Blair, Janis E.

Abstract Background Immunosuppression is a recognized risk factor for severe and disseminated coccidioidomycosis; however, data describing outcomes in patients with inflammatory bowel disease (IBD) receiving advanced therapy, including biologics and small molecules, remain limited. We aim to describe the prevalence, clinical presentation, treatment patterns, and outcomes of coccidioidomycosis in IBD patients receiving advanced therapy at an endemic tertiary care center. Methods We performed a retrospective observational study of adult patients with IBD at Mayo Clinic Arizona diagnosed with coccidioidomycosis between 2023 and 2026. Patients were included if IBD diagnosis preceded coccidioidomycosis diagnosis and advanced therapy had been active for at least 4 weeks before infection. Cases were classified as proven, probable, or possible based on microbiologic, clinical, radiographic, and serologic criteria. Clinical outcomes included antifungal treatment duration, hospitalization related to coccidioidomycosis or IBD, IBD treatment modification after diagnosis, re-emergence of coccidioidomycosis symptoms, and IBD-related surgery. Results A total of 48 patients met inclusion criteria. Among 1083 tested IBD patients receiving advanced therapy, coccidioidomycosis positivity prevalence was 4.4% when including all serologically positive patients and 1.9% when restricted to proven or probable cases. The median age at coccidioidomycosis diagnosis was 40 years (range 19-87 years), and 30 (62.5%) of 48 had Crohn’s disease. Proven or probable infection was identified in 21 (43.8%) of 48 patients, while 14 (29.2%) of 48 patients were classified as possible. Antifungal therapy was prescribed in 32 (66.7%) of 48 patients, including all proven cases, 15 (88.2%) of 17 probable cases, 9 (64.3%) of 14 possible cases, and 3 (25.0%) of 12 nondiagnostic cases. Among proven/probable/possible cases, the median antifungal treatment duration was 174 days (range 8-831 days). Advanced IBD therapy was continued in 3 (75.0%) of 4 proven cases, 9 (52.9%) of 17 probable cases, 12 (85.7%) of 14 possible cases, and all nondiagnostic cases. Hospitalization occurred in 6 (12.5%) of 48 of the cohort, all of which were proven/probable cases. Most patients remained on advanced therapy after diagnosis, although tumor necrosis factor α inhibitors were the most interrupted or discontinued agents. Conclusions In this endemic tertiary care cohort, management decisions varied according to diagnostic certainty. Patients with proven or probable coccidioidomycosis were more likely to receive antifungal therapy and undergo advanced IBD therapy modification, whereas most patients with possible or nondiagnostic serologic findings remained on advanced therapy without major IBD-related complications. Prolonged antifungal treatment was common, highlighting the complexity of managing coccidioidomycosis in immunosuppressed patients with IBD.

Abstract Among 1141 inpatients from Arizona with community-acquired pneumonia, 865 (75.8%) were tested for Coccidioides infection and 85 (9.8%) had positive results. Patients more commonly underwent testing if they had concerning radiographs, fever, dyspnea, or fatigue. Patients with night sweats, rash, headache, or eosinophilia more commonly had positive results.

Peritoneal coccidioidomycosis is a rare, disseminated manifestation of Coccidioides infection with limited representation in the literature. We report 37 proven or probable cases from a single institution, including 12 patients (32%) with immunosuppression. Thirty-six patients received antifungal therapy, all of whom demonstrated clinical response. Among 11 (29.7%) patients who completed and stopped therapy after a median duration of 26 months, 2 (5%) experienced a relapse and were successfully retreated. Nine patients (24%) had no known relapse. Thirteen patients (35%) required modification of antifungal regimens, primarily due to azole adverse effects. Treatment approaches and median duration of therapy (57 months) were similar between immunosuppressed and non-immunosuppressed groups. No deaths were attributable to infection. Overall, outcomes were favorable, with strong clinical responses to azole therapy. Patients without identifiable immunologic deficits or additional sites of dissemination, when managed with antifungal therapy and close clinical, radiologic, and serologic monitoring, may achieve good prognosis, particularly when indefinite azole therapy is not feasible.

