Impact of fluoroquinolone use on mortality among a cohort of patients with suspected drug-resistant tuberculosis

Abstract

Background. Previous retrospective and in vitro studies suggest that use of later-generation fluoroquinolones may reduce mortality risk and improve treatment outcomes for drug-resistant tuberculosis (TB) patients, including individuals resistant to a fluoroquinolone. Meta-analysis results are mixed and few studies have examined this relationship prospectively. Methods. As part of a comparative diagnostic study, we conducted a prospective cohort study with 834 Mycobacterium tuberculosis- infected patients from selected hospitals and clinics with high prevalence of drug-resistant TB in India, Moldova, and South Africa. We used Cox proportional hazards regression models to assess the association between later-generation fluoroquinolone (moxifloxacin or levofloxacin) use and patient mortality, adjusting for risk factors typically associated with poor treatment outcomes. Results. After adjusting for phenotypic resistance profile, low body mass index (<18.5 kg/m2), human immunodeficiency virus status, and study site, participants treated with a later-generation fluoroquinolone had half the risk of mortality compared with participants either not treated with any fluoroquinolone or treated only with an earlier-generation fluoroquinolone (adjusted hazard ratio, 0.46 [95% confidence interval, .26-.80]) during follow-up. Conclusions. Use of later-generation fluoroquinolones significantly reduced patient mortality risk in our cohort, suggesting that removal of a later-generation fluoroquinolone from a treatment regimen because of demonstrated resistance to an earlier-generation fluoroquinolone might increase mortality risk. Further studies should evaluate the effectiveness of later-generation fluoroquinolones among patients with and without resistance to early-generation fluoroquinolones. Clinical Trials Registration. NCT02170441.