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PubMed1984

Controlled clinical trial comparing a 6-month and a 12-month regimen in the treatment of pulmonary tuberculosis in the Algerian Sahara. Algerian working group/British Medical Research Council cooperative study.

A 6-month short-course chemotherapy regimen and a 12-month standard duration regimen have been compared in the treatment of pulmonary tuberculosis in a rural area of Algeria in a population with a relatively high proportion of nomads. The 6-month regimen was isoniazid and rifampicin throughout, with ethambutol and pyrazinamide in addition for an initial 2-month intensive phase. The 12-month regimen was isoniazid and ethambutol throughout, supplemented by streptomycin during the first month. All 601 patients admitted had one or more sputum smears positive on examination in the local laboratory. Most patients were admitted to hospital initially for 1 to 2 months, where they received their chemotherapy under full supervision; thereafter, it was self-administered. In both nomads and settled residents known to have fully sensitive strains pretreatment, the 6-month regimen was highly effective, with no failures during chemotherapy and only 3% relapses after stopping chemotherapy in 131 patients compared with a combined failure rate during chemotherapy and relapse rate of 17% in the 154 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, none of 15 and 7 of 15 patients, respectively, being classified as failures or relapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

A successful supervised outpatient short-course tuberculosis treatment program in an open refugee camp on the Thai-Cambodian border.

The operation of a tuberculosis treatment program in an open refugee camp of 45,000 refugees on the Thai-Cambodian border is described. Fifty-eight patients received 6 months of supervised daily, outpatient therapy with a protocol employing isoniazid, rifampin, streptomycin, and pyrazinamide. Patient compliance was high, with only 15 of 10,209 patient days being missed, despite a high incidence of minor side effects. Three patients died, 4 defaulted, and 1 moved to another camp for treatment. The therapies of 4 patients were extended because of the need for reduced doses of medications, the development of extrapulmonary disease, treatment failure, and slow resolution of infiltrates on radiographs. There was 1 late relapse. This report demonstrates the feasibility in integrating short-course therapies with program designs to produce high compliance under difficult field conditions.

Adolescent↗
PubMed1985

Controlled clinical trial of two 6-month regimens of chemotherapy in the treatment of pulmonary tuberculosis. Tanzania/British Medical Research Council Study.

Two 6-month daily regimens of chemotherapy for smear-positive pulmonary tuberculosis were compared in Tanzania. Both had the same initial 2-month intensive phase of streptomycin, isoniazid, rifampicin, and pyrazinamide, and the continuation phase was either thiacetazone plus isoniazid or isoniazid alone. All patients were hospital inpatients for 6 months, solely to ensure that chemotherapy was fully supervised throughout. The patients were followed up to 24 months after stopping chemotherapy. In patients with fully sensitive strains pretreatment, there were no failures during chemotherapy on either regimen; the bacteriologic relapse rates were 3% for the 105 patients receiving thiacetazone plus isoniazid in the continuation phase, and 11% for the 100 patients receiving isoniazid alone (p less than 0.05). Possible adverse reactions were reported in the initial phase in 5 (1.6%) of 319 patients who started treatment, and in 2 of 306 who started the continuation phase, chemotherapy being modified in 5 of the 7 patients.

Adolescent↗
PubMed1985

Dosage of antituberculous drugs in obese patients.

There are no published data defining efficacious drug therapy for obese patients with active tuberculosis. Current dosage recommendations are based on total body weight (TBW); drug toxicity might result in obese patients receiving TBW doses. Peak and trough serum levels were measured for rifampin, streptomycin, ethambutol, and pyrazinamide in an obese patient (166 kg TBW, 87 kg ideal body weight (IBW] with miliary and meningeal tuberculosis. The observed drug levels and the calculated serum half-lives of these drugs were compared with the expected serum levels and serum half-lives in lean patients treated with literature-recommended doses. The observed serum levels in our obese patients were within the expected range for lean patients when dosage was based on IBW rather than on TBW. The observed cerebrospinal fluid penetrations of the drugs studied in our obese patient were similar to those reported in lean patients.

Adult↗
PubMed1985

Clinical trial of three 6-month regimens of chemotherapy given intermittently in the continuation phase in the treatment of pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council.

