Tuberculosis Preventive Therapy for Contacts of Drug-Resistant Tuberculosis: A Narrative Review

Abstract

Drug-resistant (DR) tuberculosis (TB), including multidrug-resistant (MDR) and rifampicin-resistant (RR) TB, remains a major global public health problem. This narrative review aims to discuss tuberculosis preventive therapy (TPT) among contacts of DR-TB. The clinical spectrum of TB spans from infection to active disease, the progression of which can be prevented through TPT. Drug resistance in TB develops through genetic mutations. Levofloxacin (Lfx) exerts antimycobacterial activity by inhibiting the deoxyribonucleic acid (DNA) gyrase enzyme. The Vietnam Quinolones for MDR-TB Trial (VQUIN) demonstrated an incidence rate ratio of TB disease of 0.55 (95% confidence interval [CI] 0.19–1.62) in the Lfx group compared with the placebo group. In the Tuberculosis Child Multidrug-Resistant Preventive Therapy (TB-CHAMP) trial, the hazard ratio for TB disease was 0.44 (95% CI 0.15–1.25) in the Lfx group compared with placebo. Although neither trial individually achieve statistical significance in reducing TB incidence, a meta-analysis of both studies revealed a significant relative reduction in cumulative TB incidence of 0.41 (95% CI 0.18–0.92) in the Lfx group compared with placebo. The administration of Lfx was associated with low-grade musculoskeletal adverse events (risk ratio 6.36; 95% CI 4.30–9.42). Overall, daily administration of Lfx for six months is recommended as the standard TPT regimen for DR-TB, particularly among household contacts of MDR/RR-TB cases.