Speiser, Lisa

Objective Respiratory syncytial virus (RSV) is an important viral pathogen in children, older adults and adults with certain high-risk conditions. In our prospective community-based cohort study of adults 50 years and older before the COVID-19 pandemic, the incidence of RSV acute respiratory infection (ARI) was 48.6 cases/1000 person-years (PY), which decreased to near zero during the COVID-19 pandemic. Our objective was to determine the incidence of RSV-ARI during the 2 years following the initial phase of the pandemic (2021–2022 and 2022–2023). Design This is a community-based prospective cohort study. Setting Adults living in southeast Minnesota from October 2021 to September 2022 (year 3) and October 2022 to September 2023 (year 4). Participants Adults≥50 years (n=2500). Primary and secondary outcomes We calculated incidence and attack rates for RSV-ARI as primary outcome and reported hospitalisations, pneumonia and death following ARI as secondary outcome. Results There were 2500 participants in the study with a mean age of 68.2 years (SD 9.3) at the start of year 3. Participants were predominantly female (60%), non-Hispanic white (96%) and residing in urban areas (76%). The incidence rate of RSV-ARI was 6.12/1000 PY (95% CI 3.42 to 10.09) in 2021–2022 and 16.40/1000 PY (95% CI 11.66 to 22.42) in 2022–2023. We noted higher attack rates of RSV-ARI during the winter months. There were no hospitalisations, pneumonia or deaths within 30 days of RSV-ARI. Conclusions Compared with the period before the COVID-19 pandemic, RSV-ARI incidence was lower in both 2021–2022 and 2022–2023 periods. In 2022–2023, the incidence increased 2.7-fold compared with the 2021–2022 period. The observed incidence rates, particularly the significant increase in the most recent season, underscore the continued public health relevance of RSV-ARI and support the rationale for ongoing RSV vaccination efforts to mitigate its overall burden in the population.

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.

Abstract Background Data on respiratory syncytial virus (RSV) acute respiratory infection (ARI) among community-dwelling U.S. adults aged 18 to 64 years, particularly those with high-risk conditions (HRC), remain limited. This study estimated incidence and attack rates of RSV-ARI and RSV lower respiratory tract disease (LRTD) in adults with and without HRCs. Methods A multistate, community-based prospective cohort of adults aged 18 to 64 years with and without HRCs was followed from October 2022 to September 2024. Incidence rates and annual attack rates of RSV-ARI and RSV-LRTD were calculated by HRC presence and age group. Results Of 3375 adults with at least 1 HRC, the RSV-ARI incidence rate was 17.9 per 1000 person-years (attack rates: year 1, 1.87%; year 2, 1.56%), compared with 14.8 per 1000 person-years (year 1, 1.33%; year 2, 1.50%) among adults without HRCs. RSV-LRTD incidence was 10.0 per 1000 person-years in adults with HRCs versus 5.7 per 1000 person-years in those without. Asthma, congenital immunodeficiency, and immunosuppressive medication use were associated with increased incidence of RSV-ARI and RSV-LRTD; whereas adults with solid organ transplant and chronic kidney disease had a significantly higher incidence rate of RSV-LRTD compared to those without these conditions. Adults aged 18 to 49 years with HRCs had significantly higher RSV-LRTD incidence (9.6 vs 4.3 per 1000 person-years). After adjustment for age and sex, having ≥1 HRC was associated with a 62% increased RSV-LRTD risk, rising to 117% among adults aged 18 to 49 years. Conclusions Adults with HRCs—particularly asthma, congenital immunodeficiency, chronic kidney disease, immunosuppressive medication use, and solid organ transplant—experienced higher RSV-ARI and RSV-LRTD incidence. The elevated RSV-LRTD burden was most pronounced in adults aged 18 to 49 years with HRCs.

ABSTRACT Carbapenem‐resistant Acinetobacter baumannii (CRAB) are difficult‐to‐treat pathogens that primarily cause health care‐associated infections. Sulbactam/durlobactam (SUL/DUR) is a novel antibiotic combination that is uniquely formulated to target CRAB isolates. However, investigations of SUL/DUR's pharmacokinetics in obese patients are limited. Here, we report on the successful treatment of CRAB bacteremia in a patient with acute renal failure and severe obesity (weight 273 kg, body mass index 103 kg/m 2 ) with SUL/DUR and meropenem combination therapy. The patient had a calculated creatinine clearance of 25 mL/min and received therapy with intravenous SUL/DUR 1 g/1 g every 8 h over 3 h in combination with intravenous meropenem 500 mg every 8 h to complete 14 days of therapy. Pharmacokinetic analysis revealed target attainment with prolonged half‐life ( T 1/2 ) and volume of distribution (Vd) of 35.3 h and 81.3 L for sulbactam and 30.5 h and 169.1 L for durlobactam, respectively. Susceptibility testing using the broth disk elution test did not show synergy between SUL/DUR and meropenem. No adverse effects were observed, and the patient achieved clinical cure without recurrence of A. baumannii infection.