In a study in Singapore, Chinese, Malay, and Indian patients with sputum-smear-positive pulmonary tuberculosis were allocated at random to daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months (2SHRZ), 1 month (1SHRZ), or 2 months without streptomycin (2HRZ), followed, for all patients, by 3-times-weekly isoniazid and rifampin (H3R3) up to 6 months. At 2 months, the culture-negativity rate for the 2SHRZ series was statistically significantly higher than for either of the other 2 series. All 319 patients with drug-sensitive tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy except for one 2SHRZ/H3R3 patient, and among the 300 patients assessed during 24 months of follow-up after chemotherapy there was only 1 bacteriologic relapse in each series, giving an overall therapeutic failure rate of only 1%. Thus, the 2SHRZ combination had the highest early sterilizing activity, but the potent continuation therapy compensated for the initial inferiority of the other 2 regimens. Among the 32 patients with tubercle bacilli resistant pretreatment to isoniazid, streptomycin, or both drugs, there were no failures during chemotherapy and 3 subsequent relapses among the 30 assessed during 24 months of follow-up. Eleven (3%) of the 420 patients who started chemotherapy on their allocated regimen had hepatitis with jaundice during chemotherapy. However, 2 of these had cirrhosis pretreatment and 1 was a chronic alcoholic.

Adolescent↗
PubMed1985

Operational evaluation of treatment for tuberculosis. Results of 8- and 12-month regimens in Peru.

To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981. Two regimens were used: (1) isoniazid, rifampin, pyrazinamide, and streptomycin daily for 2 months, then either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily for 6 months; and (2) isoniazid, streptomycin, and thiacetazone daily for 2 months, then either isoniazid and streptomycin twice weekly or isoniazid and thiacetazone daily for 10 months. Patients were not assigned at random to the 2 treatment regimens; thus, the results cannot be directly compared. In the 8-month group, 70% had a favorable outcome, 14% abandoned, 9% failed, 3% died, and 3% relapsed. In the 12-month group, 53% had a favorable outcome, 34% abandoned, 6% failed, 4% died, and 2% relapsed. In patients who did not abandon treatment, the results of both regimens were nearly identical. Patients in both groups who had been treated previously had significantly lower rates of cure than those not treated previously.

Adolescent↗
PubMed1986

Short-course chemotherapy of pulmonary tuberculosis: a new approach to drug dosage in the initial intensive phase.

An analysis carried out on the dosage schemes adopted in several controlled clinical trials in tuberculosis has indicated that preestablishing the daily doses of isoniazid, rifampicin, and pyrazinamide in the initial intensive phase results in large deviations of the doses administered from those considered appropriate in mg/kg body weight. This is due partly to the variations in the patients' body weight and partly to the restrictions in terms of fine adjustments of dosage imposed by the unitary content of active principle in the available individual preparations of the drugs. The availability of a fixed-triple combination of the same 3 drugs where the content of each component is established multiplying the mg/kg requirement of each drug by 10, allows a complete coincidence between the appropriate and the administered dose simply administering 1 tablet every 10 kg of body weight. The implications of the large overdosing in light patients if the conventional approach is followed are discussed in terms of toxicity and drug purchasing cost, both being of great relevance for Third World countries where the majority of patients are of low body weight.

Antitubercular Agents↗
PubMed1973

Origins of the uricosuric response.

The acute effects of intravenous (i.v.) probenecid and chlorothiazide on renal urate handling were investigated in paired studies in normal men. Uricosuric responses to these agents were compared in the same subjects, both without and with pyrazinamide (PZA) pretreatment. Assuming that PZA selectively inhibits the tubular secretion of urate and that uricosuric agents act by increasing the excretion of filtered urate, then the uricosuric responses (the increment in urate excretion or clearance) should have been unaffected by PZA. Defined in this manner, however, uricosuric responses to probenecid and chlorothiazide were significantly decreased after PZA pretreatment. In order to determine whether PZA diminished other renal actions of chlorothiazide, changes in sodium and inorganic phosphorus excretion were examined. Chlorothiazide produced equivalent natriuretic and phosphaturic responses after PZA pretreatment, indicating that PZA does not interfere with at least some of the renal actions of chlorothiazide. In separate studies, PZA depressed urate excretion by at least 68% during the maintenance of chlorothiazide-induced natriuresis and phosphaturia, suggesting that chlorothiazide does not diminish the anti-secretory action of PZA. The results suggest that probenecid and chlorothiazide may derive their uricosuric properties by facilitating the excretion of both filtered and secreted urate. Possibly, increased excretion of secreted urate might occur through modulation of urate reabsorption at a site distal to tubular secretion, rather than by the direct acceleration of secretory transport. However, PZA-induced interference with the actions of probenecid and chlorothiazide on renal urate transport mechanisms cannot be excluded as a possible explanation for the present results.

