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PubMed1986

[Results of a therapeutic trial comparing a 6-month regimen to a 12-month regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara. Final report: results 3 years after the onset of treatment].

This study has compared a daily 6-month short-course chemotherapy regimen and a daily 12-month standard duration regimen in the treatment of smear positive pulmonary tuberculosis in a rural area of Algeria where the population contains a relatively high proportion of nomads. The 6-month regimen (6M) was isoniazid and rifampicin throughout with ethambutol and pyrazinamide in addition for the first 2 months, and the 12-month regimen (12M) was isoniazid and ethambutol supplemented by streptomycin during the first month. All the 601 patients admitted had one or more sputum smears positive on examination in the local laboratory and 70% had a positive culture in the reference laboratory in Algiers. Most patients were admitted to hospital initially for one or two months where chemotherapy was fully supervised and subsequently it was self-administered. In both nomads and settled residents known to have fully sensitive strains of tubercle bacilli pretreatment the 6-month regimen was highly effective with no failures during chemotherapy and only 3% relapses after stopping chemotherapy in 126 patients compared with a combined failure rate during chemotherapy and relapse rate of 21% in the 152 patients receiving the 12-month regimen (P less than 0.001). The results in patients with isoniazid-resistant strains pretreatment were also significantly better for the 6-month than for the 12-month regimen, one of 15 and 8 of 17 patients respectively being classified as failures or relapses (P = 0.03). To assess the results which might be achieved by these regimens under programme conditions the outcome at 3 years was also assessed in all patients admitted to the study irrespective of whether the disease was confirmed in the reference laboratory or at independent assessment and whether or not the allocated chemotherapy was modified or further courses of chemotherapy were given. At 3 years, 82% of the 6M and 80% of the 299 12M patients had achieved a favourable status and only one 6M patient and 4 12M patients were still known to have active disease with a positive culture. A further 23 6M and 22 12M patients were known to have died, 11 in each series probably or definitely from tuberculosis. The remaining 28 6M and 34 12M patients were lost from follow-up, but 24 and 22 respectively had completed their allocated chemotherapy before defaulting. It was estimated that, overall, 272 (94%) of the 6M and 263 (91%) of the 12M patients had a favourable status at 3 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

[Treatment of pleuropulmonary tuberculosis in 1985].

The treatment of pulmonary TB due to bacilli sensitive to antituberculous treatment should lead to 100 p. 100 therapeutic success. However, this result implies a good bacteriological knowledge of the Koch bacillus, of antituberculous drugs, of therapeutic strategy, of the duration of treatment and, finally, of the reasons for failure. The association of isoniazide (5 mg/kg/day), rifampicin (10 mg/kg/day) and ethambutol (20 mg/kg/day for the first two months) sterilizes tuberculous lesions in 9 months. The introduction of a fourth antituberculous drug, pyrazinamide (35 mg/kg/day for the first two months) enables the duration of treatment to be reduced to 6 months without any loss of efficiency. Tuberculous relapses, sometimes due to polyresistant bacilli, pose difficult problems requiring detailed bacteriological studies of antibiotic sensitivity. Specific measures have to be taken (adaptation of dosage, contra-indications of certain drugs) with respect to the individual patient (elderly patients, pregnant or lactating women). Surgery has a role to play, especially in the treatment of sequellae. Admission to a sanatorium is reserved for infectious cases at the beginning of treatment and for patients living in poor conditions. The cover of social security is essential for successful treatment. Tuberculous is a compulsory notifiable disease.

Aminoglycosides↗
PubMed1979

Identification of tubercle bacilli.

Initial screening of tubercle bacilli with 2-thiophene carboxylic acid hydrazide (TCH) or 2-furoic acid hydrazide (FAH) separates them into two groups. Resistant strains are Mycobacterium tuberculosis. Sensitive strains include M. tuberculosis, M. bovis and BCG which are separated by nitratase and oxygen requirement tests. Pyrazinamide sensitivity tests allow M. bovis and M. africanum to be identified. The niacin test is not used. Most strains of M. tuberculosis from Europeans are resistant to TCH and FAH and are in phage groups A and B, while most strains from Asians are sensitive and are in phage group I.

Bacteriological Techniques↗
PubMed1985

[Which is the best drug combination for the short-term therapy of tuberculosis? A prospective randomized study with 190 patients].

