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PubMed2006

Hereditary renal hypouricemia.

Hereditary renal hypouricemia (HRH) is an inborn error of renal membrane transport specific for uric acid, resulting in increased renal urate clearance associated with hypouricemia. Apparently in most HRH patients, the disorder is caused by loss of function mutations in the gene SLC22A12 coding for human urate transporter 1 (hURAT1), shown to control urate reabsorption in the proximal tubules. The small group of HRH patients with normal SLC22A12 may be affected with mutations in other not yet identified urate transporters. Patients affected with SLC22A12 mutations exhibit attenuated response of urinary urate excretion to pyrazinamide (PZA) and to probenecid (PBD) loading, attributed previously to reflect defective tubular presecretory urate reabsorption. HRH is inherited in an autosomal recessive mode. Most HRH patients are asymptomatic, but some may form renal tract stones and or be predisposed to exercise-induced acute renal failure.

Carrier Proteins↗

PubMed2003

Tuberculosis and pregnancy.

OBJECTIVES: There are many myths surrounding pregnancy and tuberculosis (TB), and outcome of treatment. This prospective study was conducted at the Department of Obstetrics and Gynecology, SCB Medical College, Cuttack, India, and at the authors' private clinics from 1986 to 2001 to determine the outcome of pregnancy if TB is treated properly. METHODS: A total of 111 pregnant women diagnosed as having pulmonary and glandular TB were included in the study. They were matched for age, parity, and socioeconomic status with 51 pregnant women without TB (first control group), and 51 women with pulmonary TB but without pregnancy (second control group). The usual pregnancy management was given to the women in the study group, along with a short course of chemotherapy: either ethambutol, INH, or rifampicin and pyrazinamide for 2 months followed by INH and rifampicin for 4 months; or ethambutol, INH, and rifampicin for 2 months followed by INH and rifampicin for 7 months. Statistical analysis was done using a chi(2)-test. RESULTS: There were no statistical differences in duration of gestation, preterm labor, and other complications of pregnancy, labor, and puerperium between the pregnancy groups. There were no congenital anomalies in the babies born to the groups. Pregnancy had no effect on the course of TB as regards sputum conversion, stabilization of the disease, and non-relapse even after 2-5 years of follow-up and a further delivery in a few cases. CONCLUSIONS: If proper and adequate chemotherapy is given to pregnant women with TB, they are not a higher risk than non-pregnant women with TB. Neither the disease nor chemotherapy is threatening to mother or newborn. However, today the ominous combination of human immunodeficiency virus, TB, and pregnancy poses a new challenge.

Adult↗

PubMed1999

Interference of modern antibacterials with bacillus Calmette-Guerin viability.

PURPOSE: We determine the effects of modern antibacterial chemotherapeutics on bacillus Calmette-Guerin (BCG) viability, particularly those of cycloserine, which has been recommended for treating BCG induced sepsis. MATERIALS AND METHODS: The minimal inhibitory concentrations of 31 antibacterial drugs against Connaught BCG strain were determined in vitro by the radiometric BACTEC 460TB method. Minimal inhibitory concentrations were compared with the drug concentrations achievable in blood and urine to estimate systemic or intravesical susceptibility. Susceptibility testing of cycloserine was performed with Connaught, Tice and RIVM BCG strains, using the modified proportion method on Lowenstein-Jensen agar. RESULTS: Connaught BCG was susceptible to quinolones in systemic infections but resistant to beta-lactams, macrolides and some aminoglycosides. It was resistant to pyrazinamide but showed good susceptibility toward the other antituberculosis drugs tested. All 3 BCG strains analyzed were resistant to cycloserine. Most antibacterials may interfere with BCG in the bladder because of high urinary recovery. CONCLUSIONS: Antibacterial drug interference with BCG viability should be avoided during intravesical instillation therapy. In cases of severe complications quinolones rather than cycloserine may be given in addition to standard triple antituberculosis drug therapy or if one of these drugs is not tolerated. Our data may contribute toward enhancing the therapeutic safety and efficacy of intravesical BCG immunotherapy by the appropriate use of antibacterial drugs.

Antibiotics, Antitubercular↗

PubMed1991

The possible influence of antibiotics on results of bacillus Calmette-Guérin intravesical therapy for superficial bladder cancer.

