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      Potential to Use Fingerprints for Monitoring Therapeutic Levels of Isoniazid and Treatment Adherence

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          Abstract

          A fingerprint offers a convenient, noninvasive sampling matrix for monitoring therapeutic drug use. However, a barrier to widespread adoption of fingerprint sampling is the fact that the sample volume is uncontrolled. Fingerprint samples ( n = 140) were collected from patients receiving the antibiotic isoniazid as part of their treatment, as well as from a drug-naive control group ( n = 50). The fingerprint samples were analyzed for isoniazid (INH) and acetylisoniazid (AcINH), using liquid chromatography high-resolution mass spectrometry. The data set was analyzed retrospectively for metabolites known to be present in eccrine sweat. INH or AcINH was detected in 89% of the fingerprints collected from patients and in 0% of the fingerprints collected from the control group. Metabolites lysine, ornithine, pyroglutamic acid, and taurine were concurrently detected alongside INH/AcINH and were used to determine whether the fingerprint sample was sufficient for testing. Given a sufficient sample volume, the fingerprint test for INH use has sensitivity, specificity, and accuracy of 100%. Normalization to taurine was found to reduce intradonor variability. Fingerprints are a novel and noninvasive approach to monitor INH therapy. Metabolites can be used as internal markers to demonstrate a sufficient sample volume for testing and reduce intradonor variability.

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          Most cited references36

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          Adherence to Medication

          Lars Osterberg, Terrence F. Blaschke (2005)
          New England Journal of Medicine, 353(5), 487-497
          Article 0 comments Cited 770 times – based on 0 reviews     Review now
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            Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability.

            Tawanda Gumbo, Edward C. Meek, Jotam Pasipanodya … (2011)
            It is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level of nonadherence associated with emergence of MDR-tuberculosis is unknown. Performance of a randomized controlled trial in which some patients are randomized to nonadherence would be unethical; therefore, other study designs should be utilized. We performed hollow fiber studies for both bactericidal and sterilizing effect, with inoculum spiked with 0.5% rifampin- and isoniazid-resistant isogenic strains in some experiments. Standard therapy was administered daily for 28-56 days, with extents of nonadherence varying between 0% and 100%. Sizes of drug-resistant populations were compared using analysis of variance. We also explored the effect of pharmacokinetic variability on MDR-tuberculosis emergence using computer-aided clinical trial simulations of 10 000 Cape Town, South Africa, tuberculosis patients. Therapy failure was only encountered at extents of nonadherence ≥60%. Surprisingly, isoniazid- and rifampin-resistant populations did not achieve ≥1% proportion in any experiment and did not achieve a higher proportion with nonadherence. However, clinical trial simulations demonstrated that approximately 1% of tuberculosis patients with perfect adherence would still develop MDR-tuberculosis due to pharmacokinetic variability alone. These data, based on a preclinical model, demonstrate that nonadherence alone is not a sufficient condition for MDR-tuberculosis emergence.
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              The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis.

              S Weis, P C Slocum, F Blais … (1994)
              Tuberculosis has reemerged as an important public health problem, and the frequency of drug resistance is increasing. A major reason for the development of resistant infections and relapse is poor compliance with medical regimens. In Tarrant County, Texas, we initiated a program of universal directly observed treatment for tuberculosis. We report the effect of the program on the rates of primary and acquired drug resistance and relapse among patients with tuberculosis. We collected information on all patients with positive cultures for Mycobacterium tuberculosis in Tarrant County from January 1, 1980, through December 31, 1992. Through October 1986, patients received a traditional, unsupervised drug regimen. Beginning in November 1986, nearly all patients received therapy under direct observation by health care personnel. A total of 407 episodes in which patients received traditional treatment for tuberculosis (January 1980 through October 1986) were compared with 581 episodes in which therapy was directly observed (November 1986 through December 1992). Despite higher rates of intravenous drug use and homelessness and an increasing rate of tuberculosis during this 13-year period, the frequency of primary drug resistance decreased from 13.0 percent to 6.7 percent (P < 0.001) after the institution of direct observation of therapy, and the frequency of acquired resistance declined from 14.0 percent to 2.1 percent (P < 0.001). The relapse rate decreased from 20.9 percent to 5.5 percent (P < 0.001), and the number of relapses with multidrug-resistant organisms decreased from 25 to 5 (P < 0.001). The administration of therapy for M. tuberculosis infection under direct observation leads to significant reductions in the frequency of primary drug resistance, acquired drug resistance, and relapse.
              Article 0 comments Cited 87 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): ACS Omega
                Journal ID (iso-abbrev): ACS Omega
                Journal ID (publisher-id): ao
                Journal ID (coden): acsodf
                Title: ACS Omega
                Publisher: American Chemical Society
                ISSN (Electronic): 2470-1343
                Publication date (Electronic): 21 April 2022
                Publication date Collection: 03 May 2022
                Volume: 7
                Issue: 17
                Pages: 15167-15173
                Affiliations
                [† ]Department of Chemistry, University of Surrey , Guildford, Surrey GU2 7XH, U.K.
                [‡ ]Ion Beam Centre, University of Surrey , Guildford, Surrey GU2 7XH, U.K.
                [§ ]Faculty of Health and Medical Sciences, University of Surrey , Guildford, Surrey GU2 7XH, U.K.
                [∥ ]Wexham Park Hospital, Frimley Health NHS Foundation Trust , Frimley, Surrey GU16 7UJ, U.K.
                Author notes
                Author information
                https://orcid.org/0000-0001-5792-3891
                https://orcid.org/0000-0001-9050-7910
                Article
                DOI: 10.1021/acsomega.2c01257
                PMC ID: 9089686
                PubMed ID: 35572755
                SO-VID: 102d464d-3ea9-4c82-a189-05478e17c8d6
                Copyright © © 2022 The Authors. Published by American Chemical Society
                License:

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 02 March 2022
                Date accepted : 08 April 2022
                Funding
                Funded by: Engineering and Physical Sciences Research Council, doi 10.13039/501100000266;
                Award ID: EP/P001440/1
                Funded by: Engineering and Physical Sciences Research Council, doi 10.13039/501100000266;
                Award ID: EP/R031118/1
                Categories
                Subject: Article
                Custom metadata
                document-id-old-9 ao2c01257
                document-id-new-14 ao2c01257
                ccc-price

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