Mixed mycotic infection in an immunocompromised host with advanced HIV diagnosed with the assistance of a Karius test

We report the case of a 35-year-old female with advanced HIV diagnosed with a mixed mycotic infection. Diagnosis was assisted by Karius test. She was admitted with postpartum psychosis and developed fever and acute hypoxic respiratory failure initially thought to be from a bacterial hospital-acquired pneumonia. Due to lack of sufficient improvement on appropriate antibiotics, a broad infectious workup was sent. A Karius test was performed early during the workup. It returned positive for <i>Pneumocystis jirovecii</i>, <i>Coccidioides posadasii</i>, and <i>Histoplasma capsulatum</i>. Eventually a standard work up returned with a positive bronchoalveolar lavage (BAL) <i>Pneumocystis jirovecii pneumonia (PJP)</i> test by direct fluorescent antibody (DFA), positive <i>Histoplasma</i> urine antigen, and positive serum coccidioidal titer of 1:16, corroborating the diagnosis of mixed mycotic infection. She was treated with a 21-day course of trimethoprim-sulfamethoxazole followed by primaquine and clindamycin for <i>PJP</i>. She clinically improved with over 3 weeks of IV amphotericin B to cover for histoplasmosis and coccidioidomycosis, which was later de-escalated to oral itraconazole. She was instructed to follow up in clinic where bictegravir/emtricitabine/tenofovir alafenamide was initiated. This case highlights the utility of building a broad differential diagnosis as mixed mycotic infections can coexist in an immunocompromised host, and of utilizing a Karius test early in the course of illness in an immunocompromised patient to expedite a diagnosis. This case also demonstrates the need to recognize the changing geographic distribution of fungal infections.