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Background <p>For tuberculosis management, the World Health Organization (WHO) recommends testing for rifampicin resistance in order to administer the appropriate antibiotic regimen. Almost all (95%) cases of rifampicin-resistant <i>Mycobacterium tuberculosis</i> (MTB) are the result of a chromosomal mutation in the rifampicin resistance-determining region of the <i>rpob</i> gene, located between codon 426 and codon 452. Xpert® MTB/RIF Ultra (Cepheid) is a rapid genotypic method for detecting mutations in the rifampicin resistance-determining region (RRDR).</p> Case presentation <p>A case of smear-positive pulmonary tuberculosis initially detected as rifampicin-resistant by an Xpert® MTB/RIF Ultra (Cepheid) is reported herein. An extended genotypic drug susceptibility testing (DST) using Deeplex® Myc-TB (GenoScreen) rapidly revealed the isolated presence of a P454L mutation on <i>rpob</i>, which was confirmed by whole genome sequencing. This mutation is not included in the RRDR, and is characterized as uncertain (i.e. there is no clear evidence that the mutation is associated with rifampicin resistance, group 3) by the WHO. There was no resistance mutation for other anti-tuberculosis drugs (isoniazide, pyrazinamide, ethambutol and fluoroquinolones). The patient was initially treated with rifampicin, isoniazid, pyrazinamide, ethambutol, and levofloxacin, while waiting for the results of the phenotypic DST by MGIT method (i.e. 19&#xa0;days) that found susceptibility to rifampicin, isoniazid, and ethambutol. The minimal inhibitory concentration of rifampicin was 0.125&#xa0;mg/L (microdilution method). Levofloxacin was then discontinued, as was ethambutol. Tritherapy was continued for little over 1&#xa0;month, followed by bitherapy (rifampicin, isoniazid) for a further 4&#xa0;months. At the end of the 6&#xa0;months of treatment, pulmonary tuberculosis was considered cured. Three months after the end of treatment, the patient returned for a consultation and was still in good health and without respiratory symptoms.</p> Conclusions <p>Herein, we report for the first time a false detection of rifampicin resistance using Xpert MTB/RIF Ultra (Cepheid) due to a P454L mutation on <i>rpob</i>. This clinical case illustrates the potential for personalized and effective management of pulmonary tuberculosis through cooperation between clinicians and microbiologists and access to a range of rapid molecular biology diagnostic tools.</p>

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False detection of rifampicin resistance using Xpert MTB/RIF Ultra due to a P454L mutation on rpob in Mycobacterium tuberculosis: a case report

  • 期刊论文

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  • 发表日期：

    2026年7月21日

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  • Charlotte Genestet,
  • Isabelle Eberl,
  • Brune Joannard,
  • Oana Dumitrescu,
  • Elisabeth Hodille

摘要

Background

For tuberculosis management, the World Health Organization (WHO) recommends testing for rifampicin resistance in order to administer the appropriate antibiotic regimen. Almost all (95%) cases of rifampicin-resistant Mycobacterium tuberculosis (MTB) are the result of a chromosomal mutation in the rifampicin resistance-determining region of the rpob gene, located between codon 426 and codon 452. Xpert® MTB/RIF Ultra (Cepheid) is a rapid genotypic method for detecting mutations in the rifampicin resistance-determining region (RRDR).

Case presentation

A case of smear-positive pulmonary tuberculosis initially detected as rifampicin-resistant by an Xpert® MTB/RIF Ultra (Cepheid) is reported herein. An extended genotypic drug susceptibility testing (DST) using Deeplex® Myc-TB (GenoScreen) rapidly revealed the isolated presence of a P454L mutation on rpob, which was confirmed by whole genome sequencing. This mutation is not included in the RRDR, and is characterized as uncertain (i.e. there is no clear evidence that the mutation is associated with rifampicin resistance, group 3) by the WHO. There was no resistance mutation for other anti-tuberculosis drugs (isoniazide, pyrazinamide, ethambutol and fluoroquinolones). The patient was initially treated with rifampicin, isoniazid, pyrazinamide, ethambutol, and levofloxacin, while waiting for the results of the phenotypic DST by MGIT method (i.e. 19 days) that found susceptibility to rifampicin, isoniazid, and ethambutol. The minimal inhibitory concentration of rifampicin was 0.125 mg/L (microdilution method). Levofloxacin was then discontinued, as was ethambutol. Tritherapy was continued for little over 1 month, followed by bitherapy (rifampicin, isoniazid) for a further 4 months. At the end of the 6 months of treatment, pulmonary tuberculosis was considered cured. Three months after the end of treatment, the patient returned for a consultation and was still in good health and without respiratory symptoms.

Conclusions

Herein, we report for the first time a false detection of rifampicin resistance using Xpert MTB/RIF Ultra (Cepheid) due to a P454L mutation on rpob. This clinical case illustrates the potential for personalized and effective management of pulmonary tuberculosis through cooperation between clinicians and microbiologists and access to a range of rapid molecular biology diagnostic tools.