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PubMed2000

Modified short-course chemotherapy of pulmonary tuberculosis in Ibadan, Nigeria--a preliminary report.

Over a 3 year period 3rd of April 1995 and 6th of April 1998 a controlled clinical trial of the modified short-course chemotherapy (SSC) in newly diagnosed cases of pulmonary tuberculosis in Nigeria was carried out. Between The SCC used was the one adopted from World Health Organisation/International Union Against Tuberculosis and Lung Diseases for developing countries by the Nigerian National Tuberculosis and Leprosy Control Programme (NTLCP). The regimen used consisted of streptomycin (S), isoniazid (H), Rifampicin (R) and pyrazinamide (Z) in the initial or intensive phase of 2 months. Ethambutol (E) was sometimes substituted for streptomycin. The continuation phase was 6 months of thiacetazone, (T) and isoniazid (H), i.e., 2SHRZ/6TH or 2EHRZ/6TH. Sputum conversion was 90% at the second month of treatment and there was no bacteriological relapse after 18 months of follow-up. Side effects were few and consisted mainly of acne vulgaris which occurred in twenty (20.6%) of 97 patients during the continuation phase. It is concluded that the 8-month chemotherapy regimen adopted by NTLCP is efficacious in treatment of smearpositive pulmonary tuberculosis (PTB).

Adolescent↗
PubMed2001

Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, South Africa.

SETTING: The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it is bactericidal to semi-dormant mycobacteria that are not affected by other drugs. The incidence of resistance to PZA and other drugs used in the treatment of M. tuberculosis is increasing in South Africa. OBJECTIVE: To characterise the pncA gene of M. tuberculosis isolates from Gauteng, South Africa, and to develop a rapid diagnostic method. DESIGN: The pncA gene and the putative regulatory gene were characterised by sequence analysis in a total of six PZA susceptible and 15 resistant isolates. The association with classical PZA susceptibility testing and PZase activity was determined. RESULTS: All PZA-resistant isolates were PZase negative as well as resistant to at least one other anti-tuberculosis drugs. Mutations were identified throughout the length of the pncA gene in 10/15 PZA-resistant isolates. Five lacked PZase activity, but the wild type pncA sequence was present. In all six PZase-positive strains, a PZA-susceptible pattern was obtained on BACTEC and the wild type pncA sequence was present. CONCLUSION: Sequencing is an effective means to identify mutations in the pncA gene in M. tuberculosis and therefore resistance to PZA. The fact that some PZA-resistant M. tuberculosis isolates lack mutations in the pncA gene suggests that alternative mechanisms for drug resistance exist. In PZase negative strains with no genetic changes which are resistant to 100 microg/ml and susceptible to 300 microg/ml, 300 microg/ml may be a more reliable breakpoint.

Africa, Southern↗
PubMedDate not supplied

Pattern of some haematological indices in newly diagnosed pulmonary tuberculosis cases in Iwo, Nigeria: diagnostic and therapeutic implications.

Five hundred (500) newly diagnosed (ND) cases of pulmonary tuberculosis (PTB) were seen between January 1996 and December 1997 at Iwo, Osun State of Nigeria. They were treated with the regimen of 2 months of ethambutol (E), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (2EHRZ) as directly observed treatment (DOT) followed by six months of daily thiacetazone(T) and isoniazid (6HT). The haematological indices PCV, WBC, ESR, platelet count and blood film were done (using standard methods) at diagnosis, and at 1, 2, 3, 5 and 8 months of follow up. The average values were computed and noted. The average PCV rose from 28 to 38% at diagnosis and by the completion of the eight month of chemotherapy. The mean WBC also rose from 3.5 x 10(9)/L to 5.5 x 10(9)/L during the same period. The average ESR for 200 male patients fell progressively from 20 mm/hr to 10 mm/hr while that for 300 female patients fell progressively from 42 mm/hr to 20 mm/hr during the same period. The mean platelet counts did not change significantly from the initial value of 245 x 10(3)/cm throughout the treatment period. The blood film showed that 475 (95%) had normochromic picture while 25 (5%) cases showed anisocytosis, poikilocytosis and polychromasia. The pattern of changes of these parameters during medications have also been observed. Anaemia is not striking at diagnosis of newly diagnosed pulmonary tuberculosis cases in Nigerians and the low grade anaemia of chronic disorder improves without the need for iron or folic acid supplementation. Possible reasons were given.

