The Detection of Vancomycin in Sweat: A Next-Generation Digital Surrogate Marker for Antibiotic Tissue Penetration: A Pilot Study

Abstract

<b><i>Background:</i></b> Assuring adequate antibiotic tissue concentrations at the point of infection, especially in skin and soft tissue infections, is pivotal for an effective treatment and cure. Despite the global issue, a reliable AB monitoring test is missing. Inadequate antibiotic treatment leads to the development of antimicrobial resistances and toxic side effects. β-lactam antibiotics were already detected in sweat of patients treated with the respective antibiotics intravenously before. With the emergence of smartphone-based biosensors to analyse sweat on the spot of need, next-generation molecular digital biomarkers will be increasingly available for a non-invasive pharmacotherapy monitoring. <b><i>Objective:</i></b> Here, we investigated if the glycopeptide antibiotic vancomycin is detectable in sweat samples of in-patients treated with intravenous vancomycin. <b><i>Methods:</i></b> Eccrine sweat samples were collected using the Macroduct Sweat Collector®. Along every sweat sample, a blood sample was taken. Bio-fluid analysis was performed by Ultra-high Pressure Liquid Chromatograph-Tandem Quadrupole Mass Spectrometry coupled with tandem mass spectrometry. <b><i>Results:</i></b> A total of 5 patients were included. Results demonstrate that vancomycin was detected in 5 out of 5 sweat samples. Specifically, vancomycin concentrations ranged from 0.011 to 0.118 mg/L in sweat and from 4.7 to 8.5 mg/L in blood. <b><i>Conclusion:</i></b> Our results serve as proof-of-concept that vancomycin is detectable in eccrine sweat and may serve as a surrogate marker for antibiotic tissue penetration. A targeted vancomycin treatment is crucial in patients with repetitive need for antibiotics and a variable antibiotic distribution such as in peripheral artery disease to optimize treatment effectiveness. If combined with on-skin smartphone-based biosensors and smartphone applications, the detection of antibiotic concentrations in sweat might enable a first digital, on-spot, lab-independent and non-invasive therapeutic drug monitoring in skin and soft tissue infections.

Digital biomarkers from sweat analysis for therapeutic drug monitoring in soft tissue infections

“…[13,14] as well as a glycopeptide (vancomycin) that is used for methicillin-resistant staphylococcus aureus (MRSA) infections. [8,18] Their approach was to investigate how reliably the antibiotics can be detected in eccrine sweat (standardised from the lower underarm, where mostly eccrine sweat glands are present) to pave the way for further investigations for a non-invasive TDM at the pointof-need in soft tissue infections.…”

“…In two recently published pilot studies, antibiotics were reliably detected in every collected sweat sample. [8,18] In combination with a smartphone application, daily personalised antibiotic therapy doses might be calculated and directly indicated to the patient, e.g. by smartphone application.…”

“…Further, excreted antibiotic concentrations in sweat mostly do not reach standard minimal inhibitory concentration of targeted and susceptible pathogens in tissue. [8,18] Therefore, excreted concentrations may only serve as an estimate, rather than an absolute tissue concentration. [18,30] 3…”

“…[8,18] Therefore, excreted concentrations may only serve as an estimate, rather than an absolute tissue concentration. [18,30] 3…”

Biosensor‐Enabled Multiplexed On‐Site Therapeutic Drug Monitoring of Antibiotics

“…Recent bloodbased studies are focusing on ways to alleviate these issues by decreasing the sample volume and eliminating the need for expensive equip ment and expertise. [6][7][8][9][10][11] Alternatively, other matrices such as interstitial fluid, [12][13][14][15][16][17][18] tears, [19] saliva, [20][21][22] or sweat [22][23][24][25][26][27][28][29] can be used to replace the invasive TDM. Herein, the common chal lenges stem from the complex transport mechanisms of anti biotics from the blood to the sampling site of interest, which make the interpretation of the measured concentrations unique for each medium.…”