190 patients with positive cultures for M. tuberculosis were treated in the initial phase as inpatients for 2-3 months at random with either pyrazinamide (Z) or ethambutol (E) in combination with isoniazid (H) and rifampicin (R). In the continuation phase as out-patients they were treated by their family doctor for a further seven months with a new randomization using either R or E combined with H. Regular controls of drug intake using urine test strips were 97% positive. The patients treated with Z showed a tendency to more rapid conversion to negative cultures despite the significantly shorter duration of initial-phase treatment. During the average observation period of 33 months after commencing therapy there were five relapses (without development of drug resistance). The distribution over the four patient groups did not allow statistical conclusions to be drawn. All of the relapses occurred during the first year after the treatment ended. All relapsing patients showed an unusually long delay (108 days) before the tuberculosis cultures proved negative, in comparison with only 48 days in all patients. The relapse rate of 3.6% equals comparable controlled studies in the literature of the last four years, in which patients were initially hospitalized for two months or received medication under direct supervision as out-patients. The family doctors treated their patients on average for ten months instead of the nine months recommended in the treatment scheme ("doctor's compliance"). This seems to be a direct consequence of the earlier recommendations in favour of a longer duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Ultrashort-course chemotherapy for culture-negative pulmonary tuberculosis--a qualified success.

A group of 250 patients with new or enlarging apical lung lesions which were thought to be tuberculous, and who had positive tuberculin tests but negative sputum smears and cultures for Mycobacterium tuberculosis, were treated with an ultrashort (3-month), 4-drug (rifampicin, isoniazid, pyrazinamide and ethambutol) regimen. One patient developed bacteriologically positive pulmonary tuberculosis (PTB) during the treatment period and 35 others (14%) developed bacteriologically positive PTB after completing the drug regimen.

Antitubercular Agents↗
PubMed1985

Failure of a prothionamide-containing oral antituberculosis regimen.

A group of 150 patients with sputum-positive pulmonary tuberculosis was treated with a regimen containing only orally administered drugs. Rifampicin and pyrazinamide were combined with Isoprodian, which contains isoniazid and also prothionamide and diaphenylsulphone. All the drugs were given daily for 5 months. Early analysis of the results shows 5 treatment failures, 27 relapses of pulmonary tuberculosis and another 17 patients who did not complete the prescribed regimen.

Administration, Oral↗
PubMed1979

[Tuberculosis in Romania (author's transl)].

The incidence of tuberculosis in Romania has decreased considerably over the past years, particularly since 1972 when the combined rifampicin-ethambutol-pyrazinamide therapy was introduced. During the period 1968-1977 it fell from 127.9 per 100,000 to 73.4 per 100,000. The incidence of relapses fell at a slower rate. The most endangered are the 20-24 years age-group and old people; but here again the number of cases tends to fall. Childhood tuberculosis showed a yearly decline by an average of 20%. Bacteriological examinations and diagnosis are assuming increased importance.

Adolescent↗
PubMed1979

Inborn hypouricemia due to isolated renal tubular defect.

Inborn hypouricemia due to isolated renal tubular defect is a rare disorder. Thus far eight documented families with this condition have been reported. In reviewing the data on these families, hyperuricosuria was found to be a constant associate of the hypouricemia, and hypercalciuria, mainly of the absorptive type, was frequently associated. Urolithiasis appears to be common. The mode of inheritance of this hypouricemia was autosomal, probably recessive. The magnitude of renal urate clearance and the effects on it of probenecid and pyrazinamide suggest the inborn renal hypouricemia to be of two types, due to defective re-secretory tubular urate reabsorption and to total defective tubular urate reabsorption. The question of the renal tubular abnormality for urate transport being the primary defect or secondary to an abnormal metabolite is discussed.

Adult↗
PubMed1979

[Nicotinamidase and the so-called pyrazinamidase in mycobacteria; the simultaneous occurrence of both activites (author's transl)].

Nicotin- and the so-called pyrazinamidase (in the following: "pyrazinamidase") have been found in strains of four mycobacteria species, M. fortuitum, M. gastri, M. bovis and M. microti. These findings are in contradiction to those summarized in Bergey's Manual of Determinative Bacteriology (1974). The reason for the discrepancies is that the original method (Bönicke, 1961) for amidase determination has not taken the following aspects into consideration: a) The inducibility of the nicotin- and "pyrazinamidase" (example: M. fortuitum); b) The temperature sensitivity of these enzymes (M. gastri); c) The light sensitivity of nicotinamidase (in photochromogenic M. gastri strains); d) The optimal substrate concentration which must be at least 4 mM instead of 0,8 mm. The following consequences can be drawn for the taxonomy and biochemistry of the tested organisms: e) The species status of M. gastri should be annuled. The main difference between M. gastri and M. kansasii consists only of the non-agglutinability of M. gastri by anti-M. kansasii serum. "Pyrazinamidase" and also nitrate reductase (Tarnok et al., in press) are positive in strains of both species; f) M. bovis possesses nicotin- and "pyrazinamidase" as M. tuberculosis too. Thus, these two species are more closely related than suggested earlier; g) Till now, no Mycobacterium has been found showing nicotinamidase without "pyrazinamidase" activity (or vice versa). It seems to be very probable that nicotinamidase, an enzyme of low substrate specificity, is able to hydrolyze several compounds with a nicotinamide-like structure such as pyrazinamide. Thus, we suggest the annulment of the term pyrazinamidase or the employment of quotation marks ("pyrazinamidase") to show the fictitious value of this designation.

