Abstract
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.
Highlights
Antimicrobial resistance (AMR) is significantly impacting the prevention and treatment of infectious diseases on a global scale [1]
One patient was treated with a combination of imipenem and cefepime and was included for both groups, but a protocol violation occurred for imipenem (AB treatment
One cefepime sweat sample was lost because of sample mishandling; one pair of cefepime sweat and blood samples could not be collected because the patient did not attend the follow-up visit
Summary
Antimicrobial resistance (AMR) is significantly impacting the prevention and treatment of infectious diseases on a global scale [1]. The misuse and overuse of antibiotics (ABs) accelerate the development of AMR [2]. Multidrug-resistant organisms (MDROs) threaten global health, food security, and development [2]. Data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) suggests that MDROs were responsible for approximately >670,000 infections and >30,000 deaths in the European Union in 2015 [3]. Infections caused by AB-resistant bacteria are associated with a higher rate of complications and require significantly more resources than those from non-resistant microbes [2]. Solutions to tackle AMR include antimicrobial stewardship measures, such as optimizing AB dosing. Therapeutic drug monitoring (TDM) can optimize and personalize antibiotic treatment. Antibiotic concentrations in tissues were extrapolated from skin blister studies, but sweat analyses for TDM have not been conducted
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