The diagnosis of coccidioidomycosis is often achieved serologically by the detection of antibodies against fungal antigens. While several serologic tests are available for coccidioidomycosis, all of them are performed in a laboratory setting causing delays in diagnosis and therapeutic intervention. Point-of-care testing offers the ability to provide a shorter time to result by avoiding specimen send-out, minimizing processing steps, and employing expeditious immunochemical techniques. A preliminary trial of a rapid anti-coccidioidal antibody lateral flow assay (LFA) using fingerstick blood was performed on 22 patients with coccidioidomycosis at the point of care during outpatient clinic visits. Patients were tested longitudinally over the course of one year. An LFA reader was implemented to provide an objective result by quantifying the intensity of the test line band. There was close qualitative concordance observed between positive LFA results with send-out immunodiffusion (89.5%) and complement fixation (78.4%) standard of care clinical laboratory assays. Additionally, the relationship between LFA test line density values and traditional complement fixation antibody titers was assessed.

Disseminated cutaneous coccidioidomycosis (DCC) is an uncommon manifestation of Coccidioides infection resulting from hematogenous spread to the skin. While recurrence after treatment discontinuation has been reported in 17 to 50 percent of cases, associated frequency, timing, and risk factors are not well defined. We conducted a retrospective review of biopsy-proven or probable DCC cases between January 2008 and March 2024, and investigated for evidence of recurrence. Demographic, clinical, and treatment data were abstracted, including antifungal regimen, adherence, immune status, and coccidioidal titers. A total of 45 subjects met the inclusion criteria, including 27 immunocompetent and 18 immunosuppressed patients. Eleven (24.4%) experienced one or more recurrences, totaling 22 recurrences; 19 of these (86.4%) occurred at previously affected sites. Ten immunocompetent patients (37.0%) had 21 total recurrences, while one immunosuppressed patient (5.6%) experienced a single recurrence. Median antifungal-free interval before recurrence was 14 months (range, 1–96), and 10 recurrences (90.9%) occurred while off antifungal therapy. Ten patients underwent initial surgical excision, with four (40.0%) experiencing a total of 11 recurrences afterwards. DCC recurrence was common, mostly among immunocompetent individuals not on suppressive antifungal therapy, and frequently presented with multiple recurrences. Recurrences were almost always at prior lesion sites, often years after treatment discontinuation.

Abstract Background Within the Coccidioides-endemic area, coccidioidomycosis (cocci) has been identified as the cause of pneumonia in 15-29% of patients with community-acquired pneumonia (CAP). Although efforts to improve testing CAP patients for cocci are underway in the outpatient settings in Arizona, we do not know whether testing is common among patients admitted to the hospital with pneumonia. We undertook the current study to assess the frequency of testing for cocci among hospitalized patients with pneumonia in our institution, and to understand whether positive serologic testing led to a reduction in antibiotic use. Methods We commissioned the creation of an electronic tool by our Information Technology colleagues to create a report to identify inpatients of Mayo Clinic Hospital with a pneumonia diagnosis (J18.0 – J18.9) and information regarding testing for Coccidioides by any serology (enzyme immunoassay, immunodiffusion or complement fixation) and patient receipt of antibiotics or antifungal treatment (name, inclusive dates). Results Between January 1, 2024 and December 31, 2024, 1162 patients were admitted to the Hospital Internal Medicine service at Mayo Clinic Hospital, Phoenix AZ with a pneumonia diagnosis. Among these, 771 (66%) were tested serologically for coccidioidomycosis, and 87/771 (11%) were found to be positive. By calendar month, the percent of patients tested ranged 59 – 73%, and percent test positivity ranged 3% (March) - 19% (December). The mean time from admission to test order was 0.5 days (range 0 – 6 days) and mean time from admission to positive result was 3.0 days (range 0.4 – 12.0 days). However, among seropositive patients, the duration of antibiotics was 4.2 days, not different when compared with patients who were either seronegative or not tested, (4.1 days, p=NS). 173 (14.9%) received antifungal treatment during hospitalization, among whom 55 (31.2%) had positive coccidioidal serology and 118 (68.2%) did not. Conclusion Coccidioidomycosis is an important cause of pneumonia within the inpatient setting. However, one third of patients were not tested, representing an opportunity to understand and overcome barriers to testing. Positive tests were not associated with a reduction of antibiotic use. Disclosures All Authors: No reported disclosures

This essay describes diagnostic criteria for and thoracic imaging appearances of acute and chronic coccidioidal pneumonia, unusual disease manifestations, and disseminated disease appearances.

