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Indian Pediatr 2017;54: 160 |
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Is Shorter Treatment Regimen for
Multidrug-resistant Tuberculosis feasible in Indian Children?
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Ira Shah
Pediatric TB Clinic, B J Wadia Hospital for Children,
Mumbai, India.
Email: [email protected]
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Traditionally, patients with rifampicin-resistant (RR) or multi-drug
resistant tuberculosis (MDR-TB) are treated with a combination of
second-line drugs, usually for 18 months or more [1]. Recently, World
Health Organization (WHO) recommended a shorter and cheaper treatment
regimen for MDR-TB [2]. Standardized shorter MDR-TB regimen consists of
seven drugs and a treatment duration of 9-12 months [1]. The regimen
consists of 4-6 months of kanamycin, high-dose moxifloxacin (12
mg/kg/day, not to exceed 800 mg daily), prothionamide or ethionamide,
clofazimine, pyrazinamide, high dose isoniazid (15 mg/kg, not to exceed
900 mg daily) and ethambutol followed by 5 months of moxifloxacin,
clofazimine, pyrazinamide and ethambutol [1]. These recommendations were
based on studies carried out in several countries – mostly in Africa
[1,3].
Ideally, shorter MDR-TB regimen should be given to
persons (adults or children) with MDR-TB if they have not been
previously treated with second-line drugs, and if additional resistance
to pyrazinamide, ethambutol or the second- line drugs used in the
regimen is unlikely. Therefore in children knowing the drug
susceptibility (DST) result of the source case (if identified) or the
entire DST results of all the first and second line drugs in the
patient’s sample is important when considering the use of the shorter
regimen.
In a study from Mumbai, pre-XDR TB [(MDR-TB along
with resistance to either a fluoroquinolone or an aminoglycoside (apart
from streptomycin)] was the most common form of drug-resistant
tuberculosis with observed prevalence at 56.8% compared to 29.4% for
MDR-TB in adults [4]. The proportions of patients with ofloxacin,
moxifloxacin and ethionamide resistance were 75.3%, 69.5% and 52.5%,
respectively in adults [4]. In children with drug-resistant
tuberculosis, moxifloxacin resistance was 46%, ofloxacin was 47.6%,
ethionamide resistance was 49.2%, pyrazinamide resistance was 55.6% and
ethambutol resistance was 60.3% [5]. There is also an increase in
prevalence of pre-XDR TB in children as compared to MDR-TB [5]. Most of
these children would have resistance to isoniazid, rifampicin,
ethambutol, pyrazinamide, quinolones and ethionamide. Thus the shortened
MDR-TB regimen may provide inadequate treatment to these patients.
Starting this regimen in children based only on the geneXpert results of
rifampicin-resistance without testing for DST to all the first and
second line drugs would be a logistical mistake, and may lead to more
drug-resistant forms of tuberculosis, and treatment failures. Treatment
of drug-resistant tuberculosis should be individualized based on the DST
results.
References
1. World Health Organization (WHO). Rapid Diagnostic
Test and Shorter, Cheaper Treatment Signal New Hope for
Multidrug-resistant Tuberculosis Patients. Available from:
http://www.who.int/mediacentre/news/releases/2016/multidrug-resistant-tuberculosis/en/.
Accessed June 23, 2016.
2. World Health Organization (WHO). The Shorter
MDR-TB Regimen. Available from:
http://www.who.int/tb/Short_MDR_regimen_factsheet.pdf. Accessed June
23, 2016.
3. Aung KJ, Van Deun A, Declercq E, Sarker MR, Das
PK, Hossain MA, et al. Successful ‘9-month Bangladesh regimen’
for multidrug-resistant tuberculosis among 92 over 500 consecutive
patients. Int J Tuberc Lung Dis. 2014;18:1180-7.
4. Dalal A, Pawaskar A, Das M, Desai R, Prabhudesai
P, Chhajed P, et al. Resistance patterns among
multidrug-resistant tuberculosis patients in Greater Metropolitan
Mumbai: trends over time. Gao L, ed. PLoS One. 2015;10:e0116798.
5. Shah I, Shah F. Changing prevalence and resistance
patterns in children with drug-resistant tuberculosis in Mumbai. Pediatr
Intl Child Health. 2016 [in press].
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