Coccidioides is an endemic fungus in the Southwestern United States and Central and South America. Coccidioidomycosis primary infections are typically of the lung with an asymptomatic or self-limiting course. Some infections disseminate to other parts of the body and a few can remain latent for many years. Reactivation of latent fungal disease can occur following an insult to the host immune system. Here, we describe a case of a 76-year-old Caucasian male patient who moved from California to Wisconsin with a history of coccidioidomycosis infection of the left knee that reactivated decades later in his prosthetic knee shortly after being initiated on ibrutinib (Imbruvica), a Bruton tyrosine kinase (BTK) inhibitor, for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). There have been some case reports regarding coccidioidomycosis infections after initiating ibrutinib therapy but none with a 50 year latency period before reactivation. Readers will learn the immunological effects of ibrutinib on the hosts’ innate and adaptive immunity and its role in putting the host at risk for invasive fungal infections. We also review the literature and data on treatment regimens and recommendations based on current guidelines.

BackgroundEPEC is a known cause of diarrhea, predominately in children, which has not been identified with conventional stool culture in most medical centers. MPCR testing assesses stool samples in which DNA targets for 20 or more pathogens are tested with rapid turnaround. This method has become the standard for diagnostic testing in many clinical laboratories. MPCR testing has identified EPEC as among the most frequent pathogens in published studies.MethodsWe have completed a retrospective review of medical records of patients who tested positive for EPEC in our medical center.ResultsEPEC was found in 56 of 332 MPCR samples analyzed between February 1, 2016 and July 31, 2016. EPEC was the only pathogen in 25 while co-infecting pathogens were found in 31. Co-infections included other diarrhea-causing E. coli (ETEC, EAEC and EIEC but none with STEC) in 17, C. difficile in 7, viruses (astrovirus 3, sapovirus 2, norovirus 2, rotavirus 2), Campylobacter 3, Giardia 2, Salmonella 2, Pleisiomonas 1 and Yersinia 1.Patients ages ranged from <1 to 100 with 37 over age 19. Half were female. 7/46 had received antibiotic prior to sample collection. 10 reported recent travel. 51/52 presented to the emergency department, urgent care centers or ambulatory clinics. Symptoms included fever in 15/54, nausea 16/54, vomiting 14/54 and abdominal pain in 17/56. Diarrhea was described as watery in 23/32 and bloody in only 3. Antibiotic treatment was prescribed for 6/24 with EPEC only and for 22/31 with coinfection. A follow-up encounter was documented for 24 patients with EPEC only: 13 resolved, 3 remained ill and 8 could not be assessed.ConclusionEPEC is frequently found in stools from persons with diarrhea when MPCR is employed. Symptoms cannot be attributed to EPEC alone when other pathogens are found, but our analysis does suggest that EPEC is a common cause of diarrheal illness in adults as well as children. Prospective studies on natural history and treatment are necessary.Disclosures All authors: No reported disclosures.

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