Comparative roles of moxifloxacin and levofloxacin in the treatment of pulmonary multidrug-resistant tuberculosis: a retrospective study

https://doi.org/10.1016/j.ijantimicag.2013.02.019Get rights and content

Abstract

This study compared the efficacy of moxifloxacin and levofloxacin in the treatment of multidrug-resistant tuberculosis (MDR-TB) in Shanghai, China. A retrospective analysis of 158 patients with MDR-TB receiving either moxifloxacin- or levofloxacin-containing regimens was performed. Clinical data from patients were subjected to univariate analysis, stratification and multiple logistic regression to compare the roles of moxifloxacin and levofloxacin in multidrug regimens. In total, 72 patients received 400 mg of moxifloxacin once daily and 86 patients received 509.9 ± 79.4 mg (mean ± standard deviation) of levofloxacin once daily together with similar active agents for similar durations. The times to sputum culture conversion were similar. Adverse reactions occurred at comparable rates. The combined treatment success rate was 60.1%, being higher among ofloxacin-susceptible than ofloxacin-resistant cases (67.5% vs. 52.0%; P < 0.05). The success rates for the moxifloxacin group were 65.3% (overall), 77.1% (ofloxacin-susceptible cases) and 54.1% (ofloxacin-resistant cases) in comparison with 55.8%, 60.4% and 50.0%, respectively, for the levofloxacin group. No demographic, clinical, bacteriological or treatment characteristics were independent predictors of favourable outcome. Fourteen patients from the moxifloxacin group and twelve patients from the levofloxacin group had bacteriological relapse after treatment cessation. In conclusion, compared with levofloxacin, moxifloxacin did not show superior efficacy when incorporated into multidrug regimens used for the treatment of MDR-TB.

Introduction

Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than drug-susceptible TB [1]. The main problems include the limited availability of effective drugs, reduced efficacy of second-line drugs, increased number of adverse reactions to the drugs and long duration of therapy. In addition, concerns about extensively drug-resistant (XDR) TB have been raised [2]. Patients with XDR-TB are more likely to have an unfavourable outcome compared with patients with non-XDR MDR-TB [3], [4], [5]. In 2010, there were an estimated 650 000 cases of MDR-TB among the world's 12.0 million prevalent cases of TB. China is one of the world's 27 countries with the highest burden of MDR-TB [6]. Treatment guidelines for MDR-TB have already been published [7]. However, treatment outcomes for MDR-TB and XDR-TB cases are poor [8], [9], [10]. Thus, information on safety, tolerability and efficacy of other antibiotics as well as strategies potentially useful in treatment is urgently required to improve individual outcomes and to control the spread of MDR-TB and XDR-TB.

The fluoroquinolones were found to have good activity against Mycobacterium tuberculosis [11], [12], [13], [14]. Thus, incorporation of fluoroquinolones in second-line regimens for the management of MDR-TB has been recommended by many authorities [7], [15]. Although bacillary resistance to fluoroquinolones in vitro was found, good treatment outcomes in clinical studies partly using fluoroquinolone-containing regimens in patients with MDR-TB were reported [16], [17], [18], [19], [20]. One clinical study comparing moxifloxacin- with levofloxacin-containing regimens in treating MDR-TB reported a high treatment success rate (83.3% vs. 78.9%, respectively) and suggested that fluoroquinolones might play a significant role in the treatment of MDR-TB [21]. Although the minimum inhibitory concentrations of moxifloxacin were lower than those of levofloxacin, and moxifloxacin exhibited a high treatment success rate in that clinical study, there is still a dearth of clinical evidence comparing the roles of moxifloxacin and levofloxacin in the management of MDR-TB in China. Randomised controlled clinical trials on MDR-TB are difficult to conduct and have additional ethical constraints. A retrospective analysis was therefore performed of a cohort of MDR-TB patients receiving either moxifloxacin- or levofloxacin-containing regimens in Shanghai, China, hoping to compare the safety, tolerability and efficacy of moxifloxacin and levofloxacin in the treatment of MDR-TB.

Section snippets

Data collection

The medical records of 158 patients with MDR-TB between January 2005 and December 2010 were retrospectively reviewed, of whom 72 patients received moxifloxacin-containing treatment regimens and the remaining 86 received levofloxacin-containing treatment regimens. Moreover, 127 patients had been treated unsuccessfully for the disease (defined as treatment failure or relapse) and 31 had contact with patients with MDR-TB. No patient was previously treated with moxifloxacin or levofloxacin for

Results

The results showed that there were no significant differences in demographic, clinical and other characteristics between the two groups (Table 1), apart from more cavitation on chest radiography among the moxifloxacin group. Patients treated with moxifloxacin- or levofloxacin-containing regimens had isolates resistant to similar agents for which DST testing was routinely performed [mean ± standard deviation (S.D.) number of drugs that isolates were resistant to in the two groups, 5.6 ± 1.2 vs. 5.5 ± 

Discussion

Patients with drug-resistant TB compared with drug-susceptible TB have significantly worse short- and long-term outcomes. Mitnick et al. presented the most optimistic treatment outcome results, suggesting that patients with MDR-TB treated in a community-based setting in Peru had a 60% cure rate [23]. The current study confirmed a low treatment success rate of 60.1% for patients with MTD-TB in China.

Moxifloxacin and levofloxacin are the two most frequently recommended fluoroquinolones for

Acknowledgments

The authors acknowledge all of the clinicians for indefatigable patient care, as well as administrative and technical support for this programme.

Funding: No funding sources.

Competing interests: None declared.

Ethical approval: Not required.

References (30)

  • World Health Organization

    Global tuberculosis control report 2011

    (2011)
  • World Health Organization

    Guidelines for the programmatic management of drug-resistant tuberculosis

    (2006)
  • G.B. Migliori et al.

    Extensively drug-resistant tuberculosis is worse than multidrug-resistant tuberculosis: different methodology and settings, same results

    Clin Infect Dis

    (2008)
  • G.B. Migliori et al.

    Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis?

    Eur Respir J

    (2008)
  • G.B. Migliori et al.

    Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases

    Eur Respir J

    (2008)
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    These two authors contributed equally to this paper.

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