Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series

Abstract

Background: Colistimethate sodium (CMS) is the commercialized form of colistin that is effective against multiresistant Gram-negative bacilli. Its main side effects are nephrotoxicity and neurotoxicity. Pharmacodynamic dosages showed that they were infratherapeutic. Therefore, strategies with higher doses were proposed. The aim of this study was to assess the efficiency and toxicity of higher-dose CMS by comparing two treatment strategies: high-dose CMS versus standard-dose CMS. Methods: A prospective and comparative study of two matched groups was conducted. Fourty-six patients in each group were matched for age, severity and nature of infection. In the high-dose colistin group, CMS was administered at a loading dose of 9 MIU followed by a maintenance dose of 4.5 MIU/12 h. In the second group, retrospectively analyzed, colistin was administered at 6 MIU/day. For each group, clinical results, bacteriological eradication and daily creatinine clearance were recorded. Primary outcome measures were clinical cure defined as disappearance of infectious signs and eradication of microorganisms in all the follow-up cultures. Secondary outcome measures were incidence of acute renal failure and mortality. Results: Ninety-two patients were analyzed by matching. There was a higher cure rate in the high-dose group (63 vs. 41.3%, p = 0.04). No higher risk of nephrotoxicity was found by increasing daily doses of colistin (32.2 versus 26%, p = 0.64). Similarly, there was no significant difference in the time to onset of renal failure (8.32 vs. 11 days, p = 1) or in the requirement of hemodialysis (26.6 vs. 41%, p = 1). Conclusion: The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity.