trifazid and Tuberculosis

Tuberculous liver abscess is a rare disease entity even in endemic areas of Mycobacterium tuberculosis. It is usually accompanied by pulmonary tuberculosis or enteric tuberculosis. Further, an isolated tuberculous liver abscess is extremely rare. The disease is diagnosed by laparotomy or postmortem autopsy in most cases, and some authors adopted a 9-month antituberculosis regimen. We herein report a case of an isolated tuberculous liver abscess that initially manifested as persistent fever and general malaise, which was diagnosed by liver biopsy and treated successfully with a 6-month antituberculosis regimen and percutaneous abscess drainage.

Topics: Aged; Antitubercular Agents; Biopsy; Blood Chemical Analysis; Drug Combinations; Ethambutol; Humans; Isoniazid; Laparotomy; Liver; Liver Abscess; Male; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Tuberculosis

Study conducted in a suburb of Cape Town, South Africa.. Comparison of successful tuberculosis treatment outcome rates between self supervision, supervision by lay health worker (LHW), and supervision by clinic nurse.. Open, randomised, controlled trial with intention-to-treat analysis.. All groups (n = 156) achieved similar outcomes (LHW vs. clinic nurse: risk difference 17.2%, 95% confidence interval [CI] -0.1-34.5; LHW vs. self supervision 15%, 95%CI -3.7-33.6). New patients benefit from LHW supervision (LHW vs clinic nurse: risk difference 24.2%, 95%CI 6-42.5, LHW vs. self supervision 39.1%, 95%CI 17.8-60.3) as do female patients (LHW vs. clinic nurse 48.3%, 95%CI 22.8-73.8, LHW vs. self supervision 32.6%, 95%CI 6.4-58.7).. LHW supervision approaches statistically significant superiority, but fails to reach it most likely due to the study's limitation, the small sample size. It is possible that subgroups (new and female patients) do well under LHW supervision. LHW supervision could be offered as one of several supervision options within TB control programmes.

Topics: Adult; Antitubercular Agents; Community Health Workers; Drug Combinations; Female; Humans; Isoniazid; Male; Pyrazinamide; Rifampin; South Africa; Tuberculosis

The subjective impression among clinicians that the use of Rifater was causing delayed sputum conversion and increased drug resistance was tested in a prospective study. Adults in the Cape Town municipal area with a first episode of pulmonary tuberculosis were treated either with Rifater or a regimen consisting of isoniazid, rifampicin, pyrazinamide and ethambutol. All patients who took the treatment as prescribed (67 Rifater, 39 the 4-drug regimen) converted to a negative sputum culture by the time 90 doses had been taken. The rates of inadequate compliance and of side-effects were similar in the two groups. Drug sensitivity testing of bacteria cultured from pre-treatment sputum specimens revealed an overall primary resistance rate of 4.84% in the population studied, sufficiently low to preclude any necessity for routine pre-treatment drug sensitivity testing.

Topics: Antitubercular Agents; Drug Combinations; Drug Resistance, Microbial; Ethambutol; Humans; Isoniazid; Patient Compliance; Prospective Studies; Pyrazinamide; Rifampin; Sputum; Streptomycin; Tuberculosis

Short-course chemotherapy of six-month duration with an initial combination of three drugs (isoniazid [H], rifampin [R] and pyrazinamide [Z]) is recommended as the treatment of choice in tuberculosis today. Use of fixed-combination tablet (Rifater) prevents prescription errors by physicians and selective intake by noncompliant patients. It should therefore assist in the prevention of emergence of drug resistance. In a controlled study at a chest hospital in Switzerland involving 261 patients with culture proven tuberculosis, the following two regimens were compared: 1) Six-month therapy (n = 128) with daily Rifater for two months, followed by H and R for four months. 2) Nine-month therapy (n = 133) with H and R daily for nine months, supplemented by ethambutol for the first two months. The two patient groups were comparable except for initial drug resistance (16% vs 8%, p < 0.05). Overall resistance to H was 10%. Five patients had initial resistance to two or more drugs. 227 patients were re-examined 1-8, and on average 4 years after therapy: four patients relapsed after 12, 20, 36 and 90 months. Two patients with initial drug resistance to H later developed resistance to R; both of these, as well as a third relapse patient, were cured with subsequent multi-drug therapy. Despite two and a half years of chemotherapy and repeated surgery, the fourth patient with initial resistance to H and R could not be cured. All relapse patients with initial drug resistance were randomized into the six-month therapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antitubercular Agents; Drug Combinations; Drug Resistance, Microbial; Female; Humans; Isoniazid; Male; Middle Aged; Patient Compliance; Pyrazinamide; Rifampin; Time Factors; Tuberculosis

