Levofloxacin as Tuberculosis Preventive Therapy for Household Contacts of Drug-Resistant Tuberculosis: Global Evidence and Implementation in Indonesia

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 summarize evidence regarding the effectiveness and safety of levofloxacin as tuberculosis preventive therapy (TPT) among household contacts of DR-TB patients and its implementation in Indonesia. 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) study, 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 achieves 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.