Intravesical treatment with Bacillus Calmette-Guérin is an established treatment of carcinoma in situ and an effective prophylaxis for the prevention of recurrence of transitional cell carcinoma. During instillation therapy oral antibiotics may be used to prevent or to treat urinary tract infections. Tuberculostatic agents are employed to prevent or to treat local irritative symptoms and systemic side effects caused by Bacillus Calmette-Guérin. We investigated the susceptibility of four different Bacillus Calmette-Guérin preparations to 18 antibiotics and to 11 tuberculostatic agents in vitro. All preparations were equally susceptible to most of the commonly used antibiotics and to all of the tuberculostatic agents with the exception of pyrazinamide. Our results suggest that in the absence of cystitis, instillations should not be accompanied by antibiotics because of the possible inhibition of antitumor efficacy by eradication of living Bacillus Calmette-Guérin organisms. The same inhibition may occur when tuberculostatic agents are used to prevent local and systemic complications of Bacillus Calmette-Guérin instillation therapy.

Administration, Intravesical↗

PubMed2006

[Treatment of tuberculous meningitis].

INTRODUCTION: Tuberculous meningitis and brain tuberculomas are currently rare in the western world but remain serious. Improved outcome requires early recognition and treatment of these conditions. STATE OF ART: Treatment is usually begun before diagnostic confirmation. Therapeutic principles are now better defined thanks to recent recommendations and studies. Antituberculous therapy begins with two months of a combination of four drugs: isoniazid, rifampicin, ethambutol and pyrazinamid. Then follows a longer phase of bitherapy with isoniazid and rifampicin, lasting at least four months but usually extended to seven or ten months as a precaution. Patients at risk of toxic neuropathy should receive pyridoxine supplementation. Corticosteroids must be systematically added during the first eight weeks of treatment, beginning with high dose before progressive tapering. Hyponatremia is common, often induced by emesis and cerebral salt wasting syndrome. Therefore saline supply rather than water restriction is required. Non-obstructive hydrocephaly can usually be managed with diuretic therapy including acetazolamid, sometimes complemented by serial lumbar punctures. Neurosurgical interventions are rarely needed. Monitoring of treatment tolerance and efficacy is mainly clinical. Central nervous system imaging and cerebro-spinal fluid analysis are only required to explain clinical deterioration. CONCLUSION: With adequate and prompt anti-tuberculous, anti-inflammatory and supportive treatment, the prognosis of central nervous system tuberculosis can be greatly improved.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Double-blind placebo-controlled trial of Mycobacterium vaccae immunotherapy for tuberculosis in KwaZulu, South Africa, 1991-97.

To investigate Mycobacterium vaccae immunotherapy in the treatment of human tuberculosis and to assess longer-term outcomes following treatment for tuberculosis patients, a double-blind placebo-controlled Phase-2 clinical trial was set up in the Mseleni and Manguzi health wards in north-eastern KwaZulu, South Africa. In 1991-93, 204 patients admitted with clinical tuberculosis to the 2 hospitals were allocated to receive single intradermal doses of 0.1 mL M. vaccae NCTC 11659 or 0.1 mL tetanus toxoid alongside standard 6-months chemotherapy with rifampicin, isoniazid, pyrazinamide and ethambutol. The main outcome measures were sputum bacteriology culture conversion to negativity, clinical assessment, weight gain, erythrocyte sedimentation rate and chest radiography. Patients were followed-up after 4 years to determine their health status. M. vaccae cases gained weight more quickly during the first 8 weeks compared with 'placebo' patients. Regression analysis found a synergistic relationship between BCG positive scar status and M. vaccae-induced weight gain. No further difference was found between treatment groups. The bacterial conversion rate to negativity at 2 months was much lower than expected (44.8% active, 38.8% placebo). Mortality was considerably higher than expected after treatment (7.1% each group) and after 4 years (25.8% active, 21.0% placebo; death from tuberculosis 14.5% and 16.1%, respectively). Immune sensitization to environmental mycobacteria may explain the geographical variability of M. vaccae efficacy, as occurs with BCG vaccination and occurred with Koch's tuberculins of the late 19th century. Multiple doses of M. vaccae may be more effective. Further work is required to link the ability of M. vaccae to modulate protective cytokine profiles to favourable outcome in clinical studies. The high mortality found in this study suggests urgent reviews of chemotherapy and monitoring of patients are necessary in KwaZulu.

Adult↗

PubMedDate not supplied

Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan.

