bluuebunny/crossref_metadata_2025_split huggingface dataset:
1158. D-index as a Novel Index to Predict Invasive Fungal Disease in High-Risk Neutropenic Pediatric Cancer Patients and Hematopoietic Stem Cell Transplantation
Authors: Alali Muayad , Pisano Jennifer 
Published: January 2021

Abstract

Background
Prolonged and profound neutropenia are risk factors for invasive fungal disease (IFD) during febrile neutropenia (FN) episodes. The D-index combines both depth and duration of neutropenia in a single assessment and has been proposed as a useful tool to exclude or predict IFD in high-risk adult patients. We assessed the D-index as a predictor of IFD in pediatric cancer patients.

Methods
We conducted a retrospective study of pediatric oncology patients with FN at UCM Comer Children’s Hospitals. IFD was stratified as possible, probable, and proven according EORTC/MSG criteria. Patients considered high risk of IFD were receiving intensive chemotherapy with expected prolonged neutropenia &gt;7 days, including, but not limited to, AML, high-risk acute ALL, and hematopoietic stem cell transplantation (HSCT). The D1-index was equal to 2t1 + 3t2, where t1, and t2 are the number of days from the first day of neutropenia &lt; 500mm3 and &lt; 100/ mm3 respectively, until the development of IFD. The D2-index approximates the area over the neutrophil curve during neutropenia. A cumulative D-index (c-D-index) was also calculated using the first day of neutropenia until the date of the first clinical manifestation of IFD. We compared duration of neutropenia vs D-index vs c-D-index as a predictor of IFD using receiver operating characteristic curve (ROC)/AUC analysis.
Figure 1

Figure 2

Results
We identified 455 FN episodes in 203 high-risk patients. 53/455 (11.6%) had IFD, 12 (2.6%) proven, 23 (5%) probable, and 18 (4%) possible. The median of D1, D2 indexes and c-D-index were significantly higher in patients developing IFD (38, 5225, 7352) compared to the non-IFD group (26, 3857, 5169) (P=.001, P=.001, and P=.01) respectively. The ROC curve of D-index and c-D-index (figure 1,2,3) showed better performance (AUC of 0.85,0.89, 0.81) respectively compared to the duration of neutropenia alone. The ROC was highest when D-index was combined with prolonged fever &gt;5 days (AUC 0.94)
Figure 3

Figure 4

Conclusion
The D-index may be a useful tool to stratify high-risk pediatric patients according to risk of IFD. The c-D-index, particularly, may be a useful tool to guide for empiric antifungal therapy and diagnostic testing. Prospective multi-center studies using these tools are required to refine the clinical approach to IFD.

Disclosures
All Authors: No reported disclosures
1160. Ecological Study for Pulmonary Blastomycosis
Authors: Wang James L , Shorman Mahmoud 
Published: January 2021

Abstract

Background
There has been a global increase in people who are intravenous drug user, diabetic, and elderly (aged greater than 65 years). These characteristics may alter the incidence of new diseases and potentially affect how diseases are diagnosed. As such this study’s purpose was to investigate baseline characteristics of patients with pulmonary blastomycosis. Case studies for Blastomyces have demonstrated positive cultures in 72% to 87% of patients. Therefore data will be analyzed to determine if there is any significant difference in culture results.

Methods
This study was a retrospective single-center ecological study. Patient charts were identified via ICD code search for blastomycosis. All protected health information was de-identified following data collection.

Results
32 patients were identified with either pathology or culture proven blastomycosis. 8 patients (25%) had positive fungal cultures for blastomycosis. The average age of patients with pulmonary blastomycosis was 59.5 years old with 11 elderly patients (34%). There were 11 females (34%); 2 with hepatitis C (6%); 12 with diabetes (38%); 10 with immunosuppression (pancytopenia, chronic steroid usage, organ transplant, cystic fibrosis) (32%); 9 with COPD (32%); 21 with Tobacco abuse (67%); 7 with cancer (22%); 7 with work exposure (working around turned dirt or indoor mold) (22%) and 1 with opiate use (3%). No significant difference was found for culture results.
Baseline Characteristics

Culture Characteristics

Conclusion
Our culture results were exceedingly low in part due to some samples not being collected for fungal culturing and having to send-out the samples. The average age was consistent with the endemic region of Tennessee around 59 the previous 10 years.. 2/3 of the patients were tobacco abusers which may have contributed to some impaired ability to clear the fungal spores. Less than half of the patients were elderly, diabetic, immunosuppressed, or intravenous drug users therefore endemic inoculation may still be the main cause.

Disclosures
All Authors: No reported disclosures
1161. Effectiveness of Posaconazole in the Treatment of Rare Invasive Fungal Infections: A Systematic Literature Review
Authors: Bernauer Mark , Waskin Hetty , Cossrow Nicole , Kaminski Allysen , Campbell Havilland , Patel Dipen 
Published: January 2021

Abstract

Background
Rare invasive fungal infections (IFIs) such as chromoblastomycosis (CBM), fungal mycetoma (mycetoma), hyalohyphomycosis/phaeohyphomycosis (hyalo/phaeo), and mucormycosis (mucor) cause significant morbidity and mortality in immunocompromised patients. Few effective treatment options are available for these IFIs, therefore we assessed the clinical efficacy of posaconazole, a broad-spectrum triazole antifungal compound with demonstrated activity against IFIs.

