PHARMACOKINETIC PROFILES OF HIGH-DOSE INTRAVENOUS CIPROFLOXACIN IN SEVERE SEPSIS

The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i .v.) every 8 h (q8h) in severely septic adults was documented in a mul tidisciplinary, tertiary referral intensive care unit (ICU), Sixteen e valuable patients (three pharmacokinetic profiles) without renal dysfu nction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed inter vals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8, All pharmacokinetic variables were calculated by noncompartme ntal methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: DO, 6.01 +/- 1.93 mg/liter; D2, 6.68 +/- 2.01 mg/liter; and D6 to Dg 6.45 +/- 1.54 mg/liter. Trough levels were as follows: D0, 0.6 +/- 0.5 mg/liter; D2, 0.7 +/- 0.4 mg/liter; a nd D6 to D8 0.6 +/- 0.4 mg/liter, The areas under the concentration cu rves (8 h) were as follows: D0, 13.3 +/- 3.8 mg.h/liter; D2, 16.8 +/- 5.4 mg.h/liter; and D6 to D8, 15.5 +/- 4.7 mg.h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in th e study, the causative organisms were susceptible to ciprofloxacin. On e patient developed renal failure (non-drug related) after the adminis tration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One pat ient developed a ciprofloxacin-resistant superinfection. In two patien ts the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumul ation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.