Browsing by Author "Eisenach, Kathleen D."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Direct susceptibility testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 system
    (American Society for Microbiology, 2016-05) Demers, Anne-Marie; Venter, Amour; Friedrich, Sven O.; Rojas-Ponce, Gabriel; Mapamba, Daniel; Jugheli, Levan; Sasamalo, Mohammed; Almeida, Deepak; Dorasamy, Afton; Jentsch, Ute; Gibson, Mara; Everitt, Daniel; Eisenach, Kathleen D.; Diacon, Andreas H.
    Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster. Agreement between the direct and indirect methods varied from 90 to 100% in each laboratory. The median times for obtaining PZA results from the time when the specimen was collected ranged from 11 to 16 days for the direct test and 18 to 95 days for the indirect test across laboratories. The direct method is accurate and reproducible across laboratories. It can be expected to accelerate results in >50% of cases, but it cannot replace indirect DST for PZA. Phenotypic methods remain the gold standard for DST in drug trials. If future studies can optimize the method to decrease the number of uninterpretable results, direct MGIT DST could be the new phenotypic DST standard for clinical trials, providing more rapid detection of resistance to new drugs in experimental regimens.
  • Thumbnail Image
    Item
    A metabolic biosignature of early response to anti-tuberculosis treatment
    (BioMed Central, 2014-01) Mahapatra, Sebabrata; Hess, Ann M.; Johnson, John L.; Eisenach, Kathleen D.; DeGroote, Mary A.; Gitta, Phineas; Joloba, Moses L.; Kaplan, Gilla; Walzl, Gerhard; Boom, W. H.; Belisle, John T.
    Background The successful treatment of tuberculosis (TB) requires long-term multidrug chemotherapy. Clinical trials to evaluate new drugs and regimens for TB treatment are protracted due to the slow clearance of Mycobacterium tuberculosis (Mtb) infection and the lack of early biomarkers to predict treatment outcome. Advancements in the field of metabolomics make it possible to identify metabolic profiles that correlate with disease states or successful chemotherapy. However, proof-of-concept of this approach has not been provided for a TB-early treatment response biosignature (TB-ETRB). Methods Urine samples collected at baseline and during treatment from 48 Ugandan and 39 South African HIV-seronegative adults with pulmonary TB were divided into discovery and qualification sets, normalized to creatinine concentration, and analyzed by liquid chromatography-mass spectrometry to identify small molecule molecular features (MFs) in individual patient samples. A biosignature that distinguished baseline and 1 month treatment samples was selected by pairwise t-test using data from two discovery sample sets. Hierarchical clustering and repeated measures analysis were applied to additional sample data to down select molecular features that behaved consistently between the two clinical sites and these were evaluated by logistic regression analysis. Results Analysis of discovery samples identified 45 MFs that significantly changed in abundance at one month of treatment. Down selection using an extended set of discovery samples and qualification samples confirmed 23 MFs that consistently changed in abundance between baseline and 1, 2 and 6 months of therapy, with 12 MFs achieving statistical significance (p < 0.05). Six MFs classified the baseline and 1 month samples with an error rate of 11.8%. Conclusions These results define a urine based TB-early treatment response biosignature (TB-ETRB) applicable to different parts of Africa, and provide proof-of-concept for further evaluation of this technology in monitoring clinical responses to TB therapy.