Nephrotoxicity of high and conventional dosing regimens of colistin: A randomized clinical trial

Nephrotoxicity has been a major long-standing concern about colistin.this study was designed to compare nephrotoxicity of high dose and conventional dose of colistin. a randomized open-labeled clinical trial on 40 patients with multi-drug resistant gram negative infections was designed. patients were allocated into two equal-size groups receiving high (a loading dose of 9 million international units (miu) and maintenance doses of 4.5 miu every 12 h) and conventional dose (2 miu every 8 h) of colistin. blood samples were taken on day 1,3,5,7 and 10 of treatment for measuring serum cystatin c (cys c) levels. incidence of acute kidney injury (aki) was also evaluated based on rifle criteria. mean ± sd of the difference between baseline and day 10 cys c levels in high dose and conventional dose groups were 1.610.90 ± and 1.320.48 ±,respectively (p0.30 =). within group analysis showed increase in cys c levels in both groups (p0.001 =),however,no significant difference in cys c levels was seen in between groups analysis (p0.13 =). prevalence of aki based on rifle criteria was 60% and 15% in high dose and conventional dose groups,respectively (p0.003 =). comparison of cys c between aki (mean ± sd) and non-aki (mean ±sd) patients,irrespective of colistin dosage regimens,confirmed a significant difference (p 0.0001 <). although,colistin-induced nephrotoxicity,determined by cys c levels,was not confirmed by our findings,however,higher incidence of aki in high-dose group,defined by rifle criteria,along with higher levels of cys c in aki patients are supportive of the higher risk of renal toxicity associated with high-dose regimen of colistin. more rcts with a larger sample size are recommended. © 2017 by school of pharmacy.