Primary Bedaquiline-Resistant Tuberculosis in an Afghan Migrant to Switzerland: Diagnostic and Treatment Challenges in a High-Resource Setting.

Bedaquiline, classified as a WHO 2019 group A drug, is a core component of BPaLM, revolutionizing the treatment of MDR/RR tuberculosis (TB). Since 2015, however, concerns about acquired and primary bedaquiline resistance have emerged. We report a diagnostically challenging case of a young asylum seeker from Afghanistan, previously treated for pulmonary TB with standard therapy for five months about four years earlier. After arriving in Switzerland, he presented with chronic dry cough, weight loss, and small upper-lobe nodular lesions. Rifampicin mono-resistant pulmonary TB was diagnosed, and BPaLM was initiated. Five weeks later, phenotypic antimicrobial susceptibility testing showed bedaquiline/clofazimine resistance. Next-generation sequencing revealed an IS6110 insertion in mmpR5. The patient had never received bedaquiline. An individualized regimen with pretomanid, linezolid, moxifloxacin, isoniazid, and pyrazinamide led to clinical and radiological improvement. Treatment was stopped after 9 months, with outcome classified as completed (not cured due to absent sputum production). The patient remains well 1.5 years after treatment completion. This case highlights the diagnostic and therapeutic challenges of primary bedaquiline resistance. Faster, reliable phenotypic and genotypic diagnostic methods, along with clear treatment recommendations, are urgently needed to identify bedaquiline-resistant patients promptly, treat them appropriately, and preserve the effectiveness of the BPaLM regimen.