistin-resistant Acinetobacter Baumannii: A Randomised Controlled Trial

Objectives: The aim of this study was to confirm the synergistic effect of colistin/rifampicin combination therapy compared with colistin monotherapy in pneumonia caused by colistin-resistant Acinetobacter baumannii (CoRAB). The utility of the Etest was also assessed.

Methods: Nine subjects with pneumonia caused by CoRAB were enrolled from 20 July 2016 to 21 June 2018. Subjects were randomised to colistin/rifampicin combination therapy or colistin monotherapy. After exclusion of one patient who dropped out, the microbiological response (MR) and clinical response (CR) on Day 14 and mortality on Day 30 were assessed. Etest was conducted using CoRAB isolated at study enrolment.

Results: The MR rate in the colistin/rifampicin combination group (100.0%) was better than that in the colistin group (40.0%), however the difference was not statistically significant (P=0.196). The CR rate was not significantly different between the two groups. The MR (100.0%) and CR (100.0%) rates in subjects with 'partial synergy' as shown by Etest were higher than those (25.0% and 50.0%, respectively) in subjects with 'indifferent' results (i.e. no synergistic effect), however the difference was not statistically significant (P=0.143 and 0.429, respectively). Mortality occurred in two subjects with 'indifferent' results by Etest.

Conclusions: Colistin/rifampicin combination therapy may have potential to achieve MR in pneumonia caused by CoRAB; however, achieving CR with this treatment is doubtful. 'Partial synergy' of colistin and rifampicin, as shown by Etest, may be a good prognostic factor [ClinicalTrial.gov ID: NCT03622918].