Pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin in patients with major thermal injuries

Abstract

Adequate penetration of antibiotics into burn tissue and maintenance of effective serum levels are essential for the treatment of patients sustaining major thermal injuries. The pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin were determined in 12 critically ill patients with burn injuries. Mean age for the 12 patients was 45 ± 17 (range 25-82 years), total body surface area burned (TBSAB) = 38 ± 15% and Acute Physiology and Chronic Health Evaluation (APACHE) II score = 8 ± 6. Patients received recommended doses of ciprofloxacin, 400 mg q12h iv, for three doses beginning 72 h post-burn. Serum concentrations were measured at t = 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 4.0 and 12.0 h after the first and third doses. Burn eschar biopsies were obtained after the third ciprofloxacin dose. Three of these 12 patients (25%) manifested later signs of clinical sepsis (TBSAB = 61 ± 6% and APACHE II score = 11 ± 3) and underwent a second infusion of three doses of intravenous ciprofloxacin, blood sampling and eschar biopsy. Serum and eschar concentrations were determined by high performance liquid chromatography. Serum ciprofloxacin concentrations were comparable to those of normal volunteers (C(max) = 4.0 ± 1 mg/L and AUC = 11.4 ± 2 mg.h/L) during the immediate post-burn period after dose 1 (C(max1) = 4.8 ± 3 mg/L and AUC0-12 = 12.5 ± 7 mg.h/L) and dose 3 (C(max3) = 4.9 ± 2 mg/L and AUC24-36 = 17.5 ± 11 mg.h/L). Mean burn eschar concentration during the 72 h post-burn was significantly lower than that found during clinical sepsis (18 ± 17 compared with 41.3 ± 54 μg/g; P < 0.05 by t test). Similar serum concentrations were achieved in patients with clinical sepsis (C(max1) = 4.2 ± 0.2 mg/L and AUC0-12 = 15.0 ± 3 mg.h/L; C(max3) = 5.0 ± 1 mg/L and AUC24-38 = 22.8 ± 9 mg.h/L). A positive correlation between burn eschar concentrations and C(max) (r = 0.71, r2 = 0.51, P = 0.01) was found by linear regression analysis. A C(max)/MIC ratio > 10 (MIC = 0.5 mg/L) and an AUC/MIC ratio > 100 SIT-1.h (serum inhibitory titre) (MIC = 0.125 mg/L) were achieved. High burn eschar concentrations and serum levels, similar to those found in normal volunteers, can be achieved after intravenous ciprofloxacin infusion in critically ill burns patients.