scholarly journals Early bactericidal activity of a moxifloxacin and isoniazid combination in smear-positive pulmonary tuberculosis

2005 ◽  
Vol 56 (6) ◽  
pp. 1169-1171 ◽  
Author(s):  
Stephen H. Gillespie ◽  
Roly D. Gosling ◽  
Leonard Uiso ◽  
Noel E. Sam ◽  
Esther G. Kanduma ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Smear Positive Pulmonary Tuberculosis

scholarly journals Early Bactericidal Activity and Pharmacokinetics of the Diarylquinoline TMC207 in Treatment of Pulmonary Tuberculosis

2008 ◽  
Vol 52 (8) ◽  
pp. 2831-2835 ◽  
Author(s):  
R. Rustomjee ◽  
A. H. Diacon ◽  
J. Allen ◽  
A. Venter ◽  
C. Reddy ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Dose Range ◽  
Study Drug ◽  
First Line ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Smear Positive Pulmonary Tuberculosis

ABSTRACT Tibotec Medicinal Compound 207 (TMC207) is a novel diarylquinoline with a unique mode of action that targets mycobacterial ATP synthase. TMC207 exhibits high in vitro activity against mycobacterial strains either susceptible or resistant to all first-line and many second-line drugs, including fluoroquinolones, and has shown exceptional in vivo activity against several mycobacterial species in different animal models. In this early bactericidal activity study, 75 treatment-naïve patients with smear-positive pulmonary tuberculosis were randomized to once-daily oral TMC207 (25 mg, 100 mg, or 400 mg), 600 mg rifampin (RIF), or 300 mg isoniazid (INH) for 7 days. Sixteen-hour overnight sputum collected at baseline and on each treatment day was plated in serial dilutions on selective agar plates. The bactericidal activity was expressed as the log10 decrease in CFU/ml sputum/day. Pharmacokinetic sampling was performed on day 7 of TMC207 administration up to 24 h postdose. The decreases in log10 CFU counts (± standard deviation) from baseline to day 7 were 0.04 ± 0.46 for 25 mg TMC207 (n = 14), 0.26 ± 0.64 for 100 mg TMC207 (n = 14), 0.77 ± 0.58 for 400 mg TMC207 (n = 14), 1.88 ± 0.74 for INH (n = 11), and 1.70 ± 0.71 for RIF (n = 14). Significant bactericidal activity of 400 mg TMC207 was observed from day 4 onward and was similar in magnitude to those of INH and RIF over the same period. The pharmacokinetics of TMC207 were linear across the dose range. In summary, TMC207 demonstrated bactericidal activity with a delayed onset and was well tolerated, and no study drug-related serious adverse events occurred.

scholarly journals Randomized Dose-Ranging Study of the 14-Day Early Bactericidal Activity of Bedaquiline (TMC207) in Patients with Sputum Microscopy Smear-Positive Pulmonary Tuberculosis

2013 ◽  
Vol 57 (5) ◽  
pp. 2199-2203 ◽  
Author(s):  
Andreas H. Diacon ◽  
Rodney Dawson ◽  
Florian Von Groote-Bidlingmaier ◽  
Gregory Symons ◽  
Amour Venter ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Linear Trend ◽  
Sputum Smear ◽  
Sputum Microscopy ◽  
Blinded Study ◽  
Smear Positive Pulmonary Tuberculosis ◽  
Dose Ranging ◽  
Safety Considerations ◽  
Double Blinded

ABSTRACTBedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P= 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P= 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies.

scholarly journals Early Bactericidal Activity of Paromomycin (Aminosidine) in Patients with Smear-Positive Pulmonary Tuberculosis

2000 ◽  
Vol 44 (12) ◽  
pp. 3285-3287 ◽  
Author(s):  
P. R. Donald ◽  
F. A. Sirgel ◽  
T. P. Kanyok ◽  
L. H. Danziger ◽  
A. Venter ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Dose Group ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Confidence Limits ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Smear Positive Pulmonary Tuberculosis ◽  
The Difference

ABSTRACT The early bactericidal activity of the aminoglycoside paromomycin (aminosidine) in doses of 7.5 and 15 mg/kg of body weight was measured in 22 patients with previously untreated smear-positive pulmonary tuberculosis. The fall in log10 CFU per milliliter of sputum per day during the first 2 days of treatment for 7 patients receiving a paromomycin dosage of 7.5 mg/kg/day was 0.066, with a standard deviation (SD) of 0.216 and confidence limits from −0.134 to 0.266, and that for 15 patients receiving 15 mg/kg/day was 0.0924, with an SD of 0.140 and confidence limits from 0.015 to 0.170. The difference between the mean and zero was not significant for the 7.5-mg/kg dose group but was significant for the 15-mg/kg dose group (t = 2.55, P = 0.023). Since paromomycin has no cross-resistance with streptomycin and has no greater toxicity than other aminoglycosides, these results suggest that it has the potential to substitute for streptomycin in antituberculosis regimens and may be a particularly valuable addition to the drug armamentarium for the management of multidrug-resistant tuberculosis.

Cost-effectiveness of chemotherapy for sputum smear-positive pulmonary tuberculosis in Malawi, Mozambique and Tanzania

1994 ◽  
Vol 9 (2) ◽  
pp. 151-181 ◽  
Author(s):  
Eric De Jonghe ◽  
Christopher J. L. Murray ◽  
H. J. Chum ◽  
D. S. Nyangulu ◽  
A. Salomao ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Pulmonary Tuberculosis ◽  
Sputum Smear ◽  
Smear Positive Pulmonary Tuberculosis

scholarly journals A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis

Thorax ◽  
2010 ◽  
Vol 65 (10) ◽  
pp. 863-869 ◽  
Author(s):  
A. P. Ralph ◽  
M. Ardian ◽  
A. Wiguna ◽  
G. P. Maguire ◽  
N. G. Becker ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
X Ray ◽  
Smear Positive Pulmonary Tuberculosis ◽  
Chest X Ray
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