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Toddler with extensively drug-resistant TB treated into remission
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A patient aged 2 years, who developed pneumonia after returning to the United States from a trip to India, was diagnosed with extensively drug-resistant tuberculosis and successfully treated into remission at John Hopkins Children’s Center, according to a report in The Lancet Infectious Diseases.
“This report of [extensively drug-resistant (XDR)] tuberculosis in a young child in the USA highlights the risks of acquiring drug-resistant tuberculosis overseas,” Nicole Salazar-Austin, MD, of the department of pediatrics and the center for tuberculosis research at Johns Hopkins University School of Medicine, and colleagues wrote. “Treatment was complicated by the scarcity of child-friendly drug formulations and evidence-based dosing recommendations for some drugs, and controversy regarding the infectious risk of the child to the general public.”
The child initially presented with a 2-week history of high fever after returning from a 3 month trip to India. Despite negative test results for TB, the researchers maintained high clinical suspicion and initiated first-line TB treatment of isoniazid, rifampin, pyrazinamide and ethambutol.
After 4 weeks, the patient showed clinical improvement, with dissipation of fever, decline in inflammatory markers and weight gain. However, after 12 weeks, drug-susceptibility testing identified the isolate as XDR Mycobacterium tuberculosis. Meanwhile, CT imaging showed worsening infiltrate in the lungs, with several necrotic areas and obstruction of the left main bronchus. The researchers initiated an individualized drug regimen for XDR TB, consisting of IV streptomycin, linezolid, para-aminosalicylic acid, Seromycin (cycloserine, Purdue GMP), Lamprene (clofazimine, Novartis) and vitamin B6.
The patient was discharged after 5 days of treatment, with continued drug therapy at home. After 6 weeks, CT imaging showed marked improvement in lesion volume and necrotic areas. The researchers said this individualized therapy, with 6 weeks of daily dosing, then transitioning to 3 doses per week for 6 months, was effective at treating XDR TB into remission.
According to Salazar-Austin and colleagues, these results suggest that without clinical or microbiological markers, CT imaging can be used to monitor and optimize treatment of XDR TB in children.
“Although treatment is complete, and the child is now in remission, this report highlights the unique difficulties associated with the management of drug-resistant tuberculosis in young children, a susceptible population for whom challenges in diagnosis, monitoring, and treatment could have fatal results,” Salazar-Austin and colleagues wrote. – by David Costill
Disclosure: Salazar-Austin reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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David L. Cohn, MD
This interesting case report of a child with extensively drug-resistant tuberculosis acquired in India reiterates several challenges in the diagnosis and treatment of pediatric TB: 1) potential risk for acquiring TB when traveling to high-incidence regions of the world; 2) difficulty in establishing a definitive diagnosis, given the poor sensitivities of acid-fast bacilli (AFB) smear, culture and newer molecular techniques (ie, GeneXpert [Cepheid]) from both sputum and gastric aspirates, largely due to the paucibacillary nature of pediatric TB; 3) the probable underdiagnosis of drug-resistant TB in children in the absence of cultures and susceptibility testing; 4) limited array of medications available to treat children, especially with drug-resistant TB; and 5) difficulty in monitoring treatment response in the absence of serial AFB cultures.
There are a few other noteworthy aspects to the case. The child had a reasonable initial clinical response to standard four-drug therapy for presumed drug-sensitive TB, which in retrospect turned out to be monotherapy with ethambutol owing to baseline resistance to isoniazid, rifampin and pyrazinamide. As above, this is likely due to the relatively small population of bacilli, so that even one effective drug can transiently decrease the number of organisms and secondary inflammatory response despite drug resistance. In addition, the utility of low-radiation exposure CT scans to monitor the patient’s progress was impressive, both showing the failure of the first-line regimen with an enlarging infiltrate and necrosis of the lung, and then, the striking radiographic response with the more effective multidrug regimen for XDR-TB. It is great that this technology was available at Johns Hopkins Hospital, but the author’s comment that this “could be applied more universally, including in developing countries” is overly optimistic. Even chest X-rays, much less CT scans, are not available in many resource-limited settings, except in major medical centers in large cities.
This child was fortunate to have been properly diagnosed and treated in an institution with considerable expertise in the management of TB. Think about all the children in most parts of the world who succumb to TB, both drug-sensitive and drug-resistant, due to the aforementioned deficiencies in diagnosing pediatric TB. We need better tools.
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