Pharmacokinetics of colistin in an adolescent boy with extensive burn injury

Multidrug resistance in Gram-negative bacteria has led to a resurgence in colistin use. No pharmacokinetic data exist for burn patients. A 17-year-old boy suffered a 71% TBSA full-thickness burn with deep necrosis and compartment syndrome. He developed multidrug-resistant Acinetobacter baumannii burn wound sepsis/septic shock with acute renal failure requiring dialysis. The organism was resistant to all tested antibiotics except colistin. He received colistin 2.5 mg/kg every 24 hours. Peak and trough serum concentrations, area under the concentration-time curve, and elimination half-lives of colistin were 3.6 ± 1.0 μg/ml, 0.9 ± 0.5 μg/ml, 47.1 ± 14.4 mg · hr/L, and 12.3 ± 9.4 hours (mean ± SD), respectively. Serum levels were at or above the minimum inhibitory concentration for >90% of therapy. Nevertheless, salvage therapy with colistin proved futile as the patient developed acidosis, coagulopathy, and was vasopressor-dependent without any wound healing. He died on hospital day 52. Microbiologically, the serum levels of colistin were seemingly adequate, as repeat cultures were negative. Given the peak and trough levels of colistin relative to the minimum inhibitory concentration for the organism (0.5 μg/ml), it would seem that the dosage of 2.5 mg/kg administered every 24 hours for this patient on dialysis was appropriate. Patients on dialysis infected with an organism possessing a higher inhibitory concentration (≥1 μg/ml) should probably receive the same dosage every 12 hours to avoid subtherapeutic concentrations. Large-scale study of the pharmacokinetics of colistin in patients with burn injury is urgently needed.