Effects of Fluroquinolones in Newly Diagnosed, Sputum-Positive Tuberculosis Therapy: A Systematic Review and Network Meta-Analysis

BACKGROUND: Tuberculosis is a major public health problem especially in developing countries, the comparative efficacy and safety of fluroquinolones (FQs) for adult patients with newly diagnosed, sputum-positive tuberculosis remains controversial. We aimed to investigate the benefits and risks of FQs-containing (addition/substitution) regimens in this population. METHODS: A network meta-analysis was performed to compare FQs (C: ciprofloxacin; O: ofloxacin; Lo: levofloxacin; M: moxifloxacin; G: gatifloxacin) addition/substitution regimen with standard HRZE regimen (ie isoniazid, rifampicin, pyrazinamide and ethambutol) in newly diagnosed, sputum-positive tuberculosis. Medline, Embase and Cochrane Central Register of Controlled Trials were systematically searched, randomized trials with duration longer than 8 weeks were included. The primary outcome was week-8 sputum negativity, and secondary outcomes included treatment failure, serious adverse events and death from all cause. RESULTS: Twelve studies comprising 6465 participants were included in the network meta-analysis. Löwenstein-Jensen culture method showed that HRZEM (OR 4.96, 95% CI 2.83–8.67), MRZE (OR 1.48, 95% CI 1.19–1.84) and HRZM (OR 1.32, 95% CI 1.08–1.62) had more sputum conversion than HRZE by the eighth week, whereas HRC (OR 0.39, 95% CI 0.19–0.77) and HRZO (OR 0.47, 95% CI 0.24–0.92) were worse than HRZE. Moxifloxacin-containing regimens showed more conversion than HRZE by liquid method at the end of two months. But by the end of treatment, FQs-containing regimens didn’t show superiority than HRZE on treatment failure. There were no significant differences between any regimens on other outcomes like serious adverse events and all-cause death. CONCLUSION: This comprehensive network meta-analysis showed that compared with HRZE, moxifloxacin-containing regimens could significantly increase sputum conversion by the eighth week for patients with newly diagnosed pulmonary tuberculosis while HRC and HRZO regimens were inferior. But all the FQs-containing regimens did not show superiority in other outcomes (such as treatment failure, serious adverse events and all-cause death). Thus, HRZE is still an effective regimen for this population. Although moxifloxacin-containing regimens have deomonstrated their potential, FQs-containing regimens should be used with great caution to avoid widespread FQs-resistance worldwide.