Safety of colistin

The nephrotoxicity of polymyxins is a major dose-limiting factor. Extensive tubular reabsorption of polymyxins leads to accumulation of polymyxins in kidney proximal tubular cells, thereby predisposing to nephrotoxicity. The high concentrations in these cells cause concentration- and time-dependent apoptosis (MAK Azad et al 2013).

In clinical studies acute kidney injury is independently associated with daily doses > 9 M IU of CMS (FF Tuon et al, 2013). Not adjusting the dose in patients with renal dysfunction is a major risk factor for toxicity. If the duration of therapy and the accumulative dose contributes to increased side effects is still not clear.

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