Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy.

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.

[Low cyclosporin levels induced by the brief use of rifampicin; immunosuppression may fail for several weeks]. / Lage ciclosporinespiegel na kort rifampicinegebruik; immuunsuppressie kan langdurig tekortschieten.

Cyclosporin is an immunosuppressive agent with a wide range of therapeutic uses. In transplant patients, it is used for the prevention of rejection and graft-versus-host reactions. The metabolism and bioavailability of cyclosporin can be significantly and persistently influenced through induction of CYP3A4 caused by the concomitant use of rifampicin. However, awareness of the need for the timely and frequent monitoring of cyclosporin levels during and especially after treatment with rifampicin has not fully been addressed. Here, we describe 3 patient cases concerning significant episodes of sub-therapeutic cyclosporin levels after short-term rifampicin therapy. Rifampicin was administered for three to five days and decreased cyclosporin levels were observed ± 7 days after the initiation of rifampicin, and continued during the following weeks even after the cessation of rifampicin therapy. Cyclosporin dosage-adjustments were made based on the cyclosporin blood levels and all 3 patients showed good therapeutic and clinical responses.