Amidohydrolases↗
PubMed1970

A controlled comparison of a twice-weekly and three once-weekly regimens in the initial treatment of pulmonary tuberculosis.

A previous report from the Tuberculosis Chemotherapy Centre, Madras, demonstrated the value of a fully supervised twice-weekly regimen of high-dosage isoniazid plus streptomycin in the treatment of newly diagnosed tuberculous patients with drug-sensitive cultures. A logical consequence of this finding was an investigation of regimens with a longer interval between successive doses. The present report describes the findings of a controlled study of 3 once-weekly regimens and the twice-weekly regimen. The results confirm that the twice-weekly regimen is highly effective and demonstrate that its efficacy is not influenced by the rate of inactivation of isoniazid or by a reduction (by one-fourth) in the dosage of streptomycin. The results also show that once-weekly chemotherapy from the beginning, whether with high-dosage isoniazid plus streptomycin or high-dosage isoniazid plus streptomycin plus high-dosage pyrazinamide, gives unsatisfactory results. However, when an initial daily phase of 4 weeks with a moderate dosage of isoniazid plus streptomycin preceded the once-weekly phase of high-dosage isoniazid plus streptomycin, the response was highly satisfactory in slow inactivators of isoniazid (as good as with the twice-weekly regimen) but was considerably less satisfactory in rapid inactivators. These findings suggest that if a method of compensating for the insufficiency of this regimen in rapid inactivators of isoniazid can be found, the prospects for evolving a highly satisfactory once-weekly regimen are bright.

Adolescent↗
PubMed1975

[Sensitivity of m. kansasii strains to various antibiotics and chemotherapeutics in vitro and in vivo (author's transl)].

Sensitivity of 40 strains of M. kansasii (var. luciflava) to various antibiotics and chemotherapeutics in vitro and in vivo was examined. The strains showed considerable individual variability in their susceptibility in vitro, most were more resistant to isoniazid and PAS and about one half of the investigated strains to streptomycin, too, if correlated to "wild" strains of M. tuberculosis. Susceptibility to ethionamide, thiosemicarbazone (Conteben), viomycin, kanamycin and cycloserine appears to be the same as in the case of M. tuberculosis strains, but the resistance to pyrazinamide is higher. Good effect has been observed in vitro with rifampicin, ethambutol, capreomycin and phenazine derivative B 663. Oleandomycin and gentamycin are ineffectual in the dosages of drugs we used. The activity of most of these drugs was observed in experimental infections of white mice--in mono-therapy and in various combinations-provoked by different strains of M. kansasii. The main criterion of the effectivity of the treatment was the enumeration of viable mycobacterial units in the lungs of the mice in ten-days intervals; in one part of the experiments the histological examination of the various organs of the mice was performed. The drugs of the I. and II. line of antituberculotics were ineffective or showed only a slight effect. A very good effect of rifampicin, ethambutol and phenazine derivative B 663 in monotherapy and in multiply drug therapy was observed.

Animals↗
PubMed1983

[Comparison of 3 6-month chemotherapy regimes in pulmonary tuberculosis in routine practice in Algiers. 18th-month results].

Three 6 month antituberculous regimes were compared during a controlled trial in Algiers. Isoniazid and Rifampicin were used every day for six months in all three regimes; a third drug was used as a supplement in two of the three regimes during the first three months (Ethambutol or Pyrazinamide). The aim of the study was to assess the role of the third drug and also the suitability of a self-administered regime in routine practice. The results were analysed at eighteen months, twelve months after the end of therapy. The third drug had no influence on outcome in patients with sensitive organisms. There was a 2.5% relapse rate with no significant difference between the groups. On the other hand the third drug was crucial for those patients initially resistant to Isoniazid, because a relapse or failure due to primary resistance was avoided. The 6 month regimes were well tolerated: the treatment was only changed in 0.8% of cases for major toxicity. Finally, short self-administered oral regimens were well tolerated by the patients.

