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|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 4 | Page : 1101-1102
Heading Toward Resistance, Head-On: A Case of XDR Tuberculous Meningitis
Kusum Sharma1, Megha Sharma2, Manish Modi3, Abeer Goel3, Ritu Shree3, Aman Sharma4, Pallab Ray1, Marie Claire Rowlinson5
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 Submission||23-Dec-2020|
|Date of Decision||24-Dec-2020|
|Date of Acceptance||29-Mar-2021|
|Date of Web Publication||2-Sep-2021|
Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
|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 Sep 25];69:1101-2. Available from: https://www.neurologyindia.com/text.asp?2021/69/4/1101/325329
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., 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, and bedaquiline has also been used for treating drug resistant TBM. 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,,, 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.
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