GRAND ROUNDS An Unusual Case of Low Vancomycin Exposure Despite Extremely High Vancomycin Doses Accompanied by Renal Toxicity: A Grand Round Anne M. van Schip, PharmD,* Jeske J. K. van Diemen, MD, PhD,† Reinier M. van Hest, PharmD, PhD,* and Vanessa C. Harris, MD, PhD† Abstract: This grand round describes the case of a patient who received 10 grams (143.5 mg/kg) of vancomycin every 24 hours via continuous infusion, in whom the highest observed level was only 15.4 mg/L. Despite subtherapeutic levels, renal impairment was encountered, which resolved after the discontinuation of vancomycin. Glomerular hyper- filtration was found through nuclear glomerular filtration rate measure- ment, which likely explains the need for high doses (.6 grams per 24 hours continuous infusion) without reaching therapeutic serum levels. Key Words: vancomycin, hyperfiltration, pharmacology, ADME approach (Ther Drug Monit 2023;45:136–139) CLINICIAN A 43-year-old white woman, with a medical history of melanoma with lymph node metastases presented to the emergency department with fever and malaise. She was successfully treated with ipilimumab and nivolumab 4 years before admission; however, her antibody treatment was compli- cated by chronic polyradiculitis and gastrointestinal motility disorder. This left her dependent on total parenteral nutrition (TPN) provided via a central venous catheter (CVC). The patient had a body composition with high body fat and low muscle mass. Her Body Mass Index was 21.8 (height, 180 cm; weight, 69.7 kg), whereas her corresponding creatinine level was 48 mmol/L. She was admitted to the general internal medicine ward for a suspected central line infection and empirically treated with vancomycin in line with the local antibiotic protocol. Multiple blood cultures revealed Staphylococcus epidermidis, which was susceptible to vancomycin. Given her lifelong dependency on TPN, antibiotic salvage treatment rather than CVC removal was attempted. Intravenous vancomycin treat- ment was started at 1 gram, administered 3 times daily (43 mg/kg/d). Per protocol, vancomycin trough serum level was measured on day 3 after the start of therapy, and the result was reported as ,4.0 mg/mL on the same day. TDM CONSULTANT Vancomycin is the empiric antibiotic of choice for CVC infections in our hospital. 1 It is a glycopeptide that is often used for gram-positive infections. Vancomycin-based therapeutic drug monitoring (TDM) is routinely performed in our hospital and targets an area-under-the-concentration– time-curve over the minimum inhibitory concentration of the bacteria (AUC 0–24 /MIC of 400–600 mg$h/L). Dose adjust- ments are calculated by Bayesian estimation. 2 When admin- istered via continuous infusion (CI), the target AUC 0–24 corresponds to a steady-state serum level of 17–25 mg/L. When patients do not reach the target AUC 0-24 /MIC of van- comycin, the dosage is increased step by step, with a max- imum dose increase of 200% of the current dose (Fig. 1). The maximum daily dose is always less than 10 grams per 24 hours (24 hours). The highest registered dosing regimen is 60 mg/kg/d. 1 Given that the patient’s trough serum level was below the limit of quantification, the vancomycin dose was increased to 4 grams (57 mg/kg) per 24 hours, administered via contin- uous intravenous infusion to avoid false-negative TDM results. A new sample was collected and measured the next day. CLINICIAN One day after the advised dose increase, the serum vancomycin level was 5.3 mg/L. TDM CONSULTANT The vancomycin level remained too low, and the target AUC 0–24 /MIC was not reached (estimated AUC 0–24 was 127 mg$h/L). Understanding why a patient may not attain thera- peutic serum levels despite receiving high doses of vancomy- cin requires a systematic evaluation. First, a critical assessment of how and when the samples were taken relative to vancomycin administration and how the samples were ana- lyzed, for example, by immunoassay methods, is important. In this case, repeated sampling and sample reanalysis using the same immunoassay that was used during routine clinical practice confirmed low serum levels. Second, general reasons for deviating pharmacokinetic behavior should be evaluated Received for publication June 8, 2022; accepted October 8, 2022. From the *Amsterdam UMC, Department of Hospital Pharmacy and Clinical Pharmacology, University of Amsterdam, Amsterdam, the Netherlands; and †Amsterdam UMC, Division of Infectious Diseases, Department of Internal Medicine, University of Amsterdam, Amsterdam the Netherlands. The authors declare no conflict of interest. Correspondence: Anne M. van Schip, Department of Hospital Pharmacy, Amsterdam University Medical Centre, Meibergdreef 9, 1005 AZ, Amsterdam, the Netherlands (e-mail: a.m.vanschip@amsterdamumc.nl). Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. 136 Ther Drug Monit  Volume 45, Number 2, April 2023 Copyright © 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Downloaded from http://journals.lww.com/drug-monitoring by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XM i0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 04/21/2023