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.

Fibrinogen in rat gastrointestinal lymph before, during and after intraduodenal administration of emulsified triglyceride: fibrinogen bound to chylomicrons in gastrointestinal lymph is functional.

Samples of gastrointestinal lymph were collected from fasted, male, Sprague-Dawley rats before, during and after intraduodenal administration of either a phospholipid-stabilized, triglyceride-rich emulsion or the dextrose-saline diluent of the emulsion. In lipid-treated rats, the triglyceride, total protein, and functional fibrinogen contents of lymph increased significantly during the 4 h of continuous lipid infusion, with all analytes returning to near baseline values by 20 h later. Levels of the same analytes changed little, if at all, in control animals. As assessed using immunoblotting, chylomicrons in gastrointestinal lymph are coated with fibrinogen. Fibrinogen-coated chylomicrons readily incorporate into solution phase clots and, in the presence of thrombin, adhere in heparin-preventable fashion to each other and to other fibrinogen-coated surfaces. Taken together, these data indicate that lipid feeding creates in gastrointestinal lymph a condition that is conducive temporally to the physical association of fibrinogen with newly ingested lipids before they reach the circulatory system.