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

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          Abstract

          Background: 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. Objective: Here, we investigated if the glycopeptide antibiotic vancomycin is detectable in sweat samples of in-patients treated with intravenous vancomycin. Methods: 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. Results: 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. Conclusion: 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.

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          Waterproof, electronics-enabled, epidermal microfluidic devices for sweat collection, biomarker analysis, and thermography in aquatic settings

          Waterproof epidermal microfluidics enable collection and analysis of sweat during aquatic exercise.
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            Incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a U.S. population: a retrospective population-based study

            Background Skin and soft tissue infections (SSTIs) are commonly occurring infections with wide-ranging clinical manifestations, from mild to life-threatening. There are few population-based studies of SSTIs in the period after the rapid increase in community-acquired methicillin-resistant Staphyloccus aureus (MRSA). Methods We used electronic databases to describe the incidence, microbiology, and patient characteristics of clinically-diagnosed skin and soft tissue infections (SSTIs) among members of a Northern California integrated health plan. We identified demographic risk factors associated with SSTIs and MRSA infection. Results During the three-year study period from 2009 to 2011, 376,262 individuals experienced 471,550 SSTI episodes, of which 23% were cultured. Among cultured episodes, 54% were pathogen-positive. Staphylococcus aureus (S. aureus) was isolated in 81% of pathogen-positive specimens, of which nearly half (46%) were MRSA. The rate of clinically-diagnosed SSTIs in this population was 496 per 10,000 person-years. After adjusting for age group, gender, race/ethnicity and diabetes, Asians and Hispanics were at reduced risk of SSTIs compared to whites, while diabetics were at substantially higher risk compared to non-diabetics. There were strong age group by race/ethnicity interactions, with African Americans aged 18 to <50 years being disproportionately at risk for SSTIs compared to persons in that age group belonging to other race/ethnicity groups. Compared to Whites, S. aureus isolates of African-Americans and Hispanics were more likely to be MRSA (Odds Ratio (OR): 1.79, Confidence Interval (CI): 1.67 to 1.92, and, OR: 1.24, CI: 1.18 to 1.31, respectively), while isolates from Asians were less likely to be MRSA (OR: 0.73, CI: 0.68 to 0.78). Conclusions SSTIs represent a significant burden to the health care system. The majority of culture-positive SSTIs were caused by S. aureus, and almost half of the S. aureus SSTIs were methicillin-resistant. The reasons for African-Americans having a higher likelihood, and Asians a lower likelihood, for their S. aureus isolates to be methicillin-resistant, should be further investigated.
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              The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid.

              The rising prevalence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) and the recent emergence of community-associated MRSA are major clinical, public health, and economic challenges. MRSA is a leading cause of nosocomial pneumonia and complicated skin and soft-tissue infections (cSSTI). Vancomycin and linezolid are two commonly used antimicrobial agents with activity against Gram-positive pathogens, particularly MRSA, that are used to treat both nosocomial pneumonia and cSSTI. Recently, the therapeutic efficacy of vancomycin in the treatment of hospitalized patients with MRSA infections has been questioned due to the emergence of MRSA strains with reduced susceptibility to vancomycin together with concerns related to inadequate dosing and poor tissue penetration of the drug. A literature review was conducted to investigate the pharmacokinetics and pulmonary and tissue penetration of vancomycin and linezolid. Using MEDLINE and EMBASE, the most relevant articles in English published over the past 25 years (up to October 2008) were identified and summarized. Studies in human volunteers and adult patients that measured concentrations of antibiotic in serum, epithelial lining fluid (ELF), and tissue were selected for further review. For both drugs, pharmacokinetic studies were conducted in diverse patient populations and employed varying techniques to measure tissue concentrations. Vancomycin concentrations in ELF ranged from 5 to 25% of simultaneous plasma levels, while concentrations in whole homogenized lung tissue were slightly higher (24-41%). Distribution of vancomycin into soft tissue was variable. For linezolid, overall mean concentrations in ELF and in soft tissue were generally similar or higher than simultaneous plasma levels, although variability in tissue penetration across studies in healthy volunteers and patients was seen. The studies included in this review vary greatly in their designs and patient populations; this, together with methodologic difficulties, limits the interpretation of the data. In the absence of clinical data correlating ELF concentrations and clinical outcome, the clinical significance of differences in pulmonary penetration of vancomycin and linezolid is unknown. Higher vancomycin serum concentrations may be necessary to achieve appropriate lung concentrations to optimize treatment outcomes. Linezolid demonstrates adequate penetration into lung and other soft issues with sustained concentrations above the minimum inhibitory concentrations for susceptible pathogens, including MRSA, for the majority of the dosing interval. Examination of the pharmacokinetic data adds insights not provided by the clinical trial data and together provides clinicians with a more comprehensive basis for selecting appropriate antimicrobial therapy for the treatment of serious MRSA infections.
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                Author and article information

                Journal
                DIB
                DIB
                10.1159/issn.2504-110X
                Digital Biomarkers
                S. Karger AG
                2504-110X
                2021
                January – April 2021
                14 January 2021
                : 5
                : 1
                : 24-28
                Affiliations
                [_a] aCMIO Research Group, Department of Digitalization and ICT, University Hospital Basel, Basel, Switzerland
                [_b] bDivision of Internal Medicine, University Hospital Basel, Basel, Switzerland
                [_c] cDepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
                [_d] dAnalytical Resources Core, Bioanalysis and Omics Center, Colorado State University, Fort Collins, Colorado, USA
                [_e] eDepartment of Horticulture and Landscape, Colorado State University, Fort Collins, Colorado, USA
                [_f] fDepartment of Gynaecology, Kantonsspital Luzern, Standort Wolhusen, Wolhusen, Switzerland
                [_g] gDepartment of Clinical Research, University Basel, Basel, Switzerland
                Author notes
                *Noé Brasier, CMIO Office, Department of Digitalization and ICT, University Hospital Basel, Hebelstrasse 10, CH–4031 Basel (Switzerland), noe.brasier@usb.ch
                Author information
                https://orcid.org/0000-0003-0186-0865
                Article
                512947 Digit Biomark 2021;5:24–28
                10.1159/000512947
                7371207b-2ba1-4308-b9b0-6d6ee6728533
                © 2021 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 01 September 2020
                : 09 November 2020
                Page count
                Figures: 1, Tables: 1, Pages: 5
                Categories
                Research Reports – Brief Report

                Oncology & Radiotherapy,Geriatric medicine,Cardiovascular Medicine,Clinical Psychology & Psychiatry,Public health
                Clinical study,Antibiotic stewardship,Skin and soft tissue infections,Wearable sensors,Sweat analysis,Vancomycin

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