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Abstract
Colistin has re-emerged as an essential antibiotic for the treatment of carbapenem-resistant Gram-negative infections. Unfortunately, its utility is limited by high rates of nephrotoxicity, even at potentially therapeutic concentrations, and an overall lack of understanding on how to optimally administer the agent. In this review, recent advancements in the understanding of the safety and efficacy of colistin are discussed and strategies and suggestions on how to balance the two are described.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Colistin is a crucial, last line antimicrobial retaining activity against many carbapenem-resistant Gram-negative infections.
Utility of colistin is limited by dose (and concentration) dependent nephrotoxicity, with rates commonly ranging from 20 to 50%.
Common dosing regimens for colistin result in average steady-state concentrations around 2 mg/l; however, significant (up to 10-fold) interpatient variability is seen.
The free area under the plasma concentration-versus-time curve to minimum inhibitory concentration is the pharmacokinetic/pharmacodynamic target associated with optimal activity of the polymyxins, and with commonly used dosing strategies modest targets are hit, particularly in obese patients, those with good renal function or those with MICs at the upper end of the susceptibility range.
Data showing increased efficacy with daily doses above 9 million international units (MIU)/day (270 mg/day colistin base activity [CBA]) are lacking.
Levels associated with increases in incidence or severity of nephrotoxicity range from 1.9 to 2.3 mg/l.
When taken together, these findings support more conservative dosing recommendations, such as a 9 MIU (270 mg CBA) loading dose, followed by 4.5 MIU (135 mg CBA) q12h.
Due to the inability to hit pharmacodynamic targets for efficacy in all patients with these doses, careful consideration should be given to combination therapy with a second active or synergistic agent.