Impact of fluoroquinolone resistance on the cost-effectiveness of empiric treatment for multidrug- or rifampicin-resistant tuberculosis

The WHO recommends the bedaquiline, pretomanid, and linezolid (BPaL) regimen with the additional fluoroquinolone antibiotic moxifloxacin (BPaLM) for initial treatment of multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB). However, fluoroquinolone drug susceptibility testing (DST) coverage for MDR/RR-TB is only around 55% globally, and the efficacy of moxifloxacin may be compromised in settings with high fluoroquinolone resistance. We extended a previous Markov cohort model to assess the cost-effectiveness of the empirical use of BPaLM as a replacement for BPaL for the treatment of MDR/RR-TB in four high MDR/RR-TB burden countries. We obtained fluoroquinolone resistance rates in these countries from WHO surveillance data and parameterised treatment efficacy from recent trial results. We performed scenario analyses across varying fluoroquinolone resistance prevalence and performed Monte Carlo simulations to generate uncertainty intervals for our primary cost-effectiveness estimates. BPaLM incurred higher costs than BPaL but averted more disability-adjusted life years, with incremental cost-effectiveness ratios below 50% of each country's 2019 GDP per capita. This finding remained robust across a feasible fluoroquinolone resistance prevalence range (0-70%). In the absence of fluoroquinolone DST, empirical use of BPaLM resulted in $58 (interquartile range: $49-$73), $32 (IQR: $23-$53), $35 (IQR: $28 - $51), $174 (IQR: $161 - $209) per DALY averted in Georgia, India, the Philippines, and South Africa respectively. Our findings support the empirical use of BPaLM as a potential replacement for BPaL for the treatment of MDR/RR-TB in the absence of fluoroquinolone DST, even if fluoroquinolone resistance prevalence were to increase, reinforcing recent WHO recommendations.