title: Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy.
abstract: 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.
authors.affiliation: Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands j.koedijk@student.maastrichtuniversity.nl.
authors.forename: Joost B
authors.initials: JB
authors.lastname: Koedijk
authors.affiliation: Department of Clinical Pharmacy, Bravis Hospital Bergen op Zoom and Roosendaal, Roosendaal, The Netherlands.
authors.forename: Corinne G H
authors.initials: CG
authors.lastname: Valk-Swinkels
authors.affiliation: Department of Intensive Care, Amphia Hospital Breda, Oosterhout, and Etten-Leur, Breda, The Netherlands.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Rijpstra
authors.affiliation: University Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: Amphia Academy, Amphia Hospital Breda, Oosterhout, and Etten-Leur, Breda, The Netherlands.
authors.forename: Paul G H
authors.initials: PG
authors.lastname: Mulder
authors.affiliation: Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands Tias School for Business and Society, Tilburg University, Tilburg, The Netherlands.
authors.forename: Peter H J
authors.initials: PH
authors.lastname: van der Voort
authors.affiliation: Department of Clinical Pharmacy, Amphia Hospital Breda, Oosterhout, and Etten-Leur, Breda, The Netherlands.
authors.forename: Nils E
authors.initials: NE
authors.lastname: van 't Veer
authors.affiliation: Department of Intensive Care, Amphia Hospital Breda, Oosterhout, and Etten-Leur, Breda, The Netherlands Tias School for Business and Society, Tilburg University, Tilburg, The Netherlands.
authors.forename: Nardo J M
authors.initials: NJ
authors.lastname: van der Meer
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D017582:Renal Replacement Therapy
chemical_list: D000900:Anti-Bacterial Agents; C029281:desacetylcefotaxime; D002439:Cefotaxime