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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 4  |  Page : 1101-1102

Heading Toward Resistance, Head-On: A Case of XDR Tuberculous Meningitis

1 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh; Department of Microbiology, AIIMS, Bilaspur, Himachal Pradesh, India
3 Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
5 Department of Mycobacteriology and Mycology, Bureau of Public Health Laboratories , Jacksonville, Florida, USA

Date of Submission23-Dec-2020
Date of Decision24-Dec-2020
Date of Acceptance29-Mar-2021
Date of Web Publication2-Sep-2021

Correspondence Address:
Kusum Sharma
Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.325329

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How to cite this article:
Sharma K, Sharma M, Modi M, Goel A, Shree R, Sharma A, Ray P, Rowlinson MC. Heading Toward Resistance, Head-On: A Case of XDR Tuberculous Meningitis. Neurol India 2021;69:1101-2

How to cite this URL:
Sharma K, Sharma M, Modi M, Goel A, Shree R, Sharma A, Ray P, Rowlinson MC. Heading Toward Resistance, Head-On: A Case of XDR Tuberculous Meningitis. Neurol India [serial online] 2021 [cited 2021 Nov 28];69:1101-2. Available from:


Clinical outcomes of tuberculous meningitis (TBM) are compromised further if the Mycobacterium tuberculosis isolate is extremely drug resistant (XDR). The data regarding XDR-TBM are limited to few reports, although without case discussion.[1],[2] We present here a confirmed case of XDR-TBM in an Indian male.

A 22-year-old man presented to our emergency department on February 23, 2019, with depressed sensorium and recurrent vomiting. He had a past history of low-grade intermittent fever lasting 6 weeks in June 2018 for which he was empirically treated elsewhere for suspected typhoid fever. He was started on Category I antitubercular therapy (ATT) for pulmonary tuberculosis (TB) in October 2018 based on cough and chest radiography. There was no past history of TB disease or any history of contact with a known TB case. At our center, the cerebrospinal fluid (CSF) showed 200 cells (predominant polymorphonuclear lymphocytes), low glucose (33 mg/dL), and elevated protein (240 mg/dL) with adenosine deaminase 12 IU/L. The cerebrospinal fluid (CSF) was sent for mycobacterial culture, pending which a clinical diagnosis of TBM was made and levofloxacin along with dexamethasone was added to alternating triple therapy (ATT). The patient was discharged to continue treatment but presented 3 weeks later with altered sensorium, recurrent vomiting, and ATT-induced hepatitis. Magnetic resonance imaging (MRI) of the brain [Figure 1] showed left thalamic and ganglio-capsular infarcts with multiple tuberculomas. M. tuberculosis from CSF was resistant to all the first-line drugs tested, and the patient was started on second-line ATT on March 15, 2019 (ethionamide 500 mg/day, para-amino salicylic acid 8 gm/day, cycloserine 500 mg/day, levofloxacin 750 mg/day, and kanamycin 750 mg/day). Within 2 days, his sensorium worsened further. Investigations revealed hyponatremia but delirium persisted even after correction of hyponatremia. The patient was taken home against medical advice, and he succumbed within a week.
Figure 1: MRI brain (axial sections) of diffusion weighted image (a), corresponding apparent diffusion coefficient image (b), and T2-weighted image (d) showing acute infarcts in right basal ganglia, thalamus, and gangliocapsular area. Contrast-enhanced T1-weighted axial section (c) showing intense contrast enhancement in left basal ganglia

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The isolate was resistant to fluoroquinolones (gyrA D94G), second-line injectable aminoglycosides (rrs A1401G), ethambutol (embB G306C), and pyrazinamide (pncA Lys96Thr), whereas it was susceptible to ethionamide (ethA), linezolid (rplC), and bedaquiline (atpE/mmpR) on drug susceptibility testing (DST).

It was difficult to ascertain whether our case was a primarily acquired XDR strain or there was de novo development of resistance. However, because spread to meninges occurred while the patient was on conventional ATT for pulmonary TB, resistance possibly developed sequentially as MDR (medium drug resistance), pre-XDR, and finally XDR, secondary to ATT exposure. Being paucibacillary in nature, the culture yield of M. tuberculosis in TBM is often too low to carry out phenotypic DST. Genotypic DST, targeting specific mutations causing resistance, may prove useful in such cases. Drugs such as kanamycin, levofloxacin, pyrazinamide, ethionamide, and linezolid have excellent CSF penetration,[3] and bedaquiline has also been used for treating drug resistant TBM.[4] Our isolate was susceptible to the latter three; however, the patient was lost before these could be started. Two XDR and two pre-XDR TBM cases have been reported in world literature,[1],[2],[5] and three of these cases were reported from India. This highlights the need for high clinical suspicion and prompts first- and second-line testing in India, which is heading toward resistance, head-on (meningitis).

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ajbani K, Kazi M, Naik S, Soman R, Shetty A, Rodrigues C. Utility of pyrosequencing for rapid detection of tubercular meningitis (TBM) and associated susceptibility directly from CSF specimens. Tuberculosis 2018;111:54-6.  Back to cited text no. 1
Wang DM, Li QF, Zhu M, Wu GH, Li X, Xu YH, et al. Epidemiological, clinical characteristics and drug resistance situation of culture-confirmed children TBM in Southwest of China: A 6-year retrospective study. BMC Infect Dis 2020;20:318.  Back to cited text no. 2
Garg RK, Rizvi I, Malhotra HS, Uniyal R, Kumar N. Management of complex tuberculosis cases: A focus on drug-resistant tuberculous meningitis. Expert Rev Anti Infect Ther 2018;16:813-31.  Back to cited text no. 3
Kaplan SR, Topal J, Sosa L, Malinis M, Huttner A, Malhotra A, et al. A patient with central nervous system tuberculomas and a history of disseminated multi-drug-resistant tuberculosis. J Clin Tuberc Other Mycobact Dis 2018;10:9-16.  Back to cited text no. 4
Desai U, Joshi J. Extrapulmonary drug-resistant tuberculosis at a drug-resistant tuberculosis center, Mumbai: Our experience – Hope in the midst of despair! Lung India 2019;36:3-7.  Back to cited text no. 5


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