@article{Pietersen2023,
abstract = {Background Updated World Health Organization (WHO) treatment guidelines prioritize all-oral drug-resistant tuberculosis (DR-TB) regimens. Several poorly tolerated drugs, such as amikacin and para-aminosalicylic acid (PAS), remain treatment options for DR-TB in WHO-recommended longer regimens as Group C drugs. Incomplete treatment with anti-TB drugs increases the risk of treatment failure, relapse, and death. We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. Methods We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. Results Among 242 patients, 131 (54{\%}) were male, 97 (40{\%}) were living with HIV, 175 (72{\%}) received second-line treatment prior to first hospitalization, and 191 (79{\%}) died during the study period. At initial hospitalization, 134 (55{\%}) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]) without resistance to ofloxacin or amikacin, and 102 (42{\%}) had resistance to ofloxacin and/or amikacin. Most patients (129 [53{\%}]) had multiple hospitalizations and DST changes occurred in 146 (60{\%}) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18{\%}), capreomycin (18{\%}), PAS (17{\%}) and kanamycin (16{\%}) than other DR-TB drugs (P{\textless}0.001), including ethionamide (8{\%}), moxifloxacin (7{\%}), terizidone (7{\%}), ethambutol (7{\%}), and pyrazinamide (6{\%}). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56–1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51–0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. Conclusion We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.},
author = {Pietersen, Elize and Anderson, Kim and Cox, Helen and Dheda, Keertan and Bian, Aihua and Shepherd, Bryan E and Sterling, Timothy R and Warren, Robin M and {Van Der Heijden}, Yuri F},
doi = {10.1371/JOURNAL.PONE.0281097},
editor = {Ramagopalan, Sreeram V.},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Pietersen et al. - 2023 - Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment.pdf:pdf},
isbn = {1111111111},
issn = {1932-6203},
journal = {PLOS ONE},
keywords = {Adverse events,Antibiotic resistance,Charts,Drug therapy,Extensively drug-resistant tuberculosis,HIV,Multi-drug-resistant tuberculosis,OA,OA{\_}PMC,Tuberculosis,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
month = {feb},
number = {2},
pages = {e0281097},
pmid = {36780443},
publisher = {Public Library of Science},
title = {{Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa}},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281097},
volume = {18},
year = {2023}
}

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We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. Methods We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. Results Among 242 patients, 131 (54%) were male, 97 (40%) were living with HIV, 175 (72%) received second-line treatment prior to first hospitalization, and 191 (79%) died during the study period. At initial hospitalization, 134 (55%) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]) without resistance to ofloxacin or amikacin, and 102 (42%) had resistance to ofloxacin and/or amikacin. Most patients (129 [53%]) had multiple hospitalizations and DST changes occurred in 146 (60%) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18%), capreomycin (18%), PAS (17%) and kanamycin (16%) than other DR-TB drugs (P\\textless0.001), including ethionamide (8%), moxifloxacin (7%), terizidone (7%), ethambutol (7%), and pyrazinamide (6%). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56–1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51–0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. Conclusion We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.","author":[{"propositions":[],"lastnames":["Pietersen"],"firstnames":["Elize"],"suffixes":[]},{"propositions":[],"lastnames":["Anderson"],"firstnames":["Kim"],"suffixes":[]},{"propositions":[],"lastnames":["Cox"],"firstnames":["Helen"],"suffixes":[]},{"propositions":[],"lastnames":["Dheda"],"firstnames":["Keertan"],"suffixes":[]},{"propositions":[],"lastnames":["Bian"],"firstnames":["Aihua"],"suffixes":[]},{"propositions":[],"lastnames":["Shepherd"],"firstnames":["Bryan","E"],"suffixes":[]},{"propositions":[],"lastnames":["Sterling"],"firstnames":["Timothy","R"],"suffixes":[]},{"propositions":[],"lastnames":["Warren"],"firstnames":["Robin","M"],"suffixes":[]},{"propositions":[],"lastnames":["Van Der Heijden"],"firstnames":["Yuri","F"],"suffixes":[]}],"doi":"10.1371/JOURNAL.PONE.0281097","editor":[{"propositions":[],"lastnames":["Ramagopalan"],"firstnames":["Sreeram","V."],"suffixes":[]}],"file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Pietersen et al. - 2023 - Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment.pdf:pdf","isbn":"1111111111","issn":"1932-6203","journal":"PLOS ONE","keywords":"Adverse events,Antibiotic resistance,Charts,Drug therapy,Extensively drug-resistant tuberculosis,HIV,Multi-drug-resistant tuberculosis,OA,OA_PMC,Tuberculosis,fund_not_ack,original","mendeley-tags":"OA,OA_PMC,fund_not_ack,original","month":"feb","number":"2","pages":"e0281097","pmid":"36780443","publisher":"Public Library of Science","title":"Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa","url":"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281097","volume":"18","year":"2023","bibtex":"@article{Pietersen2023,\r\nabstract = {Background Updated World Health Organization (WHO) treatment guidelines prioritize all-oral drug-resistant tuberculosis (DR-TB) regimens. Several poorly tolerated drugs, such as amikacin and para-aminosalicylic acid (PAS), remain treatment options for DR-TB in WHO-recommended longer regimens as Group C drugs. Incomplete treatment with anti-TB drugs increases the risk of treatment failure, relapse, and death. We determined whether missed doses of individual anti-TB drugs, and reasons for their discontinuation, varied in closely monitored hospital settings prior to the 2020 WHO DR-TB treatment guideline updates. Methods We collected retrospective data on adult patients with microbiologically confirmed DR-TB between 2008 and 2015 who were selected for a study of acquired drug resistance in the Western Cape Province of South Africa. Medical records through mid-2017 were reviewed. Patients received directly observed treatment during hospitalization at specialized DR-TB hospitals. Incomplete treatment with individual anti-TB drugs, defined as the failure to take medication as prescribed, regardless of reason, was determined by comparing percent missed doses, stratified by HIV status and DR-TB regimen. We applied a generalized mixed effects model. Results Among 242 patients, 131 (54{\\%}) were male, 97 (40{\\%}) were living with HIV, 175 (72{\\%}) received second-line treatment prior to first hospitalization, and 191 (79{\\%}) died during the study period. At initial hospitalization, 134 (55{\\%}) patients had Mycobacterium tuberculosis with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]) without resistance to ofloxacin or amikacin, and 102 (42{\\%}) had resistance to ofloxacin and/or amikacin. Most patients (129 [53{\\%}]) had multiple hospitalizations and DST changes occurred in 146 (60{\\%}) by the end of their last hospital discharge. Incomplete treatment was significantly higher for amikacin (18{\\%}), capreomycin (18{\\%}), PAS (17{\\%}) and kanamycin (16{\\%}) than other DR-TB drugs (P{\\textless}0.001), including ethionamide (8{\\%}), moxifloxacin (7{\\%}), terizidone (7{\\%}), ethambutol (7{\\%}), and pyrazinamide (6{\\%}). Among the most frequently prescribed drugs, second-line injectables had the highest rates of discontinuation for adverse events (range 0.56–1.02 events per year follow-up), while amikacin, PAS and ethionamide had the highest rates of discontinuation for patient refusal (range 0.51–0.68 events per year follow-up). Missed doses did not differ according to HIV status or anti-TB drug combinations. Conclusion We found that incomplete treatment for second-line injectables and PAS during hospitalization was higher than for other anti-TB drugs. To maximize treatment success, interventions to improve person-centered care and mitigate adverse events may be necessary in cases when PAS or amikacin (2020 WHO recommended Group C drugs) are needed.},\r\nauthor = {Pietersen, Elize and Anderson, Kim and Cox, Helen and Dheda, Keertan and Bian, Aihua and Shepherd, Bryan E and Sterling, Timothy R and Warren, Robin M and {Van Der Heijden}, Yuri F},\r\ndoi = {10.1371/JOURNAL.PONE.0281097},\r\neditor = {Ramagopalan, Sreeram V.},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Pietersen et al. - 2023 - Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment.pdf:pdf},\r\nisbn = {1111111111},\r\nissn = {1932-6203},\r\njournal = {PLOS ONE},\r\nkeywords = {Adverse events,Antibiotic resistance,Charts,Drug therapy,Extensively drug-resistant tuberculosis,HIV,Multi-drug-resistant tuberculosis,OA,OA{\\_}PMC,Tuberculosis,fund{\\_}not{\\_}ack,original},\r\nmendeley-tags = {OA,OA{\\_}PMC,fund{\\_}not{\\_}ack,original},\r\nmonth = {feb},\r\nnumber = {2},\r\npages = {e0281097},\r\npmid = {36780443},\r\npublisher = {Public Library of Science},\r\ntitle = {{Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa}},\r\nurl = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281097},\r\nvolume = {18},\r\nyear = {2023}\r\n}\r\n","author_short":["Pietersen, E.","Anderson, K.","Cox, H.","Dheda, K.","Bian, A.","Shepherd, B. 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