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Drug Resistance in Mycobacterial Isolates From Meningitis Cases

Jain, Amita MD; Dixit, Pratima MSc; Jaiswal, Indu MSc; Garg, Ravindra Kumar MD, DM; Kumar, Rashmi MD

The Pediatric Infectious Disease Journal: December 2012 - Volume 31 - Issue 12 - p 1317
doi: 10.1097/INF.0b013e3182717f25

Department of Microbiology, C.S.M. Medical University

Department of Neurology, C.S.M. Medical University

Department of Pediatrics, C.S.M. Medical University, Lucknow, India

The authors have no funding or conflicts of interest to disclose.

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To the Editors:

In countries with high burden of pulmonary tuberculosis (TB), the incidence of extrapulmonary TB (EPTB) is high. There has been a rising trend of tuberculous meningitis (TBM) in developing countries in the past 2 decades. There are few published reports on drug susceptibility profiling of EPTB, particularly TBM.1 Early and rapid detection of drug resistance in TBM is not always possible because bacterial load in cerebrospinal fluid (CSF) is too low to detect the resistance by both culture and molecular methods. Hence, it is important to have surveillance of drug resistance in EPTB to help in planning the treatment regimen.

Here, we report the prevalence of drug resistance in Mycobacterium tuberculosis isolates from CSF of TBM cases. CSF samples from 370 clinically suspected pediatric TBM cases were referred to the TB laboratory, Department of Microbiology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India, for laboratory confirmation of TBM. Each CSF sample was processed for acid-fast bacilli smear examination, mycobacterium culture2 and demonstration of mycobacterial DNA by in-house nucleic acid amplification method.3 All M. tuberculosis isolates were subjected to drug susceptibility testing for first-line drugs: isoniazid, rifampicin, streptomycin and ethambutol by conventional 1% proportion method.2 The laboratory is under external quality control for first-line drug susceptibility testing (provided by the National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, India).

Of the 370 cases, 106 (28.6%) patients had laboratory-proven TBM. CSF samples from all 106 laboratory-proven patients were polymerase chain reaction positive whereas 60 (16.2%) patients were positive by smear examination for acid-fast bacilli and 51 (13.7%) patients were culture positive for M. tuberculosis. Among 106 samples, 32 (30.2%) samples were positive by all the 3 tested methods. Of the 51 M. tuberculosis isolates, 34 (66.7%) isolates were pan-susceptible whereas resistance to isoniazid or streptomycin was detected in 7 (13.7%) and 5 (9.8%) isolates, respectively. Multidrug resistance (MDR) was detected in 1 isolate.

Almost 50% of MDR-TB pulmonary cases worldwide are estimated to occur in China and India. Drug resistance in M. tuberculosis isolates from TBM cases is low despite the fact that, among pulmonary cases, prevalence of MDR in our setting was higher (19.8%)4 than other parts of the country.5 MDR among cases of pulmonary TB is well documented, but reports on MDR–EPTB and MDR–TBM are limited. Continuous surveillance of drug resistance in EPTB is needed.

Amita Jain, MD

Pratima Dixit, MSc

Indu Jaiswal, MSc

Department of Microbiology

C.S.M. Medical University

Ravindra Kumar Garg, MD, DM

Department of Neurology

C.S.M. Medical University

Rashmi Kumar, MD

Department of Pediatrics,

C.S.M. Medical University

Lucknow, India

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1. Patel VB, Padayatchi N, Bhigjee AI, et al. Multidrug-resistant tuberculous meningitis in KwaZulu-Natal, South Africa. Clin Infect Dis. 2004;38:851–856
2. Central TB Division Directorate General of Health Services Ministry of Health and Family Welfare. . Revised National TB Control Programme Training Manual for Mycobacterium tuberculosis Culture & Drug susceptibility testing. 2009 Nirman Bhawan, New Delhi, India Central TB Division Directorate General of Health Services Ministry of Health and Family Welfare
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5. Nagarathna S, Rafi W, Veenakumari HB, et al. Drug susceptibility profiling of tuberculous meningitis. Int J Tuberc Lung Dis. 2008;12:105–107
© 2012 Lippincott Williams & Wilkins, Inc.