1 Centre for Medical Microbiology, Hampstead Campus, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK; 2 Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania; 3 Kilimanjaro Christian Medical Centre, PO Box 3010, Moshi, Tanzania
Received 24 June 2005; returned 4 September 2005; revised 7 September 2005; accepted 22 September 2005
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Abstract |
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Patients and methods: We measured the decline in the sputum viable count of 13 patients who were given a combination of moxifloxacin 400 mg daily and isoniazid 300 mg daily.
Results: The time required to reduce the viable count by 50% (vt50) was 0.38 days (95% CI 0.030.78 days, SEM 0.13) and the mean early bactericidal activity (EBA) was 0.60 log10 cfu/day (95% CI 0.230.97, SEM 0.14). This compares with the vt50 calculated for isoniazid and moxifloxacin alone in the same population of 0.48 and 0.88 days, respectively. The EBA values for isoniazid and moxifloxacin alone were 0.77 and 0.53 log10 cfu/day, respectively.
Conclusions: The combination of moxifloxacin and isoniazid is not antagonistic, but the combination does not significantly enhance bactericidal activity above that of isoniazid alone.
Keywords: Mycobacterium tuberculosis , clinical trials , drug effects , quinolones
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Introduction |
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Patients and methods |
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Our study was approved by the ethical committee of Kilimanjaro Christian Medical College, the National Institute of Medical Research and the National Aids Control Programme of Tanzania, and each patient gave witnessed oral consent.
Patients and treatment
Patients were recruited from those presenting to the Kibong'oto National Tuberculosis Hospital, Sanya Juu, Tanzania with sputum smear-positive pulmonary tuberculosis. Inclusion criteria for the study were (i) presence of acid fast organisms found in a ZiehlNeelsen stained smear of sputum, (ii) mild to moderate disease on clinical grounds, (iii) age over 18 years, (iv) no prior chemotherapy, (v) production of an adequate volume of sputum, (vi) weight between 40 and 60 kg and (vii) consent to HIV serology. Patients were excluded from the study if they had severe, rapidly progressive disease or had any serious concomitant condition, renal or hepatic failure, as judged by the admitting physician or if there was a history of hypersensitivity to the trial agents. A total of 13 patients received the 400 mg moxifloxacin and 300 mg isoniazid combination daily for 5 days.
Bacteriology and data analysis
Sputum was collected over 16 h and serial colony counts by culture on 7H11 Middlebrook agar made selective by the addition of polymyxin B sulphate (200 units/mL), carbenicillin (100 mg/L), trimethoprim lactate (20 mg/L) and amphotericin B (10 mg/L) using Selectatabs (Mast, UK) were performed as described previously.6 The results of sputum viable count were recorded and the time taken to reduce the viable count by 50% (vt50) and the 48 h early bactericidal activity (EBA) were calculated using methods published previously.8,9 Additional data from Jindani et al.9 for other combinations was recalculated by the vt50 method for comparison as described previously.810
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Results |
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Discussion |
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It has been suggested that moxifloxacin might antagonize the effect of isoniazid.3 Our data demonstrates that at worst this combination makes no difference to the activity of isoniazid and there is a suggestion that it may augment it. Our study did not demonstrate a significant difference between isoniazid, moxifloxacin or the combination as the numbers were too small; the same inability of other drug combinations to enhance the bactericidal activity of isoniazid alone has been shown by other groups.9,11 Further studies with larger numbers of patients concentrating on finding the most potent combination of antituberculous drugs and moxifloxacin are required. These should initially focus on the first 2 months of therapy as this agent has been shown to be safe in extended therapy in patients with tuberculosis.12
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Transparency declarations |
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Acknowledgements |
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References |
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