Adolescent↗
PubMed2001

Tuberculous meningitis: is a 6-month treatment regimen sufficient?

SETTING: The British Thoracic Society and the American Thoracic Society advise 12 months treatment for tuberculous meningitis, with at least isoniazid (H), rifampicin (R) and pyrazinamide (Z). OBJECTIVE: To establish whether a 6-month treatment regimen for tuberculous meningitis is equally as effective as longer treatment. METHOD: Medline search for papers published between 1978 and 1999. INCLUSION CRITERIA: study populations of patients with tuberculous meningitis in whom the diagnosis was confirmed with clinical, cerebrospinal fluid and epidemiological findings; a treatment regimen with at least HRZ and at least 12 months of follow-up after the completion of treatment. OUTCOME MEASURE: the number of relapses. RESULTS: There were four 6-month treatment regimens (G6) and seven longer treatment regimens (G>6); 160/197 (81%) patients completed the 6-month treatment regimens, while 577/675 (85%) completed the longer-term regimens. The clinical stage of patients in the G6 group was poorer than in the G>6 group. Relapse occurred in two out of 131 (1.5%) G6 and in 0 out of 591 G>6 patients. CONCLUSION: Although no studies have compared 6-month treatment regimens with longer treatment, it can be concluded on the basis of this literature review that 6-month treatment is sufficient for tuberculous meningitis with fully susceptible mycobacteria.

Adult↗
PubMed2001

Isonicotinic acid hydrazide induced anagen effluvium and associated lichenoid eruption.

A 32 year-old woman developed generalised lichenoid eruptions on her body followed by diffuse loss of scalp hair of the anagen effluvium type. She was receiving several anti-tubercular drugs, including rifampicin, isonicotinic acid hydrazide (INH), pyrazinamide, and ethambutol, for abdominal tuberculosis. INH, which is a leading cause of drug eruptions in the above group of drugs was withdrawn. However, the other antitubercular drugs were continued along with 40 mg of prednisolone in a single daily morning dose. The latter was discontinued slowly over a period of 10 weeks. There was complete recovery of hair loss and the regrowth started after 12 weeks of alopecia. Such anagen effluvium with lichenoid eruption following INH therapy has not been observed previously. The complete recovery from anagen effluvium is difficult to explain, but it could have been because of the early initiation of corticosteroid.

Adult↗
PubMed1979

Tuberculosis: genitourinary tuberculosis.

Genitourinary tuberculosis should be managed on an outpatient basis, patients being seen once a week. The treatment of choice is a short-course regimen comprising 2 months of either three or fours drugs - streptomycin, rifampicin, isoniazid, and pyrazinamide - followed by isoniazid and rifampicin three times a week for either 2 or 4 months, depending on the severity of the lesion. Patients should be followed-up, normally for one year, and be told to report to their doctors if they have any recurrence of urinary symptoms. However, if they have renal calcification they should be followed-up as for any other case of calcification and seen annually for at least 10 years. Surgery still has an important part to play in the present management. Radical surgery, nearly always nephrectomy or epididymectomy, should be carried out when there are destructive lesions. Reconstructive surgery, mainly the the repair of strictures at the lower end of the ureter and bladder augmentation for a small fibrotic bladder, is frequently required. Both radical and reconstructive surgery should be carried out in the first 2 months of intensive chemotherapy. There is no reason now why all patients should not be able to return to a normal efficient life - free from all association with the disease - not later than 4 months after the start of treatment.

Cystoscopy↗
PubMed2002

Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Final report at 5 years: prognostic value of various measures.