This is a descriptive report of a pilot project of tuberculosis (TB) treatment in a conflict zone. A TB programme was implemented by Médecins Sans Frontières(MSF)-Holland in a semi-nomadic population in a very insecure and underdeveloped area of Upper Nile province in Southern Sudan. Outcome measures were operational feasibility, default rate, and sputum smear conversion at 4 months. A cohort of TB patients was admitted over a 10-week period (July-September 2001). Adherence strategy, project implementation, and and contingency planning were adapted to local conditions. The treatment regimen (4 HRZE [4-month daily supervised regimen] followed by 3EH or 3TH [3-month unsupervised regimen]: isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E) and thiacetazone (T)) was a variant on the Manyatta regimen developed for semi-nomads in Kenya. Of 163 patients, 84 (52%) were children aged < 15 years. Lymph node TB comprised 34% and spinal TB 15% of all patients. Among adults, 41% had smear-positive pulmonary disease. Only 1 patient (0.6%) defaulted. All sputum smear-positive patients who completed 4 months of therapy converted to smear-negative, although 2 were subsequently found to have relapsed. TB in complex emergency situations is an underrecognized priority. Using an approach adapted especially to this setting, TB treatment was successfully implemented with minimal risk of promoting drug resistance, in an unstable setting.

Adolescent↗

PubMed2004

Sacral tuberculosis: a case report and review of the literature.

BACKGROUND: We present a patient with a heterogeneously enhancing lesion within the body of the sacrum and the sacral canal. Sacral tuberculosis (TB) was suspected because of a history of familial exposure. Few cases isolated to the sacrum have been reported in the literature. The characteristic histopathologic and magnetic resonance imaging (MRI) findings are also presented. CASE DESCRIPTION: A 31-year-old African-American male presented with an 8-month history of lower back pain radiating into his legs as well as numbness and weakness of the right foot. His history revealed PPD conversion following an exposure to active pulmonary TB 3 years prior for which he received 6 months of isoniazid prophylaxis. An MRI scan revealed a large heterogeneously enhancing lesion involving the sacrum with extension into the sacral canal. The patient underwent computed tomography (CT)- guided needle biopsy of the sacral lesion. Cytopathologic examination revealed caseating granulomas. Acid-fast bacilli cultures were positive for Mycobacterium tuberculosis. He was placed on a 6-month course of isoniazid, rifampin, pyrazinamide, and ethambutol. At 3-month follow-up, his examination and symptoms had improved. CONCLUSIONS: Sacral TB is an extremely rare cause of lower back pain with radiation into the lower extremities. TB should always be considered in the differential diagnosis of isolated sacral masses, especially in light of today's increasing multidrug resistance and immunosuppressed population.

Adult↗

PubMed2001

Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan.

BACKGROUND: DOTS is the control strategy for tuberculosis promoted by WHO. Pakistan is currently developing its National Tuberculosis Programme, and requires guidance on types of direct observation of treatment appropriate for the local conditions. We did a randomised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan. METHODS: We enrolled 497 adults with new sputum-positive tuberculosis. 170 were assigned DOTS with direct observation of treatment by health workers; 165 were assigned DOTS with direct observation of treatment by family members; and 162 were assigned self-administered treatment. The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purposes of the research, with a standard daily short-course drugs regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 6 months of isoniazid and ethambutol). The main outcome measures were cure, and cure or treatment completion. Analysis was by intention to treat. FINDINGS: Within the strengthened tuberculosis services, the health-worker DOTS, family-member DOTS, and self-administered treatment strategies gave very similar outcomes, with cure rates of 64%, 55%, and 62%, respectively, and cure or treatment-completed rates of 67%, 62%, and 65%, respectively. INTERPRETATION: None of the three strategies tested was shown to be superior to the others, and direct observation of treatment did not give any additional improvement in cure rates. The effectiveness of direct observation of treatment remains unclear, and further operational research is needed.

Adolescent↗

PubMed2002

Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru.

BACKGROUND: There are no data on the feasibility and cost-effectiveness of using second-line drugs to treat patients with chronic tuberculosis, many of whom are infected with multidrug resistant (MDR) strains of Mycobacterium tuberculosis, in low or middle-income countries. METHODS: A national programme to treat chronic tuberculosis patients with a directly observed standardised 18-month daily regimen, consisting of kanamycin (3 months only), ciprofloxacin, ethionamide, pyrazinamide, and ethambutol, was established in Peru in 1997. Compliance and treatment outcomes were analysed for the cohort started on treatment between October, 1997, and March, 1999. Total and average costs were assessed. Cost-effectiveness was estimated as the cost per DALY gained. FINDINGS: 466 patients were enrolled; 344 were tested for drug susceptibility and 298 (87%) had MDR tuberculosis. 225 patients (48%) were cured, 57 (12%) died, 131 (28%) did not respond to treatment, and 53 (11%) defaulted. Of the 413 (89%) patients who complied with treatment, 225 (55%) were cured. Among MDR patients, resistance to five or more drugs was significantly associated with an unfavourable outcome (death, non-response to treatment, or default; odds ratio 3.37, 95% CI 1.32-8.60; p=0.01). The programme cost US $0.6 million per year, 8% of the National Tuberculosis Programme budget, and US $2381 per patient for those who completed treatment. The mean cost per DALY gained was $211 ($165 at drug prices projected for 2002). INTERPRETATION: Treating chronic tuberculosis patients with high levels of MDR with second-line drugs can be feasible and cost-effective in middle-income countries, provided a strong tuberculosis control programme is in place.

