Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: IV. colistimethate sodium

Abstract

Patients with cystic fibrosis (CF) often experience acute pulmonary exacerbations (APE) and may be treated with a wide variety of intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing the intravenous (IV) polymixin antibiotic colistimethate sodium (CMS) in the treatment of APE and to identify areas where further study is warranted. Currently, there is not an international standard on the labeling of CMS products. As a result, this has lead to confusion in the interpretation of the literature with respect to efficacy, tolerance, and optimal dosing strategy. The dosing ranges of IV CMS from the literature are 5.3-12.9 mg/kg/day, maximum 480 mg per day for 60 kg patient (Colomycin® injection-European product) and 8-21.3 mg/kg/day, maximum 800 mg per day for 60 kg patient (Coly-Mycin M® parenteral-US product).The literature supports a CMS dose of 8 mg/kg/day divided every 8 hr (maximum 480 mg/day) for the treatment of APE secondary to Pseudomonas aeruginosa. The maximum recommended CMS dose of 480 mg/day is less than is recommended by the FDA-approved and CFF dosing guidelines but in agreement with UK CF Trust Antibiotic Working Group recommendations. There is debate over the frequency of CMS administration (once daily vs. thrice-daily) and its impact on resistance and clinical efficacy. Further study is needed to determine the tolerability and efficacy of extended-interval dosing of CMS in the treatment of APE.