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Community-based short-course treatment of pulmonary tuberculosis in a developing nation. Initial report of an eight-month, largely intermittent regimen in a population with a high prevalence of drug resistance.

A community-based tuberculosis case-finding and short-course chemotherapy program was conducted in a suburb of Manila and featured 1 month of daily isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) followed by 7 months of twice-weekly, high dose, directly observed INH + EMB + PZA. Church-affiliated lay workers obtained 1,990 sputum specimens from subjects who complained of chronic cough or wasting symptoms; 207 of the specimens were positive on Ziehl-Neelsen smears. On culture, 176 yielded a significant growth of M. tuberculosis. Of these 176 patients, 144 were selected to enter the study; 10 were lost because of withdrawal or death and four (2.7%) because of drug toxicity. This left 130 patients who were followed long-term. Remarkably, 80% (104) were initially shedding drug-resistant organisms; 26% (34) were resistant to one drug, 30% (40) were resistant to two drugs, and 24% (30) were resistant to three or more drugs. Responses to therapy corresponded closely to the extent of drug resistance: 80% (48 of 60) of patients with drug-susceptible or single resistance had a favorable outcome; 43% (28 of 65) were resistant to two or three drugs, and 0% (0 of 5) of those were resistant to four or more drugs. Notable findings of this study were the success of a community-based program in conducting prolonged, directly observed treatment, the unexpectedly high prevalence of multiple-drug-resistant organisms in this population, and the inadequacy of INH + PZA + EMB during the continuation phase of therapy in this setting.

Antitubercular Agents↗

A controlled clinical comparison of 6 and 8 months of antituberculosis chemotherapy in the treatment of patients with silicotuberculosis in Hong Kong. Hong Kong Chest Service/tuberculosis Research Centre, Madras/British Medical Research Council.

Patients with silicotuberculosis have been reported to respond poorly to antituberculosis chemotherapy. Therefore, in a study in Hong Kong, 240 Chinese male patients with both silicosis and pulmonary tuberculosis were all prescribed treatment three times weekly with streptomycin, isoniazid, rifampin, and pyrazinamide, allocated at random to be given for a total duration of either 6 (M6 regimen) or 8 months (M8 regimen) in a concurrent comparison. Those with a history of previous antituberculosis chemotherapy received ethambutol as well for the first 3 months. The intake in the M6 regimen was terminated when preliminary results showed that it was inadequate, and a further 53 patients were assigned to the M8 series. Of 91 assessable patients in the concurrent comparison with susceptible strains pretreatment, 44% were culture negative at 1 month, 80% at 2 months, and 98% at 3 months, and 1 had an unfavorable bacteriologic response during chemotherapy. During 3 yr of assessment, bacteriologic relapse after chemotherapy occurred in 22% of the M6 compared with 7% of the M8 patients (p less than 0.025, log-rank test). Inadequate chemotherapy was received by 12% of the 240 patients in the concurrent comparison because of default and by 22% because of adverse effects, but by 3 yr 92% of patients with susceptible strains pretreatment in each series had a favorable status following retreatment for relapse or for initially inadequate chemotherapy when required. The results show that patients with silicosis require at least 8 months of treatment.

Adult↗

Combined toxicity of zidovudine and antituberculosis chemotherapy.

