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PubMedDate not supplied

Simplified diagnostic susceptibility testing of mycobacteria against thiacetazone, hydroxylamine, p-nitrobenzoic acid and picric acid.

In order to simplify diagnostic susceptibility testing of mycobacteria against thiacetazone, hydroxylamine, p-nitrobenzoic acid and picric acid, we modified the standard procedure by using Middlebrook 7H11 agar in a single quadrant petri dish. This plate can be inoculated and read in parallel with routine susceptibility tests done by the proportion method. We present results of 449 consecutive routine strains tested with our method.

Bacteriological Techniques↗

PubMed1996

Cost-effectiveness and total costs of three alternative strategies for the prevention and management of severe skin reactions attributable to thiacetazone in the treatment of Human Immunodeficiency Virus positive patients with tuberculosis in Kenya.

SETTING: Severe skin reactions due to thiacetazone (T) in Human Immunodeficiency Virus (HIV) positive tuberculosis patients have been reported in several publications, one of them from Kenya. However, the abandoning of T may not be feasible in Kenya as this may increase the cost of drugs by about three-fold per regimen. OBJECTIVE: To compare the cost-effectiveness and total cost of three strategies in which T is replaced with ethambutol (E). DESIGN: Three strategies are compared with a baseline strategy in which T is not replaced. The indicator for cost-effectiveness is the cost-per-averted-death attributable to T. RESULTS: Education of patients on the possibility of side-effects and replacement of T with E is the most cost-effective strategy at HIV prevalence rates of 1-90%. Abandonment of T and replacement with E is the most cost-effective at over 90% HIV prevalence. CONCLUSION: In Kenya, education of patients on the possibility of skin reactions should be preferred at low range HIV prevalence rates. Routine HIV testing would be the most attractive strategy in the middle range, and total replacement of T with E is to be preferred in the higher range of HIV prevalence.

AIDS Serodiagnosis↗

PubMed2006

Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3.

Thiacetazone (TAZ) and ethionamide (ETA) are, respectively, thiourea- and thioamide-containing second line antitubercular prodrugs for which there is an extensive clinical history of cross-resistance in Mycobacterium tuberculosis. EtaA, a recently identified flavin-containing monooxygenase (FMO), is responsible for the oxidative activation of ETA in M. tuberculosis. We report here that EtaA also oxidizes TAZ and identify a sulfinic acid and a carbodiimide as the isolable metabolites. Both of these metabolites are derived from an initial sulfenic acid intermediate. Oxidation of TAZ by EtaA at basic pH favors formation of the carbodiimide, whereas neutral or acidic conditions favor formation of the sulfinic acid. The same metabolites are formed from TAZ by human FMO1 and FMO3. The sulfenic acid and carbodiimide metabolites, but not the sulfinic acid product, readily react with glutathione, the first to regenerate the parent drug and the second to give a glutathione adduct. These reactions may contribute to the antitubercular activity and/or toxicity of TAZ.

Antitubercular Agents↗

PubMed1989

[Initial resistance to streptomycin, isoniazid, thiacetazone, rifampicin and ethambutol in bacilliferous tuberculosis in Maniema, Zaire].

Initial resistance to streptomycin, isoniazid, thiacetazone, rifampicin and ethambutol was tested in 102 patients with bacilliferous tuberculosis in Kalima, a rural area in eastern Zaïre. The initial resistance for at least one of these tuberculostatics was 43%. The highest resistance recorded was for streptomycin (31%). No resistance to rifampicin or ethambutol was found. The practical interest of these findings is discussed.

Antitubercular Agents↗

PubMedDate not supplied

Pharmacokinetic evaluation of thiacetazone.

