Phenotypic drug susceptibility characterization and clinical outcomes of tuberculosis strains with A-probe mutation by GeneXpert MTB/RIF

BMC Infect Dis. 2023 Nov 27;23(1):832. doi: 10.1186/s12879-023-08509-0.

Abstract

Background: GeneXpert MTB/RIF (Xpert) assay was applied widely to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance.

Methods: Retrospectively investigated the association among treatment histories, phenotypic drug susceptibility testing (pDST) results, and clinical outcomes of patients infected with probe A absent mutation isolate confirmed by Xpert.

Results: 63 patients with only probe A absent mutation and 40 with additional pDST results were analyzed. 24 (60.0%) patients had molecular-phenotypic discordant rifampicin (RIF) susceptibility testing results, including 12 (12/13, 92.3%) new tuberculosis (TB) patients and 12 (12/27, 44.4%) retreated ones. 28 (28/39, 71.8%) retreated patients received first-line treatment regime within two years with failed outcomes. New patients had better treatment outcomes than retreated ones (successful: 83.3% VS. 53.8%; P value = 0.02). The clinical results of RIF-susceptible TB confirmed by pDST were not better than RIF-resistant TB (successful: 62.5% VS. 50.0%; P value = 0.43). INH-resistant TB and INH-susceptible TB had similar treatment outcomes too (successful: 61.5% VS. 50.0%; P value = 0.48). 11 (11/12, 91.7%) new patients treated with the short treatment regimen (STR) had successful outcomes.

Conclusions: More than half of mono probe A absent isolates had RIF molecular-phenotypic discordance results, especially in new patients. Probe A mutations were significantly associated with unsuccessful clinical outcomes, whether the pDST results were RIF susceptible or not. STR was the best choice for new patients.

Trial registration: retrospectively registered in Wuhan Jinyintan Hospital (No. 2021-KY-16).

Keywords: Clinical outcome; GeneXpert MTB/RIF; Mutation; Mycobacterium tuberculosis; Rifampicin-resistant.

MeSH terms

  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • Mycobacterium tuberculosis* / genetics
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Sensitivity and Specificity
  • Tuberculosis* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / diagnosis
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • Rifampin