Fluoroquinolones for the treatment of pulmonary tuberculosis

Tuberculosis (TB) continues to be a significant problem globally. Treatment includes a multiple drug regimen with isoniazid, rifampicin (rifampin), pyrazinamide and ethambutol. Often, one of these medications needs to be replaced as a result of adverse events or because Mycobacterium tuberculosis develops resistance against one these first-line agents. Fluoroquinolones, particularly the newer ones, possess good in vitro (levofloxacin, gatifloxacin, moxifloxacin) and in vivo (gatifloxacin and moxifloxacin) bactericidal activity against M. tuberculosis, making them attractive agents for the treatment of pulmonary TB. All relevant clinical trials, cohort studies and case reports investigating the clinical efficacy and tolerability of fluoroquinolones when used for the treatment of pulmonary TB were evaluated for this review. Specifically, efficacy and safety in the following indications were investigated: (i) first-line treatment of drug-sensitive pulmonary TB; (ii) first-line treatment for multi-drug resistant (MDR) TB; and (iii) treatment of patients with drug intolerance. Twenty-seven articles met our inclusion criteria; nine articles presented data from randomised, controlled or cohort studies. Seven studies used fluoroquinolones as first-line agents in drug-sensitive TB (1469 patients), 15 studies used fluoroquinolones to treat MDR-TB (1025 patients) and six studies (951 patients) investigated the use of fluoroquinolones in patients intolerant to other TB medications. In patients with susceptible M. tuberculosis strains, substitution with a fluoroquinolone did not have an effect on cure or radiological improvement at 8 weeks or failure at 12 months. Substitution of older fluoroquinolones into a regimen, especially ciprofloxacin, resulted in a higher rate of relapse and a longer time to sputum-culture conversions. The use of fluoroquinolones in patients with MDR-TB is supported by some trials where others show a lack of improvement in efficacy of a regimen. Our review of the literature does not support the use of older fluoroquinolones, especially ciprofloxacin, as substitute agents for drug-sensitive or drug-resistant TB. However, newer fluoroquinolones, such as moxifloxacin, may be a reasonable alternative based on results from one large clinical trial. Fluoroquinolones have an important role as substitute agents for those who are intolerant of first-line TB agents.