Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs. Extensively-resistant tuberculosis (XDR-TB) is defined as resistance to at least isoniazid and rifampicin, and to any fluoroquinolone, and to any of the three second-line injectables (amikacin, capreomycin, and kanamycin) [1]. Pre XDR-TB is defined as people with MDR-TB, but who also have some resistance to second line drugs, but not sufficient for them to be categorized as having XDR-TB [2]. World Health Organization’s current policy recommends that Xpert MTB/RIF (Mycobacterium tuberculosis/Rifampicin) should be used as an initial diagnostic test in children suspected of having tuberculosis [3]. We conducted this study to determine efficacy of Xpert MTB/RIF for diagnosis of tuberculosis, and also to compare rifampicin resistance found on Xpert MTB/RIF with that of drug susceptibility tests (DST).

Thirty-four children (age 3 mo-15 yr) newly diagnosed clinically as tuberculosis [4], and referred to the Pediatric TB clinic at a tertiary children’s hospital in Mumbai, and who had underwent Xpert MTB/RIF, cultures by Mycobacteria growth indicator tube (MGIT) and smear examination for acid-fast bacillus (AFB) as part of their diagnostic work-up were enrolled in the study. Both pulmonary and extrapulmonary cases were included. Specimens sent for testing included respiratory specimens [sputum, bronchial or tracheal aspirates, bronchoalveolar lavage (BAL) and gastric lavage (GL)] and extrapulmonary specimens [tissue biopsy, pus from abscess, cerebrospinal fluid (CSF), ascitic and pericardial fluid].

Xpert MTB/RIF was positive in 20 (58.8%) patients. TB MGIT culture revealed M tuberculosis in 19 (63.3%) out of 30 patients tested. Acid-fast bacillus (AFB) positivity of smear was seen in 10 (29.4%) patients. Association of Xpert MTB/RIF with culture is depicted in Table I.

TABLE I	Results of Xpert MTB/RIF When Compared with AFB Smear and  TB Cultures 

Xpert MTB/RIF was positive in 58.8% of clinically diagnosed cases of tuberculosis, and had sensitivity of 78.9% and specificity of 81.8%. Sensitivity and specificity of Xpert MTB/RIF for bacteriologically (either AFB or culture positive) confirmed cases of tuberculosis was 80% and 71.4%, respectively (P=0.003)

On DST, Pre XDR-TB was present in 5 (29.4%) patients, MDR-TB was seen in 5 (29.4%) and 1 (9%) had polyresistant TB. In 6 (35.2%), there was no resistance seen. Rifampicin-resistance was seen in 11 (55%) on Xpert MTB/RIF of which 3 (27.3%) were subsequently found to be pre-XDR on DST, 3 (27.3%) were MDR with additional resistance to ethambutol, streptomycin and ethionamide and 2 (9%) were MDR-TB. Of the 11 patients with rifampicin-resistance on Xpert MTB/RIF, DST was not done in 2 patients and 1 was culture negative. One patient with no rifampicin-resistance on Xpert MTB/RIF was found to have pre-XDR TB on conventional DST. One patient each with pre-XDR TB, polyresistant TB (rifampicin and streptomycin resistance) and MDR-TB had a negative Xpert MTB/RIF result. Sensitivity of Xpert MTB/RIF to pick up drug resistant TB as compared to conventional DST was 72.7% and specificity was 83.3%.

We conclude that although Xpert MTB/RIF test could be a useful tool for rapid identification of rifampicin resistant M. tuberculosis the test results must always be confirmed by culture and DST to increase the yield of bacteriological diagnosis, and also to detect additional drug resistance.

Contributors: Both authors were involved in conception and design; the acquisition, analysis, and interpretation of data; drafting the manuscript; and final approval of the version to be published.

Funding: None; Competing interest: None stated.

1. WHO. Stop TB Department. Drug-resistant Tuberculosis. Frequently Asked Questions, 2012. Available from: http://www.who.int/tb/challenges/mdr/tdrfaqs/en/. Accessed June 15, 2016.

2. Types of Drug Resistant TB – MDR and XDR TB. Available from: http://www.tbfacts.org/types-of-drug-resistant-tb/. Accessed June 15, 2016.

3. World Health Organization (WHO). Automated Real-time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children Policy update 2013. Available from: http://apps.who.int/iris/handle/10665/112472. Accessed June 15, 2016.

4. World Health Organization (WHO). Definitions and Reporting Framework for Tuberculosis – 2013 Revision. Geneva. Available from: http://apps.who.int/iris/handle/10665/112472. Accessed November 17, 2014.

5. Shah I, Chilkar S. Clinical profile of drug resistant tuberculosis in children. Indian Pediatr. 2012;49:741-4.

6. Zetola NM, Shin SS, Tumedi KA, Moeti K, Ncube R, Nicol M, et al. Mixed Mycobacterium tuberculosis complex infections and false-negative results for rifampin resistance by GeneXpertMTB/RIF are associated with poor clinical outcomes. J Clin Microbiol. 2014;52:2422-9.