Because antituberculosis agents and zidovudine are commonly used in HIV-infected patients, we performed a cohort study to determine the toxicity of such combined therapy. A group of 24 consecutive human immunodeficiency virus (HIV)-infected patients with tuberculosis who received concomitant antituberculosis therapy and zidovudine (tuberculosis group) were compared with 24 patients who received zidovudine but not antituberculosis medications (comparison group). Comparison patients were matched to tuberculosis patients by age, sex, ethnic group, month of starting zidovudine, and CD4 cell count. Most tuberculosis patients received isoniazid, rifampin, pyrazinamide, and ethambutol initially, followed by isoniazid and rifampin for a mean total duration of 8.4 months. Baseline clinical and laboratory parameters in tuberculosis and comparison patients were similar, except for the mean hemoglobin (11.2 g/dl in tuberculosis patients versus 12.9 g/dl in comparison patients, p = 0.03). The mean zidovudine dose in tuberculosis and comparison patients was approximately 500 mg/day, and the mean duration of zidovudine therapy was 10.3 and 9.6 months, respectively. Symptoms occurred during therapy with similar frequency in both groups. The frequency and severity of leukopenia and granulocytopenia were similar in tuberculosis and comparison patients, but marked anemia (hemoglobin less than 9.5 g/dl) developed in 50% of tuberculosis patients and 17% of comparison patients (p = 0.03). The maximum decrease in hemoglobin during therapy was similar in both groups (mean of 2.0 versus 1.6 g/dl, respectively), suggesting that the higher frequency of marked anemia in tuberculosis patients was due to their lower baseline hemoglobin values. Although transfusions were required in five tuberculosis patients and one comparison patient, zidovudine was not permanently discontinued in any patient because of anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Quantitative bacillary response to treatment in HIV-associated pulmonary tuberculosis.

A group of 122 patients with culture-proven pulmonary tuberculosis were recruited to examine the concentrations of Mycobacterium tuberculosis in sputum and the relationship to HIV-1 antibody status. They were followed for up to 28 days from the start of antituberculous chemotherapy to assess the early bacillary response to two chemotherapeutic regimens. Of 67 treated with streptomycin, thiacetazone, and isoniazid 17 were HIV positive, and subsequently 55, of whom 20 were HIV positive, were treated with streptomycin, rifampin, isoniazid, and pyrazinamide. The mean initial concentration of M. tuberculosis in the sputum of the HIV-negative patients was significantly higher than in HIV-positive patients (6.95 and 6.34 log colony-forming units respectively; p = 0.019). The HIV-positive patients had less radiologic evidence of disease and significantly fewer zones of lung affected with cavities. The response to treatment was similar, but with HIV-positive patients more likely to become culture negative by 28 days. The differences that exist between HIV-positive and HIV-negative patients are minor, and standard regimens are at least as effective in HIV-positive patients in the first month of treatment.

AIDS-Related Opportunistic Infections↗

Cerebrospinal fluid drug concentrations and the treatment of tuberculous meningitis.

Tuberculous meningitis is a very serious form of tuberculosis. In the absence of randomized controlled trials of alternative treatment regimens, its management depends on employing potent drugs that penetrate well into the cerebrospinal fluid (CSF). The penetration of isoniazid, rifampin, and streptomycin into the CSF of 27 Chinese patients was studied using fluorimetric and microbiologic procedures. Isoniazid rapidly diffused into the CSF, peak concentrations in excess of 3 mg/L, or over 30 times its minimal inhibitory concentration (MIC) against Mycobacterium tuberculosis being attained within 4 hr. In contrast, rifampin and streptomycin penetrated very slowly across the meninges, and CSF levels only slightly in excess of their MICs against M. tuberculosis were achieved. The penetration of the drugs into the CSF correlated poorly with differences in their partitioning between octanol/water and cyclohexane/water but could be predicted using a simple model based on their renal clearance rates and plasma protein binding. It is recommended that patients with tuberculous meningitis should be treated for at least 9 months with a combination of isoniazid, rifampin, and pyrazinamide, which may be supplemented in the first 2 mo with streptomycin.

Administration, Oral↗

Tuberculosis control policies in major metropolitan health departments in the United States. V. Standard of practice in 1992.

