Chesdachai, Supavit

Abstract Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection.

Abstract Background In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection. Methods All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations. Results A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0–6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia. Conclusions Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality.

Abstract Introduction During the early phase of the coronavirus disease 2019 (COVID‐19), remdesivir was only approved for hospitalized patients. Our institution developed hospital‐based, outpatient infusion centers for selected hospitalized patients with COVID‐19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods Retrospective study of all hospitalized adult patients with COVID‐19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results Among 3029 hospitalized patients who received treatment with remdesivir for COVID‐19, the majority (89.5%) completed the recommended 5‐day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5‐day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001). Conclusions This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5‐day course of remdesivir.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.

AbstractBackgroundCurrent guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease‐2019 (COVID‐19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients.MethodsA retrospective cohort study of transplant patients with severe COVID‐19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID‐19 diagnosis. Secondary outcomes were 90‐day mortality, ventilatory days, and thromboembolic events.ResultsA total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90‐day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001).ConclusionThe use of immunomodulators in transplant patients with severe COVID‐19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all‐cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID‐19. image

Abstract Background Deep brain stimulator (DBS)–related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections. Methods This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester. Results There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9–6.9) months. The odds of infection were higher with longer operative length (P = .002), higher body mass index (BMI; P = .006), male sex (P = .041), and diabetes mellitus (P = .002). The association between infection and higher BMI (P = .002), male sex (P = .016), and diabetes mellitus (P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation (P = .015). Only 1 individual had complications with brain abscess at failure. Conclusions Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications.

Abstract Background Isavuconazole (ISA) is a relatively recent triazole antifungal with several attractive qualities and so increased clinical experience and data on the use of ISA are desirable. However, the data on the pattern of ISA use in invasive fungal infections (IFI) is limited. Methods We conducted a retrospective study of patients with probable or proven IFI treated with ISA at Mayo Clinic from 1/1/2015 to 4/1/2020 to examine temporal trends and characteristics of ISA use. Results The use of ISA rose over this period, from 4 cases in 2015 to 42 cases in 2019. Of 131 patients identified, ISA was used as the initial antifungal in 15 (11.5%) patients and as the secondary agent in 116 (88.5%) patients. The most cited reasons for choosing ISA as first-line therapy were drug-drug interactions (5, 33%) and baseline QTc prolongation (3, 20%). In cases of ISA used as a secondary agent, the reasons for transitioning to ISA were QTc prolongation (22, 19%), followed by judged failure of the primary therapy (20, 17%), drug-drug interactions (12, 10%), and various toxicities with the first agent. ISA was discontinued early in 81 (62%) patients. Common reasons for early discontinuation were patient death or comfort care (27, 33%), intolerance (18, 22%), failure of therapy (17, 21%), cost or access (6, 7%), drug-drug interaction (3, 4%), issues with absorption or drug delivery (3, 4%), and microbe susceptibility (1, 1%). ISA was judged successful and used as definitive treatment in the remaining 50 (38%) patients. About 30 patients took &gt;1 year of ISA, and no major adverse effects from long-term therapy were noted. Conclusion Although ISA is approved for pulmonary aspergillosis and mucormycosis, we found that few patients were treated with ISA as either primary or salvage therapy. In cases where it was used, shortening the QTc and fewer drug-drug interactions were its most attractive qualities. Although it is a newer azole, the morbidity common with other antifungals should prompt more studies on ISA’s efficacy to increase clinicians’ confidence in this option. Disclosures All Authors: No reported disclosures.

Abstract Background Bloodstream infection (BSI) following arterial aneurysm repair may signify vascular graft infection (VGI). The incidence of BSI and its implications in patients with arterial grafts have received scant attention with limited contemporary study. Therefore, the aim of the current investigation is to describe the incidence and epidemiology of BSI following arterial aneurysm repair in a population-based cohort. Methods Retrospective case-cohort study using the expanded Rochester Epidemiology Project (e-REP) to identify all arterial aneurysm repairs performed in adults (&gt;18 years) residing in eight counties in southern Minnesota between January 1, 2010 and December 31, 2020. All repairs were performed at Mayo Clinic Rochester. Electronic health records were screened for initial BSI episode following aneurysm repair and complicating VGI. Results Overall, 643 patients underwent 708 aneurysm repairs: 417 endovascular and 291 open surgical repairs. Forty-two patients developed BSI during 2,992 cumulative person-years of follow-up. The median time from repair to BSI was 3.1 [interquartile range 0.5, 6.4] years. The BSI incidence rate, in cases per 1000 person-years, was 14.0 (95% CI 10.1-19.0) overall, including 18.2 (95% CI 11.9-26.7) following open surgical repair and 10.2 (95% CI 5.8-16.6) following endovascular repair (p=0.148). Thirty-nine (92.9%) of the BSI cases were monomicrobial, with 18 (46.2%) due to Gram-positive organisms and 21 (53.8%) due to Gram-negative organisms. Of the 42 patients with BSI, 10 (23.8%) had VGI. VGI occurred in 8/18 (44.4%) monomicrobial Gram-positive BSI as compared to 2/21 (9.5%) monomicrobial Gram-negative BSI (p=0.013). The 3-year mortality rate following BSI was 52.3%. Conclusion There was no statistically significant difference in incidence rates of BSI following open surgical repair and endovascular repair. Higher rates of VGI were seen with Gram-positive BSI as compared to Gram-negative BSI. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties.

Abstract Background Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety (i.e., hepatotoxicity, QTc prolongation); however, little is known about clinical effects of very high serum posaconazole serum levels (i.e., ≥ 5000 mg/mL). Reported incidence rate of adverse drug reactions (ADRs) with posaconazole per most recent clinical trial was ∼30%. The primary objective was to compare the ADR incidence in patients with serum posaconazole levels of 3000-4999 ng/mL to ≥5000 ng/mL. Methods This retrospective cohort study included adult patients with a posaconazole serum level ≥3000 ng/mL from 1/1/2019 to 04/30/2021. The primary outcome was symptomatic ADR at time of first serum level ≥3000 ng/mL. Secondary outcomes were laboratory defined hepatoxicity, electrolyte and adrenal laboratory abnormalities, QTc changes, and dose changes in response to TDM. Patient outcomes were censored after the first serum level and were compared between groups using Fisher’s exact tests. Results Ninety patients met inclusion criteria, 80 with a level of 3000-4999 ng/mL and 10 with a level of ≥ 5000 ng/mL occurring at a median of 91 days (26-443) and 27 days (12-45) from posaconazole initiation, respectively. Majority of patients were immunocompromised (55.6% transplant recipients, 28.9% active malignancy, 5.6% other) with a split of treatment (50%) and prophylaxis (42.2%) indication. Symptomatic ADRs were very common in patients with posaconazole levels of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; p=0.31), primarily neurologic (49.1% overall) followed by gastrointestinal (32.7% overall). Hepatotoxicity was also common (≥5000 ng/mL 40% vs 3000-4999 ng/mL 23.4%, p=0.26). Fifty percent of patients had the posaconazole dose continued without change. Electrolytes and QTc results were similar between groups, but median overall QTc was borderline high (456 [IQR 435, 479]). Conclusion There are safety concerns for patients with serum posaconazole levels ≥3000 ng/mL. Posaconazole levels should be monitored and, importantly, dose adjusted according to serum level and patient symptoms for both treatment and prophylaxis indications. Disclosures Christina G. Rivera, PharmD, Gilead: Grant/Research Support|Gilead: Honoraria|Insmed: Honoraria.