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PubMedDate not supplied

Incorporation of antibiotics in liposomes designed for tuberculosis therapy by inhalation.

Liposomal encapsulation of tuberculostatic drugs can potentially increase their therapeutic index. The incorporation of isoniazid, pyrazinamide, rifampicin, ethionamide, and streptomycin in extruded distearoylphosphatidylcholine/cholesterol liposomes designed for administration through inhalation was evaluated. Ethionamide and rifampicin were incorporated during lipid film formation, whereas solutions of the remaining drugs were used to hydrate preformed lipid bilayers. Final drug to lipid ratios around 0.3 were achieved for isoniazid and pyrazinamide, and mean vesicle diameters varied from 286 to 329 nm. No expressive drug leakage or mean vesicle diameter changes occurred during 3 weeks. No significant incorporation was achieved for streptomycin, ethionamide, and rifampicin.

Administration, Inhalation↗
PubMed2000

Increasing drug resistance of Mycobacterium tuberculosis isolates in Ontario, Canada, 1987-1998.

We examined trends in resistance to first-line antituberculous agents for Mycobacterium tuberculosis strains isolated in Ontario, Canada from 1987 through 1998 (n=8069). The proportions resistant were as follows: isoniazid, 9.6%; rifampin, 1.9%; streptomycin, 4. 9%; ethambutol, 1.3%; and pyrazinamide, 1.7%. Resistance to isoniazid has increased markedly since 1990, whereas resistance to streptomycin, ethambutol, and pyrazinamide increased from 1997 through 1998. Resistance to both isoniazid and rifampin did not increase. The incidence of persistence and reactivation (early or late treatment failure) was 1-2 per 100 person-years (PY) in the first 7-12 months and 0.3-0.9 per 100 PY from 13 months to 5 years thereafter. For initially susceptible strains, the incidence of resistance to isoniazid was 0.11 per 100 PY and for and rifampin was 0.06 per 100 PY in the first year and negligible thereafter, with an overall risk of 0.14% for isoniazid and 0.10% for rifampin. Resistance of M. tuberculosis to antituberculous agents, and in particular to isoniazid, is a growing problem in Ontario and is higher than elsewhere in Canada.

Antitubercular Agents↗
PubMed2002

Drug-drug interactions in inmates treated for human immunodeficiency virus and Mycobacterium tuberculosis infection or disease: an institutional tuberculosis outbreak.

The use of rifamycins is limited by drug interactions in human immunodeficiency virus (HIV)-infected persons who are receiving highly active antiretroviral therapy (HAART). During a tuberculosis (TB) outbreak at a prison housing HIV-infected inmates, rifabutin was used to treat 238 men (13 case patients and 225 contacts). Steady-state peak plasma rifabutin concentrations were obtained after rifabutin dosages were adjusted for men receiving single-interacting HAART (with either 1 protease inhibitor [PI] or efavirenz), multi-interacting HAART (with either 2 PIs or > or =1 PI with efavirenz), and for noninteracting HAART (>1 nucleoside reverse-transcriptase inhibitor or no HAART) without rifabutin dose adjustments. Low rifabutin concentrations occurred in 9% of those receiving noninteracting HAART, compared with 19% of those receiving single-interacting and 29% of those receiving multi-interacting HAART (chi2, 3.76; P=.05). Of 225 contacts treated with rifabutin-pyrazinamide, 158 (70%) completed treatment while incarcerated. Rifabutin-pyrazinamide therapy was difficult to implement, because of the need for dosage adjustments and expert clinical management.

Adult↗
PubMed1995

Mycobacterium xenopi infection masquerading as pulmonary tuberculosis in two patients infected with the human immunodeficiency virus.

