Browsing by Author "Sirgel, F. A."

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    Early bactericidal activity of ethambutol, pyrazinamide and the fixed combination of isoniazid, rifampicin and pyrazinamide (Rifater) in patients with pulmonary tuberculosis
    (Health & Medical Publishing Group, 1996) Botha, F. J. H.; Sirgel, F. A.; Parkin, D. P.; Van de Wal, B. W.; Donald, P. R.; Mitchison, D. A.
    The early bactericidal activity (EBA) of ethambutol, pyrazinamide and the fixed combination of isoniazid, rifampicin and pyrazinamide (Rifater: Mer National) was evaluated in patients with pulmonary tuberculosis who were sputum-positive on microscopy for acid-fast bacilli. Twenty-eight patients (mean age 33 years and weight 51 kg on average; range 40-59 kg) were studied. The fall in viable counts of Mycobacterium tuberculosis in sputum collections during the 2 days following the start of treatment was estimated from counts of colony-forming units (CFUs) of M. tuberculosis per ml of sputum cultured on selective 7H10 agar medium. The EBA for ethambutol determined in 9 patients was 0.245 ± 0.046, log10 CFU/ml sputum/day, that for pyrazinamide was 0.003 ± 0.014 log10 CFU/ml sputum/day and that for Rifater 0.558 ± 0.054 log10 CFU/ml sputum/day. The results obtained are similar to those reported in a previous study of the first 2 days of treatment, but in smaller numbers of patients, and confirm the moderate EBA of ethambutol while pyrazinamide is again shown to have very little EBA. Rifater has a marked EBA which may be due mainly to the action of isoniazid. This methodology may be valuable in the rapid evaluation of the bactericidal activity of new antituberculosis agents and the comparison of different dose sizes of agents of the same class.
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    'n Oorsig van die bepaling van die vroeë bakterisidiese aktiwiteit van verskeie antituberkilosemiddels
    (AOSIS, 2003) Donald, P. R.; Sirgel, F. A.; Venter, A.; Fourie, P. B.; Parkin, D. P.; Seifart, H. I.; Van de Wal, B. W.; Maritz, J. S.
    The early bactericidal activity (EBA) of an antituberculosis agent is the daily decline in log10 colony forming units of M tuberculosis per ml of sputum during the first two days of treatment with the agent. It reflects the capacity of an agent to kill the actively metabolising organisms in tuberculosis lung cavities. It offers a relatively cheap means to evaluate the antituberculosis activity of an agent in a small group of patients within a matter of months. This article summarizes the authors’ experience in seven published EBA studies and identifies sources of variation in the procedure. The patients who participated in these studies had a mean age of 33 years, a mean weight of 50 kg and there was extensive or massive involvement of the lungs in 55% of patients. The highest EBA values (0,50-0,66) were found in groups of patients receiving isoniazid and the lowest values (0,05 and 0,09 respectively), in patients receiving the aminoglycosides amikacin and paromomycin in a dose of 15 mg/kg body weight. The variation in EBA in 248 patients was 0,0312 and the variation ascribable to the process of sputum production and collection was 0,0233. This implies that the different aspects of sputum production and collection involved in obtaining a representative sputum sample are responsible for most of the variation in EBA results. The selection of patients for inclusion in EBA studies and their ability to co-operate in producing a representative sputum specimen are of critical importance in the successful completion of EBA studies.
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    Rifampicin resistance in Mycobacterium tuberculosis : rapid detection and implications in chemotherapy
    (Health & Medical Publishing Group, 1996-01) Pretorius, G. S.; Sirgel, F. A.; Schaaf, H. Simon; Van Helden, P. D.; Victor, T. C.
    Objectives. Tuberculosis treatment and susceptibility testing are cumbersome, especially in the case of multidrug-resistant (MDR) Mycobacterium tuberculosis. It is known that mutations in the rpoB gene of M. tuberculosis lead to resistance to rifampicin (RMP). In this study an attempt was made to apply molecular techniques for rapid detection of antibiotic resistance in clinical isolates of M. tuberculosis. Design. settings and subjects. RMP-resistant clinical isolates of M. tuberculosis from South Africa (N = 120) with unique resistant patterns were selected for calculation of resistance frequencies, and 74 MDR isolates of M. tuberculosis from different geographical origins were used for microbiological and molecular analysis. The polymerase chain reaction (PCR) technique was applied for amplification of a previously described region around a cluster of mutations in the rpoB gene, and single-stranded conformational polymorphism (SSCP) analysis was optimised to screen for mutations in the amplified region. Results. The results showed that an optimised PCR-SSCP procedure could detect a cluster of mutations in the rpoB gene (for RMP resistance) in 95% of RMP-resistant isolates. This procedure could therefore be used in the prediction of RMP resistance. Evidence was obtained that these mutations can be screened for directly from BACTEC cultures or even directly from Ziehl-Neelsen-positive sputum samples. Statistical analysis also showed that this locus can be used to predict the presence of an MDR isolate, which may have important implications in decisions concerning chemotherapy. Conclusions. It is currently not feasible to test all tuberculosis cases, but application of the PCR-SSCP technology in the prediction of multidrug resistance in M. tuberculosis isolates may be important in patients, especially where frequencies are high for drug-resistant isolates. This methodology could reduce the time required for sensitivity testing from approximately 6-12 weeks to a few days.