title: Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis.
abstract: It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (n = 25; 30.9%), loss to follow-up (n = 2; 2.5%), and death (n = 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646, P = 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59, P = 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the gyrA gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54, P = 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Chest Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
authors.forename: Jung-Yien
authors.initials: JY
authors.lastname: Chien
authors.affiliation: Chest Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
authors.forename: Shun-Tien
authors.initials: ST
authors.lastname: Chien
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wei-Yih
authors.initials: WY
authors.lastname: Chiu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan hsporen@ntu.edu.tw.
authors.forename: Po-Ren
authors.initials: PR
authors.lastname: Hsueh
mesh_terms: D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D027081:DNA Gyrase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D000077266:Moxifloxacin; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D015242:Ofloxacin / Q000627:therapeutic use*; D013624:Taiwan; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D015242:Ofloxacin; D027081:DNA Gyrase; D000077266:Moxifloxacin