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Although colistin has been used extensively in critically ill patients infected with multidrug-resistant (MDR) organisms, our knowledge about the pharmacokinetic and pharmacodynamic parameters correlating with efficacy is very limited and little consensus exists on the optimum dosing regimen of this agent. In our center, during the past 2 years several patients treated with colistin were given the total daily dose once every 24 hours. The aim of this study was to analyze the efficacy and safety of this dosing regimen in critically ill patients.
The medical files of all patients who were admitted to the ICU in 2008 and who received colistin for an infection due to MDR bacteria were retrospectively analyzed. Criteria for inclusion were: dosing regimen of colistin 9 million units (MU) every 24 hours (colistin methanesulphonate - CMS, Norma, 1 vial = 1 MU, 1 mg = 13,300 U), administration of CMS for at least 7 days and normal renal function at initiation of treatment with CMS (serum creatinine ≤1 mg/dl or creatinine clearance >80 ml/min). Mortality was evaluated at 28 days.
Thirteen patients were included in the study (69% male, median age 71 years). The underlying diseases were surgical in seven patients and medical in six patients. The median APACHE and SOFA scores on the first day of CMS administration were 15 and 10, respectively. Eleven patients had nosocomial pneumonia, two had peritonitis and one osteomyelitis. Causative bacteria were isolated in 10 patients (six Acinetobacter baumanii, three Pseudomonas aeruginosa and one Klebsiella pneumonia) and were all MDR. Of the 10 isolated bacteria, six were susceptible only to colistin, while the other four were also susceptible either to aztreonam or sulbactam. In cases of susceptibility of the isolate only to colistin, it was given in combination with a carbapenem, while in the other cases either aztreonam or sulbactam was added. The median length of CMS administration was 11 days (mean 19; range 7 to 79 days). Median serum creatinine on initiation and completion of treatment with CMS was 0.7 and 0.9 mg/dl, respectively (P = 0.357). No cases of neurotoxicity were found. Mortality at 28 days was 15%.
The total daily dose of 9 MU of CMS, given as one dose every 24 hours in critically ill patients, seems to be efficient and safe, without resulting in increased nephrotoxicity or other adverse events. A prospective study should be done to confirm the findings we have presented herein.