Rapid suppression of unresolving disseminated coccidioidomycosis infection with combined IL-15 super-agonist (N-803) and invariant natural killer T cell therapy

Failure to restore an effective host immune response during critical illness contributes to prolonged intensive care unit stays, morbidity, and mortality, yet few immunomodulatory therapies are available. An elderly man with chronic obstructive pulmonary disease, mitral valve prolapse, and stage 2B chronic kidney disease presented with acute decompensated diastolic heart failure and supraventricular tachycardia. He required cardioversion and intubation for acute hypoxemic respiratory failure. Imaging showed a persistent left upper lung infiltrate first seen 6 weeks prior to this admission, with cultures positive for Coccidioides immitis . Despite antifungal and broad-spectrum antimicrobial therapy, his 30-day course was complicated by pneumonia caused by pan-sensitive Pseudomonas aeruginosa , persistent fungal infection, recurrent arrhythmias, and respiratory failure. At week three, he was reintubated, and the family elected emergency investigational immunotherapy with N-803 followed by invariant natural killer T cells. This led to pathogen suppression and a multiphasic immune response, though care was later withdrawn.