Contents lists available at ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/cca Cefepime therapeutic drug monitoring: Evaluation of agreement between peripheral and central venous blood sampling Matthias Gijsen a, ⁎ , Johan Maertens b , Katrien Lagrou c , Willy E. Peetermans d , David Fage e , Yves Debaveye f , Isabel Spriet a a Pharmacy Department, UZ Leuven and Clinical Pharmacology and Pharmacotherapy, KU Leuven, Leuven, Belgium b Laboratory of Clinical Bacteriology and Mycology, UZ Leuven and Academic Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium c Clinical Department of Laboratory Medicine, UZ Leuven and Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium d Department of Internal Medicine, UZ Leuven and Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium e Clinical Chemistry Department, LHUB-ULB, Brussels, Belgium f Clinical Department and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium ARTICLE INFO Keywords: Cefepime Carryover Catheter Therapeutic drug monitoring ABSTRACT Background: Therapeutic drug monitoring for cefepime is increasingly being performed because of the potential relation between exposure and neurotoxicity. An in vitro pilot study suggested significant carryover of cefepime from central venous catheters when blood sampling is carried out via the same catheter used for administration of cefepime. Therefore, the aim of this study was to evaluate carryover of cefepime in a real-life clinical setting. Methods: A prospective single-center study was conducted at the hematology department of the University Hospitals Leuven. Patients treated with cefepime, and having a central venous catheter, were included. Cefepime trough samples were taken simultaneously via the central venous catheter and peripheral venepuncture. Results: Twenty-four patients were included in this study, resulting in 28, 11 and 5 paired samples for tunnelled catheters, implantable port catheters and peripherally inserted central catheters, respectively. No statistically nor clinically significant difference was found between cefepime concentrations measured in centrally versus peripherally obtained blood samples, overall and for all three types of central venous catheters separately. Of note, four paired samples showed a difference larger than 10%, with lower central concentrations probably reflecting a dilution error. Conclusion: There was no significant carryover of cefepime from long-term central venous catheters. Cefepime samples can be drawn reliably via the central venous catheter, after flushing and discarding the first blood sample. Although, flushing and discard volumes should be standardized to avoid potential dilution errors. 1. Introduction Cefepime, an extended-spectrum cephalosporin antibiotic, is widely endorsed [1], and even preferred over piperacillin-tazobactam or car- bapenem antibiotics, as first line treatment of febrile neutropenia (FN) [2–4]. A recent study has demonstrated that treatment with piper- acillin-tazobactam in hematopoietic stem cell transplantation recipients was associated with an increased graft versus host disease related mortality, whereas cefepime was not associated. Presumably, this effect is mediated through intestinal microbiota injury by broad-spectrum antibiotics [5]. A phase II randomized controlled trial (NCT03078010) investigating this association is currently underway [6]. A dose of 2 g cefepime q8h should be administered, even in prolonged or continuous infusions (6 g/24 h), to ensure adequate empiric coverage against Gram-negative bacteria [7]. On the other hand, dose-dependent and potentially serious neurotoxicity has been reported with cefepime. Al- though the jury is still out, a few studies suggest a relation between cefepime exposure and neurotoxicity, especially for drug trough levels above 20–36 mg/L. Additionally, plasma concentrations are highly variable in critically ill patients [8,9]. Therefore, therapeutic drug monitoring for cefepime is increasingly being performed. Hematopoietic cell transplant recipients frequently present with FN, for which they may receive cefepime. Because most of these patients have a long-term indwelling venous catheter, blood sampling for ther- apeutic drug monitoring is usually done through this access line. However, there might be carryover of cefepime from the central venous https://doi.org/10.1016/j.cca.2020.08.015 Received 8 April 2020; Received in revised form 7 August 2020; Accepted 7 August 2020 Abbreviations: FN, febrile neutropenia; PICC, peripherally inserted central catheter ⁎ Corresponding author at: Hospital Pharmacy UZ Leuven, Herestraat 49, 3000 Leuven, Belgium. E-mail address: matthias.gijsen@uzleuven.be (M. Gijsen). Clinica Chimica Acta 510 (2020) 450–454 Available online 12 August 2020 0009-8981/ © 2020 Elsevier B.V. All rights reserved. T