title: Pharmacokinetics of meropenem in critically ill patients receiving continuous venovenous haemofiltration: a randomised controlled trial of continuous infusion versus intermittent bolus administration.
abstract: The objective of this study was to describe the pharmacokinetics of meropenem, administered by continuous infusion (CI) or intermittent bolus (IB), in critically ill patients receiving continuous venovenous haemofiltration (CVVH) and to evaluate the frequency of pharmacokinetic/pharmacodynamic target attainment with each dosing strategy. This was a prospective, randomised controlled trial in critically ill patients receiving CVVH and administered meropenem by CI or IB. Serial meropenem concentrations in plasma and ultrafiltrate were measured after administration of a standard total daily dose (4 g/day on Day 1, followed by 3g/day thereafter) on two occasions during antibiotic therapy. Meropenem pharmacokinetic parameters were calculated using a non-compartmental approach. Sixteen critically ill patients receiving CVVH concurrently treated with meropenem were randomised to CI (n = 8) or IB dosing (n = 8). IB administration resulted in higher maximum concentrations (C(max)) [64.7 (58.9-80.3) and 64.8 (48.5-81.8) mg/L, respectively] on both sampling occasions compared with CI (P < 0.01 and P = 0.04, respectively). CI resulted in a higher meropenem steady-state concentration (Css) on occasion 1 [26.0 (24.5-41.6) mg/L] compared with the minimum concentration (C(min)) observed for IB patients [17.0 (15.7-19.8)mg/L; P < 0.01]. CVVH contributed to ca. 50% of meropenem total clearance in these patients. The administered meropenem doses resulted in plasma drug concentrations that were >4× the targeted susceptibility breakpoint (2mg/L) for 100% of the dosing interval, for both groups, on both occasions. CI could be an alternative to IB for meropenem administration in critically ill patients receiving CVVH.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: janattul.jamal@uq.net.au.
authors.forename: Janattul-Ain
authors.initials: JA
authors.lastname: Jamal
authors.affiliation: Department of Anaesthesiology and Intensive Care, Kulliyyah of Medicine, International Islamic University of Malaysia, Kuantan, Pahang, Malaysia.
authors.forename: Mohd-Basri
authors.initials: MB
authors.lastname: Mat-Nor
authors.affiliation: Department of Nephrology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia.
authors.forename: Fariz-Safhan
authors.initials: FS
authors.lastname: Mohamad-Nor
authors.affiliation: Department of Hyperbaric and Intensive Care Medicine, The Alfred Hospital, Commercial Road, Prahran, Melbourne, Victoria, Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Udy
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Department of Pharmacy, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D006440:Hemofiltration; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: CVVH; Continuous infusion; Intensive care; Meropenem