We present a case of a man immunocompromised due to myelodysplastic syndrome with Candida krusei fungemia who had a rising cell-free DNA (cfDNA) giant magnetoresistance (GMR) signal when tested daily using plasma blood samples. With the rise in GMR signal paralleling the development of skin lesions in this patient, we conclude that cfDNA can be used to indicate uncontrolled infection and thus help monitor response to therapy. This index patient provides evidence that an invasive fungal infection requires both direct antifungal therapy and an intact immune system to control the infection. This biosensing platform has been simplified to potentially serve as a point-of-care test, setting it apart by overcoming the three common barriers of cfDNA testing: complexity, cost, and time.

Clinical suspicion and diagnosis of Pneumocystis infections rely on a combination of compatible clinical, radiologic, and diagnostic findings. We noted an extrapulmonary Pneumocystis infection when evaluating residual plasma samples from patients with possible invasive fungal infections using cell-free DNA (cfDNA) Giant Magnetoresistance (GMR) (FungiFlex^®, Zepto Life Technology). A man, immunocompromised for 27 years due to kidney transplantations, developed fever and rising aminotransferase enzyme levels during transient escalation of immunosuppressive therapy. Except for an elevated (1,3)-beta-D-glucan, further laboratory testing did not find the highly suspected histoplasmosis. Daily plasma blood samples for cfDNA fungal GMR testing were examined for histoplasmosis; however, the fungal GMR signal was only positive for Pneumocystis jirovecii in all four samples. In retrospect, the transient escalation of immunosuppressive dosing created a temporary net state of over-immunosuppression that was permissive for Pneumocystis. Additionally, the assay corroborated pulmonary pneumocystosis for a second patient, was negative for a third patient with colonization, and was negative for a fourth patient when fevers correlated with an abdominal bacterial process. Within the exploratory nature of the findings, we find that the reference standard for defining Pneumocystis is imperfect and may not accurately identify all cases. cfDNA testing may supplement existing laboratory testing and improve the diagnosis of Pneumocystis.