Pre-extensive drug resistant {XDR} Tuberculosis
 
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Ira Shah
Medical Sciences Department, Pediatric Oncall, Mumbai, India

Address for Correspondence: Dr Ira Shah, 1, B Saguna, 271, B St Francis Road, Vile Parle {W}, Mumbai 400056


Clinical Problem :
A 14 years old girl presented with low grade fever for 8 months along with loss of weight and appetite. She had received 3 drug antituberculous therapy {ATT} 2 years ago for 6 months in view of positive mantoux test. On examination, her weight was 28.2 kg, height was 148 cms. Systemic examination was normal. Chest X-Ray was normal. Ultrasound of abdomen showed multiple mesenteric lymph nodes with largest being 2 x 1.5 cm. CT abdomen showed multiple necrotic lymphnodes. CT guided biopsy of lymph node showed granulomas and tuberculosis {TB} culture did not grow mycobacterium tuberculosis {MTB}. She was started on 4 drug antituberculous therapy with 2 drugs as continuation phase. At end of 4 months of therapy, her weight was 32 kg but ultrasound showed increase in size of nodes to 3.6 cms. At end of 7 months of therapy, the nodes were the same but weight had increased to 37 kg. At end of 1 year of therapy, nodes had regressed in size {largest being 2.7 cm} and weight was 40.6 kg. ATT was stopped. After 3 months of stopping ATT, she presented with amenorrhea for 1½ months and fever for 15 days. She had achieved her menarche one year ago and menses were regular every 28 days. A repeat ultrasound abdomen was done that showed hypoechoic mass in right iliac fossa 6.8 cm x 2.8 x 2.0 cm adherent to the right ovary. A CT guided aspiration of the pus was done. She was started on IV ceftriaxone, metronidazole for the right tubo-ovarian mass along with medroxy progesterone for 5 days following which she had withdrawl bleeding. Her pus culture grew extended spectrum beta lactamase {ESBL} producing E.coli sensitive to carbapenems, amikacin, and colistin. She was shifted to IV Meropenem and fever responded to the same. TB culture after 6 weeks grew MTB resistant to isoniazid {H}, rifampicin {R}, pyrazinamide {Z}, ethambutol {E}, streptomycin {S} and moxifloxacin {Mfx} but sensitive to aminoglycosides, PAS, ethionamide and clofazimine.


Question :
What should be her ATT schedule now_?

Expert Opinion :
This child has pre-extensively drug resistant {XDR} TB with resistance to both HR and even quinolones. Multidrug-resistant {MDR} TB implies resistant to both isoniazid and rifampicin whereas XDR TB implies MDR TB with additional resistance to at least a fluoroquinolones and one of the injectables i.e. kanamycin, amikacin or capreomycin. {1} Since she has resistance to quinolones but not to aminoglycosides, she has pre- XDR TB. She would need to be started on second line ATT. Drugs are chosen with a stepwise selection process through five groups. Among the first group {the oral first-line drugs} high-dose isoniazid, pyrazinamide and ethambutol are thought of as an adjunct for the treatment of MDR and XDR tuberculosis. The second group is the injectable drugs {capreomycin, kanamycin, amikacin}. The third group include the flouroquinolones. The fourth group are called the second-line drugs {thionamide, cycloserine and aminosalicylic acid}. The fifth group includes drugs that have sparse clinical data {clofazimine, amoxicillin with clavulanate, linezolid, carbapenems, thioacetazone and clarithromycin}. {2} In this child since all the first line drugs were resistant, the child was treated with amikacin, cycloserine, PAS, clofazamine and linezolid. She received injectable for 6 months and remaining drugs for 20 months. She responded to her therapy.

References:
1. World Health Organization {WHO} Global Tuberculosis Control Report 2011. Available at website: ww.who.int, tb, publications, global_report, 2011, gtbr11_full.pdf. Accessed on 8th March 2012
2. Caminero JA, Sotgiu G, Zumla A, Migliori GB. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis. 2010` 10: 621-629.


Correct Answers :  yes 42%
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