Limited Effect of Later-Generation Fluoroquinolones in the Treatment of Ofloxacin-Resistant and Moxifloxacin-Susceptible Multidrug-Resistant Tuberculosis

Antimicrob Agents Chemother. 2018 Jan 25;62(2):e01784-17. doi: 10.1128/AAC.01784-17. Print 2018 Feb.

Abstract

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 for 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 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 resistance to the drugs 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 for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 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 to 18.53) times more likely than the ofloxacin-resistant group (P < 0.001) to have favorable outcomes. Despite in vitro moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that 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.

Keywords: drug resistance; fluoroquinolones; moxifloxacin; ofloxacin; pulmonary tuberculosis; treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / therapeutic use*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Female
  • Fluoroquinolones / therapeutic use*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Moxifloxacin / therapeutic use*
  • Mycobacterium tuberculosis / drug effects
  • Ofloxacin / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents
  • Fluoroquinolones
  • Ofloxacin
  • Moxifloxacin