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

Abstract

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.

Detection of katG and inhA Gene Mutation in Rifampicin-resistant Mycobacterium Tuberculosis Using Line Probe Assay (LPA) in Kebbi, Nigeria.

“…From the study conducted, every sample (100%) with rifampicin-resistant tuberculosis had mutations in all three genes. This is in similarities with results obtained from a similar study, which shows a 75% of multidrug resistance in all rifampicin-resistant tuberculosis (Demers et al 2021). In this study, although inhA mutations were seen in all rifampicin-resistant MTB, no Non-rpoB/katG mutation was exclusively responsible for drug resistance of any kind.…”

Sputum Smear Non-conversion at the End of Intensive Phase of Tuberculosis Treatment at a Tertiary Center: A Descriptive Cross-sectional study

“…3 TB epidemiology and resistance patterns could have changed in recent years needing different screening and rapid DST approaches. 17 This study provided valuable insight regarding the non-conversion rates among new cases, which might be important in exploring this in detail with another survey.…”

High Prevalence of Tuberculosis Infection and Disease in Child Household Contacts of Adults With Rifampin-resistant Tuberculosis

“…A sputum sample was also tested for TB microbiology. 10 Their household members were enumerated and a household questionnaire completed, which included questions describing the physical characteristics of the dwelling.…”

“…Additional details on resistance testing can be found elsewhere. 10 The index participant was the parent for 32% of child HHCs. When the index participant was the child HHC's parent, 66% shared the same room; whereas when the index participant was not the parent, 29% shared the same room.…”