c Nephrotoxicity is a dose-limiting factor of colistin, a last-line therapy for multidrug-resistant Gram-negative bacterial infections. An earlier animal study revealed a protective effect of ascorbic acid against colistin-induced nephrotoxicity. The present randomized controlled study was conducted in 28 patients and aimed to investigate the potential nephroprotective effect of intravenous ascorbic acid (2 g every 12 h) against colistin-associated nephrotoxicity in patients requiring intravenous colistin. Thirteen patients received colistin plus ascorbic acid, whereas 15 received colistin alone. Nephrotoxicity was defined by the RIFLE classification system. Additionally, urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG) were measured as markers of renal damage, and plasma colistin concentrations were quantified. The baseline characteristics, clinical features, and concomitant treatments of the patients in the two groups were comparable. The incidences of nephrotoxicity were 53.8% (7/13) and 60.0% (9/15) in the colistin-ascorbic acid group and the colistin group, respectively (P ‫؍‬ 0.956; relative risk [RR], 0.9; 95% confidence interval, 0.47 to 1.72). In both groups, the urinary excretion rates of NGAL and NAG on day 3 or 5 of colistin treatment and at the end of colistin treatment were significantly higher than those at the respective baselines (P < 0.05). However, the urinary excretion rates of these biomarkers at the various times during colistin treatment did not differ significantly between the groups (P > 0.05). The plasma colistin concentrations in the two groups were not significantly different (P > 0.28). The clinical and microbiological outcomes and mortality of the patients in the two groups were not significantly different. This preliminary study suggests that ascorbic acid does not offer a nephroprotective effect for patients receiving intravenous colistin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01501968.) I nfections caused by carbapenem-resistant Gram-negative bacteria, such as Acinetobacter baumannii, have become a serious problem globally, including in Thailand (1-3). Colistin (i.e., polymyxin E) and polymyxin B have been reintroduced over the past decade for therapy of multidrug-resistant (MDR) Gram-negative bacterial infections, especially those caused by carbapenem-resistant Gram-negative pathogens (4). Colistin is administered parenterally as colistimethate sodium (CMS), an inactive prodrug that is converted to colistin, the entity that possesses both antibacterial activity and the potential to cause toxicity (5, 6). The efficacy of colistin for treatment of infections by MDR Gram-negative bacteria is modest, and nephrotoxicity is the major dose-limiting factor in the clinical use of colistin (7, 8). The incidence of colistinassociated nephrotoxicity ranges from approximately 10% to 55%, and it appears to be related to the total dose of CMS, the duration of therapy, and the plasma colistin concentrat...