Patron, Roberto L.

Abstract Background Literature on the natural course of neuroinvasive West Nile virus (WNV) infection in solid organ transplant (SOT) recipients is sparse. In the setting of a 2021 WNV outbreak in Arizona, we reviewed our institution's experience with neuroinvasive WNV infection in patients with SOT. Methods We retrospectively identified SOT recipients treated for neuroinvasive WNV at Mayo Clinic in Arizona from 2007 through 2021. Clinical manifestations, disease course, and outcomes were analyzed. Results Among 24 SOT recipients with WNV infection identified during the study period, 13 infections occurred in 2021. Most patients had gastrointestinal tract symptoms and fever at disease presentation. Five patients had cognitive impairment, and 14 initially or eventually had acute flaccid paralysis. Clinically significant deterioration occurred at a median of 4 (range, 1–11) days after hospital admission. Seventeen patients (71%) were transferred to the intensive care unit, with 15 requiring mechanical ventilation. Initial cerebrospinal fluid analysis mainly demonstrated a neutrophil‐predominant pleocytosis. Almost all patients ( n = 23) were treated with intravenous immunoglobulin alone or in combination with interferon alfa‐2b. Sixteen patients had clinical improvement, 4 of whom recovered completely. Six patients died during hospitalization due to complications of neuroinvasive WNV infection. Two patients were discharged to hospice without clinical recovery. The overall 30‐day mortality rate was 36%. Conclusion Despite advances in supportive care, neuroinvasive WNV infection is associated with substantial morbidity and mortality in SOT recipients. Flaccid paralysis is an indicator of poor prognosis. image

Abstract Background GIP offers detection via PCR for a wide array of common microbes associated with diarrheal illness. Its rapid turnaround time and high sensitivity has made GIP testing commonplace for the evaluation of diarrhea. The purpose of this study is to determine if GIP influences antibiotic management in patients hospitalized with diarrhea. Methods Fifty patients hospitalized at Mayo Clinic Arizona between July and December 2019 who underwent BioFire® FilmArray™ GI PCR Panel testing were randomly selected. Medical records were reviewed to capture gender, age, immunocompromised state, antibiotic use within 30 days, prior hospitalization within 3 months, history of Clostridioides difficile infection, time from admission to testing and GIP results, and to determine if GIP results directly contributed towards antibiotic management. This study was exempt from Institutional Review Board approval. Results Twenty-six patients were male and twenty-four were female. The average age was 61.7 years. Thirty-four patients (68%) were immunocompromised. Forty-one GIPs were ordered within 24 hours of admission. Twenty-two patients (44%) had a positive GIP result; five were positive for 2 concurrent organisms. C. difficile was the most commonly detected organism, found in 16/24 (66.7%) positive tests. Eleven patients (68.8%) with C. difficile had a recent hospitalization, antibiotics within 30 days, or a history of C. difficile infection. There were 3 cases of Enteropathogenic Escherichia coli, 2 of Enterotoxigenic Escherichia coli, 2 of adenovirus, 2 of norovirus, 1 of rotavirus, and 1 of Vibrio cholerae. Excluding C. difficile positive patients, GIP testing contributed in changing antibiotic management in 3/50 (6%) patients tested. One patient had antibiotics stopped, one received correct antibiotics, and one received inappropriate antimicrobial therapy. Conclusion These results suggest that except in the setting of C. difficile infection, GIP has little utility in guiding antimicrobial management, even in the immunocompromised patient. GIP testing is expensive and it may be more resourceful to screen patients hospitalized with diarrhea for C. difficile alone, especially in those with risk factors for C. difficile infection. Furthermore, GIP testing can lead to antibiotic overuse. Disclosures All Authors: No reported disclosures

Abstract We report 8 cases of coccidioidomycosis associated with ruxolitinib treatment. Among 135 patients living in the coccidioidal-endemic region receiving ruxolitinib, 5 cases were diagnosed after starting and 4 had extrathoracic dissemination. Periodic serological screening while on ruxolitinib is warranted for patients residing in the coccidioidal-endemic region.

AbstractBackgroundHematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections.MethodsPatients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28.ResultsFrom 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22–1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo.ConclusionsPresatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia.Clinical Trials RegistrationNCT02254408; EUDRA-CT#2014-002474-36.

Clostridioides difficile infection (CDI) has become an increasingly common infection both within and outside of the hospital setting. The management of this infection has been evolving as we learn more about the role of the human microbiota in protecting us from this gastrointestinal opportunist. For many years the focus of treatment had been on eradication of the vegetative, toxin-producing form of the organism, with little regard for its collateral impact on the host’s microbiota or risk of recurrence. With the marked increase in C. difficile disease, and, particularly, recurrent disease in the last decade, new guidelines are more focused on targeting and reducing collateral damage to the colonic microbiota. Immune-based strategies that manipulate the microbiota and provide a humoral response to toxins have now become mainstream. Newer strategies are needed to look beyond simply resolving the primary episode but are focused on delayed outcomes such as cure at 90 days, reduced morbidity and mortality, and patient quality of life. The purpose of this review is to familiarize readers with the most recent evidence-based guidelines for C. difficile management, and to describe the role of newer antimicrobials, immunological-, and microbiota-based therapeutics to prevent recurrence and improve the outcomes of people with CDI.

AbstractVerruconis gallopava is an environmental dematiaceous fungus that is recognized increasingly as a cause of human disease, especially for immunocompromised persons. Infection can range from superficial and localized lesions to pulmonary involvement and disseminated disease, including central nervous system abscesses. Optimal therapy is undefined. We report a patient post cardiac transplant who had pulmonary infection with V gallopava and was treated successfully with posaconazole.

BACKGROUNDSt. Louis encephalitis virus is a mosquito‐borne flavivirus that infrequently causes epidemic central nervous system infections. In the United States, blood donors are not screened for St. Louis encephalitis virus infection, and transmission through blood transfusion has not been reported. During September 2015, St. Louis encephalitis virus infection was confirmed in an Arizona kidney transplant recipient. An investigation was initiated to determine the infection source.STUDY DESIGN AND METHODSThe patient was interviewed, and medical records were reviewed. To determine the likelihood of mosquito‐borne infection, mosquito surveillance data collected at patient and blood donor residences in timeframes consistent with their possible exposure periods were reviewed. To investigate other routes of exposure, organ and blood donor and recipient specimens were obtained and tested for evidence of St. Louis encephalitis virus infection.RESULTSThe patient presented with symptoms of central nervous system infection. Recent St. Louis encephalitis virus infection was serologically confirmed. The organ donor and three other organ recipients showed no laboratory or clinical evidence of St. Louis encephalitis virus infection. Among four donors of blood products received by the patient via transfusion, one donor had a serologically confirmed, recent St. Louis encephalitis virus infection. Exposure to an infected mosquito was unlikely based on the patient's minimal outdoor exposure. In addition, no St. Louis encephalitis virus‐infected mosquito pools were identified around the patient's residence.CONCLUSIONThis investigation provides evidence of the first reported possible case of St. Louis encephalitis virus transmission through blood product transfusion. Health care providers and public health professionals should maintain heightened awareness for St. Louis encephalitis virus transmission through blood transfusion in settings where outbreaks are identified.