Appendix 2. Interpretation of Xpert assay results

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    Update: October 2022

     

    2.1 Xpert MTB/RIF and Xpert MTB/RIF Ultra

    MTB: M. tuberculosis; RIF: rifampicin

     

    Results

    Interpretation and decisions

    Invalid/Error/No result

    Perform a 2nd test on a new specimen.

    MTB not detected

    • Child with suspected PTB: perform a 2nd test on a new (respiratory or stool) specimen.
    • Adult: re-evaluate clinically, perform x-ray if indicated, perform a 2nd test and/or a culture on a new specimen.

    MTB detected

    No RIF resistance detected

    • Treat for DS-TB.
    • Perform Xpert MTB/XDR, LPA or pDST to detect H resistance (a) Citation a. For all patients if possible, and at least those with high risk of H resistance (patients with previous TB treatment with H, or contact with a TB case resistant to H, or from an area with a prevalence of resistance to H ≥ 3%). ; adjust treatment according to DST.

    MTB detected

    RIF resistance detected

    Evaluate risk factors for rifampicin resistance (RR):

    • High risk of RR (b) Citation b. Patients with previous TB treatment with R, or contact with a TB case resistant to R, or from an area of high prevalence of resistance to R. : treat for MDR/RR-TB.
    • Low risk of RR (c) Citation c. Patients with no previous TB treatment with R, or contact with a TB case resistant to R, and from an area of low prevalence of resistance to R. : perform a 2nd test on a new specimen (d) Citation d. A 2nd test is necessary because in a population with a prevalence of resistance to rifampicin < 5%, the positive predictive value of one test is < 80%, i.e. > 20% of rifampicin resistant results are false positive. . If 2nd test shows:
      • R susceptibility: treat for DS-TB.
      • R resistance: treat for MDR/RR-TB.

     

    For patients with MDR/RR-TB, perform:

    MTB detected

    RIF resistance indeterminate

    • Xpert MTB/RIF:
      • Perform a 2nd test on a new specimen. If still “indeterminate”, treat for DS-TB while investigating RR.
      • Perform pDST or other gDST to confirm or rule out RR.
      • Perform Xpert MTB/XDR, LPA or pDST to detect H resistance (a) Citation a. For all patients if possible, and at least those with high risk of H resistance (patients with previous TB treatment with H, or contact with a TB case resistant to H, or from an area with a prevalence of resistance to H ≥ 3%). .
    • Xpert MTB/RIF Ultra:
      • Send an extraction of the raw results (gxx file) to a reference laboratory for identification of possible mutations (interpretation of melting curves).
      • If not feasible or still “indeterminate”: proceed as for Xpert MTB/RIF.

    MTB detected “trace”

    RIF resistance indeterminate

    (Xpert Ultra)

    • HIV-infected patients, children and EP specimens: a “trace” result should be considered as positive.
    • Adults with history of TB in the previous 5 years: a “trace” result cannot be interpreted, culture should be performed.
    • No interpretation of RR is possible.
    • If suspected resistance to R or other TB drugs: perform pDST or other gDST. Adjust treatment according to DST.  
    • Do not test the specimen with Xpert MTB/XDR as the Xpert MTB/XDR has a higher detection limit than Ultra.

    2.2 Xpert MTB/XDR

    MTB: M. tuberculosis; RIF: rifampicin; INH: isoniazid; FLQ: fluoroquinolones; ETH: ethionamide; AMK: amikacin; KAN: kanamycin; CAP: capreomycin

     

    Results

    Interpretation and decisions

    Invalid/Error/No result

    Perform a 2nd test on a new specimen.

    MTB detected

    After a positive Xpert MTB/RIF, an “MTB detected” result is expected because Xpert MTB/XDR and Xpert MTB/RIF have similar detection limit.

    MTB not detected

    No resistance detected

    • After a positive Xpert MTB/RIF: perform a 2nd test on a new specimen. If the 2nd test is negative, it can be performed on culture isolates.
    • After a “trace” result with Ultra, a negative result is expected because the Xpert MTB/XDR has a higher detection limit than Ultra.

    MTB detected

    No resistance detected

    • Treat according to the result of Xpert MTB/RIF or Ultra.
      Resistance cannot be ruled out because other resistance-conferring mutations are not detected by Xpert MTB/XDR (e.g. only 30% of Eto resistance conferring mutations are detected).
    • Perform pDST for resistance to other TB drugs and monitor treatment.

    MTB detected

    • Low INH resistance detected
    • INH resistance detected
    • Low FLQ resistance detected
    • FLQ resistance detected
    • ETH resistance detected
    • AMK, KAN and/or CAP resistance detected

    Evaluate risk factors of resistance for each drug:

    • High risk of resistance (e) Citation e. Patients with previous TB treatment with the drug or contact with a TB case resistant to the drug, or from an area of high prevalence of resistance to the drug. : consider as resistant to the drug.
      • If low-level H resistance detected (inhA mutation and no katG mutation): Hh can be used, but not counted as a likely effective drug.
      • If low-level resistance to FQs detected: Mfxh can be used, but not counted as a likely effective drug [2] Citation 2. World Health Organization. WHO operational handbook on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment. Geneva 2020.
        https://www.who.int/publications/i/item/9789240006997
        .
      • Resistance to Eto can be detected (inhA mutation). However, a negative result does not rule out resistance.
      • Perform pDST for resistance to other TB drugs and monitor treatment.
    • Low risk of resistance (f) Citation f. Patients with no previous TB treatment with the drug or contact with a TB case resistant to the drug, and from an area of low prevalence of resistance to the drug. : perform a 2nd test on a new specimen (g) Citation g. A 2nd test is necessary because in a population with a prevalence of resistance < 5%, the positive predictive value of one test is < 80% (i.e. > 20% of resistant results are false positive). . If the 2nd test shows:
      • Drug susceptibility: treat with the drug.
      • Drug resistance: consider as resistant (see above for “High risk of resistance to the drug).

    MTB detected

    Drug resistance indeterminate (h) Citation h. No “indeterminate” result is given for Eto.

    Perform a 2nd test on a new specimen. If still “indeterminate”: treat with likely effective drug(s) while investigating resistance with pDST or other gDST (second-line LPA, genome sequencing).

    • (a) For all patients if possible, and at least those with high risk of H resistance (patients with previous TB treatment with H, or contact with a TB case resistant to H, or from an area with a prevalence of resistance to H ≥ 3%).
    • (b)Patients with previous TB treatment with R, or contact with a TB case resistant to R, or from an area of high prevalence of resistance to R.
    • (c)Patients with no previous TB treatment with R, or contact with a TB case resistant to R, and from an area of low prevalence of resistance to R.
    • (d)A 2nd test is necessary because in a population with a prevalence of resistance to rifampicin < 5%, the positive predictive value of one test is < 80%, i.e. > 20% of rifampicin resistant results are false positive.
    • (e)Patients with previous TB treatment with the drug or contact with a TB case resistant to the drug, or from an area of high prevalence of resistance to the drug.
    • (f)Patients with no previous TB treatment with the drug or contact with a TB case resistant to the drug, and from an area of low prevalence of resistance to the drug.
    • (g)A 2nd test is necessary because in a population with a prevalence of resistance < 5%, the positive predictive value of one test is < 80% (i.e. > 20% of resistant results are false positive).
    • (h)No “indeterminate” result is given for Eto.
    References