Mycobacterium xenopi infections have rarely been reported among patients infected with the human immunodeficiency virus (HIV). We recently treated two HIV-infected men, neither of whom had a history of pulmonary disease or AIDS-defining conditions, and who had M. xenopi lung infections. Both patients presented with night sweats, cough, and pleuritic chest pain. Chest radiographs showed an upper-lobe nodule in the first patient and a perihilar cavitary infiltrate in the second patient. Both patients were initially believed to have pulmonary tuberculosis and were treated accordingly; however, only M. xenopi grew on cultures of multiple respiratory specimens. This diagnosis was confirmed by cultures of biopsied lung tissue from the first patient and of fluid from a peritracheal abscess in the second patient. Both patients' clinical conditions improved after multidrug therapy (isoniazid, rifampin, pyrazinamide, ethambutol, and ciprofloxacin in the first case; isoniazid, rifampin, and pyrazinamide in the second case). The second patient's condition improved despite in vitro resistance of his isolate to isoniazid and rifampin.

AIDS-Related Opportunistic Infections↗
PubMed2004

Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis.

OBJECTIVES: This study was carried out to explore lectin-functionalized poly (lactide-co-glycolide) nanoparticles (PLG-NPs) as bioadhesive drug carriers against tuberculosis (TB), in order to reduce the drug dosage frequency of antitubercular drugs and thus improve patient compliance in TB chemotherapy. METHODS: Wheat germ agglutinin (WGA)-coated PLG-NPs were prepared by a two-step carbodiimide procedure. This formulation was administered to guinea pigs through the oral/aerosol route for a detailed pharmacokinetic and chemotherapeutic evaluation. Immunological or hepatotoxic effects of WGA lectin, if any, were also determined. RESULTS: WGA-functionalized PLG-NPs were in the size range of 350-400 nm, with binding of 3-3.5 microg of WGA/mg of PLG-NPs and drug encapsulation efficiency of 54%-66%. Upon administration of lectin-coated PLG-NPs through the oral/aerosol route, the presence of drugs in plasma was observed for 6-7 days for rifampicin and 13-14 days for isoniazid and pyrazinamide. However, upon administration of uncoated PLG-NPs (oral/aerosolized) rifampicin was detectable in plasma for 4-6 days, whereas isoniazid and pyrazinamide were detectable for 8-9 days. All three drugs were present in lungs, liver and spleen for 15 days. Administration of WGA-coated PLG-NPs caused a significant (P < 0.001) increase in the relative bioavailability of antitubercular drugs. Chemotherapeutic studies revealed that three doses of oral/nebulized lectin-coated nanoparticles fortnightly could yield undetectable mycobacterial colony forming units (cfu); this was achievable with 45 doses of oral free drugs. CONCLUSION: WGA-functionalized PLG-NPs could be potential drug carriers for antitubercular drugs through the oral as well as aerosol route for effective TB control.

Administration, Oral↗
PubMed1998

Effect of trifluoperazine, a potential drug for tuberculosis with psychotic disorders, on the growth of clinical isolates of drug resistant Mycobacterium tuberculosis.

The effect of the antipsychotic drug trifluoperazine (TFP) on the in-vitro growth of 50 clinical isolates of Mycobacterium tuberculosis was tested. Of these isolates, 29 were susceptible to all five of the antitubercular drugs isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide, and 21 were resistant to one or more of the five drugs. The minimum inhibitory concentration (MIC) of TFP was 4 microg/ml for 40% of both the susceptible (12/29) and resistant (8/21) isolates and 8 microg/ml for 55% (16/29) and 48% (10/21) of the susceptible and resistant isolates respectively. Further analysis of the data for resistant isolates indicated that the MIC of TFP was 4 microg/ml and 16 microg/ml respectively for 50% (4/8) and 75% (6/8) of the isolates resistant to one drug only from isoniazid, streptomycin or pyrazinamide. Of the nine isolates resistant to two drugs, isoniazid and streptomycin, the MIC was 4 microg/ml for 33% (3/9) and 16 microg/ml for 80% (7/9). The MIC of TFP for two isolates resistant to the three drugs isoniazid, rifampicin and streptomycin was 8 microg/ml for one and 32 microg/ml for the other. Of two isolates resistant to all five drugs, it is of interest to note that the MIC of TFP was only 4 microg/ml for one but 32 microg/ml for the other. Because the above MICs are for TFP as a single drug, it would be desirable to study the antitubercular activity of the serum of tuberculosis patients with psychotic problems receiving regular antitubercular therapy supplemented with TFP at its recommended and tolerated dose.

