A new anti-TB drug called moxifloxacin proved just as effective as ethambutol as part of a four-drug induction regimen for TB treatment, the Tuberculosis Trials Consortium reported on Friday at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington DC.
Moxifloxacin is of particular interest in the treatment of TB in HIV-positive people because it has no interactions with antiretrovirals and may be potent enough to shorten the duration of TB treatment, which currently stands at a minimum of six months.
The drug is an antibiotic already licensed in over 100 countries with a well-understood side-effect profile.
The TB Trials Consortium enrolled patients in North America and Africa to compare the efficacy of moxiflaxacin and ethambutol, and presented a preliminary efficacy analysis as a late breaker at this year’s ICAAC meeting.
The analysis reported on efficacy during the first two months of treatment, when current guidelines recommend that patients with a smear-positive diagnosis should receive a combination of four drugs (rifampicin, isoniazid, pyrazinamide and ethambutol). This randomised, double blind study compared moxifloxacin with ethmabutol as the fourth component of this regimen, and patients in each arm were also randomised to receive isoniazid and either ethambutol or moxifloxacin either five days or three days a week after two weeks of initial, daily therapy.
All participants had smear-positive pulmonary TB and 75% had cavitation of the lung on x-ray. Twenty-two per cent were HIV-positive. 43% were also receiving TB treatment prior to enrolment.
The study recruited 336 patients in North America and Africa (59%). 277 were available for the efficacy analysis.
A variety of parameters of efficacy were assessed:
- Sputum culture conversion to negative at two months: rates were almost identical (70% moxifloxacin vs 69% ethambutol). Rates were also similar between HIV-positive and HIV-negative patients (71% vs 70%).
- African patients were significantly less likely to be culture-negative at 2 months (63% vs 85%, p<0.0001).
- Patients already exposed to part of a course of TB treatment were significantly more likely to be culture-negative at month 2 (79% vs 65%, p=0.01).
- Median time to sputum culture conversion: moxifloxacin achieved significantly faster conversion (median 43 days vs 56 days ethambutol, p=0.03).
- Dosing frequency and efficacy: dosing frequency did not affect 2-month culture conversion or time to culture conversion.
- Adverse events: moxifloxacin-treated patients were significantly more likely to report nausea than ethambutol-treated patients.
Burman WJ et al. Moxifloxacin vs ethambutol in multidrug treatment of pulmonary tuberculosis – final results of a randomized double-blind trial. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, abstract LB-31, 2005.