Adult↗
PubMed1997

Pancreatic insufficiency due to antituberculous therapy.

OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.

Antitubercular Agents↗
PubMed2003

Low level of compliance with tuberculosis treatment in children: monitoring by urine tests.

Patient compliance should be ensured in an effective tuberculosis control programme. We measured patient compliance by detecting antituberculous drugs in the urine of 237 outpatients receiving one to three antituberculous drugs. Positive controls were 20 hospitalised patients, supervised to receive isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA), and negative controls were not on any drugs. Among the 237 study patients, only 67% were found to be taking the appropriate treatment and 8% had taken none. We conclude that a remarkable number of patients (33%) were non-compliant with treatment. The detection of antituberculous drugs in the urine is a quick, simple and inexpensive means of measuring adherence to treatment. Unless directly observed therapy (DOT) is adopted, we recommend routine urine testing for antituberculous drugs to identify defaulting patients.

Antibiotics, Antitubercular↗
PubMed2002

The triad of weight loss, fever and night sweating: isolated bone marrow tuberculosis, a case report.

Extrapulmonary tuberculosis is known to be the infection in an organ with or without pulmonary involvement. The infection in extrapulmonary tuberculosis is insidious and the symptoms and signs are generally nonspecific. We describe a 56-year-old male patient complaining of weight loss, fever, and night sweats. Although there were no signs and symptoms attributable to pulmonary tuberculosis, polymerase chain reaction (PCR), microscobical and cultural examination of bone marrow aspirate revealed isolated bone marrow tuberculosis. A treatment protocol of isoniazid, rifampicin, pyrazinamide, and streptomycin was administered. After 9 months of treatment, re-examination of the bone marrow revealed no signs of tuberculosis. Tuberculosis should be kept in mind especially in endemic areas and bone marrow should be examined in case of suspected tuberculosis infection.

Antitubercular Agents↗
PubMed2001

pncA mutations in clinical Mycobacterium tuberculosis isolates from Korea.

BACKGROUND: Pyrazinamide (PZA) is among the first-line drugs for the treatment of tuberculosis. In vitro, it kills semidormant mycobacteria only at low pH. The purpose of this study was to compare PZA resistance with pyrazinamidase (PZase) activity and the genotype to better understand the molecular basis of PZA resistance and to expand the profile of pncA mutations worldwide. RESULTS: Of the 28 tested strains of Mycobacterium tuberculosis, 6 were susceptible to PZA and positive for PZase activity and had no pncA mutations. Twenty-one strains were resistant to PZA and negative for PZase activity and had mutations in the pncA gene, including 15 point mutations, 5 insertions, and 2 deletions. One strain had no mutation in the pncA gene, even though it was resistant to PZA and negative for PZase activity. Three isolates had adenine to guanine point mutations in the -11 upstream region, making this the most common type of pncA mutations in this study, with at least two different RFLP patterns. CONCLUSION: These data help in the understanding of the molecular basis of PZA resistance. An adenine to guanine point mutation in the -11 upstream region was the most common type of pncA mutation in our isolates. The results of pncA mutation analyses should be carefully interpreted for epidemiologic purposes.

Amidohydrolases↗
PubMed2003

A case of exercise-induced acute renal failure in a patient with idiopathic renal hypouricemia developed during antihypertensive therapy with losartan and trichlormethiazide.

Exercise-induced acute renal failure (ARF) developed in a 45-year-old man during antihypertensive therapy with losartan and trichlormethiazide. The antihypertensive therapy was stopped and marked hypouricemia became apparent during improvement of his renal function. The daily urinary excretion of uric acid was normal and an increased fractional excretion of uric acid was observed. Renal biopsy revealed that the kidney was recovering from acute tubular necrosis with interstitial fibrosis. Based on the results of pyrazinamide and benzbromarone tests, we classified this case as one of presecretory reabsorption defect of uric acid. Antihypertesive therapy with benidipine and candesartan was initiated, and the patient has not had any ARF episodes since. Because idiopathic renal hypouricemia can be associated with exercise-induced ARF and chronic renal dysfunction, careful antihypertensive therapy and follow-up evaluation of renal function might be necessary for hypertensive patients with idiopathic renal hypouricemia.