SETTING: Clinical trial in 672 patients with newly diagnosed pulmonary tuberculosis in Hong Kong. After an initial 2 months of a four-drug intensive phase consisting of thrice-weekly streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ), a random allocation was made to a continuation phase of once-weekly 600 mg rifapentine + 15 mg/kg isoniazid (HRp1), HRp1 given in 2 of every 3 weeks (HRp1.2/3), or to thrice-weekly isoniazid + rifampicin (HR3), the standard treatment in Hong Kong. OBJECTIVE: Final report evaluating adverse events (46 relapses and one failure) after 5 years and the prognostic influence of various factors. METHODS: Kaplan-Meier analysis of adverse events and Cox proportional hazards analysis of prognostic factors. RESULTS: The two rifapentine regimens, HRp1 and HRp1.2/3 had similar final rates of adverse events of 10.8% and 11.7%, respectively, compared to 4.2% for the HR3 regimen (P = 0.02 and 0.009, respectively). In the initial univariate proportional hazards analysis, adverse events were significantly related to the regimen, age, sex, pretreatment radiographic extent of disease and cavitation, and also to sputum culture at 2 months. In the final multivariate analysis, after step-wise removal of non-significant factors, adverse events were related only to the regimen, patients' sex and pretreatment radiographic extent of disease. Elderly male patients were more at risk of an adverse event, as were those with more severe disease. Adverse events occurred at life table rates of 9.0% in patients with drug-sensitive strains and in 8.9% of those with initially isoniazid-resistant organisms at 5 years. CONCLUSIONS: The two rifapentine regimens were unsatisfactory because of their high incidence of adverse events. Isoniazid appeared not to contribute to preventing relapse. Further studies with increased rifapentine dosage are necessary.

Adolescent↗
PubMed2002

Chemotherapeutic treatment for spinal tuberculosis.

AIM: To evaluate whether 6 months of chemotherapy for patients with spinal tuberculosis prevents relapse as effectively as more than 6 months of chemotherapy. METHOD: Literature review. Medline search including references, from January 1978 to November 2000. Inclusion criteria for publications: diagnosis of spinal tuberculosis confirmed bacteriologically and/or histologically, or probable on the basis of clinical and radiological parameters; treatment regimen (whether or not in combination with surgery) included isoniazid (H), rifampicin (R) and pyrazinamide (Z); follow-up period after completion of treatment of 12 months or more. EXCLUSION CRITERIA: patients with relapse who had previously been treated adequately for tuberculosis. OUTCOME PARAMETERS: Relapse rate. RESULTS: Four publications were found with HRZ regimens of 6 months' duration and 10 publications with HRZ regimens of >6 months' duration. A number of patients had received HRE (E = ethambutol) for > or = 9 months. In the results, no distinction was made between treatment groups. HRZ for 6 months led to a relapse rate of 0% (0/56, 95%CI 0.0-6.4); follow-up after surgical intervention ranged from 6 to 108 months. HRZ for > or = 9 months (> or = 119 patients) or HRE for > or = 9 months (< or = 71 patients) led to a relapse rate of 2% (4/218, 95%CI 0.6-5.0); follow-up after surgical intervention was 6-168 months. Despite the small number of studies, 6 months of therapy is probably sufficient for patients with spinal tuberculosis.

Adult↗
PubMed2002

[Latent tuberculosis infection: diagnosis and treatment].

The essential component of tuberculosis elimination strategy is to identify and treat persons with latent tuberculosis infection (LTBI) who are at high risk for developing active tuberculosis. The tuberculin skin test is the only proven method for identifying LTBI. Although the specificity and the sensitivity are decreased by cross reaction with BCG vaccination and by non tuberculous mycobacteria, there is no better diagnostic tool. The test's positive predictive value is poor in populations with low risk for tuberculosis. Identification of persons with LTBI is focused on groups at high risk who would benefit from therapy (targeted tuberculin testing). The interpretation of the tuberculin skin test reaction is dependent on the risk factors and the immune status of the patient. For the past 30 years, Isoniazid has been the drug of choice for treating patients with LTBI, but its application has been limited by poor compliance and toxicity. Therefore, there has been interest in the development of shorter course treatments such as rifampin (4 months) or rifampin and pyrazinamide (2 months). We describe the new guidelines for targeted tuberculin testing and different treatment regimens for LTBI as recommend by the American Thoracic Society.

Antitubercular Agents↗
PubMed1975

The pharmacology of hypouricemic effect of benzbromarone.