Since 1978, we have surveyed the 28 metropolitan health departments initially reporting > 250 cases of tuberculosis/yr to determine the standard of practice in the control of pulmonary tuberculosis and the factors affecting treatment policy. In this survey, results were compared with data obtained in 1978, 1980, 1984, and 1988. As in the previous years, all departments completed the survey. The predominant treatment regimen was 6 months of chemotherapy (64 +/- 1.33% of patients) involving isoniazid (I), rifampin (R), and pyrazinamide (Z). Estimated duration of treatment, which had decreased from 20.2 +/- 2.1 months in 1980 to 7.58 +/- 1.02 months in 1988, increased to 9.34 +/- 2.32 months in 1992 (p < 0.01). This was attributed to an increase in drug-resistant cases (17 of 25 programs) and to increased incidence of HIV infection during the previous 4 yr. In 1984, HIV infection was estimated to coincide with tuberculosis in 2.54% of all patients, 7.72% in 1988, and 17.42% in 1992. Several other major departures from prior perceived practices were reported. In 1980, 32.1% of all patients were hospitalized initially for tuberculosis treatment, and this number decreased progressively to 17.8% in 1988; in 1992, 34.2 +/- 1.32% of patients with tuberculosis were hospitalized for initial treatment. In 1988, no program reported regular use of alternative therapy to isoniazid for chemoprophylaxis; in 1992, 21 programs used alternative regimens (predominantly R-containing). In 1992, nine programs reported increased funds for treatment of tuberculosis (27.2 +/- 1.97% after inflation), whereas 16 reported a mean decrease of 14% after inflation.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

Relationship between Mycobacterium simiae and Mycobacterium habana.

Strains of the species Mycobacterium simiae give a positive niacin test. On the basis of their cultural and biochemical characteristics and by seroagglutination they can be classified into 2 subspecies. (1) The strains of serotype M. simiae 1 hydrolyze urea regularly and nicotinamide and pyrazinamide irregularly. They are photochromogenic after prolonged exposure to light. (2) The strains of serotype M. simiae 2 hydrolyze urea only. Three of 4 strains are scotochromogenic; the fourth has a pale pink pigment. Two of these strains possess alpha- and beta-esterase activity. The other two are negative in this test. Strains of M. habana are culturally and biochemically identical with the serotype M. simiae 1 and show the same serologic specificity as M. simiae 1. M. habana sera, after having been absorbed by M. simiae 1, retain a small amount of agglutinins specific for M. habana. We believe that the M. habana strains belong to the species M. simiae and are closely related to the serotype M. simiae 1.

Agglutination↗

A controlled trial of a 2-month, 3-month, and 12-month regimens of chemotherapy for sputum smear-negative pulmonary tuberculosis: the results at 30 months. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council.

Of 1,033 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on 5 initial microscopic examinations, 370 (36%) had 1 or more initial sputum cultures that yielded tubercle bacilli. All patients were randomly allocated to (1) selective chemotherapy, antituberculosis chemotherapy not being started until active disease had been confirmed, or to (2) daily streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months or (3) the same 4 drugs daily for 3 months, or toi (4) a 12-month control regimen. In patients with 1 or more of their initial sputum cultures positive, the short-course regimens were inadequate, being followed by bacteriologic relapse rates of 15 and 9%, respectively, during 30 months, compared with 0% in the control series. In patients with all their initial cultures negative, the corresponding relapse rates were 4, 2, and 0%, and in the selective chemotherapy series, 53% of the patients had treatment started during the 30 months because active disease was confirmed (bacteriologically in 40%). It is important to continue studying short-course chemotherapy for smear-negative patients because in many countries they represent a high proportion of those treated.

Adolescent↗

A controlled trial of 2-month, 3-month, and 12-month regimens of chemotherapy for sputum-smear-negative pulmonary tuberculosis. Results at 60 months.