The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant

Topics: Antitubercular Agents; Drug Combinations; Drug Therapy, Combination; Ethambutol; Humans; Hydrogen-Ion Concentration; Hypoxia; Isoniazid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Nitroimidazoles; Oxazolidinones; Pyrazinamide; Rifampin; Tuberculosis

Experimental and clinical studies have indicated that the antileprosy drug clofazimine may contribute treatment-shortening activity when included in tuberculosis treatment regimens. Clofazimine accumulates to high levels in tissues, has a long half-life, and remains in the body for months after administration is stopped. We hypothesized that in tuberculosis treatment, accumulated clofazimine may contribute sustained antimicrobial activity after treatment cessation, and we used the BALB/c mouse model of chronic tuberculosis chemotherapy to address this hypothesis. Mycobacterium tuberculosis-infected mice were treated for 4 weeks or 8 weeks with either isoniazid alone, clofazimine alone, the first-line regimen rifampin-isoniazid-pyrazinamide-ethambutol, or a first-line regimen where clofazimine was administered in place of ethambutol. To evaluate posttreatment antimicrobial activity, bacterial regrowth in the lungs and spleens was assessed at the day of treatment cessation and 2, 4, 6, and 8 weeks after treatment was stopped. Bacterial regrowth was delayed in all mice receiving clofazimine, either alone or in combination, compared to the mice that did not receive clofazimine. This effect was especially evident in mice receiving multidrug therapy. In mice not receiving clofazimine, bacterial regrowth began almost immediately after treatment was stopped, while in mice receiving clofazimine, bacterial regrowth was delayed for up to 6 weeks, with the duration of sustained antimicrobial activity being positively associated with the time that serum clofazimine levels remained at or above the 0.25-μg/ml MIC for M. tuberculosis Thus, sustained activity of clofazimine may be important in the treatment-shortening effect associated with this drug.

Topics: Animals; Antitubercular Agents; Clofazimine; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Ethambutol; Female; Isoniazid; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Tuberculosis; Withholding Treatment

Assessment of the activity of thioridazine towards Mycobacterium tuberculosis (Mtb), in vitro and in vivo as a single drug and in combination with tuberculosis (TB) drugs.. The in vitro activity of thioridazine as single drug or in combination with TB drugs was assessed in terms of MIC and by use of the time-kill kinetics assay. Various Mtb strains among which the Beijing genotype strain BE-1585 were included. In vivo, mice with TB induced by BE-1585 were treated with a TB drug regimen with thioridazine during 13 weeks. Therapeutic efficacy was assessed by the change in mycobacterial load in the lung, spleen and liver during treatment and 13 weeks post-treatment.. In vitro, thioridazine showed a concentration-dependent and time-dependent bactericidal activity towards both actively-replicating and slowly-replicating Mtb. Thioridazine at high concentrations could enhance the activity of isoniazid and rifampicin, and in case of isoniazid resulted in elimination of mycobacteria and prevention of isoniazid-resistant mutants. Thioridazine had no added value in combination with moxifloxacin or amikacin. In mice with TB, thioridazine was poorly tolerated, limiting the maximum tolerated dose (MTD). The addition of thioridazine at the MTD to an isoniazid-rifampicin-pyrazinamide regimen for 13 weeks did not result in enhanced therapeutic efficacy.. Thioridazine is bactericidal towards Mtb in vitro, irrespective the mycobacterial growth rate and results in enhanced activity of the standard regimen. The in vitro activity of thioridazine in potentiating isoniazid and rifampicin is not reflected by improved therapeutic efficacy in a murine TB-model.

