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Indian Pediatr 2011;48:
977-979 |
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Partial Extensively Drug Resistance (XDR)
Tuberculosis in Children |
Ira Shah and Aarti Rahangdale
From the Pediatric TB Clinic, BJ Wadia Hospital for
Children, Mumbai, India.
Correspondence to: Dr Ira Shah, 1/B Saguna, 271/B
St. Francis Road, Vile Parle (W), Mumbai 400056.
Email:
[email protected]
Received: May 26, 2010;
Initial review: June 30, 2010;
Accepted: August 23, 2010.
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Emergence of resistance to two most potent first line anti-TB drugs
i.e. isoniazid and rifampicin (multidrug resistant TB – MDR TB) is
well known, but, the second line drugs used to treat MDR-TB are also
showing resistance to the same strain of Mycobacteria
(extensively drug resistance TB, XDR-TB). We report 3 children with
partial XDR TB. Two responded to treatment while one was lost to
follow-up.
Key words: Children, India, Treatment, XDR-TB.
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Multidrug-resistant tuberculosis (MDR-TB) is defined
as TB caused by organisms that are resistant to isoniazid and rifampicin,
two first-line anti-TB drugs, The emergence of extensively drug-resistant
TB (XDR-TB), defined as MDR-TB that is also resistant to any one of the
fluoroquinolones and to at least one of three injectable second-line drugs
(amikacin, capreomycin or kanamycin), has been identified in all regions
of the world since 2006. Treatment outcomes are significantly worse in XDR-TB
patients than in MDR-TB patients [1,2]. There is no term currently to
identify drug resistant TB with either fluoroquinolone resistance or
aminoglycoside resistance. Hence we have coined a term as partial XDR TB
for these patients. The prevalence of XDR TB in Indian adults has been
reported to be 2.4% among those with drug resistant TB [3].
Case Report
Case 1: A 2˝-years old girl presented in July
2007 with swelling over left foot associated with non foul smelling
discharge, cough and fever for 1 month. She also had loss of appetite and
loss of weight. For these complaints, the child showed to a physician who
started her on 4 drugs anti tuberculous therapy (ATT) consisting of
isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) but
there was no improvement and she was referred to us. On examination, her
weight was 9.5 kg (z score = -2), height was 78 cm (z score
= -3), she had matted cervical lymphnodes and discharging sinus over left
foot. There was decreased air entry in left infra-axillary and
infrascapular region with bronchial breathing and hepatosplenomegaly.
Other systems were normal. Mantoux test was positive. Sputum for acid fast
bacillus (AFB) was negative on smear. Her X-ray of the feet showed
osteomyelitis of left fibula, left talus, left 5th metatarsal and right
5th metatarsal. X-ray spine was normal. CSF examination was normal.
Pus from left foot showed AFB on smear. She was started on 6 drugs ATT
consisting of HRZE, streptomycin (S) and ciprofloxacin (C) pending her
culture and sensitivity report. After one month of 6 drug ATT, her fever
persisted, she had loss of weight to 7.9 kg and she developed a gibbus.
X-ray spine showed vertebral collapse at T 4-T5
level. There was no neurological deficit. TB culture sensitivity showed
resistance to all first line drugs (HRZES) and to oflxacin. The child was
thus started on ATT consisting of amikacin, ethionamide, PAS and
moxifloxacin. However, in December 2007, she had still not gained weight,
though her fever had subsided and she was able to stand without support
and walk with support. Her MRI spine showed destruction of T4
vertebral body with gibbus formation at
T4-T5
level and collapse and destruction of L5
vertebral body and large prevertebral, paravertebral and anterior epidural
abscess. Amikacin was stopped by the patient in Dec 2007 due to pain on
injecting. The psoas abscess was drained and sent for culture and
sensitivity in Jan 2008. Her culture still grew M. tuberculosis
which was resistant to HRZESO. The child was subsequently started on
injection kanamycin, linezolid, prothionamide, clofazimine and cycloserine
to which she responded and had a weight gain of 2 kg. In September 2008,
her MRI spine showed healing at
T4-T5
vertebra with reduction in kyphoid deformity. There was no healing at L4-L5
level. She was advised to continue same drugs. Subsequently the child was
lost to follow-up.
Case 2: A 6-year old girl presented with fever
and cough for 2 months. On examination, she was malnourished with a weight
of 13 kg (z score = 0 to 2) and height 106 cm (z score >3).
She had bilateral inguinal adenopathy with left sided otorrhea, and
hepatomegaly. Auscultation revealed decreased air-entry on left side with
bilateral crepitations. There was no shift of mediastinum. CT chest showed
cavity and consolidation in left lower lobe with confluent centrilobular
nodules in left upper lobe and lingula. Her sputum culture report showed
resistance to H,R,E,S and O. She was treated with Z, amikacin,
moxifloxacin, PAS and ethionamide. The patient was asymptomatic till one
month when she developed cervical adenopathy with parotid enlargement that
responded to non-steroidal anti-inflammatory medicines (NSAIDS). Her chest
X-ray showed improvement in the consolidation. By 3 months of
therapy, she had no sputum production, her weight had increased to 17 kg.
