Colistin in the 21st century

Abstract

Purpose of review Colistin is a 50 year-old antibiotic that is being used increasingly as a ‘last-line’ therapy to treat infections caused by MDR Gram-negative bacteria, when essentially no other options are available. Despite its age, or because of its age, there has been a dearth of knowledge on its pharmacological and microbiological properties. This review focuses on recent studies aimed at optimizing the clinical use of this old antibiotic. Recent findings A number of factors, including the diversity in the pharmaceutical products available, have hindered the optimal use of colistin. Recent advances in understanding of the pharmacokinetics and pharmacodynamics of colistin, and the emerging knowledge on the relationship between the pharmacokinetics and pharmacodynamics, providing a solid base for optimization of dosage regimens. The potential for nephrotoxicity has been a lingering concern, but recent studies provide useful new information on the incidence, severity and reversibility of this adverse effect. Recent approaches to the use of other antibiotics in combination with colistin hold promise for increased antibacterial efficacy with less potential for emergence of resistance. Summary Because few, if any, new antibiotics with activity against MDR Gram-negative bacteria will be available within the next several years, it is essential that colistin is used in ways that maximize its antibacterial efficacy and minimize toxicity and development of resistance. Recent developments have improved use of colistin in the 21st century.

Old drug, new findings: colistin resistance and dependence of Acinetobacter baumannii

“…Current treatment options for XDR A. baumannii infections remain quite limited. In addition to tigecycline, a recently developed antibiotic-an old drug, colistinis often the last resort for treating XDR A. baumannii [6,20].…”

Pulmonary and Systemic Pharmacokinetics of Inhaled and Intravenous Colistin Methanesulfonate in Cystic Fibrosis Patients: Targeting Advantage of Inhalational Administration

“…As a consequence of the rising rates of resistance to multiple antibiotics among P. aeruginosa isolates and the lack of new antibiotics available, colistin (also known as polymyxin E), which entered into clinical use in late 1950s, is now used increasingly in CF patients (7,8). Colistin methanesulfonate (CMS), an inactive prodrug that converts to the antibacterial form of colistin (9), is administered intravenously (i.v.)…”

Systematic review of the evidence for rational dosing of colistin

“…[38] Colistin's exact mechanism of nephrotoxicity is not established. [11,12,40,41] Patients with abnormal renal function at the start of colistin therapy have consistently been identified as being at high risk for nephrotoxic events. [28] General measures to limit colistin's nephrotoxicity include regular monitoring of renal function with appropriate dose adjustment (especially with prolonged use), adequate hydration and limited use of concomitant nephrotoxic drugs.…”