Acute Kidney Injury↗
PubMedDate not supplied

Effect of tuberculosis preventive therapy on HIV disease progression and survival in HIV-infected adults.

PURPOSE: To determine whether tuberculosis (TB) preventive therapies alter the rate of disease progression to AIDS or death and to identify significant prognostic factors for HIV disease progression to AIDS. METHOD: In a randomized placebo-controlled trial in Kampala, Uganda, 2,736 purified protein derivative (PPD)-positive and anergic HIV-infected adults were randomly assigned to four and two regimens, respectively. PPD-positive patients were treated with isoniazid (INH) for 6 months (6H; n = 536), INH plus rifampicin for 3 months (3HR; n = 556), INH plus rifampicin plus pyrazinamide for 3 months (3HRZ; n = 462), or placebo for 6 months (n = 464). Anergic participants were treated with 6H (n = 395) or placebo (n = 323). RESULTS: During follow-up, 404 cases progressed to AIDS and 577 deaths occurred. The cumulative incidence of the AIDS progression was greater in the anergic cohort compared to the PPD-positive cohort (p < .0001). Among PPD-positive patients, the relative risk of the AIDS progression with INH alone was 0.95 (95% CI 0.68-1.32); with 3HR it was 0.83 (95% CI 0.59-1.17); and with 3HRZ it was 0.76 (95% CI 0.52-1.08), controlling for significant baseline predictors. Among anergic patients, the relative risk of the AIDS progression was 0.81 (95% CI 0.56-1.15). Survival was greater in the PPD-positive cohort compared to the anergic cohort (p = .0001). CONCLUSION: The number of signs or symptoms at baseline and anergic status are associated with increasing morbidity and mortality. Even though the tuberculosis preventive therapies were effective in reducing the incidence of TB for HIV-infected adults, their benefit of delaying HIV disease progression to AIDS was not observed.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Sequential evaluation of serum adenosine deaminase in patients treated for tuberculosis.

STUDY OBJECTIVE: To delineate the course of serum adenosine deaminase (s-ADA) in patients with tuberculosis who are receiving effective therapy. SETTING: A medical ward and an outpatient clinic in a general hospital. PATIENTS: Twenty-five immunocompetent patients with pleural or pulmonary tuberculosis. INTERVENTIONS: All patients received standard chemotherapeutic regimens with isoniazid, rifampin, and pyrazinamide. MEASUREMENTS AND RESULTS: Six measurements of several variables, including s-ADA, were carried out at different periods of time during the 6 months of follow-up. There were no significant differences in s-ADA values between sexes and there was no significant correlation with age or with the other variables analyzed. There was a significant decline in the s-ADA values during the first 2 months in the patients as a whole (p=0.04), followed by a stabilization of the s-ADA activity. This decline was due to a marked decrease in the s-ADA in the 13 patients (52%) who had initial high levels of the enzyme (p=0.03), whereas there were no changes in those patients with normal initial levels (p=0.27). Patients with increased s-ADA activity at the time of the first measurement reported symptoms for a longer period than patients with normal s-ADA (median, 15 vs 10 days; p=0.02). CONCLUSIONS: s-ADA levels in patients with tuberculosis decrease during the initial months of effective treatment. Perhaps this decrease might reflect the normalization of the altered lymphocyte turnover induced by tuberculosis. The measurement of s-ADA could be of some help to evaluate the response to therapy, particularly in those patients with increased values of the enzyme.

Adenosine Deaminase↗
PubMed2004

Erythema induratum of Bazin and renal tuberculosis: report of an association.

