Mixed nontuberculous mycobacteria in an immunocompromised patient with progressive multifocal leukoencephalopathy

Background: Nontuberculous mycobacteria (NTM) represent an overlooked yet increasingly recognized disease that is gaining global attention. NTM mixtures present significant challenges due to its difficult-to-treat nature, lack of clear treatment guidelines, uncertain prognostic outcomes, and limited diagnostic modalities. This case report sheds light on the intricate decision-making process involved in managing NTM mixed disease, addressing both laboratory and treatment impediments. Description: A 40-year-old male presented with constitutional symptoms and chest X-ray changes indicative of structural lung disease, initially suggestive of tuberculosis. The patient was started on rifampicin-sensitive pulmonary tuberculosis treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol). However, mixed NTM were cultured, including Mycobacterium avium from the blood, Mycobacterium kansasii from repeated sputum cultures, and Mycobacterium chelonae once from the sputum. The commonly used GenoType Mycobacterium CM (Common mycobacteria) line probe assay (LPA) failed to detect mixed NTM in the same sample. Subsequently, management was changed to rifabutin, ethambutol, azithromycin, and isoniazid. During the current admission, he received fluconazole continuation therapy for confirmed Cryptococcus neoformans. In addition, the patient was known to be infected with human immunodeficiency virus (HIV, CD4 T-cell count = 3), but defaulted antiretroviral treatment. In a previous admission computed tomography brain image showed a right superior cerebellar peduncle infarct. Secondary to the cerebrovascular accident and Epstein-Barr virus, the patient had visual impairment, managed by ophthalmology as an outpatient. After initial clinical improvement, new neurological symptoms developed, including dysarthria and upper motor neuron weakness. Magnetic resonance imaging of the brain indicated progressive multifocal leukoencephalopathy (PML) with JC virus DNA confirmation in the cerebrospinal fluid. The patient and family were counseled on the disease prognosis, and shortly after, he passed away. Discussion: The case highlights the complexities of treating patients with advanced HIV disease and opportunistic infections, particularly NTM mixtures. Challenges in NTM mixture treatment include uncertainties in selecting multi-drug regimens, treatment duration, patient tolerance, relapse frequency, and susceptibility testing. LPAs could potentially overlook subpopulations in NTM mixtures, as shown in previous research. In this regard, next-generation sequencing and metagenomics have demonstrated superiority over DNA-DNA hybridization platforms (LPAs) in identifying NTM mixtures, suggesting their integration into diagnostic algorithms. The potential role of liposomal amikacin in mixed NTM disease warrants further investigation and could have been considered in this case. However, its use in patients with NTM and a subsequent diagnosis of PML remains debatable due to the condition's poor prognosis. Finally, the high mortality associated with PML raises questions about withdrawing antibiotic treatment and transitioning to supportive palliative care. Conclusion: Overall, the case highlights the need for comprehensive diagnostic approaches and personalized treatment strategies to address the complexities of NTM mixture disease, especially in immunocompromised and critically ill patients, with a focus on improving patient outcomes and quality of life.