Despite concerns of nephrotoxicity, polymyxin antibiotics often remain the only susceptible agents for multidrug-resistant (MDR) Gram-negative bacteria. Colistin has been more commonly used clinically due to a perceived safety benefit. We compared the nephrotoxicity of colistin to polymyxin B. The in vitro cytotoxicity of colistin was compared to polymyxin B in two mammalian renal cell lines. To validate the clinical relevance of the findings, we evaluated adult patients with normal renal function who received a minimum of 72 h of polymyxin therapy in a multicenter study. The primary outcome was the prevalence of nephrotoxicity, as defined by the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Colistin exhibited an in vitro cytotoxicity profile similar to polymyxin B. A total of 225 patients (121 receiving colistimethate, 104 receiving polymyxin B) were evaluated. Independent risk factors for colistimethate-associated nephrotoxicity included age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00 to 1.07; P ‫؍‬ 0.03), duration of therapy (OR 1.08; 95% CI, 1.02 to 1.15; P ‫؍‬ 0.02), and daily dose by ideal body weight (OR 1.40; 95% CI, 1.05 to 1.88; P ‫؍‬ 0.02). In contrast, cystic fibrosis was found to be a protective factor in patients who received colistimethate (OR, 0.03; 95% CI, 0.001 to 0.79; P ‫؍‬ 0.04). In a matched analysis based on the risk factors identified (n ‫؍‬ 76), the prevalence of nephrotoxicity was higher with colistimethate than with polymyxin B (55.3% versus 21.1%; P ‫؍‬ 0.004). Polymyxin B was not found to be more nephrotoxic than colistin and may be the preferred polymyxin for MDR infections. A prospective study comparing the two polymyxins directly is warranted.

Daptomycin treatment was well tolerated at a mean dose of 8 mg/kg for a median duration of 25 days. The incidence of symptomatic CPK level elevation was within the range reported with lower doses of daptomycin and/or for shorter treatment durations.

Risk factors for nephrotoxicity onset associated with polymyxin B were identified. In conjunction with susceptibility and other pharmacokinetic/pharmacodynamic data, our results can be used to optimize treatment for MDR Gram-negative infections.

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Coagulase-negative staphylococci (CoNS) are the main pathogens causing hospital-acquired external-ventricular-drain- (EVD-) and lumbar-drain- (LD-) associated meningitis and ventriculitis. The treatment of these infections can be challenging and may require combination of intraventricular and intravenous administration of antibiotics. Limited animal data demonstrate rapid daptomycin bactericidal activity, adequate penetration in the setting of inflamed meninges, and extended half-life in the ventricles Steenbergen et al. (2009). There are limited clinical data using daptomycin intravenously and/or intraventricularly for the treatment of central nervous system infections (CNS) Elvy et al. (2008), Stucki et al. (2007), Lee et al. (2008) and Wallace et al. (2009). We report here our experience in the treatment of an EVD-related infection.