Abstract Background/Objective: Decentralized research has many advantages; however, little is known about the representativeness of a source population in decentralized studies. We recruited participants aged 18-64 years from four states from June to December 2022 for a prospective cohort study to assess viral epidemiology. Our aim was to determine the association between age, gender, race/ethnicity, rurality, and socioeconomic status (SES) on study participation in a decentralized prospective cohort study. Methods: We consented 9,286 participants from 231,099 (4.0%) adults with the mean age of 45.6 years (±12.0). We used an electronic decentralized approach for recruitment. Consented participants were more likely to be non-Hispanic White, female, older, urban residents, have more health conditions, and possessed higher socioeconomic status (SES) compared to those non-consented. Results: We observed an interaction between SES and race-ethnicity on the odds of consent (P = 0.006). Specifically, SES did not affect non-Hispanic white participation rates(OR 1.24 95% CI 1.16 – 1.32] for the highest SES quartile compared to those with the lowest SES quartile) as much as it did participants combined across the other races (OR 1.73; 95% CI 1.45 – 2.98]) Conclusion: The relationship between SES and consent rates might be disproportionately greater in historically disadvantaged groups, compared to non-Hispanic White. It suggests that instead of focusing on enrollment of specific minority groups in research, there is value in future research exploring and addressing the diversity of barriers to trials within minority groups. Our study highlights that decentralized studies need to address social determinants of health, especially in under-resourced populations.

Abstract Background The incidence of respiratory syncytial virus (RSV)–acute respiratory infection (ARI) in community-dwelling adults after the Omicron variant of the COVID-19 pandemic is unknown. Our aim was to assess the incidence of RSV-ARI in adults aged 18 to 64 years over 2 consecutive RSV seasons (October–April 2022–2024) in 4 US states. Methods This community-based prospective cohort study comprised 7501 participants in Minnesota, Wisconsin, Florida, and Arizona. We calculated RSV-ARI and RSV–lower respiratory tract disease (LRTD) incidence and attack rates. We reported unadjusted incidence by age group, gender, race and ethnicity, Charlson Comorbidity Index, socioeconomic status, residential state, and rural/urban setting. Results Seasons 1 and 2 had 2250 and 2377 ARI episodes, respectively, with an RSV-ARI positivity rate of 5.5% for season 1 and 5.8% for season 2 among those tested. In season 1, the overall incidence of RSV-ARI was 27.71 (95% CI, 22.82–33.34) per 1000 person-years (1.49% attack rate). Almost half (49.0%) had RSV-LRTD, with an incidence of 13.53 (95% CI, 10.19–17.61) per 1000 person-years (0.73% attack rate). In season 2, the RSV-ARI and RSV-LRTD incidence rates were 26.39 (95% CI, 21.73–31.75) per 1000 person-years (1.51% attack rate) and 12.43 (95% CI, 9.31–16.26) per 1000 person-years (0.72% attack rate). RSV-ARI incidence peaked in November 2022 and December 2023. Conclusions Our observations suggest that RSV-ARI incidence and seasonal pattern are shifting to prepandemic RSV epidemiology.

Abstract Mpox, caused by infection with Monkeypox virus, usually presents as a mild, self-limited illness in immunocompetent persons that resolves within 2–4 weeks. Serious complications have been reported when mpox lesions involve vulnerable anatomic sites, such as the eye, and in those with substantial immunosuppression. We describe a patient with advanced human immunodeficiency virus infection and sustained viral shedding of mpox with ocular involvement, which resulted in vision loss.