Topics: Animals; Antitubercular Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Isoniazid; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbial Viability; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Stem Cells; Thioridazine; Tuberculosis

It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007-2010 were investigated to assess whether interventions on dosing were effective.. Lists of all notified culture positive TB cases in 2007-2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007-2010 (p<0.001). The proportion of patients treated with consistent dosing of a 3-drug fixed-dose combination (FDC) increased from 73.9% in 2003 to 87.7% in 2007-2010 (p<0.001), and that for 2-drug FDC from 76.0% to 86.1% (p = 0.024), for rifampicin (RMP) from 62.8% to 85.5% (p<0.001), and for isoniazid from 87.8% to 95.3% (p<0.001). In 2007-2010, among 2917 patients treated with either FDCs or RMP in single-drug preparation, the dosage of RMP was adequate (8-12 mg/kg) in 2571(88.1%) patients, too high in 282(9.7%), too low in 64(2.2%). In multinomial logistic regression models, factors significantly associated with adequate dosage of RMP were body weight and preparations of RMP. Patients weighting <40 kg (relative risk ratio (rrr) 6010.5, 95% CI 781.1-46249.7) and patients weighting 40-49 kg (rrr 1495.3, 95% CI 200.6-11144.6) were more likely to receive higher-than-recommended dose of RMP.. Prescribing practice in the treatment of TB in Taipei City has remarkably improved after health authorities implemented a series of interventions.

Topics: Adult; Aged; Antitubercular Agents; Body Weight; Dose-Response Relationship, Drug; Drug Combinations; Drug Prescriptions; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Pyrazinamide; Rifampin; Taiwan; Tuberculosis; Young Adult

Tuberculous otitis media (TOM) is a rare cause of chronic suppurative infection of the middle ear. Due to that the symptoms and signs are often indistinguishable from those of nontuberculosis chronic otitis media and the fact that the index of suspicion is low, there is frequently a considerable delay prior to diagnosis. This can lead to irreversible complications such as facial nerve paralysis and labyrinthitis. Medical therapy with antituberculous drugs is usually effective. We report three cases with TOM diagnosticated and followed up in our Service from january 1993 to july 2001. Their charts were retrospectively reviewed for relevant historical data, physical findings, complementary studies, treatment and clinical response. We performed a review of the literature, emphasizing that TOM should be considered in the differential diagnosis of chronic otitis media.

Topics: Adult; Aged; Amoxicillin; Antitubercular Agents; Cerebrospinal Fluid Otorrhea; Drug Combinations; Ear Diseases; Female; Humans; Isoniazid; Male; Mycobacterium Infections; Mycobacterium tuberculosis; Otitis Media; Penicillins; Proteus Infections; Proteus mirabilis; Pyrazinamide; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Tuberculosis

Topics: Antitubercular Agents; Drug Combinations; Humans; Isoniazid; Pyrazinamide; Rifampin; Trimethoprim; Tuberculosis

Topics: Antitubercular Agents; Blood Donors; Drug Approval; Drug Combinations; Electromagnetic Phenomena; Equipment and Supplies; Equipment Failure; HIV Infections; HIV Seronegativity; Humans; Isoniazid; Pyrazinamide; Rifampin; Tuberculosis; United States; United States Food and Drug Administration; Wheelchairs

The bioavailability of isoniazid, rifampin, and pyrazinamide in 2 combined formulations of the 3 drugs (Rifater) for use primarily in the short-course chemotherapy of tuberculosis has been studied in Chinese patients in Singapore and Hong Kong. One formulation, containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet is suitable for daily use, whereas the other, containing higher proportions of isoniazid and pyrazinamide, is designed for intermittent treatment, each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide. Appropriate dosages for the Chinese patients, whose average weight was approximately 50 kg, were 5 and 6 tablets, respectively. Plasma concentrations of the 3 drugs after giving such dosages of the 2 combined formulations were compared in 16 patients, 8 in Singapore and 8 in Hong Kong, by means of a crossover study, with the concentrations obtained when identical doses of the 3 drugs were given using standard separate drug formulations. The concomitant urinary excretions of the drugs and their major metabolites were also estimated. Very similar results were obtained whether the drugs were given as the combined preparations or in their standard separate formulations, demonstrating the excellent bioavailability of all 3 drugs in each of the 2 combined formulations.

Topics: Acetylation; Adolescent; Adult; Biological Availability; Drug Combinations; Humans; Isoniazid; Middle Aged; Osmolar Concentration; Phenotype; Pyrazinamide; Rifampin; Time Factors; Tuberculosis