Limited Effect of Later-generation Fluoroquinolones in the Treatment of Ofloxacin-resistant and Moxifloxacin-susceptible Multidrug-resistant Tuberculosis [PublishAheadOfPrint]

Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant/moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used in all patients. Overall, 171 patients (82%) had ofloxacin-susceptible/moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group) and 37 (18%) had ofloxacin-resistant/moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a previous history of MDR-TB treatment (P < 0.001) and cavitary lesions on chest radiography (P < 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have drug resistance to pyrazinamide (P = 0.003), streptomycin (P = 0.015), prothionamide (P < 0.001), and para-aminosalicylic acid (P < 0.001). Favorable outcomes were more frequently achieved in the ofloxacin-susceptible group than in the ofloxacin-resistant group [91% (156/171) vs. 57% (21/37), respectively; P < 0.001]. In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval = 1.55-18.53) times more likely than the ofloxacin-resistant group (P < 0.001) to have favorable outcomes. Despite in vitro moxifloxacin susceptibility, favorable treatment outcomes for ofloxacin-resistant MDR-TB were significantly lower than for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more aggressive therapies may be needed for ofloxacin-resistant MDR-TB.

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