Adolescent↗

PubMed1987

Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei.

In Transkei, 143 patients with active tuberculous constrictive pericarditis without significant pericardial effusion all received the same daily 6-month antituberculosis regimen of streptomycin, isoniazid, rifampicin, and pyrazinamide for 14 weeks followed by isoniazid and rifampicin. They were randomly allocated to receive in addition either prednisolone or placebo for the first 11 weeks; the comparison was double-blind throughout treatment and follow-up. In the 114 patients assessable up to 24 months, improvement was significantly more rapid in the prednisolone group, as shown by the rate of fall in the mean pulse rate and the rate at which jugular venous pressure and level of physical activity became normal. During follow-up, 2 (4%) of the 53 prednisolone and 7 (11%) of the 61 placebo patients died from pericarditis, and 11 (21%) and 18 (30%), respectively, required pericardiectomy. By 24 months 50 (94%) prednisolone and 52 (85%) placebo patients had a favourable status. 3 patients (1 prednisolone, 2 placebo) were normally active but were classified as not having achieved a favourable status. It is recommended that, in the absence of a specific contraindication, antituberculosis chemotherapy should be initially supplemented by steroids.

Adolescent↗

PubMed1989

Comparison of daily and twice-weekly regimens to treat pulmonary tuberculosis.

A randomised controlled trial compared the effectiveness and toxicity in pulmonary tuberculosis of two drug regimens containing rifampicin and isoniazid given daily or twice-weekly for 4 months after a 2-month period of intensive treatment with daily isoniazid, rifampicin, and pyrazinamide. 667 patients with newly diagnosed pulmonary tuberculosis were randomly allocated to continue daily treatment with isoniazid (400 mg) and rifampicin (600 mg) or to twice-weekly treatment with isoniazid (900 mg) and rifampicin (600 mg). 544 of the 667 patients (81%) completed the 6-month course (287 of 337 [85%] treated daily and 257 of 330 [79%] treated twice-weekly). Drug toxicity was not a great problem; the treatment was permanently discontinued in only 2% of patients. There was no significant difference at the end of months 5 and/or 6 of chemotherapy between the groups treated daily and twice-weekly in the proportions with bacteriological failure (at least one positive sputum culture with more than 20 colonies) or who had died from tuberculosis (17 [6%] vs 10 [3%]). Nor was there a significant difference in the relapse rate (17 [7%] treated daily vs 10 [4%] treated twice-weekly) during follow-up of 12 months. Thus, the twice-weekly regimen was at least as effective as the daily regimen for treatment of pulmonary tuberculosis.

Administration, Oral↗

PubMed1995

Anti-tuberculous therapy and acute liver failure.

The incidence of tuberculosis has been increasing since 1987, exposing a greater number of patients to the risks of three potentially hepatotoxic drugs, isoniazid, rifampicin, and pyrazinamide. Awareness of potentially severe drug hepatotoxic reactions is vital because fulminant hepatic failure is a devastating and often fatal condition without liver transplantation. We report four cases of fulminant hepatic failure caused by rifampicin, isoniazid, or both. These cases highlight the need for stricter adherence to and review of current guidelines on liver function tests after starting anti-tuberculous therapies.

Adult↗

PubMed1999

Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberculosis Trials Consortium.

BACKGROUND: Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin. The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase (the last 4 months) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients. This report concerns only the HIV-seropositive part of the trial, which has ended. The HIV-seronegative part will stop follow-up in 2001. METHODS: Adults with culture-positive, drug-susceptible pulmonary tuberculosis who completed 2 months of four-drug (isoniazid, rifampin, pyrazinamide, ethambutol) treatment (induction phase) were randomly assigned 900 mg isoniazid and 600 mg rifapentine once weekly, or 900 mg isoniazid and 600 mg rifampin twice weekly. All therapy was directly observed. Statistical analysis used univariate, Kaplan-Meier, and logistic and proportional hazards regression methods. FINDINGS: 71 HIV-seropositive patients were enrolled: 61 completed therapy and were assessed for relapse. Five of 30 patients in the once-weekly isoniazid/rifapentine group relapsed, compared with three of 31 patients in the twice-weekly isoniazid/rifampin group (log rank chi2=0.69, p=0.41). However, four of five relapses in the once-weekly isoniazid/rifapentine group had monoresistance to rifamycin, compared with none of three in the rifampin group (p=0.05). Patients who relapsed with rifamycin monoresistance were younger (median age 29 vs 41 years), had lower baseline CD4 cell counts (median 16 vs 144 microL), and were more likely to have extrapulmonary involvement (75% vs 18%, p=0.03) and concomitant therapy with antifungal agents (75% vs 9%, p=0.006). No rifamycin monoresistant relapse has occurred among 1004 HIV-seronegative patients enrolled to date. INTERPRETATION: Relapse with rifamycin monoresistant tuberculosis occurred among HIV-seropositive tuberculosis patients treated with a once-weekly isoniazid/rifapentine continuation-phase regimen. Until more effective regimens have been identified and assessed in clinical trials, HIV-seropositive people with tuberculosis should not be treated with a once-weekly isoniazid/rifapentine regimen.

