Variation in missed doses and reasons for discontinuation of anti-tuberculosis drugs during hospital treatment for drug-resistant tuberculosis in South Africa

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....

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Vydané v:	PloS one Ročník 18; číslo 2; s. e0281097
Hlavní autori:	Pietersen, Elize, Anderson, Kim, Cox, Helen, Dheda, Keertan, Bian, Aihua, Shepherd, Bryan E., Sterling, Timothy R., Warren, Robin M., van der Heijden, Yuri F.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 13.02.2023 Public Library of Science (PLoS)
Predmet:	Adult Amikacin Amikacin - pharmacology Amikacin - therapeutic use Aminosalicylic Acid - therapeutic use Antibiotics Antitubercular agents Antitubercular Agents - pharmacology Biology and Life Sciences Capreomycin Care and treatment Clinical outcomes Computer and Information Sciences Diagnosis Dosage and administration Drug dosages Drug resistance Drug resistance in microorganisms Drug therapy Drug therapy, Combination Drugs Ethambutol Ethionamide Ethionamide - therapeutic use Female Health services HIV HIV Infections - drug therapy HIV Infections - epidemiology Hospital patients Hospitalization Hospitals Human immunodeficiency virus Humans Isoniazid Kanamycin Laboratories Male Medical records Medicine and Health Sciences Methods Microbial Sensitivity Tests Moxifloxacin Multidrug resistance Mycobacterium tuberculosis Ofloxacin Ofloxacin - pharmacology Oral administration Patient compliance Patient outcomes Patients Prescribing Prescription drugs Prevention Public health Pyrazinamide Research and Analysis Methods Retrospective Studies Rifampin Severe acute respiratory syndrome coronavirus 2 South Africa - epidemiology Tuberculosis Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - microbiology South Africa
ISSN:	1932-6203, 1932-6203
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Shrnutí:	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. 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. 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<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. 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exists.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0281097