Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial.

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.

Pre-treatment mycobacterial sputum load influences individual on-treatment measurements.

Time to culture positivity (TTP) in liquid medium is now widely available as a measure of viable mycobacterial sputum load. TTP correlates well with and could replace colony-forming unit (CFU) counting in studies of antituberculosis drug effects. We investigated the influence of the pre-treatment mycobacterial sputum load on 4428 CFU measurements obtained within the first 14 days of treatment. Using a prediction model we show that pre-treatment CFU counts contribute 29% to the variation of on-treatment CFU counts and increase the precision of the prediction of on-treatment CFU from TTP by 12%. On the other hand, pre-treatment TTP contributed only 12% to the variation of on-treatment TTP and only added 2% to the prediction of TTP from CFU. We conclude pre-treatment measurements are covariates that can enhance the accuracy of statistical estimates of treatment effects, particularly when measured by CFU counts.

Time to positivity in liquid culture predicts colony forming unit counts of Mycobacterium tuberculosis in sputum specimens.

Time to liquid culture positivity (TTP) is a technically accessible and widely available measure of viable mycobacterial load in sputum samples. We describe the ability of TTP to predict colony forming unit counts of Mycobacterium tuberculosis from sputum samples collected before or during the first 14 days of antituberculosis therapy.