Antipsychotic Agents↗
PubMed1994

Activity of levofloxacin in a murine model of tuberculosis.

The activity of levofloxacin (LEV) was evaluated in a murine model of tuberculosis. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 were given intravenously to 4-week-old female outbred mice. In a dose-response study, treatment with LEV at 100, 200, and 400 mg/kg of body weight was started 1 day after infection and was given daily for 28 days. Viable cell counts were determined from homogenates of spleens and lungs. A dose-related reduction in organism cell counts in organs was noted for LEV. The activities of LEV at 100, 200, and 300 mg/kg were compared with those of first-line antituberculosis agents. Both isoniazid and rifampin were more active than LEV. There was no difference in activity between LEV and either ethambutol or pyrazinamide against splenic organisms. The activities of ethambutol and LEV at the two higher doses were comparable against lung organisms. LEV at 300 mg/kg was more active than pyrazinamide against lung organisms. The activity of LEV was compared with those of two other quinolones, ofloxacin and sparfloxacin. LEV at 200 mg/kg had more than twofold greater activity than ofloxacin at the same dose. Sparfloxacin at 100 mg/kg was more active than LEV at 200 mg/kg; however, the activities of sparfloxacin at 50 mg/kg and LEV at 200 mg/kg were comparable. The promising activity of LEV in M. tuberculosis-infected mice suggests that it is a good candidate for clinical development as a new antituberculosis agent.

Animals↗
PubMed1995

Activities of poloxamer CRL8131 against Mycobacterium tuberculosis in vitro and in vivo.

A poloxamer surfactant, CRL8131, was evaluated for activity against Mycobacterium tuberculosis (Erdman) by itself and in combination with antibiotics in broth culture, in a macrophage cell line assay, and in testing with mice. In the broth culture, CRL8131 suppressed the growth of M. tuberculosis and produced synergistic effects in combination with isoniazid, rifampin, and streptomycin. It also displayed synergy with isoniazid and rifampin against two drug-resistant isolates. In the macrophage cell line assay, CRL8131 produced a synergistic effect on intracellular killing of M. tuberculosis by isoniazid, rifampin, streptomycin, pyrazinamide, thiacetazone, D-cycloserine, ethionamide, amikacin, clindamycin, and p-aminosalicylic acid. It demonstrated no synergy or antagonism with ethambutol, gentamicin, kanamycin, ciprofloxacin, or nalidixic acid. Finally, with C57BL/6 mice infected with M. tuberculosis, a combination of CRL8131 and either thiacetazone or pyrazinamide produced 100% survival at 40 days whereas the antibiotics produced only 33% survival and CRL8131 produced 0% survival when used as single agents. This improved survival rate was associated with a significant reduction in the number of organisms in the lungs and spleens of infected mice.

Animals↗
PubMed1987

Mycobacterium malmoense infections in Scotland: an increasing problem.

