Overcalling Rifampicin Resistance by Rapid Molecular Xpert MTB/RIF Ultra - A Diagnostic Pitfall and Treatment Dilemma

Abstract

Tuberculosis (TB) is a worldwide pandemic and Sarawak constitutes the top three most TB prevalent state in Malaysia. Molecular WHO-recommended rapid diagnostic tests for TB (mWRDs) such as Cepheid GeneXpert’s Xpert MTB/RIF Ultra has been a game-changer in early detection of Mycobacterium tuberculosis (MTB), with additional rifampicin resistance information, enabling prompt and effective treatment of possible multidrug-resistant TB (MDR-TB). However, improved test sensitivity comes at the expense of specificity, causing higher risk of false positivity. We report a false-positive rifampicin resistance detected by Xpert MTB/RIF Ultra in a newly-diagnosed  pulmonary TB patient without MDR-TB risk factors. A 39-year-old healthy gentleman was admitted to the hospital for productive cough, increasing breathlessness, and constitutional symptoms for three months. Following his sputum acid-fast bacilli (AFB) smear positivity, first-line anti-TB treatment was started. The initial sputum culture was tested susceptible to first-line antibiotics. He completed the intensive phase, but during his maintenance phase, on the third day his sputum sample was positive for AFB, alerting of MDR-TB possibility. Sputum Xpert MTB/RIF Ultra showed MTB detection with rifampicin resistance. Repeated Xpert a week later revealed absence of rifampicin resistance. Additional testing using line probe assay and cultures no longer detected MTB complex, however, the incidental AFB-positive sputum was identified by culture to be a non-tuberculous mycobacterium. The patient responded with first line anti-TB re-treatment regime, and was discharged well. False-positive rifampicin resistance in Xpert MTB/RIF Ultra is uncommonly reported but may lead to overcalling and complicate MTB treatment. Patient clinical evaluation and careful MDR-TB risk assessment should be performed prior to treatment escalation.