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Non-invasive Drug Monitoring of β-Lactam Antibiotics Using Sweat Analysis-A Pilot Study.

  • Brasier N CMIO Research Group, University Hospital Basel, Basel, Switzerland.
  • Widmer A Department of Infectious Disease and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
  • Osthoff M Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
  • Mutke M CMIO Research Group, University Hospital Basel, Basel, Switzerland.
  • De Ieso F CMIO Research Group, University Hospital Basel, Basel, Switzerland.
  • Brasier-Lutz P Department of Gynaecology, Standort Wolhusen Kantonsspital Luzern, Wolhusen, Switzerland.
  • Wolfe L Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, United States.
  • Aithal V Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, United States.
  • Broeckling CD Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, United States.
  • Prenni J Department of Horticulture and Landscape, Colorado State University, Fort Collins, CO, United States.
  • Eckstein J CMIO Research Group, University Hospital Basel, Basel, Switzerland.
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  • 2020-09-28
Published in:
  • Frontiers in medicine. - 2020
antibiotics
antimicrobial resistance
cefepime
flucloxacillin
imipenem
sweat
therapeutic drug monitoring
English Background: Antimicrobial resistance is a major challenge in treating infectious diseases. Therapeutic drug monitoring (TDM) can optimize and personalize antibiotic treatment. Previously, antibiotic concentrations in tissues were extrapolated from skin blister studies, but sweat analyses for TDM have not been conducted. Objective: To investigate the potential of sweat analysis as a non-invasive, rapid, and potential bedside TDM method. Methods: We analyzed sweat and blood samples from 13 in-house patients treated with intravenous cefepime, imipenem, or flucloxacillin. For cefepime treatment, full pharmacokinetic sampling was performed (five subsequent sweat samples every 2 h) using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The ClinicalTrials.gov registration number is NCT03678142. Results: In this study, we demonstrated for the first time that flucloxacillin, imipenem, and cefepime are detectable in sweat. Antibiotic concentration changes over time demonstrated comparable (age-adjusted) dynamics in the blood and sweat of patients treated with cefepime. Patients treated with standard flucloxacillin dosage showed the highest mean antibiotic concentration in sweat. Conclusions: Our results provide a proof-of-concept that sweat analysis could potentially serve as a non-invasive, rapid, and reliable method to measure antibiotic concentration and as a surrogate marker for tissue penetration. If combined with smart biosensors, sweat analysis may potentially serve as the first lab-independent, non-invasive antibiotic TDM method.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/130394
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