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Published ahead of print on August 13, 2003, doi:10.1164/rccm.200305-682OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 11, December 2003, 1342-1345

A more recent version of this article appeared on December 1, 2003
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Submitted on June 25, 2003
Accepted on August 11, 2003

The bactericidal activity of moxifloxacin in patients with pulmonary tuberculosis

Stephen H Gillespie1*, Roly D Gosling1, Leonard O Uiso2, Noel E Sam3, Emily Bongard1, Esther G Kanduma4, Mramba Nyindo3, and Richard W Morris5

1 Medical Microbiology, University College London Medical Schools, London, United Kingdom, 2 Kibong'oto National Tuberculosis and Leprosy Hospital, Sanya Juu, Tanzania, United Republic of, 3 Clinical Laboratory, Kilimanjaro Christian Medical College, Moshi, Tanzania, United Republic of, 4 Clinical Laboratory, Kilimanjaro Christian Medical College, Moshi, Tanzania, United Republic of; Medical Microbiology, University College London Medical Schools, London, United Kingdom, 5 Primary Care and Population Sciences, University College London Medical Schools, London, United Kingdom

* To whom correspondence should be addressed. E-mail: stepheng{at}rfc.ucl.ac.uk.

Patients with newly diagnosed AFB smear-positive pulmonary tuberculosis were randomised to receive 400mg moxifloxacin, 300mg isonaizid, or 600mg rifampin daily for 5 days. Sixteen hour overnight sputa collections were made for the 2 days before and for five days of monotherapy. Bactericidal activity was estimated by the time taken to kill 50% of viable bacilli (vt50) and the fall in sputum viable count during the first 2 days designated as the Early Bactericidal Activity (EBA). The mean vt50 of moxifloxacin, was 0.88 days (95% CI 0.43- 1.33 days) and the mean EBA 0.53 (95% CI 0.28- 0.79). For the isoniazid group the mean vt50 was 0.46 days (95% CI 0.31- 0.61 days) and mean EBA was 0.77 (95% CI 0.54- 1.00). For rifampin the mean vt50 was 0.71 days (95% CI 0.48 - 0.95 days ) and mean EBA was 0.28 (95% CI 0.15-0.41). Using the EBA method isoniazid was significantly more active than rifampin (p<0.01) but not moxifloxacin. Using the vt50 method isonizid was more active than both rifampin and moxifloxacin (p=0.03). Moxifloxacin has an activity similar to rifampin in human subjects with pulmonary tuberculosis suggesting that it should undergo further assessment as part of a short course regimen for the treatment of drug susceptible tuberculosis.
Key words: Clinical trials, Africa, tuberculosis, quinolone




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