The hypouricemic effect of benzbromarone has been investigated in six subjects. Benzbromarone increased urate: creatinine by 371 per cent over control values at two to four hours after administration. Over a 24 hour period, the mean serum uric acid decreased from a control value of 7.8 +/- 0.8 to 4.3 +/- 0.6 mg/dl. This uricosuric effect was completely reversed by pyrazinamide, partially inhibited by acetylsalicyclic acid and sulfinpyrazone, and was not accompanied by an elevation of the creatinine clearance or an inhibition of urate binding to plasma protein. In vitro studies showed only 22 per cent inhibition of urate binding by benzbromarone five muM, a concentration which is transiently reached in man. Kinetic studies of human liver xanthine oxidase demonstrated non-competitive inhibition with variable hypoxanthine and a Ki slope of 8.5 muM. The Ki slopes for benzarone and allopurinol were 19.0 muM and 0.05 muM respectively. There was no elevation of the urinary oxypurines following benzbromarone ingestion. These observations suggest that only the renal tubular activity of benzbromarone is relevant to its hypouricemic effects in man. (J Rheumatol 2: 437-445, 1975).

Adult↗
PubMed2002

Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore.

SETTING: The Singapore Tuberculosis (TB) Control Unit, a high volume national referral centre. OBJECTIVES: To determine the incidence, clinical course and outcome of TB drug-induced hepatitis (DH) and the risk factors associated with DH under general programme conditions. DESIGN: A retrospective review of adult patients started on TB treatment in 1998. RESULTS: There were 55 cases of DH in the cohort of 1036 patients treated in 1998. The median time to diagnosis of DH was 38 days. Factors significantly associated with DH were abnormal baseline transaminases/ bilirubin (OR 2.1, 95%CI 1.1-4.3, P = 0.02), age >60 years (OR 1.97, 95%CI 1.14-3.34, P = 0.01) and female sex (OR 1.9, 95%CI 1.07-3.4, P = 0.02). Ethnicity, self-reported alcohol consumption and body weight were not associated with development of DH. All three patients with fatal DH had received pyrazinamide-containing regimens. Treatment was re-introduced in 48 patients and successfully completed in 45 patients. The median time to reinstitution of TB treatment was 23 days. CONCLUSION: The incidence of TB drug-induced hepatitis was 5.3%. Age >60 years, abnormal baseline transaminase/bilirubin levels and female sex were risk factors associated with the development of TB drug-induced hepatitis.

Alanine Transaminase↗
PubMed2002

[A case of tuberculosis pleuritis developing contralateral pleural effusion during anti-tuberculosis chemotherapy, falling into chronic respiratory failure].

The patient was a 74 year-old male presenting right pleural effusion with mild fever. His temperature was 37.0 degrees C. Culture of a pleural biopsy specimen revealed Mycobacterium tuberculosis, although culture of sputum and pleural effusion were negative. Therapy was begun with 300 mg of isoniazid (INH) per day, 600 mg of rifampicin (RFP) per day, and 1200 mg of pyrazinamide (PZA) per day. His temperature improved temporarily. One week after beginning of the therapy he had a fever over 38.0 degrees C. On the 17th day after starting chemotherapy, a chest radiological examination showed left pleural effusion in which numerous lymphocytes were found but Mycobacterium tuberculosis was negative. We assumed that the left pleural effusion was due to a paradoxical reaction to the anti-tuberculosis chemotherapy. After 3 days' discontinuation, the same regimen was resumed with an addition of prednisolone, but bilateral pleural effusion remained and the case finally fell into chronic respiratory failure.

Aged↗
PubMed2002

[Chemotherapy with isoniazid and rifampicin for pulmonary tuberculosis].

Two-drug regimen of chemotherapy with isoniazid and rifampicin for pulmonary tuberculosis is the one of the standard methods of treatment for active pulmonary tuberculosis in Japan since 1996, while ATS/CDC and WHO/IUATLD recommended the three-drug or four-drug regimen containing chemotherapy pyrazinamide unless the prevalence of drug resistance, among new tuberculosis cases is low. We sent a questioners of 141 tuberculosis centers in Japan to investigate the rate of each standard chemotherapy regimen employed and reasons for selecting the two-drug regimen in each center. Of 3840 newly diagnosed cases in the 57 centers, 47.4% were treated with the four-drug regimen and 37.1% with the three-drug regimen, and two-drug regimen was employed in only 2.6%. Sputum smear-negative status was the major reason for selecting the two-drug regimen of chemotherapy. Though the two-drug regimen was used in few cases, taking into account the prevalence of primary resistance to isoniazid in Japan in 1997 was 4.4%, it was concluded to discontinue recommending the two-drug regimen as one of standard methods of treatment for pulmonary tuberculosis.

