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.
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.
Authors: Elize Pietersen; Elisa Ignatius; Elizabeth M Streicher; Barbara Mastrapa; Xavier Padanilam; Anil Pooran; Motasim Badri; Maia Lesosky; Paul van Helden; Frederick A Sirgel; Robin Warren; Keertan Dheda Journal: Lancet Date: 2014-01-17 Impact factor: 79.321
Authors: Courtney M Yuen; Ekaterina V Kurbatova; Thelma Tupasi; Janice Campos Caoili; Martie Van Der Walt; Charlotte Kvasnovsky; Martin Yagui; Jaime Bayona; Carmen Contreras; Vaira Leimane; Julia Ershova; Laura E Via; HeeJin Kim; Somsak Akksilp; Boris Y Kazennyy; Grigory V Volchenkov; Ruwen Jou; Kai Kliiman; Olga V Demikhova; Irina A Vasilyeva; Tracy Dalton; J Peter Cegielski Journal: PLoS Med Date: 2015-12-29 Impact factor: 11.069
Authors: Mohammad H Al-Shaer; Wael A Alghamdi; Abdullah Alsultan; Guohua An; Shahriar Ahmed; Yosra Alkabab; Sayera Banu; Ketevan Barbakadze; Eric Houpt; Maia Kipiani; Lali Mikiashvili; J Peter Cegielski; Russell R Kempker; Scott K Heysell; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2019-06-24 Impact factor: 5.191