Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

Vesa Cheng; Mohd H Abdul-Aziz; Fay Burrows; Hergen Buscher; Amanda Corley; Arne Diehl; Bianca J Levkovich; Vincent Pellegrino; Claire Reynolds; Sam Rudham; Steven C Wallis; Susan A Welch; Jason A Roberts; Kiran Shekar; John F Fraser; ASAP ECMO Investigators

doi:10.1016/j.accpm.2022.101080

Population pharmacokinetics of ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study)

Anaesth Crit Care Pain Med. 2022 Jun;41(3):101080. doi: 10.1016/j.accpm.2022.101080. Epub 2022 Apr 25.

Authors

Affiliations

¹ University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Adult Intensive Care Services and Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia; Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, China.
² University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
³ Department of Pharmacy, St Vincent's Hospital, Sydney, New South Wales, Australia.
⁴ Department of Intensive Care Medicine, St Vincent's Hospital, Sydney, New South Wales, Australia; St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Adult Intensive Care Services and Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia.
⁶ Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Melbourne, Victoria, Australia and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁷ Experiential Development and Graduate Education and Centre for Medicines Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.
⁸ Department of Intensive Care Medicine, St Vincent's Hospital, Sydney, New South Wales, Australia.
⁹ University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France. Electronic address: j.roberts2@uq.edu.au.
¹⁰ Adult Intensive Care Services and Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia.

PMID: 35472580
DOI: 10.1016/j.accpm.2022.101080

Abstract

Introduction: This study aimed to describe the pharmacokinetics (PK) of ciprofloxacin in critically ill patients receiving ECMO and recommend a dosing regimen that provides adequate drug exposure.

Methods: Serial blood samples were taken from ECMO patients receiving ciprofloxacin. Total ciprofloxacin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. Dosing simulations were performed to ascertain the probability of target attainment (PTA) represented by the area under the curve to minimum inhibitory concentration ratio (AUC_0-24/MIC) ≥ 125.

Results: Eight patients were enrolled, of which three received concurrent continuous venovenous haemodiafiltration (CVVHDF). Ciprofloxacin was best described in a two-compartment model with total body weight and creatinine clearance (CrCL) included as significant predictors of PK. Patients not requiring renal replacement therapy generated a mean clearance of 11.08 L/h while patients receiving CVVHDF had a mean clearance of 1.51 L/h. Central and peripheral volume of distribution was 77.31 L and 90.71 L, respectively. ECMO variables were not found to be significant predictors of ciprofloxacin PK. Dosing simulations reported that a 400 mg 8 -hly regimen achieved > 72% PTA in all simulated patients with CrCL of 30 mL/min, 50 mL/min and 100 mL/min and total body weights of 60 kg and 100 kg at a MIC of 0.5 mg/L.

Conclusion: Our study reports that established dosing recommendations for critically ill patients not on ECMO provides sufficient drug exposure for maximal ciprofloxacin activity for ECMO patients. In line with non-ECMO critically ill adult PK studies, higher doses and therapeutic drug monitoring may be required for critically ill adult patients on ECMO.

Keywords: Antibiotics; Continuous renal replacement therapy; Dosing; Extracorporeal membrane oxygenation; Fluoroquinolone; Pharmacokinetics.

MeSH terms

Adult
Anti-Bacterial Agents / therapeutic use
Ciprofloxacin* / pharmacokinetics
Ciprofloxacin* / therapeutic use
Critical Illness / therapy
Extracorporeal Membrane Oxygenation* / methods
Humans
Renal Replacement Therapy / methods

Substances

Anti-Bacterial Agents
Ciprofloxacin