Toxicity after prolonged (more than four weeks) administration of intravenous colistin

Abstract

Background: The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).

Methods: An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken.Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied.

Results: We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (+/- SD) 43.4 (+/- 14.6) days, mean daily dosage (+/- SD) 4.4 (+/- 2.1) million IU, mean cumulative dosage (+/- SD) 190.4 (+/- 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin.

Conclusions: No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.

Figure 1

The distribution of serum creatinine and blood urea levels on the 1^st day of colistin treatment (start), at the peak value (max), and the end of colistin treatment (end) in all studied courses of prolonged treatment with colistin. (The horizontal line within the boxes represents the median creatinine or blood urea baseline value at the 1^st day of colistin treatment. "Shaded" boxes in the figures represent the distribution of the laboratory values contained between the 25^th and 75^th percentiles (the interquartile range). Dotted lines (whisker lines) extend from the box, down and up, to the minimum and maximum values of the distributions that are not outliers (i.e. that are within 1.5 times the interquartile range); these values of the distribution are shown as "brackets". Any value, which is an outlier, is drawn as a "horizontal line").

Figure 2

The distribution of liver function tests [SGOT (AST = aspartate aminotransferase), γ-GT, and total bilirubin] on the 1^st day of colistin treatment (start), at the peak value (max), and at the end of colistin treatment (end) in studied courses of prolonged treatment with colistin. (The horizontal line within the boxes represents the median creatinine or blood urea baseline value at the 1^st day of colistin treatment. "Shaded" boxes in the figures represent the distribution of the laboratory values contained between the 25^th and 75^th percentiles (the interquartile range). Dotted lines (whisker lines) extend from the box, down and up, to the minimum and maximum values of the distributions that are not outliers (i.e. that are within 1.5 times the interquartile range); these values of the distribution are shown as "brackets". Any value, which is an outlier, is drawn as a "horizontal line").