AIDS-Related Opportunistic Infections↗

PubMed2000

Superior vena cava syndrome during the treatment of pulmonary tuberculosis in an HIV-1 infected patient.

Tuberculosis is nowadays an uncommon cause of superior vena cava syndrome (SVCS). We report the case of an HIV-infected patient who presented with respiratory symptoms accompanied by cervical and mediastinal lymphadenopathy. Sputum examination showed acid-fast bacilli, and treatment was instituted with isoniazid, rifampicin, pyrazinamide and ethambutol. A few days later SVCS developed, presumably as a consequence of inflammatory lymphadenitis. With corticosteroids, all symptoms disappeared. To our knowledge, no cases of SVCS provoked by this kind of paradoxical reaction have been described previously.

AIDS-Related Opportunistic Infections↗

PubMed1988

Use of radiolabelling and fluorescent staining methods in the evaluation of viability and drug susceptibility testing of mycobacterial cultures.

The utility of radiolabelling and fluorescent staining was investigated for the assessment of viability and drug susceptibility testing of mycobacteria. Fast growing Mycobacterium w was used as a test organism for optimization of experimental conditions. A fairly good correlation was found between the profiles obtained for radiolabelling with 14C-acetate and Fluorescein diacetate-Ethidium bromide (FDA-EB) staining of heat-killed and live M.w. The reliability of two methods for determining the viability of mycobacteria was further established by comparing them with the traditional method of counting of colony forming units (CFU) on solid medium (p less than 0.001). Using radiolabelling and fluorescent staining procedures similar pattern of differential response of M.w was detected against pyrazinamide and rifampicin. This was in agreement with CFU of the cultures. The feasibility of applying these techniques for other mycobacteria was investigated by using Mycobacterium tuberculosis strain H37Ra. The methods could monitor the anti-mycobacterial effect of isoniazid and rifampicin on M. tuberculosis strain H37Ra in shorter duration of time thereby suggesting their use for rapid screening of drugs against slow growing mycobacteria.

Acetates↗

PubMedDate not supplied

[Drugs with activity against Mycobacterium tuberculosis].

Treatment for Mycobacterium tuberculosis has to be lengthy, since populations of this bacillus differ in metabolic activity, and it has to consist of various associated drugs, since spontaneous chromosome mutations can give rise to drug resistance. The multiresistant phenotype emerges with sequential acquisition of mutations in several loci of separate genes. Knowledge of the mechanisms of resistance permits the development of molecular techniques for the early detection of resistant strains, thereby making proper control possible. Tuberculosis treatment includes isoniazid, rifampicin and pyrazinamide during the first two months and isoniazid and rifampicin to complete six months of treatment. In specific situations, a fourth drug is added, ethambutol for adults and streptomycin for children in whom visual acuity cannot be monitored. This review describes the characteristics, activity, resistance mechanisms and side effects associated with the various antituberculosis drugs.

Adult↗

PubMed2002

[Efficacy of the sparfloxacin-ethambutol combination in a case of cerebral tuberculosis].

INTRODUCTION: Treatment of cerebral tuberculomas demands the combination of rifampicin, isoniazid, pyrazinamide and ethambutol. The place of fluoroquinolones remains to be defined. EXEGESIS: A 36-year-old woman presented with a cerebral tuberculoma. Treatment with an antituberculous quadritherapy regimen was begun, but because of serious side effects, isoniazid and rifampicin weren't withdrawn during the fourth month. Sparfloxacin and ethambutol biotherapy was then started and continued for 12 months, which led to the disappearance of the cerebral lesion. CONCLUSION: Our observation proves that sparfloxacin is an alternative for cerebral tuberculoma treatment in case of intolerance or resistance to first-line antituberculosis drugs.

Adult↗