However, at end of 5 months of therapy, she was detected to have bilateral
moderate to severe mixed hearing loss at high frequency on audiological
evaluation and thus amikacin was omitted. Her remaining ATT were continued
and regular screening for adverse effects was done. She is on regular
follow up. She underwent left lower lobe lobectomy after 15 months of this
therapy and culture from the specimen did not show any growth of acid fast
bacillus. The remaining drugs are still being continued.
Case 3: A 9˝-year old boy presented with dry
cough and evening rise of fever with abdominal pain for 1 month. He also
had decreased appetite and was not gaining weight. On examination his
weight was 20 kg and height was 126.0 cm. He had generalized non
significant cervical, inguinal and axillary lymph nodes. Systemic
examination was normal and mantoux was positive (12 × 12mm). Chest X-ray
was normal. Ultrasound of abdomen showed mild hepatomegaly with multiple
enlarged mesenteric lymphnodes in right paraumbilical and umbilical
regions measuring 7 mm in short axis. He was started on 4 drug ATT with
HRZE, which was shifted to consolidation phase of 2 drug ATT after 2
months. He was asymptomatic on follow up and at the end of 9 months of
therapy gained 3 kg. However, his ultrasound abdomen showed persistence of
lymphnodes and increase in size to 11.2 mm. Thus he was continued on ATT
for a longer duration and was stopped after total duration of 10 months. A
repeat ultrasound had shown decrease in size of node to 0.5 cm. After 3
months, child again presented with cough for 1 week and abdominal pain. CT
abdomen showed 1.3 cm nodes in mesentery, paracaval regions with central
hypodense areas. At the same time, parents informed that the grandmother
had died due to TB 6 months ago. Thus, he was suspected to have drug
resistant TB. Child underwent abdominal lymphnode biopsy and was started
on category 2 of ATT regimen as per WHO consisting of HRZES. Culture after
6 weeks grew M. tuberculosis complex resistant to HRZES, ofloxacin
and moxifloxacin., Treatment was started with PAS, amikacin, ethionamide
and gatifloxacin. Child had currently completed 15 months of this second
line therapy (gatifloxacin was stopped after one year) and asymptomatic.
His ultrasound shows complete regression of lymphnodes.
Discussion
Patients with XDR-TB have poor outcomes, prolonged
infectious periods and limited treatment options. Childhood TB is usually
a paucibacillary TB, thus making the acquisition of drug resistance in
previously treated patient less likely, unless the child has been infected
by a resistant strain. In our patients, two had contact with an adult
suffering from TB who had died. Two of the patients had been on ATT for a
year but had no improvement on their therapy suggesting that failure to
respond to standard ATT therapy or contact with suspected drug resistance
should be considered as a clue to suspect drug resistance in the child.
In all our patients, we documented drug resistance
based on the culture of M. tuberculosis. This becomes essential as
diagnosis of drug resistant TB is difficult in children and prognosis is
guarded. In these patients, it is prudent to label it as a partial XDR TB
as the resistance pattern is mid-way between MDR-TB and XDR-TB. It is
feasible to classify different type of tuberculosis in children in
different pattern of resistance for future prognosis and treatment.
Although treatment success
rates of 40% to 80% have been observed in a number of
settings, this remains lower than the 85% to 99%
cure ratesachievable for
drug-susceptible TB [4].
References
1. Gandhi NR, Moll A, Sturm AW, Pawins Ki R, Govender
T, Lalloo U, et al. Extensively drug-resistant tuberculosis as a
cause of death in patients co-infected with tuberculosis and HIV in a
rural area of South Africa. Lancet. 2006;368:1575-80.
2. Shah NS, Wright A, Bai GH, Barrera L, Boulah BalF,
Martin-Casabona N, et al. Worldwide emergence of extensively
drug-resistant tuberculosis. Emerg Infect Dis. 2007;13:380-7.
3. World Health Organization (WHO). Guidelines for the
programmatic management of drug resistance tuberculosis. Emergency Update
2008. Geneva. Available at URL: http://whqlibdoc.who.int/publications/2008/9789241547581_eng.pdf.
Accessed on 15th May, 2010.
4. Shah NS, Pratt R, Armstrong L, Robison V, Castro KG,
Cegielski JP. Extensively drug-resistant tuberculosis in the United
States, 1993-2007. JAMA. 2008;300:2153-60.
5. Kant L. Childhood tuberculosis : increasing but neglected. Indian J
Tuberculosis. 2001;48:1.
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