Of 1,019 Chinese patients with radiologically active pulmonary tuberculosis but with sputum negative for acid-fast bacilli on 5 initial microscopic examinations who were studied for 5 yr, 364 (36%) had 1 or more initial sputum cultures positive for Mycobacterium tuberculosis. All 1,019 patients were randomly allocated to (1) selective chemotherapy (antituberculosis chemotherapy not being started until the disease had been confirmed to be active); or to (2) daily streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months; or (3) for 3 months; or to (4) a standard 12-month control regimen. In the 364 patients with 1 or more of their initial sputum cultures positive, the short-course regimens were inadequate, being followed by relapse rates of 32 and 13%, respectively, during 60 months, compared with 5% in the control series. In the 655 patients with all their initial cultures negative, the corresponding relapse rates were 11, 7, and 2%. In the selective chemotherapy series, 57% of the patients had treatment started during the 60 months because their disease was confirmed to be active.

Antitubercular Agents↗

Clinical trial of two short-course (6-month) regimens and a standard regimen (12-month) chemotherapy in retreatment of pulmonary tuberculosis in Pakistan. Results 18 months after completion of treatment (Lahore Tuberculosis Study).

This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol (RHZ and RHE regimens) against a standard daily regimen of streptomycin, isoniazid, and ethambutol (SHE regimen) given for 6 months followed by isoniazid and ethambutol for an additional 6 months. Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study. Three hundred and fifty-eight patients were admitted to the study and 267 (75%) completed chemotherapy. Eighty-five percent of RHZ-regimen and 82% of RHE-regimen patients achieved sputum culture negativity compared to 55% of patients in SHE regimen. Successfully treated patients were followed up for 18 months, and among these, all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period. Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period, and no statistically significant difference in relapse rate was noticed in the 3 regimens. Severe drug intolerance necessitated discontinuation of therapy in only 2 patients.

Antitubercular Agents↗

Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis.

RATIONALE: Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study. OBJECTIVE: To evaluate the activity of intermittent rifabutin-based therapy. METHODS: Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid. MEASUREMENTS: Culture-positive treatment failure or relapse. MAIN RESULTS: A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35-175) and 5.3 log10 copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4 < 100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p < 0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs. CONCLUSIONS: Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.

AIDS-Related Opportunistic Infections↗

The safety of antituberculosis medications during breastfeeding.

Most antituberculosis drugs appear to be safe for use with breastfeeding. These agents are excreted in breast milk at relatively small concentrations. No adverse effects have been reported to date. The percentages of the therapeutic dose of antituberculosis agents that potentially may be delivered to the nursing infants range from 0.05% to 28%. Currently isoniazid, rifampin, ethambutol, streptomycin (first-line agents), kanamycin and cycloserine (second-line agents) are the only agents considered by the AAP to be compatible with breastfeeding. Unfortunately, there are still no clear data on the safety of pyrazinamide, ethionamide, and capreomycin during breastfeeding. If the mother chooses to breastfeed, it may be prudent to examine the infant for signs and symptoms of toxicity. In infants requiring treatment with antituberculosis agents, it is important to use therapeutic doses since drug concentrations in breast milk are not adequate as effective therapy for treatment or prevention. However, dosing at the lower end of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid) to decrease the risk of toxicity.

Adult↗

Patterns of antimicrobial susceptibility in Michigan wildlife and bovine isolates of Mycobacterium bovis.

The state of Michigan has recognized the presence of Mycobacterium bovis in its free-ranging white-tailed deer population since 1994. This endemic infection is primarily located in a 12-county area in the northeastern lower peninsula of Michigan. A statewide surveillance and eradication program of the disease has been in effect since 1994. Worldwide, Mycobacterium tuberculosis complex organisms have a known predilection toward development of antimicrobial resistance. The objective of this study was to investigate the antimicrobial susceptibility of M. bovis isolates from white-tailed deer in Michigan and detect any changes in susceptibility over time. M. bovis isolates from 2 fall hunting seasons (1999 and 2004) were used in this study. The fall season of 2004 marked the first documented case of direct transmission of M. bovis from a wild deer to a human in Michigan. Since M. bovis is a zoonotic disease, knowledge of susceptibility can expedite treatment options in humans. M. bovis isolates were obtained from 58 deer, 4 coyotes, 3 cattle, 2 raccoons, and 1 human case from the 2 years combined. Methods of susceptibility testing included 1% proportion agar plates and Bactec radiometric broth testing. M. bovis was found to be uniformly resistant to the antibiotic pyrazinamide; this resistance is common to all M. bovis isolates. No other antimicrobial resistance was found in any of the tested M. bovis isolates, which may be, in part, attributed to the lack of any significant treatment pressure in wildlife.

