BackgroundData regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.MethodsA prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.ResultsOne hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.ConclusionsWhen using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.

A warning about the use of nevirapine (NVP) by its pharmaceutical manufacturer has been issued in which it has been recommended that NVP should not be prescribed in patients with increased risk of toxicity based on CD4 cut-offs and gender. The aim of this study was to determine whether these recommendations are of use in preventing side effects. MethodsThis retrospective study included antiretroviral drug-naïve patients who started treatment with NVP. Patients were divided into two groups: those with high CD4 counts (H; women: CD4 count 4250 cells/mL; men: CD4 count 4400 cells/mL) and those with low CD4 counts (L; women: CD4 count o250 cells/mL; men: CD4 count o400 cells/mL). ResultsA total of 142 patients were included in the study, 61 in the H group and 81 in the L group. Skin rash developed in 6.56% of patients [95% confidence interval (CI) 2.67-15.70%] in the H group and in 14.81% of patients (95% CI 8.72-24.17%) in the L group (P 5 0.18). Hepatotoxicity developed in 4.92% (95% CI 1.79-13.50%) and 6.17% (95% CI 2.73-13.66%) of patients with high and low CD4 cell counts, respectively (P 5 1.0). ConclusionThe recommendations not to use NVP in drug-naïve patients at increased risk of toxicity on the basis of gender and CD4 cell count do not seem to be of use in preventing the occurrence of side effects. However, a small number of patients were included in this study, and hence the possibility cannot be excluded that the recommendations are appropriate in another clinical practice setting.Keywords: adverse events, hepatotoxicity, nevirapine, rash Introduction Nevirapine (NVP) was the first nonnucleoside reverse transcriptase inhibitor approved for use in HIV-infected patients and is a widely used antiretroviral drug, the efficacy of which has been well demonstrated in numerous clinical trials. It is easy to administer and is generally well tolerated [1]. The main limitation of its use is the risk of the occurrence of potentially serious side effects, such as hepatic toxicity and hypersensitivity reactions.In order to avert or reduce such reactions, an attempt has been made to identify the risk factors for presentation of hypersensitivity reactions or hepatotoxicity. In a retrospective analysis of Boehringer-Ingelheim databases, it was found that the risk of symptomatic hepatotoxicity was 12 times greater in women with a CD4 count above 250 cells/ mL, in comparison with women with a CD4 count below 250 cells/mL (11 vs. 0.9%) [2]. In men, there was a 6.3% risk if the CD4 count was above 400 cells/mL, compared with 1.2% when the CD4 count was below 400 cells/mL [2]. In the case of hepatotoxicity with skin rash, the increased risk was This warning about NVP also appears in the guidelines for antiretroviral treatment [6,15]; the purpose of the warning is to decrease the frequency of symptomatic liver toxicity. Analysis of the results of a large randomized clinical trial, the 2NN study, demonstrated that the rate of skin rash and hepatic events was higher in patients with CD4 counts 4200 cells/mL, and also that women ...

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Colistin use has reemerged for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the information on its pharmacokinetics is limited, especially in patients with end-stage renal disease, in which dosage adjustments are contradictory, and evidences the need to investigate the removal of colistin through renal replacement therapies like haemodialysis. This case study showed efficient removal of colistin methanesulphonate and formed colistin during intermittent haemodialysis in a patient infected by polymyxin-only-susceptible Pseudomonas aeruginosa. These results suggest the importance to monitor colistin plasma concentrations in these patients to minimize treatment failure due to suboptimal exposure to antibacterial colistin.

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