desacetylcefotaxime and Acute-Kidney-Injury

The objective of this study was to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). This single-center prospective observational pilot study was performed among ICU-patients with AKI receiving ≥48 h concomitant CRRT and CTX. CTX was administered intravenously 1,000 mg (bolus) every 6 h for 4 days. CRRT was performed as continuous venovenous hemofiltration (CVVH). Plasma concentrations of CTX and its active metabolite desacetylcefotaxime (DAC) were measured during CVVH treatment. CTX plasma levels and patient data were used to construct concentration-time curves. By using this data, the duration of plasma levels above 4 mg/liter (four times the MIC) was calculated and analyzed. Twenty-seven patients were included. The median CTX peak level was 55 mg/liter (range, 19 to 98 mg/liter), the median CTX trough level was 12 mg/liter (range, 0.8 to 37 mg/liter), and the median DAC plasma level was 15 mg/liter (range, 1.5 to 48 mg/liter). Five patients (19%) had CTX plasma levels below 4 mg/liter at certain time points during treatment. In at least 83% of the time any patient was treated with CTX, the CTX plasma level stayed above 4 mg/liter. A dosing regimen of 1,000 mg of CTX given four times daily is likely to achieve adequate plasma levels in patients with AKI treated with CVVH. Dose reduction might be a risk for suboptimal treatment.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Cefotaxime; Critical Illness; Female; Humans; Intensive Care Units; Male; Pilot Projects; Prospective Studies; Renal Replacement Therapy

Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 gm intravenous dose were evaluated in five groups of subjects: group I, normal creatinine clearance (CLCR greater than 90 ml/min); group II, mild renal insufficiency (CLCR 30 to 89 ml/min); group III, moderate renal insufficiency (CLCR 16 to 29 ml/min); group IV, severe renal insufficiency (CLCR 4 to 15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR less than 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR. The terminal t1/2 values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 hours in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.

Topics: Acute Kidney Injury; Adult; Analysis of Variance; Cefotaxime; Chromatography, High Pressure Liquid; Creatinine; Female; Half-Life; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Kinetics; Male; Middle Aged