G303(P) Successful treatment of multidrug-resistant tuberculous meningitis in a child with HIV treatment failure

Abstract

Tuberculous meningitis (TBM) is a deadly disease more common in children than adults. The management of multidrug-resistant tuberculous meningitis (MDR TBM) in children is particularly problematic with limited published data about successful outcomes, especially in resource limited settings. This case discusses the successful treatment of a child with MDR TBM in rural South Africa using terizidone and linezolid. An 8 year old child presented to a district hospital in July 2018 with lethargy, hallucinations and seizures. She had completed treatment for pulmonary TB in 2017 and been on antiretroviral therapy since 2015 with a persistently high HIV viral load. On examination, she was severely underweight and her left eye was depressed and abducted with a unilateral ptosis and dilated pupil. Chest radiography demonstrated military TB and sputum analysis detected mycobacterium tuberculosis resistant to rifampicin. An abdominal ultrasound demonstrated para-aortic lymph nodes, hepatomegaly and multiple hypoechoic splenic lesions. She was referred to a tertiary hospital for a computed tomography scan which showed dural venous sinus thrombosis, right frontal lobe infarct and leptomeningeal enhancement. A diagnosis of disseminated MDR TB with probable TBM was made, as well as HIV treatment failure. She was started on second-line antiretroviral drugs and initiated on a MDR TB drug regimen which included terizidone and linezolid. The child completed two months of intensive therapy. Treatment was tolerated well and side effects including anaemia, visual disturbance (linezolid) and psychiatric symptoms (terizidone) were not observed. The child gained weight and signs of left oculomotor palsy significantly improved with no serious neurological sequelae seen as yet. The child was discharged to complete the remaining course of treatment as an outpatient. This case illustrates that MDR TBM can be successfully treated even in children with disseminated disease and advanced immunosuppression. Despite concerns regarding side-effects and cost, linezolid and terizidone appear to be well tolerated in children and further research is needed to better understand safety and effectiveness in paediatric MDR TBM. Therapy must be carefully supervised to prevent acquired resistance to these potentially attractive options in children.