During 1982-4 20 cases of Mycobacterium malmoense infection were identified in Scotland (13 male, seven female; age 34-82, median 62 years). Features of the disease were obtained from case notes and radiographs of 19 patients and were found to be indistinguishable from those of patients with pulmonary tuberculosis. Chronic chest disease, predominantly chronic airflow obstruction, was the most frequent associated disease. The organisms showed in vitro resistance in eight patients to rifampicin, in 19 patients to isoniazid, and in all patients to pyrazinamide and p-aminosalicylic acid. Nevertheless, all patients showed an early response to standard combination chemotherapy with rifampicin, isoniazid, and ethambutol, with or without pyrazinamide. Five have been cured and none had died of the infection, although four died of unrelated disease. Of nine patients still having treatment, five had relapsed after completing a course of antituberculosis drugs. All had received ethambutol for less than five months. The response to standard drugs was more satisfactory when the course included administration of ethambutol for at least nine months. Currently one new infection with M malmoense occurs in Scotland for every 40 with tuberculosis, and the incidence appears to be rising. In view of this, it is suggested that when tuberculosis is suspected the chemotherapeutic regimen should include ethambutol until the culture results are reported. If these then show M malmoense, ethambutol should be continued in the combination for at least nine months.

Adult↗
PubMed1996

Molecular mechanisms of drug resistance in Mycobacterium tuberculosis.

In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed. Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to act on the same targets in M. tuberculosis as they do in E. coli. Resistance to these agents results from single mutagenic events that lead to amino acid substitutions in their target proteins. The mechanisms of action of the unique antitubercular drugs, including isoniazid, ethambutol, and pyrazinamide have also recently been defined. Resistance to isoniazid can be caused either by mutations in the katG-encoded catalase-peroxidase, the enzyme responsible for drug activation, or by the molecular target, the inhA-encoded long chain enoyl-ACP reductase. Ethambutol appears to block specifically the biosynthesis of the arabinogalactan component of the mycobacterial cell envelope, and pyrazinamide has no known target. With the resurgence of tuberculosis and the appearance of strains which are multiply resistant to the above compounds, present tuberculosis chemotherapies are threatened. New approaches to the treatment of multi drug-resistant tuberculosis are needed.

Antitubercular Agents↗
PubMed1994

Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention.

Treatment of Tuberculosis. 1. A 6-mo regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 mo followed by isoniazid and rifampin for 4 mo is the preferred treatment for patients with fully susceptible organisms who adhere to treatment. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should be included in the initial regimen until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (i.e., there is less than 4% primary resistance to isoniazid in the community, and the patient has had no previous treatment with antituberculosis medications, is not from a country with a high prevalence of drug resistance, and has no known exposure to a drug-resistant case). This four-drug, 6-mo regimen is effective even when the infecting organism is resistant to INH. This recommendation applies to both HIV-infected and uninfected persons. However, in the presence of HIV infection it is critically important to assess the clinical and bacteriologic response. If there is evidence of a slow or suboptimal response, therapy should be prolonged as judged on a case by case basis. 2. Alternatively, a 9-mo regimen of isoniazid and rifampin is acceptable for persons who cannot or should not take pyrazinamide. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should also be included until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (see Section 1 above). If INH resistance is demonstrated, rifampin and ethambutol should be continued for a minimum of 12 mo. 3. Consideration should be given to treating all patients with directly observed therapy (DOT). 4. Multiple-drug-resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended. 5. Children should be managed in essentially the same ways as adults using appropriately adjusted doses of the drugs. This document addresses specific important differences between the management of adults and children. 6. Extrapulmonary tuberculosis should be managed according to the principles and with the drug regimens outlined for pulmonary tuberculosis, except for children who have miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis who should receive a minimum of 12 mo of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1997

Tuberculosis control policies in major metropolitan health departments in the United States. VI. Standard of practice in 1996.

