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

BMC Infect Dis. 2021 Feb 24;21(1):205. doi: 10.1186/s12879-021-05884-4.

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.

Keywords: Antimicrobial susceptibility testing; Drug-resistance; Preventive therapy; Trial; Tuberculosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antitubercular Agents / therapeutic use
  • Cross-Sectional Studies
  • Feasibility Studies
  • Female
  • Humans
  • Isoniazid / therapeutic use*
  • Male
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / isolation & purification*
  • Rifampin / therapeutic use*
  • Sputum / microbiology*
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents
  • Isoniazid
  • Rifampin