Erythema induratum of Bazin is a disease that usually affects women, in whom erythematous subcutaneous nodules and plaques appear on the posterior part of the lower extremities, some of which ulcerate. In many countries, tuberculosis is still the main etiologic factor. We report a case of a 40-year-old woman who presented a course of protracted and recurrent episodes over five years of cutaneous lesions on her legs. These tend to involute, but new crops appear at irregular intervals. It was painful, erythematous-violaceous nodules, some of which drained a reddish secretion. The histopathologic features of the lesions demonstrated inflammatory infiltration, with predominance of neutrophils in dermis and hypodermis, necrotizing vasculitis in the arterioles and septal fibrosis. There was no granuloma. The Ziehl-Neelsen stain did not revealed acid-fast bacilli, and the culture of biopsy specimen was negative. The tuberculin skin test was strongly positive (17 mm). The chest X-ray was normal. Few months later she presented adynamia and urinary complaints, such as polacyuria and dysuria. It has been done an urynalysis, which demonstrated acid pH urine, sterile pyuria and microscopic hematuria. It was then raised the diagnostic hypothesis of renal tuberculosis. The urine culture for M. tuberculosis was positive in two out of ten samples. The treatment was instituted with rifampin, isoniazid and pyrazinamide, with complete regression. This case illustrates a clear association between erythema induratum and renal tuberculosis, demonstrated by the remission of the cutaneous lesions after the treatment of the renal tuberculosis.

Adult↗
PubMed2002

Noncompliance with tuberculosis treatment by patients at a tuberculosis and AIDS reference hospital in midwestern Brazil.

INTRODUCTION: In developing countries, there is little information about the risk factors that predict noncompliance with tuberculosis (TB) treatment in hospitals. OBJECTIVE: This study analyzes possible factors associated with noncompliance with TB treatment among patients treated at HAA. DESIGN: A retrospective cohort study was made including all patients who initiated TB treatment at HAA, from January to December 1998. A standard form was used to review medical records and to collect data on each patient. This data was evaluated in comparison with data from the state TB control program. RESULTS: Of the 341 patients included in the study, 186 (61.2%) were considered cured and 67 (22%) were non-compliant. The factors associated with noncompliance were: previous anti-TB treatment (RR = 1.95, 95% CI 1.29 to 2.93), prescription of drugs other than the standard first-line regimen proposed by the Brazilian Health Ministry (Rifampin + Isoniazide + Pyrazinamide) (RR = 0.54, 95% CI 0.35 to 0.83), the need for hospitalization (RR = 2.19, 95% CI 1.46 to 3.29) and non-inclusion in the hospital s TB Control Program for treatment follow up (RR = 0.54, 95% CI 0.35 to 0.82). SETTING: Anuar Auad Hospital (HAA) Goiânia, Goiás, Brazil. CONCLUSION: Our results indicate the importance of establishing Tuberculosis Control Programs in hospitals, while paying special attention to patients with risk factors for noncompliance with TB treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Use of Rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial.

It has been postulated that deficient or incomplete clinical and/or microbiological response to tuberculosis treatment is associated with cell-mediated immunological dysfunction involving monocytes and macrophages. A phase 2 safety trial was conducted by treating patients with either recombinant human granulocyte-macrophage colony-stimulating factor (rhu-GM-CSF) or a placebo, both in combination with anti-tuberculosis chemotherapy. Thirty-one patients with documented pulmonary tuberculosis were treated with rifampin/isoniazid for six months, plus pyrazinamide for the first two months. At the beginning of treatment, rhu-GM-CSF (125mg/M(2)) was randomly assigned to 16 patients and injected subcutaneously twice weekly for four weeks; the other 15 patients received a placebo. The patients were accompanied in the hospital for two weeks, then monthly on an out patient basis, for 12 months. Clinical outcomes were similar in both groups, with no difference in acid-fast bacilli (AFB) clearance in sputum at the end of the fourth week of treatment. Nevertheless, a trend to faster conversion to negative was observed in the rhu-GM-CSF group until the eighth week of treatment (p=0.07), after which all patients converted to AFB negative. Adverse events in the rhu-GM-CSF group were local skin inflammation and an increase in the leukocyte count after each injection, returning to normal 72 hours after rhu-GM-CSF injection. Three patients developed SGOP and SGPT > 2.5 times the normal values. All patients included in the GM-CSF group were culture negative at six months, except one who had primary TB resistance. None of the patients had to discontinue the treatment in either group. We conclude that rhu-GM-CSF adjuvant immunotherapy could be safely explored in a phase 3 trial with patients who have active tuberculosis.

Adjuvants, Immunologic↗