Faculty Bibliography

BACKGROUND/UNASSIGNED:Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. OBJECTIVE/UNASSIGNED:The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. METHODS/UNASSIGNED:This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. RESULTS/UNASSIGNED:Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. CONCLUSION AND RELEVANCE/UNASSIGNED:Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

BACKGROUND:infection (CDI) in patients requiring concomitant systemic antibiotics. OBJECTIVES/OBJECTIVE:To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence. METHODS:(VRE). RESULTS:= .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1). CONCLUSIONS:Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

OBJECTIVE/UNASSIGNED:To evaluate whether an antimicrobial stewardship bundle (ASB) can safely empower frontline providers in the treatment of gram-negative bloodstream infections (GN-BSI). INTERVENTION AND METHOD/UNASSIGNED:From March 2021 to February 2022, we implemented an ASB intervention for GN-BSI in the electronic medical record (EMR) to guide clinicians at the point of care to optimize their own antibiotic decision-making. We conducted a before-and-after quasi-experimental pre-bundle (preBG) and post-bundle (postBG) study evaluating a composite of in-hospital mortality, infection-related readmission, GN-BSI recurrence, and bundle-related outcomes. SETTING/UNASSIGNED:New York University Langone Health (NYULH), Tisch/Kimmel (T/K) and Brooklyn (BK) campuses, in New York City, New York. PATIENTS/UNASSIGNED:Out of 1097 patients screened, the study included 225 adults aged ≥18 years (101 preBG vs 124 postBG) admitted with at least one positive blood culture with a monomicrobial gram-negative organism. RESULTS/UNASSIGNED:= 0.043. CONCLUSIONS/UNASSIGNED:GN-BSI bundle worked as a nudge-based strategy to guide providers in VAN DC and increased de-escalation to aminopenicillin-based antibiotics without negatively impacting patient outcomes.

The additive role of non-culture-based methods for the diagnosis of candidemia remains unknown. We evaluated 2 clinical practices followed in our hospitals for the diagnosis of candidemia, namely practice#1 including a combination of blood cultures and T2Candida, and practice#2 that also included Beta-D-glucan (BDG). Three out of 96 patients testing positive with practice#1 received a complete antifungal course. Of the 120 patients evaluated with practice#2, 29 were positive. Only 55.2% of those received a complete course. We observed significant differences in antifungal utilization, with 268.5 antifungal days/1000 patient-days for practice#1, as opposed to 371.9 days for practice#2, a nearly 40% difference. However, we found similar rates of antifungal discontinuation among negative patients at 3 days of testing (36.8% and 37.0% respectively). No differences were detected in death and/or subsequent diagnosis of candidemia. In summary, addition of BDG was interpreted variably by clinicians, was associated with an increase in antifungal utilization, and did not correlate with measurable clinical benefits for patients.

BACKGROUND/UNASSIGNED: METHODS/UNASSIGNED:infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. RESULTS/UNASSIGNED:= .001), while treatment with carbapenem-sparing therapy was not. CONCLUSIONS/UNASSIGNED:Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.

INTRODUCTION: Clostridium difficile infection (CDI) is associated with significant morbidity and mortality. Salvage therapy may include IVIG, fecal microbiota transplant (FMT) or colectomy. There is limited data regarding the effectiveness of IVIG for CDI (43-65%) or optimal dosing strategies.
METHOD(S): This is a retrospective review of critically ill patients who received IVIG (Gamunex-C) for severe or fulminant CDI at NYU Langone Health. The primary outcome was response to therapy, defined as hospital survival and complete resolution of CDI symptoms by the last day of CDI treatment without need for surgery or FMT.
RESULT(S): Fifteen patients received IVIG for severe (n=6) or fulminant (n=9) CDI, with the BI/NAP1/027 strain isolated in 27% of cases. Patients were primarily female (66%) with a median age of 62 years and had a SOFA score of 7 (IQR 4,8) at the time of IVIG administration. Twelve patients were immunosuppressed (e.g., transplant, malignancy) and nine had chronic kidney disease. There were five patients with recurrent CDI for the index infection, defined as CDI in the previous 8 weeks. Active anti-CDI therapies prior to IVIG administration included enteral vancomycin (93%), IV metronidazole (80%), rectal vancomycin (27%), fidaxomicin (7%), tigecycline (7%) and cholestyramine (7%). Median time to IVIG administration from the date of CDI positivity was 41 hours (21,75). The median total dose of IVIG administered per patient was 1.2 g/kg given over 2 days (1.5,3). Response to treatment was observed in 11 patients (73%); 4 required either colectomy (n=3) or FMT (n=1). Among the 5 patients with recurrent disease who received IVIG, response was observed in 4 cases (80%). Adverse events related to IVIG were not reported, and there were no cases of CDI recurrence within 6 months of CDI therapy completion. One in-hospital mortality was observed, which was unrelated to CDI.
CONCLUSION(S): For severe or fulminant CDI, IVIG pharmacotherapy was associated with a favorable treatment response in 73% of patients, possibly averting the need for care escalation to colectomy or FMT. Various dosing strategies were utilized, limiting assessment of a doseresponse relationship. Further data and a comparison to a cohort of critically ill patients who did not receive IVIG is needed to delineate place in therapy