Adolescent↗
PubMed1978

Familial hypouricemia due to isolated renal tubular abnormality.

A family with genetic hypouricemia due to isolated renal tubular abnormality in urate handling is reported. Urinary urate excretion was decreased by 61% following administration of pyrazinamide, and increased by 25% following administration of probenecid. The response to these drug suggest genotype heterogeneity of renal hypouricemia in man.

Chromosome Aberrations↗
PubMed1982

[Sterilizing activity of the main drugs on the mouse experimental tuberculosis (author's transl)].

In a first experiment mice infected intravenously with 10(6) Mycobacterium tuberculosis were randomly treated either with isoniazid (INH) + rifampicin (RMP) 25 mg/kg or with INH + RMP + pyrazinamide (PZA) or with INH + RMP + PZA + streptomycin (SM). The decrease of the viable counts (CFU) in the lungs was similar with all three regimens. In a second experiment, mice were treated for six months either with INH + RMP 25 mg/kg or INH + RMP 10 mg/kg. After a follow-up of six months, mice were killed and their lungs and spleen cultivated. Positive cultures were obtained in 7.5 p. cent of the mice treated with the high dose of RMP and 36.5 p. cent in the mice treated with the low dose (p less than 0.05). A third experiment demonstrated that, during the first two months of treatment, adding PZA to INH + RMP 10 mg/kg increased significantly the overall effectiveness of INH + RMP 10 mg/kg combination. A fourth experiment demonstrated that after three initial months of INH + RMP 10 mg/kg, RMP alone was as effective as RMP + INH or RMP + INH + PZA. It may be concluded that RMP and PZA are both active on the intracellular population of Mycobacterium tuberculosis and that RMP is the only drug to act on persisting Mycobacterium tuberculosis in extracellular lesions.

Animals↗
PubMed1983

A comparative evaluation of drug combinations used in the treatment of pulmonary tuberculosis.

A retrospective analysis was undertaken of the hospital records of 185 patients admitted for the first time for treatment of pulmonary tuberculosis. The time to sputum conversion was used to evaluate the efficacy of short-course antituberculosis therapy and to determine the effect of including rifampicin (RMP) in various chemotherapeutic combinations. RMP per se was not found to be a significant variable in the drug combinations studied. The combination of RMP and pyrazinamide, however, showed greater efficacy in achieving earlier sputum conversion. The therapeutic advantage of using these two drugs in combination should be more readily appreciated.

Antitubercular Agents↗
PubMed1983

Hepatic complications of antituberculosis therapy revisited.

Since 1973, when the incidence and pattern of adverse reactions to antituberculosis therapy were described by Rossouw and Saunders, para-amino-salicylic acid, the major cause of drug-induced hepatitis, has been withdrawn from the regimen used in Cape Town and replaced with pyrazinamide (PZA). Our study in the same hospital indicates that although the substitution has resulted in a significant reduction in the incidence of all side-effects (4,1% v. 9%; P less than 0,001), the incidence of hepatitis is unchanged (0,3%). PZA is currently the major cause of hepatitis associated with antituberculosis therapy.

Adolescent↗
PubMed1980

Hypouricemia due to an isolated defect in renal tubular urate reabsorption.

During investigation of chronic glomerulonephritis, a 24-year-old man was found to have a low serum urate concentration (0.6-1.3 mg/100 ml). Daily urinary excretion of urate and oxypurines was normal. His urate clearance was markedly increased (43.3-98.0 ml/min), and was substantially unchanged after both the administration of pyrazinamide, an inhibitor of the renal tubular secretion of uric acid, and the administration of probenecid, an inhibitor of the renal tubular reabsorption of uric acid. No other renal tubular abnormalities were detected. It was concluded that the patient had an isolated defect in the renal tubular reabsorption of uric acid. The patient's brother was also found to have hypouricemia due to renal uricosuria, suggesting a genetic origin of the defect.

Adult↗
PubMed1982

Hypouricemia due to an increment in renal tubular urate secretion.

Two patients had hypouricemia due to increased uric acid clearance. Their daily urinary uric acid excretions were normal. In both patients, pyrazinamide decreased urinary uric acid clearance to almost while probenecid increased it markedly. No other renal tubular or metabolic abnormalities were found. The serum electrolytes and the urinary electrolytes excretions showed no abnormalities. It appears that increased secretion of uric acid in the renal tubule is most probably responsible for hypouricemia in these patients. This report adds to the list of hypouricemic conditions due to a new isolated renal tubular abnormality.

Adult↗