Clinical Effectiveness and Nephrotoxicity of Aerosolized Colistin Treatment in Multidrug-Resistant Gram-Negative Pneumonia

Background: Colistin (polymyxin E) is active against multidrug-resistant Gram-negative bacteria (MDR-GNB). However, the effectiveness of inhaled colistin is unclear. This study was designed to assess the effectiveness and safety of aerosolized colistin for the treatment of ventilator-associated pneumonia (VAP) caused by MDR-GNB. Methods: In this retrospective longitudinal study, we evaluated the medical records of 63 patients who received aerosolized colistin treatment for VAP caused by MDR-GNB in the medical intensive care unit (MICU) from February 2012 to March 2014. Results: A total of 25 patients with VAP caused by MDR-GNB were included in this study. The negative conversion rate was 84.6% after treatment, and acute kidney injury (AKI) occurred in 11 patients (44%, AKI group). The average length of MICU stay and colistin treatment-related factors, such as daily and total cumulative doses and administration period, were not significantly different between groups. In-hospital mortality tended to be higher in the AKI group (p = 0.07). Multivariate analysis showed that a body mass index less than 18 was an independent risk factor of mortality (odds ratio [OR] = 21.95, 95% confidence interval [CI] 1.59-302.23; p = 0.02). Notably, AKI occurrence was closely related to the administration of more than two nephrotoxic drugs combined with aerosolized colistin (OR = 15.03, 95% CI 1.40-161.76; p = 0.025) and septic shock (OR = 8.10, 95% CI 1.40-161.76; p = 0.04). Conclusions: The use of adjunctive aerosolized colistin treatment appears to be a relatively safe and effective option for the treatment of VAP caused by MDR-GNB. However, more research on the concomitant use of nephrotoxic drugs with aerosolized colistin will be necessary, as this can be an important risk factor of development of AKI.