Utility of para-aminosalicylic acid in drug-resistant tuberculosis: Should it be classified as Group D3 or Group C?

BACKGROUND: The World Health Organization drug-resistant tuberculosis (DR-TB) 2016 guidelines reclassified para-aminosalicylic acid (PAS) as Group D3 “add-on” drug. We studied our DR-TB data wherein PAS was widely and preferably used as a substitute in the standardized regimen in varied situations and report its utility in DR-TB. METHODOLOGY: This retrospective observational study enrolled both pulmonary and extrapulmonary DR-TB patients receiving PAS in the programmatic management of DR-TB from March 2012 to June 2013. They were divided into seven subgroups on the basis of indication for PAS substitution in the standardized regimen for DR-TB cases. The clinical profile and outcomes were analyzed. RESULTS: PAS was substituted in 250 cases (225 – pulmonary DR-TB and 25 – extrapulmonary DR-TB). PAS was used in (1) pre-extensively drug-resistant TB (XDR-TB) fluoroquinolones (FQs) – 136 (54.4%), (2) XDR-TB – 15 (6%), (3) substitute drug for serious adverse events – 3 (1.2%), (4) pregnant DR-TB patients – 5 (2%), (5) patients on successful private-based second-line therapy adopted under the Revised National Tuberculosis Control Program – 10 (4%), (6) substitute drug for previous FQ exposure – 5 (2%), and (7) Category V – 76 (30.4%). Although 51.2% had an unfavorable response (UFR) against 48.8% with FR, wide disparity was noted in subgroups. FR was observed in 68.4% pre-XDR-TB (FQ), 80% pregnant patients, 90% adopted from private on successful second-line therapy, 80% previous FQ exposure against 40% XDR-TB, 7.9% Category V, and 0% PAS substitution for adverse drug reactions (ADRs). UFR was seen in 31.6% pre-XDR-TB (FQ), 20% pregnant patients, 10% adopted from private on successful second-line therapy, 20% of previous FQ exposure against 60% XDR-TB, 92.1% Category V, and 100% on PAS substitution for ADR. CONCLUSION: In view of the safety and efficacy of PAS in our DR-TB patients except for XDR and Category V group, we recommend larger studies with PAS and consider its reclassification into Group C rather than Group D3.