Abstract Background The BioFire® FilmArray® Gastrointestinal Pathogen Panel (GIPP) tests for 22 potential pathogens in stool, including Clostridioides difficile. C. difficile nucleic acid is detected via nested polymerase chain reaction (PCR) targeting toxin A (TcdA) and/or toxin B (TcdB) genes. While PCR-based diagnostic methods are highly sensitive, they lack specificity to differentiate colonization from C. difficile infection (CDI). Mayo Clinic Arizona (MCA) uses enzyme immunoassay (EIA) testing for toxin A/B and glutamate dehydrogenase antigens with reflex to PCR for discordance as the primary algorithm for diagnosing CDI; however, GIPP PCR testing circumvents this algorithm. When used in patients with low pretest probability for CDI, clinical false positives can lead to inappropriate diagnosis and treatment of colonization. GIPA Results in the Electronic Medical Record Pre-Intervention MCA Standalone C. difficile Testing Algorithm Abbreviations – EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test Methods We convened a multidisciplinary quality improvement team to reduce the detection and treatment of C. difficile colonization secondary to GIPP test results. Surveys were sent to providers and nurses as part of a formal gap analysis and included questions around ordering patterns, knowledge of appropriate tests, and associated costs. Baseline data was compiled from GIPP orders in MCA from 1/1/2022-9/30/2022. Results There were 1978 GIPP orders for 1694 patients during the study period (∼7 GIPPs/day). Most orders (65%) originated from ambulatory settings. The most common positive target was C. difficile (355/723, 49%), which resulted in treatment for suspected CDI in 94.9% (337/355) of cases. Of the 49 providers who responded to the survey, 86% ordered the GIPP at least monthly. Testing for C. difficile was the 2nd most common reason for ordering the GIPP. Most providers underestimated the cost of the panel and were unfamiliar with the differences between the GIPP and EIA testing algorithm. Nurses sought clarification on stool samples suitable for GIPP testing. Following education and modifications to ordering in the electronic health record, the decision was made to remove the C. difficile target from the GIPP. Provider Understanding of C. difficile Testing Methods GIPA Results in the Electronic Medical Record Post-Intervention Conclusion Multiplex PCR panels are comprehensive but require careful implementation to facilitate diagnostic stewardship. Facilities with robust standalone C. difficile testing algorithms may consider removing the C. difficile target from the GIPP. Disclosures All Authors: No reported disclosures

Abstract Melioidosis, an infection caused by Burkholderia pseudomallei, has a very high risk of mortality when treated, with an even higher risk of fatality if undiagnosed or not treated appropriately. It is endemic to Asia, Australia, South America, and the Caribbean; however, the number of melioidosis cases reported in the United States has been increasing. Therefore, physicians should be aware of this clinical entity and its possible presentations. Mycotic aneurysms due to B. pseudomallei are extremely rare, accounting for ~1%–2% of cases. Here we describe a rare case of melioidosis presenting as a mycotic aneurysm in the United States, highlight the potential for diagnostic challenges and epidemiologic concerns, and provide a review of mycotic aneurysm cases due to B. pseudomallei published to date.

Abstract Background Despite the endemic nature of Coccidioides sp. to the American Southwest, the incidence Coccidioides sp. infective endocarditis (CIE) is rare. Following successful treatment of a patient with CIE at our institution, we reviewed the literature to identify trends in disease presentation, patient characteristics, and outcomes. Methods We reviewed all cases of CIE reported since 1938. Details including patient demographics, underlying immunodeficiency, time to diagnosis, treatment, and outcome were collected for analysis of diagnostic challenges and survival. Results Including ours, we identified 11 published cases of CIE. The majority (7) occurred in men. 5 patients were of either African American or Hispanic descent. Of the 10 patients with reported ages, the median age was 35.5 years (range 3 weeks – 61 years). 5 patients had a previous diagnosis of coccidioidomycosis and only 3 had an immunocompromising condition. These comprised pregnancy, heart transplant, and juvenile inflammatory arthritis. Three cases had multi-valvular involvement, but the majority affected the mitral (5) and the aortic (4) valves. Only 2 of the 11 cases involved a prosthetic valve. Of the 8 cases with reported blood cultures, only 2 were positive. Ten of the 11 cases had extra-cardiac disease. Complement fixation (CF) titers were heterogenous with a median of 1:32 and a range of 1:1 to 1:2048. There was no obvious correlation between a patient’s CF titer and their survival. Average time to diagnosis was 3.5 months (range 2.5 – 36 months). Diagnosis was made post-mortem in 4 of the 11 cases. 6 patients (54%) did not survive. Notably, 2 of the fatal cases preceded the discovery of amphotericin B (1969) and 4 occurred prior to the discovery of fluconazole (1990). Of the five patients that survived, four required surgical intervention in addition to azole therapy. Conclusion CIE is a diagnostic and therapeutic challenge. The diagnosis itself is rare, culture incubation times are long, and the symptoms are often non-specific thus delaying definitive therapy. The introduction of azole therapy appears to have had significant impact on rates of survival. Despite this, successful management of CIE still requires concurrent surgical intervention with aggressive, indefinite anti-fungal therapy. Disclosures All Authors: No reported disclosures