Abstract Early diagnosis and treatment are essential for improving outcomes of coccidioidal meningitis. While the detection of IgG by serologic testing of the cerebrospinal fluid (CSF) has been a mainstay of diagnosis for years, the diagnosis of coccidioidal meningitis in clinical practice can be very challenging due to suboptimal sensitivity of laboratory tests. We reviewed the results of the CSF diagnostic test results from the initial lumbar puncture in 110 patients with proven, probable, and likely coccidioidal meningitis from 1989 to 2024. One hundred four patients were diagnosed with coccidioidal meningitis on the initial CSF examination. The positivity rate of the first CSF testing was 89.1% (n = 64) for IgG by enzyme immunoassay, 62.2% (n = 98) for IgG by immunodiffusion, and 70.2% (n = 104) for IgG by complement fixation, 4.4% (n = 90) for fungal culture, 18.8% (n = 69) for polymerase chain reaction, and 33% (n = 21) for Coccidioides antigen. The non-specific fungal marker 1,3-β-d-glucan was positive in the CSF in 70.4% (n = 27) of samples. Contrasted brain magnetic resonance imaging identified leptomeningeal enhancement in 53.1%. Optimal detection of coccidioidal meningitis requires a combination of diagnostic modalities.

Abstract Objective To create a short-term medical service trip (MST) focused, standardized, evidence-based, cost-effective, locally appropriate formulary. Methods Documents from the World Health Organization (WHO), related entities, and primary literature were reviewed to determine best practices. Specific diagnosis and treatment formularies (DTFs) for MST use in the WHO Regions of Africa and the Americas were created. Key findings The DTF guiding principles were being WHO-region specific, addressing primary health needs, including essential medications based on disease prevalence, local availability and affordability, and optimizing patient labeling. Conclusions A thoughtfully crafted DTF for MSTs is one way to advance equitable and safe health care.

Abstract Background Coccidioidomycosis (cocci) is a fungal infection caused by Coccidioides and a common cause of community acquired pneumonia in endemic regions. Disseminated cocci occurs in ≤ 1% of persons with cocci, and among these, disseminated cutaneous coccidioidomycosis (DCC) is estimated to occur in 15 to 67% of cases, however little data exists to describe its frequency and timing of recurrence. Limited small studies show recurrence rates from 17 to 50% and often do not distinguish skin dissemination from other soft tissues. Our aim was to determine the frequency, timeframe and risk factors for relapsed DCC. Methods Potential cases of disseminated cocci were identified by ICD-10 codes 38.3, 38.7, 38.9 (& ICD-9 equivalents) and keyword-based search of pathology reports from 1/1/2008 - 3/31/2024. We included patients with proven or probable DCC. We excluded patients with primary cutaneous cocci or reactive rash. We performed a retrospective review to identify episodes of recurrence, comorbidities, and antifungal regimen. Results We identified 44 proven and 3 probable cases of DCC (33 males, 14 females), median age 48 years, 66.0% white, 21.3% black, 5.4% Hispanic. 18 (38.3%) were immunosuppressed and 6 (13.6%) had diabetes mellitus. Median follow-up duration was 68 months; 12 (25.5%) patients had ≥1 recurrence, 7 (14.9%) of whom relapsed ≥2 times. Median interval off of antifungals until recurrence was 14 months (range: 1 - 96). 3 (6.4%) patients had recurrence within three months of diagnosis, and 6 (13.0%) and 11 (23.9%) had a recurrence by the 1st and 5th follow-up year, respectively. 21 (87.5%) recurrences were at the same site as a prior occurrence, 4 (18.2%) occurred on antifungal therapy. There were no significant differences in recurrence rates by race or diabetes. Of the 18 immunosuppressed cases, there was 1 (5.6%) recurrence, though 14 (77.8%) continued antifungal therapy throughout follow-up. Conclusion Once antifungal treatment was discontinued, recurrence of disseminated cutaneous cocci was common, and among those whose DCC relapsed, multiple relapses were noted. Longer follow up is needed to better characterize the risk of long-term recurrence. Disclosures All Authors: No reported disclosures