Background. Candidemia is a common hospital acquired infection that is associated with significant morbidity and mortality. The optimal strategy for diagnosis remains unknown. Methods. We evaluated 2 distinct diagnostic strategies in hospitalized patients with suspicion of Candida bloodstream infection, namely strategy #1 that included simultaneous blood cultures and T2Candida and strategy #2 that included blood cultures, T2Candida testing and Beta-D-glucan (BDG). We examined the consistency with which each diagnostic algorithm led to changes in antifungal prescribing, the overall rate of antifungal utilization and patients' clinical outcomes. Flow Chart. Results. Among 96 patients tested with strategy #1, 3 had a positive result. Of those 100% completed a 14-day antifungal course for candidemia or were on antifungals until hospital discharge. Of the 29 out 120 patients that tested positive with strategy #2, 55.2% received a complete 14-day course or were on antifungals until hospital discharge. The percentage of completed treatment increased to 75.0% and 80.0% when the threshold for BDG positivity was increased at 200 pg/ml and 500 pg/ml respectively. We observed a significant difference in the overall antifungal utilization with 268.5 days of antifungals per 1,000 patient days for strategy #1, as opposed to 371.9 days of antifungals for strategy #2, a 38.5% increase. Negative tests at both diagnostic strategies led to a similar rate of antifungal discontinuation 3 days after testing (36.8% and 37.0% for strategy #1 and #2 respectively). We did not find significant benefits in death and/or subsequent diagnosis of candidemia between the 2 diagnostic strategies. Sensitivity analyses performed based on indication for testing and severity of illness did not significantly alter results. Conclusion. In summary, the addition of BDG in diagnostic algorithms for candidemia was interpreted variably by clinicians, was associated with a significant increase in antifungal utilization, and it did not appear to lead to measured clinical benefits for patients. Diagnostic strategies of common and serious infections that incorporate non-culture diagnostics need to be evaluated for added benefit. (Figure Presented)

Background/UNASSIGNED:Patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) have poor outcomes and frequently develop comorbid conditions, including cytomegalovirus (CMV) reactivation. The implications of CMV reactivation in this setting are unknown. We aimed to investigate if treatment of CMV viremia improved in-hospital mortality in ICU patients with COVID-19. Methods/UNASSIGNED:In this single-center retrospective study, we analyzed clinical outcomes in patients diagnosed with COVID-19 pneumonia and CMV viremia admitted to an ICU from March 1, 2020, to April 30, 2021, who either received treatment (ganciclovir and/or valganciclovir) or received no treatment. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were total hospital length of stay (LOS), ICU LOS, requirement for extracorporeal membrane oxygenation (ECMO) support, duration of mechanical ventilation (MV), and predictors of in-hospital mortality. Results/UNASSIGNED: = .749). There was no significant difference in hospital LOS, though CMV-treated patients had a longer ICU LOS. Conclusions/UNASSIGNED:Treatment of CMV viremia did not decrease in-hospital mortality in ICU patients with COVID-19, but the sample size was limited. CMV viremia was significantly associated with total steroid dose received and longer ICU stay.

Background/UNASSIGNED:The epidemiology of nosocomial bloodstream infections (NBSIs) in patients with coronavirus disease 2019 (COVID-19) is poorly understood, due in part to substantial disease heterogeneity resulting from multiple potential pathogens. Methods/UNASSIGNED:We identified risk factors for NBSIs and examined the association between NBSIs and mortality in a retrospective cohort of patients hospitalized with COVID-19 in 2 New York City hospitals during the height of the pandemic. We adjusted for the potential effects of factors likely to confound that association, including age, race, illness severity upon admission, and underlying health status. Results/UNASSIGNED:infections did not have an identifiable source and were not associated with common risk factors for infection by these organisms. Conclusions/UNASSIGNED:Pathogen species and mortality exhibited temporal differences. Early recognition of risk factors among COVID-19 patients could potentially decrease NBSI-associated mortality through early COVID-19 and antimicrobial treatment.

Background/UNASSIGNED:Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. Methods/UNASSIGNED:This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. Results/UNASSIGNED:, in-hospital mortality, or 30-day infection-related readmission. Conclusions/UNASSIGNED:We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.