Unexpected Vancomycin Pharmacokinetic Profile Secondary to Macromolecular Complexing: A Case Series.
Journal
Therapeutic drug monitoring
ISSN: 1536-3694
Titre abrégé: Ther Drug Monit
Pays: United States
ID NLM: 7909660
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
22
01
2021
accepted:
01
03
2021
pubmed:
19
3
2021
medline:
18
11
2021
entrez:
18
3
2021
Statut:
ppublish
Résumé
The optimal dosing and monitoring of vancomycin has been largely debated for decades, with key guideline changes for recommended monitoring in 2009 and 2020. Current and past practices for pharmacokinetic dose optimization use serum drug assays to guide dose adjustment to effectively balance efficacy and the risks of toxicity. These assays detect both bound and unbound serum concentrations. Vancomycin is believed to be 50%-55% protein bound in most cases; however, some variability in this parameter has been previously published. The authors report 2 cases of abnormal vancomycin pharmacokinetics discovered based on unexpected serum levels during routine clinical care. Unexpected vancomycin levels, observed during clinical care for 2 separate patients, were further evaluated to determine the source of the abnormal pharmacokinetics. In case 1, serial dilution was performed to assure that assay interference was not associated with the significant elevation (>100 mg/L). In both cases, samples were filtered using a Millipore Centrifree 30 KDa centrifugal filter to separate bound vancomycin, with a Protein G spin kit used to bind IgG and remove IgG complexes from the patient sample. In case 2, a polyethylene glycol precipitation was also performed to precipitate large-molecular-weight complexes. In both cases, laboratory analysis revealed abnormal vancomycin protein-binding profiles with macromolecular complex formation. Immunoglobulin G played a role in the macrocomplex in both patients. In cases of unusual or unexpected vancomycin pharmacokinetics in the absence of renal dysfunction, an abnormal protein-binding profile should be considered. Bound vancomycin may yield elevated serum levels, leading to poorly informed dose adjustments and risk for treatment failure. Given implications for therapeutic drug monitoring and unknown impacts on efficacy and toxicity, further investigations into population incidence and risk factors for abnormal protein binding of vancomycin are warranted.
Sections du résumé
BACKGROUND
The optimal dosing and monitoring of vancomycin has been largely debated for decades, with key guideline changes for recommended monitoring in 2009 and 2020. Current and past practices for pharmacokinetic dose optimization use serum drug assays to guide dose adjustment to effectively balance efficacy and the risks of toxicity. These assays detect both bound and unbound serum concentrations. Vancomycin is believed to be 50%-55% protein bound in most cases; however, some variability in this parameter has been previously published. The authors report 2 cases of abnormal vancomycin pharmacokinetics discovered based on unexpected serum levels during routine clinical care.
METHODS
Unexpected vancomycin levels, observed during clinical care for 2 separate patients, were further evaluated to determine the source of the abnormal pharmacokinetics. In case 1, serial dilution was performed to assure that assay interference was not associated with the significant elevation (>100 mg/L). In both cases, samples were filtered using a Millipore Centrifree 30 KDa centrifugal filter to separate bound vancomycin, with a Protein G spin kit used to bind IgG and remove IgG complexes from the patient sample. In case 2, a polyethylene glycol precipitation was also performed to precipitate large-molecular-weight complexes.
RESULTS
In both cases, laboratory analysis revealed abnormal vancomycin protein-binding profiles with macromolecular complex formation. Immunoglobulin G played a role in the macrocomplex in both patients.
CONCLUSIONS
In cases of unusual or unexpected vancomycin pharmacokinetics in the absence of renal dysfunction, an abnormal protein-binding profile should be considered. Bound vancomycin may yield elevated serum levels, leading to poorly informed dose adjustments and risk for treatment failure. Given implications for therapeutic drug monitoring and unknown impacts on efficacy and toxicity, further investigations into population incidence and risk factors for abnormal protein binding of vancomycin are warranted.
Identifiants
pubmed: 33734211
doi: 10.1097/FTD.0000000000000888
pii: 00007691-202110000-00015
doi:
Substances chimiques
Anti-Bacterial Agents
0
Vancomycin
6Q205EH1VU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
696-700Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Levine DP. Vancomycin : a history. Clin Infect Dis. 2006;42(suppl 1):5–12.
Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American society of health-system pharmacists, the infectious Diseases society of America, and the society of infectious Diseases pharmacists. Am J Heal Pharm. 2009;66:82–98.
Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatr. Am J Heal Pharm. 2020;77:835–863.
Sun H, Maderazo EG, Krusell AR. Serum protein-binding characteristics of vancomycin. Antimicrob Agents Chemother. 1993;37:1132–1136.
Legatt DF, Blakney GB, Higgins TN, et al. The effect of paraproteins and rheumatoid factor on four commercial immunoassays for vancomycin: implications for laboratorians and other health care professionals. Ther Drug Monit. 2012;34:306–311.
Tsoi V, Bhayana V, Bombassaro AM, et al. Falsely elevated vancomycin concentrations in a patient not receiving vancomycin. Pharmacotherapy. 2019;39:778–782.
Singer B, Stevens RW, Westley BP, et al. Falsely elevated vancomycin-concentration values from enzyme immunoassay leading to treatment failure. Am J Health Syst Pharm. 2020;77:9–13.
Cantu TG, Dick JD, Elliott DE, et al. Protein binding of vancomycin in a patient with immunoglobulin A myeloma. Antimicrob Agents Chemother. 1990;34:1459–1461.
Global KDI; Group O (KDIGO) AKIW. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;2:1–138.
Florin L, Vantilborgh A, Pauwels S, et al. IgM interference in the Abbott iVanco immunoassay: a case report. Clin Chim Acta. 2015;447:32–33.
Simons SA, Molinelli AR, Sobhani K, et al. Two cases with unusual vancomycin measurements. Clin Chem. 2009;55:578–580.
Levy RH, Moreland TA. Rationale for monitoring free drug levels. Clin Pharmacokinet. 1984;9(suppl 1):1–9.