What question did this study set out to answer?

To highlight a case of false rifampicin resistance detection in Mycobacterium tuberculosis due to a P454L mutation on the rpob gene.

July 23, 2026Mycobacteria0 citationsOpen Access

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

CGCharlotte Genestet IEIsabelle Eberl BJBrune Joannard

Key Points

To highlight a case of false rifampicin resistance detection in Mycobacterium tuberculosis due to a P454L mutation on the rpob gene.
Case report of a patient with smear-positive pulmonary tuberculosis and initial rifampicin resistance detected by Xpert MTB/RIF Ultra.
Extended genotypic drug susceptibility testing using Deeplex Myc-TB revealed the P454L mutation, confirmed by whole genome sequencing.
Phenotypic DST performed via the MGIT method after 19 days confirmed susceptibility to rifampicin and other antibiotics.
Initial detection of rifampicin resistance due to P454L mutation, classified as uncertain by WHO.
Patient treated successfully, leading to a cure after 6 months of treatment and healthy 3-month follow-up.
No resistance mutations were found for isoniazid, pyrazinamide, ethambutol, and fluoroquinolones.

Abstract

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). 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. 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.

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