Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence

Objectives: The epidemic dimensions of the emergence of multidrug-resistant (MDR) Gram-negative bacterial infections have led to the revival of old antibiotics, including the polymyxins. Methods: We performed a review and meta-analysis to evaluate the current literature data regarding the effectiveness and safety of intravenous polymyxin B in patients with MDR Gram-negative bacterial infections and the overall mortality and nephrotoxicity in patients treated with intravenous polymyxin B either as monotherapy or combination therapy. Results: A total of 5 prospective and 28 retrospective studies, 1 cross-sectional study, 2 retrospective case series and 7 case reports provided data regarding the effectiveness and/or toxicity of intravenous polymyxin B. All-cause mortality of 2910 patients (from 27 studies) who received intravenous polymyxin B was 41.2% (95% CI 35.5–47.0%). All-cause nephrotoxicity of 2994 patients (from 28 studies) treated with intravenous polymyxin B was 40.7% (95% CI 35.0–46.6%). Renal failure among 2111 patients (from 14 studies) was 11.2% (95% CI 8.7–13.9%). Conclusion: Mortality of patients treated with intravenous polymyxin B is similar to the literature-reported mortality of patients treated with intravenous colistin, while nephrotoxicity associated with polymyxin B use is possibly milder compared with colistin use based on literature data. Head-to-head prospective studies would help to clarify the benefit of polymyxin B over colistin. However, a critical evaluation of the existing worldwide literature data supports the need for availability of the intravenous formulation of polymyxin B as a potentially useful option for the treatment of patients with MDR and extensively drug-resistant (XDR) Gram-negative bacterial infections