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Pulmonary aspergillosis has been reported at high rates in patients with coronavirus disease 2019 (COVID-19) and is associated with high morbidity and mortality. We retrospectively assessed all patients admitted to an intensive care unit during the early COVID-19 surge (3/17/20–5/10/20) at our medical center in the midwestern USA for the presence of COVID-19-associated pulmonary aspergillosis (CAPA). Patients were not routinely screened for CAPA; diagnostic work-up for fungal infections was pursued when clinically indicated. Among 256 patients admitted to the ICU with severe COVID-19, 188 (73%) were intubated and 62 (24%) ultimately expired within 30 days of admission to the ICU. Only three patients (1%) were found to have CAPA; diagnosis was made by tracheal aspirate cultures in two cases and by bronchoalveolar lavage fluid Aspergillus galactomannan in one case. None of the patients who developed CAPA had classic risk factors for invasive fungal infection. The occurrence of CAPA was much lower than that reported at other centers, likely reflecting the local epidemiology.

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014–2019. Patients had primary AML (n = 148, 59%), antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018–1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585–22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

Background Asynchronous virtual patient care is growing in popularity; however, the effectiveness of virtually delivering guideline-concordant care in conjunction with antibiotic stewardship initiatives remains uncertain. We developed a bundled stewardship intervention aimed at improving antibiotic use in E-visits for upper respiratory tract infections (URTIs). Methods In this pre-post study, adult patients who completed an E-visit for “cough,” “flu,” or “sinus symptoms” at Michigan Medicine between 1/1/2018 and 9/30/2020 were included. Patient demographics, diagnoses, and antibiotic details were collected. The multi-faceted intervention occurred over 6 months (Figure 1). We performed segmented linear regression to estimate the effect of the intervention on the level and trend of appropriate antibiotic use for URTI diagnosis (defined as no antibiotic prescribed) and sinusitis (defined as guideline-concordant antibiotic selection and duration). Regression lines were fit to data before (March 2019) and after (May 2019) the physician championing period. Results Among 5151 E-visits, the mean age was 46 years old, and most patients were female (71.3%, N=3674). 3405/5151 E-visits were for URTI. Inappropriate antibiotic use for URTI was stable in trend prior to the audit and feedback intervention (Figure 2), followed by a 12% (P-value = 0.01) decrease in inappropriate antibiotic use post-intervention. The trend in inappropriate antibiotic use continued to decrease after the intervention by 1.1%/month (P-value = 0.02) (Figure 2a). Of 2493/5151 E-visits specifically for sinus symptoms, guideline-concordant antibiotic use was low (intercept = 8%) pre-intervention (Figure 2b). Post-intervention, there was an estimated 47% increase (P-value < 0.001) in patients receiving guideline-concordant antibiotics. Solid line represents time of the webinar, dashed line represents time of modified questionnaire roll out and electronic medical record “nudges”, and shaded area is time of physician champion intervention. Guideline-concordant antibiotic prescribing for sinusitis included amoxicillin/clavulanate or doxycycline prescribed for a duration of 5-7 days Conclusion A multifaceted stewardship bundle for E-visits improved guideline-concordant antibiotic use for URTIs. Changes implemented in the EMR are most beneficial after a period of audit and feedback. This approach can aid stewardship efforts in the ambulatory care setting particularly with regards to telemedicine. Disclosures Tejal N. Gandhi, MD, Blue Cross Blue Shield of Michigan (Individual(s) Involved: Self): Grant/Research Support Lindsay A. Petty, MD, Nothing to disclose

We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia (AML). We performed a retrospective analysis of all adult patients admitted to the University of Michigan Health System for AML over a 3-year period from 2010 to 2013. We determined comorbidities, hematopoietic cell transplant (HCT) status, antifungal prophylaxis, proven and probable IFI, and outcomes at 12 weeks after initiation of appropriate antifungal therapy. Of 333 patients in our cohort, 116 of whom had received a HCT, 98 (29%) developed an IFI. Of the 30 (9%) patients who had a proven or probable IFI, 18 had breakthrough infection while on micafungin (n = 5), voriconazole (n = 4), posaconazole (n = 5), or fluconazole (n = 4). Breakthrough IFIs were due to Aspergillus species (n = 11), other molds (n = 4), and Candida species (n = 3). Factors associated with breakthrough IFI were prolonged severe neutropenia (p = .05) and having received tacrolimus (p = .04). Antifungal therapy was successful in 7 of the 18 (39%) patients with breakthrough IFI and 8 of the 12 (67%) patients with non-breakthrough IFI, p = .13. Mortality at 12 weeks was 27%, 5 with breakthrough IFI and 3 with non-breakthrough IFI and was associated with prolonged severe neutropenia, p = .04. Patients with AML remain at risk for IFI despite the use of several different antifungal agents for prophylaxis. Mortality remains high in patients with AML who develop IFI.

