Disseminated Mycobacterium intracellulare subsp. chimaera infection, undiagnosed for years, highlights the enduring clinical utility of "old school" microbiological testing and a robust differential.

Disseminated Mycobacterium intracellulare subsp. chimaera (MC) infections are rare, slow-progressing, and easily overlooked, particularly when a patient's history of prior cardiac surgery is not incorporated into the diagnostic evaluation. In a recent ASM Case Reports article (1:e00003-25, 2025, https://doi.org/10.1128/asmcr.00003-25), Ladines-Lim et al. describe a disseminated MC infection in a patient with prior aortic and mitral valve replacement that remained undiagnosed for over 4 years. Conventional microbiological testing was not pursued early in the course of illness because the history of cardiopulmonary bypass was not linked with the constellation of unexplained symptoms. This case urges clinicians to remain vigilant and suspect MC in patients with prior open-chest cardiac surgery who present with gradually worsening, systemic symptoms. Since 2013, global outbreaks of delayed-onset MC infections have been traced to contaminated heater cooler devices, yet many centers continue to face barriers to replacing or monitoring such equipment. A delayed diagnosis in this case was eventually established by cell-free metagenomic next-generation sequencing (cfmNGS). However, the result was not acted upon until weeks later, after central nervous system involvement. A more timely, cost-effective diagnosis might have been achieved using traditional, widely available, culture-based testing guided by a robust exposure-driven differential. Clinicians should suspect MC in patients with prior cardiac surgery-even years earlier-who develop unexplained, progressive systemic symptoms. Early suspicion and appropriate testing are critical to improved outcomes. This case shows that next-generation sequencing assays are only as useful as the clinical reasoning guiding their use. Traditional microbiological testing-when leveraged early and thoughtfully-remains an accessible cornerstone of diagnosing complex MC infections.