Since 1980, we have surveyed at 4-yr intervals the metropolitan health departments initially reporting > 250 cases of tuberculosis to determine the perceived standard of practice for tuberculosis control and the factors affecting formulation of treatment policies. Between 1992 and 1996, use of supervised short-course (6 to 9 mo) intermittent therapy with multiple drugs including isoniazid, ethambutol, pyrazinamide, and rifampin increased from 4.3% to 46% of all new patients. Pyrazinamide use for initial treatment for children has increased substantially and now predominates (74.2% of patients in 1996 versus 48.1% of patients in 1992). Duration of treatment, which was 20 +/- 2.1 mo in 1980, is now 8.00 +/- 2.29 mo in 1996. The incidence of human immunodeficiency virus-associated tuberculosis, which was virtually unrecognized in 1984, has remained the same between 1992 and 1996 (18.0%). As in previous years, there was a wide variance among health departments in the incidence (< 5% to > 40%) of HIV-associated tuberculosis. After years of funding decreases, there has been an impressive increase in resources in the past 4 yr. In 1988, mean budget allocation for health departments decreased by 7.9% versus the prior 4 yr and, in 1992, there was no overall change in budget allocation after inflation versus 1988. In 1996, however, funds for treatment increased by 84 +/- 33%. This increase in funding has been translated into the greatly expanded use of supervised intermittent therapy and aggressive screening programs, which likely have resulted in the decreased incidence of tuberculosis since the prior survey.

AIDS-Related Opportunistic Infections↗
PubMed2003

Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis.

Tuberculosis continues to be a major cause of morbidity and mortality in the world. The expansion of tuberculosis control programs has been limited by the lengthy and cumbersome nature of current chemotherapeutic regimens. A new drug that improves the sterilizing activity of current regimens would reduce the duration of therapy without sacrificing efficacy, thereby enhancing treatment completion rates and preserving precious public health resources. The new 8-methoxyfluoroquinolone moxifloxacin has potent activity against both actively multiplying and nonactively multiplying tubercle bacilli. Using a murine model that is representative of chemotherapy for human tuberculosis, we show that the combination of moxifloxacin, rifampin, and pyrazinamide reduced the time needed to eradicate Mycobacterium tuberculosis from the lungs of infected mice by up to 2 months when compared with the standard regimen of isoniazid, rifampin, and pyrazinamide. The findings suggest that this regimen has the potential to substantially shorten the duration of therapy needed to cure human tuberculosis.

Analysis of Variance↗
PubMed2005

The diagnosis and therapy of tuberculosis during the past 100 years.

Methods for the radiographic diagnosis of tuberculosis have improved from simple fluoroscopy to computerized tomography. Although direct smear examination is still the most widely used bacteriological method of diagnosis, cultural methods with selective liquid media are sensitive and rapid. The use of antituberculosis drugs has changed tuberculosis from a disease with about a 50% mortality, treated by measures to collapse the affected lung lesions and by rest for the patient, to a condition successfully curable by chemotherapy. Key steps in the development of modern chemotherapy regimens were the demonstrations in clinical trials that (1) streptomycin was effective; (2) combination of drugs prevented the emergence of drug-resistant Mycobacterium tuberculosis; (3) chemotherapy under domiciliary conditions was effective and did not put family members at risk of infection; (4) patient compliance could be assisted by fully supervised intermittent regimens, or more effectively, by (5) shortening treatment by the introduction of rifampin and pyrazinamide, the two most potent sterilizing drugs, into the regimens. Regimens were divided into an initial intensive phase, while bacterial populations were high, and a longer continuation phase to complete sterilization. Pyrazinamide was shown to sterilize only in the intensive phase. The treatment of nonpulmonary tuberculosis followed the same plan, but when bacterial populations are low, fewer drugs are required in combination.

Antitubercular Agents↗
PubMed2005

Rifapentine, moxifloxacin, or DNA vaccine improves treatment of latent tuberculosis in a mouse model.

