title: Effects of Fluroquinolones in Newly Diagnosed, Sputum-Positive Tuberculosis Therapy: A Systematic Review and Network Meta-Analysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Su
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Junxian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Tang
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000627:therapeutic use*; D006801:Humans; D017594:Publication Bias; D013183:Sputum / Q000382:microbiology*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones