Time to Detection of Mycobacterium Tuberculosis in Sputum Culture Correlates With Outcome in Patients Receiving Treatment for Pulmonary Tuberculosis

Epstein, Marcia; Schluger, Neil W.; Davidow, Amy L.; Bonk, Stanley; Rom, William N.; Hanna, Bruce A.

doi:10.1378/chest.113.2.379

Cited by 78 publications

(48 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eligibility criteria were identical for all sites; however, the radiographic extent of disease (no cavitary disease but more lung fields involved by any tuberculous lesions) was greater in Uganda, and the time to positive liquid culture, a measure of initial sputum bacillary load (26), was higher in Uganda. No patients relapsed with TB at the Philippines site where radiographic lesions were less profuse and the initial sputum bacillary load was lower.…”

Section: Discussionmentioning

confidence: 99%

Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion

Johnson¹,

Hadad²,

Dietze³

et al. 2009

Am J Respir Crit Care Med

129

108

View full text Add to dashboard Cite

Rationale: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients. Objectives: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months. Methods: This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or to stop treatment. Patients were followed for relapse for 30 months after beginning treatment. Measurements and Main Results: Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10). Conclusion: Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.

show abstract

Section: Discussionmentioning

confidence: 99%

Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion

Johnson¹,

Hadad²,

Dietze³

et al. 2009

Am J Respir Crit Care Med

129

108

View full text Add to dashboard Cite

show abstract

“…Time to detection in broth culture (TTD) is a potential end point that has a good correlation with quantitative culture on solid medium (11,13). An initial small study had suggested a correlation between a shorter time to detection (an indication of higher numbers of viable bacilli) and poor treatment outcomes (9). In this study, TTD was evaluated as a marker of regimen potency.…”

mentioning

confidence: 98%

Evaluation of Time to Detection of Mycobacterium tuberculosis in Broth Culture as a Determinant for End Points in Treatment Trials

Weiner¹,

Prihoda

Burman

et al. 2010

J Clin Microbiol

View full text Add to dashboard Cite

Time to detection of Mycobacterium tuberculosis in broth culture was examined for utility as a treatment efficacy end point. Of 146 patients in a phase IIB trial, a decreased mean time to detection was found in 5 with treatment failure. Time to detection in an analysis-of-covariance model was associated with lung cavities, less intensive treatment, and differences in the bactericidal effects of treatment regimens.Development of new treatments for tuberculosis is hampered by the lack of an accurate surrogate end point and the high degree of efficacy of current 6-month regimens. Sputum culture status after 2 months of therapy, a binary test, is widely used for phase IIB trials but has only moderate accuracy for predicting failure/relapse (12) and requires large sample sizes (4,8). Changes in the number of colonies found in dilutions of sputum applied to solid medium is an end point that has been used to assess activities of single drugs and doses in phase IIA (early-bactericidal-activity) studies (10) and has also been suggested as an end point for phase IIB trials (15). Though promising, quantitative culture on solid medium involves prolonged sputum collections and intensive laboratory techniques and has been difficult to standardize at multiple sites. Time to detection in broth culture (TTD) is a potential end point that has a good correlation with quantitative culture on solid medium (11,13). An initial small study had suggested a correlation between a shorter time to detection (an indication of higher numbers of viable bacilli) and poor treatment outcomes (9). In this study, TTD was evaluated as a marker of regimen potency. Preliminary results have been reported elsewhere (16). MATERIALS AND METHODSExperimental design. Patients for this study were drawn from Tuberculosis Trials Consortium (TBTC) Study 27, a randomized phase IIB trial that compared moxifloxacin to ethambutol and treatment 5 versus 3 times per week during the initial 2 months of treatment among patients with smear-positive, pulmonary tuberculosis (4). After completion of intensive-phase therapy, patients received standard continuation-phase treatment (3). The primary end point of the treatment trial was the dichotomous end point of 2-month culture status.For this post hoc study, TTD data were available from two African sites. Of 176 African patients in study 27, TTD data were available for 163 (93%). Treatment failure occurred in six of these patients, and although the patients were not routinely followed after therapy, one with a relapse was identified 5 weeks after treatment.Specimen collection and laboratory procedures. Spontaneously expectorated (spot) sputum samples were cultured every 2 weeks during the first 2 months and monthly thereafter. Standard culture methods were used but differed somewhat between sites. In Uganda, samples were processed using a final concentration of 1% sodium hydroxide, inoculated into Bactec 12B bottles, and monitored with the Bactec 460 system. In South Africa, a final concentration of 1.25% sodium hydroxide, M...

show abstract

“…A positive culture was defined as a growth index (GI) Ͼ 30. The number of days until positive (DTP) BACTEC culture was recorded as the time after inoculation until a positive GI was obtained (7). The data were analyzed by using SAS software 9.1.…”

mentioning

confidence: 99%

Cavitary Disease and Quantitative Sputum Bacillary Load in Cases of Pulmonary Tuberculosis

et al. 2007

View full text Add to dashboard Cite

show abstract

Time to Detection of Mycobacterium Tuberculosis in Sputum Culture Correlates With Outcome in Patients Receiving Treatment for Pulmonary Tuberculosis

Cited by 78 publications

References 12 publications

Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion

Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion

Evaluation of Time to Detection of Mycobacterium tuberculosis in Broth Culture as a Determinant for End Points in Treatment Trials

Cavitary Disease and Quantitative Sputum Bacillary Load in Cases of Pulmonary Tuberculosis

Contact Info

Product

Resources

About