RATIONALE: Priorities for developing improved regimens for treatment of latent tuberculosis (TB) infection include (1) developing shorter and/or more intermittently administered regimens that are easier to supervise and (2) developing and evaluating regimens that are active against multidrug-resistant organisms. OBJECTIVES AND METHODS: By using a previously validated murine model that involves immunizing mice with Mycobacterium bovis bacillus Calmette-Guérin to augment host immunity before infection with virulent Mycobacterium tuberculosis, we evaluated new treatment regimens including rifapentine and moxifloxacin, and assessed the potential of the Mycobacterium leprae heat shock protein-65 DNA vaccine to augment the activity of moxifloxacin. MEASUREMENTS: Quantitative spleen colony-forming unit counts, and the proportion of mice with culture-positive relapse after treatment, were determined. MAIN RESULTS: Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxacin were as active as daily isoniazid for 6-9 mo. Six-month daily combinations of moxifloxacin with pyrazinamide, ethionamide, or ethambutol were more active than pyrazinamide plus ethambutol, a regimen recommended for latent TB infection after exposure to multidrug-resistant TB. The combination of moxifloxacin with the experimental nitroimidazopyran PA-824 was especially active. Finally, the heat shock protein-65 DNA vaccine had no effect on colony-forming unit counts when given alone, but augmented the bactericidal activity of moxifloxacin. CONCLUSIONS: Together, these findings suggest that rifapentine, moxifloxacin, and, perhaps, therapeutic DNA vaccination have the potential to improve on the current treatment of latent TB infection.

Animals↗
PubMed2006

Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis.

RATIONALE: Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans. OBJECTIVE: To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens. METHODS: Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed. MEASUREMENTS: The primary endpoint was sputum culture status at 2 mo of treatment. RESULTS: Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy. CONCLUSIONS: The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.

Adult↗
PubMed1993

Controlled trial of ciprofloxacin in short-term chemotherapy for pulmonary tuberculosis.

The study was undertaken in patients with newly diagnosed bacteriologically positive pulmonary tuberculosis. The patients were randomly allocated to receive one of two regimens. In one of the regimens, patients received 2 months of daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide (SHRZ) followed by isoniazid plus rifampin for 4 months (4 HR). In the other regimen, patients received 2 months of daily streptomycin, isoniazid, pyrazinamide, and ciprofloxacin (SHZ Cipro) followed by isoniazid plus ciprofloxacin for 4 months. All patients in the SHRZ/HR regimens and all but one in the SHZ Cipro/H Cipro regimens had a favorable bacteriologic response during chemotherapy. In the patients in the SHZ Cipro/H Cipro regimen, ciprofloxacin was well tolerated during the period of treatment. After chemotherapy, one (5.9 percent) of 17 patients in the SHRZ/HR group and three (16.6 percent) of 18 patients in the SHZ Cipro/H Cipro group relapsed bacteriologically.

Adult↗
PubMed2002

Direct sensitivity test of the MB/BacT system.

In order to evaluate the direct-method test of sensitivity to drugs used in the principal tuberculosis treatment regimes, in the Organon Teknika MB/BacT system, we tested 50 sputum samples positive to microscopy taken from patients with pulmonary tuberculosis and with clinical indications for an antibiogram, admitted sequentially for examination during the routine of the reference laboratory. The material was treated v/v with 23% trisodium phosphate solution, incubated for 24 h at 35 degrees C, and neutralized v/v with 20% monosodium phosphate solution. The material was then centrifuged and the sediment inoculated into flasks containing Rifampin - 2 micro g/ml, Isoniazid - 0.2 micro g/ml, Pyrazinamide - 100 micro g/ml, Ethambutol - 2.5 micro g/ml, Ethionamide - 1.25 micro g/ml, and Streptomycin - 2 micro g/ml. The tests were evaluated using the indirect method in the BACTEC 460 TB (Becton Dickinson) system as the gold standard. The results showed that the Rifampin test performed best, i.e., 100% sensitivity at 95% Confidence Interval (82.2-100) and 100% specificity at 95% Confidence Interval (84.5-100), followed by Isoniazid and Pyrazinamide. In this experiment, 92% of the materials showed a final reading in 30 days; this period represents the time for primary isolation as well as the results of the sensitivity profile, and is within Centers for Disease Control and Prevention recommendations regarding time for performance of the antibiogram. The inoculated flasks showed no contamination during the experiment. The MB/BacT is shown to be a reliable, rapid, fully automated nonradiometric system for the tuberculosis antibiogram.

Antitubercular Agents↗