Impact of the change in the antitubercular regimen from three to four drugs on cure and frequency of adverse reactions in tuberculosis patients from Brazil: A retrospective cohort study

Autoři: María B. Arriaga aff001;  Ninfa M. C. Torres aff001;  Nelia C. N. Araujo aff001;  Simone C. C. Caldas aff002;  Bruno B. Andrade aff002;  Eduardo M. Netto aff001
Působiště autorů: Universidade Federal da Bahia, Salvador, Brazil aff001;  Instituto Brasileiro de Investigação da Tuberculose, Salvador, Brazil aff002;  Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil aff003;  Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil aff004;  Universidad Militar Nueva Granada, Bogotá, Colombia aff005;  Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil aff006;  Curso de Medicina, Universidade Salvador (UNIFACS), Salvador, Brazil aff007;  Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil aff008
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227101



The Ministry of Health in Brazil included ethambutol in the intensive phase of sensible tuberculosis (TB) treatment in March 2010, due to the increasing drug resistance, and implemented the fixed dose combination in the TB treatment guidelines.


A retrospective cohort study was performed to determine the impact of change from three to four drugs schemes on the TB cure and frequency of adverse drug reactions (ADRs) in TB patients. To answer this question, we used data from 730 randomly selected patients who received anti-TB treatment between January 2007 and December 2014 in a reference center from Salvador, Brazil.


TB patients who received the RHEZ regimen (n = 365) developed ADRs more frequently than those treated with the RHZ (n = 365) (86 [23.6%] vs. 55 [15.1%]; p = 0.01). This difference in ADR incidence was even higher in patients above 30 years-old (64 [74.4%] vs. 36 [65.5%]; p = 0.01). The overall number of ADR episodes was greater in patients from the RHEZ group than in the group that received RHZ (170 [61.4%] vs. 107 [38.6%]; p = 0.03). Multivariable logistic regression analysis adjusted for age, alcohol use and diabetes demonstrated that patients receiving the RHEZ regimen had increased odds of developing ADRs than those undertaking the RHZ scheme (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.10–2.35; p = 0.015). The overall cure rate was similar between the distinct treatment groups.


The patients treated with the four-drug regimen exhibited increased risk of ADRs compared to those who received the three-drug regimen, and especially in patients older than 30 years of age.

Klíčová slova:

Adverse reactions – Antibiotic resistance – Brazil – Drug therapy – Extensively drug-resistant tuberculosis – Isoniazid – Tuberculosis – Tuberculosis diagnosis and management


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