Background Despite the use of antifungal prophylaxis, IFD remains a serious complication of AML causing extensive morbidity and mortality. This study seeks to clarify our experience with breakthrough infections in patients with AML. Methods This retrospective study included all adult patients undergoing induction chemotherapy for a new diagnosis of AML from June 2014 – Dec 2019 at the University of Michigan Hospital. Chart review determined co-morbidities, chemotherapy regimens, allogeneic hematopoietic cell transplant (HCT), antifungal prophylaxis, development of IFD, and outcomes. Patients were followed for 1 year from first induction chemotherapy. EORTC-MSGERC definitions for proven, probable, and possible IFD were used, as were MSGERC-ECMM definitions for breakthrough IFD. Results Of 251 patients, mean age was 61.8±14 years, 55% were men, and 73 (29%) underwent allogeneic HCT, 52 of whom developed GVHD. Thirty-one patients developed 33 IFD (12.3%): 4 proven, 12 probable, and 17 possible IFD. Four IFD occurred in patients with GVHD post-HCT; all were treated with high dose steroids and one received an anti-TNF agent. Of the 16 proven and probable IFD, 8 were breakthrough IFD. Mucormycosis occurred in 2 patients on voriconazole; fusariosis occurred in 3 patients taking fluconazole (2), or posaconazole (1). Aspergillosis occurred in 2 patients taking isavuconazole (1) or fluconazole (1), and pneumocystosis occurred in a patient receiving inhaled pentamidine. There were 8 non-breakthrough IFD, including 2 pneumocystosis, 4 aspergillosis, and 2 candidiasis. Risk for IFD increased with subsequent episodes of induction chemotherapy, p=.04. Six of 8 patients with breakthrough IFD and 5 of 8 without breakthrough IFD died within 12 weeks of IFD diagnosis. Excluding the 15 patients who had only possible IFD, 69% (11/16) patients with proven/probable IFD died compared with 35% (77/220) patients without IFD, p=.01. Conclusion Patients with AML remain at risk for fatal IFD despite the use of antifungal prophylaxis. Failure of prophylaxis in our patients who developed breakthrough IFD was associated with a shift towards less common fungi. Disclosures All Authors: No reported disclosures

Background A major challenge in patients with AL receiving chemotherapy is to decrease the risk of IFI during the prolonged neutropenic period. Even with antifungal prophylaxis, the incidence of breakthrough IFI can be as high as 14%. Our objectives were to determine the incidence of all IFI and breakthrough IFI, to define risk factors associated with IFI, and to assess outcomes. Methods Single-center retrospective cohort analysis of all adult patients admitted to the University of Michigan for AL from January 1, 2010 to December 31, 2013. Chart review determined co-morbidities, chemotherapy regimens, antifungal prophylaxis, occurrence of IFI as determined by EORTC/MSG criteria, and outcomes. Chi-square, Fischer’s, ANOVA, and binary logistic regression tests were performed when appropriate. Results Of 363 patients, all but 4 had acute myeloid leukemia (AML); 124 had a stem cell transplant (SCT). A total of 103 (28%) had proven (n = 13), probable (n = 22), or possible (n = 68) IFI. Considering only those 35 patients who had proven or probable IFI, the only risk factor for development of IFI by logistic regression analysis was IFLAG chemotherapy (P = .006). Mold infections occurred in 27 patients: Aspergillus (19), Mucorales (5), both Aspergillus and Mucorales (1), Alternaria (1), and Scedosporium (1). Additionally, 5 patients had invasive candidiasis and 3 had Pneumocystis. Eighteen of 35 patients (51%) had breakthrough IFI while on posaconazole suspension (6), fluconazole (5), micafungin (5) or voriconazole (2). Factors significantly associated with breakthrough IFI were SCT (P = .04), neutrophils Conclusion Patients receiving chemotherapy for AL remain at risk for IFI despite the the use of antifungal prophylaxis. In our study, prophylaxis with posaconazole suspension was found to be an independent risk factor for breakthrough IFI. Mortality was high among patients with breakthrough IFI. Disclosures All authors: No reported disclosures.