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

Abstract

BackgroundGeneXpert MTB/RIF (Xpert) assay was applied widely to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance.MethodsRetrospectively 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.Results63 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.ConclusionsMore 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 registrationretrospectively registered in Wuhan Jinyintan Hospital (No. 2021-KY-16).