Animals↗

In vitro susceptibility testing of Mycobacterium tuberculosis strains to trifluoperazine.

The presence of calmodulin-like protein (CAMLP) has been demonstrated in mycobacteria and it has been observed that there is a positive correlation between levels of CAMLP, phospholipids as well as lipids and growth. Thus the use of trifluoperazine, which is a calmodulin antagonist, would inhibit the growth of mycobacterial cells. The authors carried out in vitro susceptibility testing of Mycobacterium tuberculosis strains to trifluoperazine with their minimum inhibitory concentrations (MIC) determination. 70 strains of M. tuberculosis isolated from cases of pulmonary as well as extrapulmonary tuberculosis were included. The following antimycobacterial drugs: streptomycin, isonized, rifampicin, ethambutol were tested on Lowerstein and Jenson (LJ) slopes using the resistance ratio method and the proportion method for pyrazinamide testing. All strains and the control H37RV were cultured into Youmans and Karlson's liquid medium and MICS were determined for trifluoperazine. Trifluoperazine MICs ranged between 8-32 microg/ml for strains susceptible to routine antimycobacterial drugs while strains resistant to streptomycin and isoniazid had lower MIC values, between 8-16 microg/ml. As trifluoperazine is already in human use for psychotic disorders, its antitubercular activity could pave the way for human trials as an antitubercular drug.

Antitubercular Agents↗

Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter?

A nested case-control study was conducted in order to examine whether dosing schedules of standard pyrazinamide-containing anti-tuberculosis (TB) treatment (standard treatment) might affect hepatotoxicity. The present authors retrospectively identified all patients with hepatitis using biochemical criteria from a cohort of 3,007 clinic patients who commenced anti-TB treatment from January 1 to June 30, 2001. Each case with hepatitis between 1-9 weeks post-TB treatment was compared using conditional logistic regression analysis with two controls selected randomly from patients without hepatitis in the same period and matched by sex, age and standard treatment. Impacts of sex and age were examined by logistic regression analysis of cases and patients without hepatitis. Hepatitis occurred in 167 patients, of whom 96 qualified as cases. A conditional logistic risk model identified hepatitis B surface antigen carriage as the only risk factor (odds ratio (95% confidence interval (CI)) 1.8 (1.1-3.1)). Logistic regression analysis showed that sex was nonsignificant but ageing increased the odds of hepatitis. The risk of hepatitis increased from 2.6% (1.9-3.5%) to 4.1% (3.2-5.3%) as age exceeded 49 yrs. Dosing schedules in the first 9 weeks have little impact on hepatotoxicity. If patients at risk of both hepatitis and relapse receive standard treatment, daily dosing is preferable.

Adult↗

Tuberculosis therapy: past, present and future.

The major historical landmarks of tuberculosis (TB) therapy include: the discovery of effective medications (streptomycin and para-aminosalicylic acid) in 1944; the revelation of "triple therapy" (streptomycin, para-aminosalicylic acid and isoniazid) in 1952, which assured cure; recognition in the 1970s that isoniazid and rifampin could reduce the duration of treatment from 18 to 9 months; and the observation in the 1980s that adding pyrazinamide to these drugs allowed cures in only 6 months. To combat noncompliance, intermittent regimens, twice or thrice weekly, have been proven to cure even far-advanced TB in as few as 62-78 encounters over 26 weeks. However, these regimens are not sufficiently short or convenient to facilitate effective treatment in resource-poor countries. Therefore, drug-resistant strains have emerged to threaten TB control in various areas of the world, including India, China, Russia and the former Soviet Union. For these reasons, it is vital that new medications are developed to shorten the duration of therapy, increase the dosing interval of intermittent regimens and replace agents lost to resistance. Other special considerations include identifying optimal therapy for persons with acquired immune deficiency syndrome, particularly noting the problems of drug/drug interactions for those receiving antiretroviral treatment. Finally, the Alchemist's Dream of tuberculosis should be pursued: modulating the immune response to shorten treatment and/or overcome drug resistance.

Antitubercular Agents↗

Drug-resistant pulmonary tuberculosis in Berlin, Germany, 1987-1993.

Resistance of Mycobacterium tuberculosis (M.tb) strains is an increasing problem worldwide. Since no public health data are available for urban populations in Germany, we investigated resistance in our hospitalized patients (n = 1,011) over the last 7 yrs. We therefore evaluated clinical data and results of susceptibility tests (breakpoint technique/proportion method) for isoniazid, streptomycin, rifampin, pyrazinamide, protionamide and ethambutol. Since 1987, there has been a relatively constant rate of 5.9% (3.9%-7.8%) for single-drug resistance (SDR), but an increasing rate of multidrug-resistant (MDR) strains (> or = 2 first-line drugs) from 1.7% in 1987 to 5.8% in 1993. Sixty nine percent of patients with MDR strains showed resistance to two drugs, and 31% to three or more drugs. Risk factors for SDR and MDR tuberculosis revealed previous therapy (odds ratio (OR) (95% confidence interval (95% CI)); SDR 2.2 (1.7-4.0); MDR 4.5 (2.3-8.8)); and foreign-born status (SDR 2.2 (1.3-3.6); MDR 3.5 (1.8-6.8)) to be the most important factors associated with resistance. Both primary and acquired resistance were higher in foreign-born than in German-born patients. We conclude that there was a considerable increase in multidrug-resistant tuberculosis in our hospital from 1987 to 1993. Since previously treated patients and patients born in countries with a high level of primary resistance had an increased risk of drug-resistant tuberculosis, we would advise a four drug regimen as initial therapy in those patients.

Adult↗

Rapid drug susceptibility testing of Mycobacterium tuberculosis using conventional solid media.

Radiometric methods for M. tuberculosis drug susceptibility testing yield much faster results than standard techniques; however, these methods require sophisticated equipment and are expensive. We investigated a rapid drug susceptibility testing method for isoniazid, rifampin, ethambutol, streptomycin and pyrazinamide in specimens from 197 patients with pulmonary tuberculosis using a simplified agar-dilution method. Middlebrook 7H11 agar solid medium and microcolony detection were used to test sputum from 64 smear-positive, and from 70 culture-positive but smear-negative patients. Culture-positive material from bronchoscopy, surgical biopsy, pleural fluid or gastric fluid of 63 patients was tested. In 64 smear-positive patients, the median time for final susceptibility results was 11 days (95% confidence interval (95% CI) 10-12 days) compared to 62 days (95% CI 56-66 days) with the standard method. In 133 smear-negative patients, results were available after a median of 35 days (95% CI 32-40 days) in contrast to 72 days (95% CI 62-83 days) with the standard method, regardless of whether or not sputum or other materials were used for primary culture. The rapid method detected all cases of single-drug resistance (n = 20) and multidrug resistance (n = 14) within 13 days (95% CI 9-17 days) in smear-positive patients (n = 8), or within 38 days (95% CI 35-48 days) in smear-negative patients (n = 26). Only one discrepancy was encountered in 985 resistance tests. Moreover, contamination was not observed. Our rapid susceptibility testing method for M. tuberculosis on Middlebrook 7H11 agar is fast, practical and inexpensive. It provides an alternative when more sophisticated techniques are not available or affordable.

Adolescent↗