Antitubercular Agents↗
PubMed2002

[Effect of levofloxacine on cell elements of the lung tissue and on the growth of drug resistant Mycobacteria tuberculosis].

Levofloxacin effect on morphokinetic parameters of the murine lung tissue culture was investigated. This model allowed also to evaluate the levofloxacin activity against drug-resistant intracellular and extracellular Mycobacterium tuberculosis: MBC was 0.5-1.0 mg/l. Bactericidal effect started on the 3d day of incubation and was maximal on 7th day. Tissue cells vitality was not changed. Combination of levofloxacin with antimycobacterial drugs of first choice was investigated: isoniazid demonstrated synergistic effect, pyrazinamide also demonstrated synergistic effect. Combination of levofloxacin with rifampicin was antagonistic.

Animals↗
PubMed2002

[Myrin P in the combined treatment of tuberculosis].

Experimental and clinical evaluation of the new antimycobacterial quadrocomposition Myrin P was performed. The composition consists of isoniazid, rifampicin, pyrazinamide and ethambutol in fixed doses. The results of the formulation application at 474 patients with primary pulmonary tuberculosis caused by drug-susceptible and drug-resistant mycobacteria are presented. High efficacy and good tolerability of the formulation was demonstrated.

Adolescent↗
PubMed2003

[Tuberculous peripheral multifocal choroiditis].

CASE REPORT: A healthy 57 year-old woman with past untreated pulmonary tuberculosis, disclosed a bilateral uveitic syndrome characte rized by iritis, vitreitis, multiple peripheral retinal punched-out lesions, and cystoid macular edema. Systemic evaluation was unremarkable except for a 30 mm tuberculin skin test. Relapses occurred after oral and periocular corticosteroids were interrupted, but the inflammation completely disappeared after a 6 month course of isoniazid, rifampicin and pyrazinamide. DISCUSSION: Intraocular tuberculosis should be considered as a treatable cause of peripheral multifocal choroiditis, after ruling out other etiologies.

Adrenal Cortex Hormones↗
PubMed2003

The clearance of theophylline is increased during the initial period of tuberculosis treatment.

OBJECTIVE: To evaluate the effects of combined anti-tuberculosis treatment including isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA), on the pharmacokinetics of theophylline during the initial phase of treatment. DESIGN: Prospective, controlled clinical study. PATIENTS AND METHODS: Twenty patients with pulmonary tuberculosis received 7.35 mg/kg/day of aminophylline intravenously combined with anti-tuberculosis agents. The first theophylline serum concentration was measured before administration of INH, RMP, EMB and PZA, and samples were obtained once daily for 6 consecutive days after initiation of treatment. All patients in this study were non-smokers with normal hepatic and renal function, and they were not given any other drugs that could affect the clearance of theophylline. RESULTS: The concentration and half-life of theophylline was decreased and its clearance was increased significantly at days 5-7 after administration of antituberculosis agents compared to before the therapy was started. CONCLUSIONS: These results suggest that patients with asthma or chronic obstructive pulmonary disease administered combinations of anti-tuberculosis agents and theophylline during the initial phase of tuberculosis treatment should be monitored closely for changes in theophylline concentration, and that the dose of theophylline should be adjusted accordingly.

Adult↗
PubMed1992

Fixed dose combination short course chemotherapy in the treatment of pulmonary tuberculosis.

In this study two highly effective chemotherapeutic regimens of 6 and 8 months duration were studied and compared with the standard 12 month therapy under full supervision at the National TB Centre and St. Peter's TB Hospital in Addis Abeba. Patients with direct smear positive pulmonary tuberculosis were admitted to hospital during the initial phase of treatment for two months. At two months, sputum conversion rates, by direct smear and culture respectively, were 82% and 80% on Rifater, and 86 or 88% and 86% on the regimens containing separate preparations of isoniazid rifampicin and pyrazinamide, compared to 60% and 30% on the standard regimen. It was concluded that short course regimens of six or eight months with drugs either in combined form or separate preparations are more effective than the standard regimen.

Adolescent↗