Colisin Dosing Altered
I uploaded a new version of the antibiotic dosing in renal failure document. This version has a completely new method of dosing colistin. I was very pleased to find the article by Garonzik in AAC;55:3284 2011 with a detailed PK analysis of colistin dosing across a broad range of creatinine clearance values. Their study was based on using colistin methanesulfonate (CMS), a prodrug which is hydrolyzed into colistin A (polymyxin E1) and colistin B (polymyxin E2). They have elected to limit the total daily dose to around 300 mg based on the manufacturers recommendations over concerns for renal dysfunction. Indeed, they did see some associated renal dysfunction, not all reversible, with the higher doses. The target level of colistin is 1 mg/L for the equations used. That target can be increased in if needed, but for persons with normal renal function the daily dose will quickly increase above 300 mg. The authors recommended that colistin be used in combination with another drug for organisms with mic $>0.5-1$ mg/L. Another recent editorial appears to support these dosing equations. Roberts in Clinical Infectious Diseases, vol 54, pages 1727-1729, has a nice recap of issues with colistin dosing and pertinent references. Importantly, colistin does have concentration-dependent bacterial killing with rapid bactericidal activity and a postantibiotic effect according to this article (or rather another referenced). I think it would be a good idea to start writing the colistin orders in international units, that way it does not matter which colistin the pharmacy has to dispense, you know exactly how much the patient will get. The IU equivalents per 1 mg of each colistin base or CMS is 30,000 and 12,500 respectively. However, our pharmacy has serious issues with their ability to translate IU into milligrams. They cannot do it. Shameful.