Emergence of Dual Bedaquiline and Linezolid Resistance During Treatment of Pre-Extensively Drug-Resistant Tuberculosis: A Case Report from Zambia

Background Drug-resistant tuberculosis remains a major public health threat, particularly among HIV co-infected individuals in resource-limited settings. The emergence of resistance to bedaquiline and linezolid during treatment poses a serious challenge to current therapeutic strategies. We present a case that highlights critical gaps in drug-resistant tuberculosis care. Case Presentation A 28-year-old HIV-positive Zambian man, virologically suppressed on tenofovir-lamivudine-dolutegravir, was initially treated for drug-sensitive pulmonary tuberculosis. Following relapse and treatment failure, rifampicin resistance was confirmed, and he was initiated on a second-line regimen. He was lost to follow-up and later returned with pre-extensively drug-resistant tuberculosis. A six-month regimen of bedaquiline, pretomanid, and linezolid was commenced. Despite initial improvement, persistent symptoms and hemoptysis at month five prompted resubmission of sputum for drug susceptibility testing and empirical extension of treatment; results were delayed and only became available at month 11, revealing acquired resistance to both bedaquiline and linezolid and meeting criteria for extensively drug-resistant tuberculosis. A salvage regimen comprising delamanid, ethambutol, cycloserine, clofazimine, and meropenem was initiated, and the patient remains on treatment under close clinical and laboratory monitoring. Conclusion This case demonstrates the consequences of treatment interruption, delayed drug susceptibility testing, and inadequate monitoring in drug-resistant tuberculosis care. The simultaneous acquisition of resistance to bedaquiline and linezolid significantly limits treatment options. Strengthening adherence support, improving laboratory turnaround times, and enhancing pharmacovigilance systems are essential to preserve the effectiveness of novel regimens in Zambia and similar settings.