Impact of Fluoroquinolone Use on Mortality Among a Cohort of Patients With Suspected Drug-Resistant Tuberculosis. (5th May 2017) - Seifert, Marva
Summary: Among patients with suspected drug resistant tuberculosis, treatment with a later generation fluoroquinolone versus earlier generation or no fluoroquinolone significantly reduced mortality risk after adjusting for risk factors typically associated with poor outcomes. 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/m 2 ), 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