STUDY OBJECTIVE: To investigate the steady-state pharmacokinetics of thiacetazone (TB-1), which is active in vitro against Mycobacterium avium complex (MAC). DESIGN: Open-label phase I study. SETTING: Specialized referral hospital. PATIENTS: Twelve healthy men and women. INTERVENTIONS: Oral TB-1 150 mg/day was administered for 7 days, followed by blood and urine collection over 48 hours. MEASUREMENTS AND MAIN RESULTS: The serum concentration versus time curves of TB-1 showed sustained concentrations, with maximum values of 1.59 +/- 0.47 micrograms/ml, time to maximum 3.30 +/- 1.18 hours, and serum half-life of 15-16 hours. Less than 25% of TB-1 was recovered unchanged in the urine over 48 hours. Rashes occurred in two subjects at the end of the 7-day dosing period and resolved without progression or sequelae. CONCLUSIONS: Based on these data, we initiated a phase II study of TB-I in patients with pulmonary MAC infection who do not have the acquired immunodeficiency syndrome.

Adult↗

PubMed1997

HIV seroprevalence rate and incidence of adverse skin reactions in adults with pulmonary tuberculosis receiving thiacetazone free anti-tuberculosis treatment in Yaounde, Cameroon.

To determine the HIV seroprevalence in adult patients with pulmonary tuberculosis in Yaounde and to compare the incidence of adverse skin reactions in patients with and without HIV infection receiving thiacetazone-free antituberculosis treatment, we studied 235 consecutive patients aged 15 years or more admitted into the Chest Clinic of Hospital Jamot in Yaounde with a diagnosis of pulmonary tuberculosis from July 1 to December 31, 1994. HIV testing was done using two ELISAs and confirmed by Western blot. Each patient was monitored for adverse skin reactions to antituberculosis treatment during the two month initial phase of therapy in hospital. Of the 235 patients studied, 156 (66%) were males (mean age: 33 years) and 79 were females (mean age: 30.3 years). Overall, 16.6% (39 cases) of the 235 patients were HIV seropositive. The prevalence of HIV infection was significantly higher in women (24%) than in men (12.5%) (p = 0.02). Adverse skin reactions to antituberculosis treatment were observed in eleven (4.7%) of the 235 patients. The incidence of the reactions was significantly higher in HIV seropositive (23.1%) than in HIV seronegative patients (1.0%) (p < 10 - 7). Two HIV seropositive patients who developed Stevens-Johnson syndrome died. The drugs incriminated for adverse skin reactions in the nine patients who survived were pyrazinamide (four cases) and rifampicin (five cases).

Adolescent↗

PubMed1998

Current HIV seroprevalence rate and incidence of adverse skin reactions in adults with pulmonary tuberculosis receiving thiacetazone-free antituberculosis treatment in Yaounde, Cameroon.

OBJECTIVES: To determine the current HIV seroprevalence in adult patients with pulmonary tuberculosis in Yaounde and to compare the incidence of adverse skin reactions in these patients with and without HIV infection receiving thiacetazone-free antituberculosis treatment. DESIGN: Case series. SETTING: Chest clinic of Hospital Jamot in Yaounde, Cameroon. SUBJECTS: 235 consecutive patients aged > or = 15 years with a diagnosis of pulmonary tuberculosis from July 1 to December 31, 1994. MAIN OUTCOME MEASURES: HIV seroprevalence and incidence of adverse skin reactions to antituberculosis treatment. RESULTS: Of the 235 patients studied, 156 (66%) were male (mean age: 33 range 17 to 84 years) and 79 were female (mean age: 30.3, range 16 to 64 years). Overall 16.6% (39 cases) of the 235 patients were HIV seropositive. The prevalence of HIV infection was significantly higher in women (24%) than in men (12.5%) (p = 0.045). Adverse skin reactions to antituberculosis treatment were observed in 11 (4.7%) of the 235 patients. The incidence of the reactions was significantly higher in HIV seropositive (23.1%) than HIV seronegative patients (1.0%) (p < 0.001). Two HIV seropositive patients who developed Steven-Jonson syndrome died. The drugs incriminated for adverse skin reactions in the nine patients who survived were pyrazinamide (four cases) and rifampicin (five cases). CONCLUSION: HIV infected patients on antituberculosis drug should be monitored for adverse skin reactions which are sometimes fatal.

AIDS-Related Opportunistic Infections↗

PubMed1963