Dosage of CMS/Colistin Base

The dosage of intravenous CMS recommended by the manufacturers in the USA is 2.55 mg/kg (31,25062,500 IU/kg) per day, divided into two to four equal doses.[1] Dosage adjustments are recommended for patients with mild-to-moderate renal dysfunction. Specifically, when the serum creatinine level is 1.31.5, 1.62.5 or 2.6 mg/dl, the recommended dosage of intravenous colistin for serious infections is 2 million IU every 12, 24 or 36 h, respectively.[32] For patients with renal failure that necessitates dialysis, the recommended intravenous dosages of CMS are 23 mg/kg after each hemodialysis treatment and 2 mg/kg daily during peritoneal dialysis.[33,34] The two most common commercially available parenteral formulations of CMS are Colomycin (Dumex-Alpharma A/S, Copenhagen, Denmark) and Coly-Mycin (Parkedale Pharmaceuticals, NY, USA). It has been reported that the recommended daily dose of Coly-Mycin (400800 mg) is almost double that of Colomycin (240480 mg) for patients with normal renal function and bodyweight of 60 kg. This difference has important implications for therapeutic doses.[3]

It should be noted that that there is a substantial difference in the recommended doses of the European and US products. The dosage recommended by the manufacturers in the UK is 46 mg/kg (50,00075,000 IU/kg) per day, in three divided doses for adults and children with bodyweights of 60 kg and 80160 mg (12 million IU) every 8 h for those with bodyweights of >60 kg. When colistin is given by inhalation, the dosage recommended by the manufacturers in the UK is 40 mg (500,000 IU) every 12 h for patients with bodyweights of 40 kg and 80 mg (1 million IU) every 12 h for patients with bodyweights of >40 kg.[1]

Pure colistin base has been assigned a potency of 30,000 IU/mg, and CMS has a potency of 12,500 IU/mg. Thus, recommendations regarding dosing should clearly refer to colistin base and CMS to avoid possible confusion.[35]

CMS is mostly administered for 1014 days. Dose regimens varied considerably. Doses were adjusted for renal function depending on serum creatinine levels or creatinine clearance. Colistin PKs are different in critically ill patients and they have fluctuations in renal clearance. Many authors reported the administration of CMS at a dose of 3MIU every 8 h, especially in critically ill patients with normal renal function.[34,3638]