Methods
We performed a systemic literature review of Medline and EMBASE to identify studies published from 2005 (year of posaconazole approval) to October 30, 2019, reporting the efficacy/effectiveness of posaconazole monotherapy or combination therapy for treating CBM, mycetoma, hyalo/phaeo, and mucor. Two reviewers screened and extracted data based on predefined PICOS criteria. Effectiveness outcomes included cure, response, relapse, radiologic improvement; mortality and any other effectiveness measures reported. Study quality was assessed using National Institute for Health and Care Excellence-recommended checklists. A narrative descriptive summary was used to summarize study findings.

Results
Of 2612 articles identified, 351 articles (mostly case reports) were included. Positive clinical outcomes with posaconazole therapy were observed in most patients with CBM (73.9%, 17/23), mycetoma (100%, 2/2), hyalo/phaeo (53.3%, 49/92), and mucor (66.7%, 564/845). The population for mycetoma was small; only 2 positive cases (Figure). Overall survival was ~70% or greater across the IFIs examined. Posaconazole efficacy and mortality differed by line of therapy as well as for monotherapy versus combination therapy. Positive response was higher in second line monotherapy than first line monotherapy in CBM and mucor. Higher mortality was observed with combination therapy than monotherapy in hyalo/phaeo and mucor infections (except for first line use in mucor).
Figure. Overall Results of Posaconazole Treatment

Conclusion
Despite the rarity of these IFIs, substantial data have been published since posaconazole’s initial approval in the year 2005, and the evidence demonstrates that posaconazole is an effective therapeutic option alone or in combination for the treatment of these rare IFIs.

Disclosures
Mark Bernauer, BPharm, RPh, Merck & Co, Inc. (Consultant) Hetty Waskin, MD/MPH, Merck & Co, Inc. (Employee) Nicole Cossrow, PhD, Merck & Co, Inc. (Employee) Allysen Kaminski, BA, Merck & Co, Inc. (Consultant) Havilland Campbell, BS, Merck & Co, Inc. (Employee) Dipen Patel, BPharm, PhD, Merck & Co, Inc. (Consultant)
1162. Engraftment fever (EF) in Pediatric stem cell transplantation (SCT): Risk Factors, Etiology and Outcomes
Authors: Alali Muayad , Elmuti lena , Bartlett Allison 
Published: January 2021

Abstract

Background
Engraftment fever (EF) during stem cell transplantation (SCT) is likely due to non infectious causes like immune reconstitution syndrome (IRS) or engraftment syndrome (ES). Few studies have looked at the rate of infection causing fever during engraftment. There is no good evidence to guide the approach to evaluation and empiric treatment of infections during EF.

Methods
Retrospective record review of pediatric SCT (autologous and allogenic) patients with a diagnosis of febrile neutropenia (FN) during engraftment period (days +7 to +30 post transplant). FN episodes classified as either EF or non-engraftment fever (NEF). EF = new onset fever in temporal relationship to neutrophil recovery (4 days before through 1 day after neutrophil engraftment (ANC &gt;500/mm3). NEF = fever without signs of neutrophil recovery (ANC &lt; 100/mm3 without significant rise ±4 days of fever onset). Only first FN during engraftment was included. Episodes meeting neither criteria were excluded.

Results
112 patients had 115 FN episodes (FNEs) identified: NEF 81 (71.5%); EF 34 (29.5%). In multivariable analysis: Neuroblastoma as underlying diagnosis (odds ratio [OR]=3.2, 95% CI 2.31-6.54, P&lt; 0.01), G-CSF administration before day +7 (OR=2.8, 95% CI 1.92-4.65, P=0.03), absolute monocyte count (AMC) &gt;100/mm3 at FN presentation (OR=2.9, 95% CI, 1.11 to 7.55, P=0.02), were associated with an increased risk of EF compared with NEF. Most EF episodes (26/34, 76%) had no specific infectious etiology identified; 8 had IFIs (24%) [3 proven, 2 probable, 3 possible). IFI rate was higher in EF than NEF group (24% vs 5%) (OR=4.5, 95% CI, 2.11 to 9.55, P&lt; 0.01. EF episodes were more likely to be admitted to the intensive care unit (OR=2.3, 95% CI, 1.88 to 6.35) and had higher 30-day mortality (OR =4.52, 95% CI, 0.37 to 6.55) than NEF.
Table 3

table 2

Conclusion
Engraftment fever may have an infectious component. Work-up to exclude IFI and empirical antifungal therapy should be considered especially with prolonged fever and supportive clinical or radiological data. Large multi-center prospective studies are needed to further define infectious complications and determine the approach to engraftment fever. Early detection of IFI in this high-risk group may lead to improved morbidity and mortality.

Disclosures
All Authors: No reported disclosures
1163. Epidemiology of Candidemia: Can Candida Spread from Patient to Patient in the Hospital?
Authors: Erayil Serin Edwin , Selmecki Anna , Kline Susan E 
Published: January 2021

Abstract

Background
Candidemia has become an increasingly important infection in recent years. Antifungal drug resistance in non-albicans species of Candida is increasingly common. Recent global emergence of Candida auris is a concern, owing to person-to-person transmission and survival on fomites. Our study aimed to determine if hospital transmission of diverse Candida species is occurring similar to what is seen in Candida auris. We analyzed all candidemia infections for signatures of transmission, including species, geographical, and temporal clusters. Here we present our preliminary data from December 2019 - May 2020.

Methods
This is a prospective and retrospective analytical observational study. Patients with candidemia were identified with the help of the Clinical Microbiology Lab at a University Medical Center. Data was collected on all identified patients by retrospective chart review. Data was described in terms of frequency distributions and percentages, and analyzed using SPSS. Isolates have been stored prospectively as glycerol stocks at -80 C for ongoing analyses.

Results
37 patients were identified (Tables 1 and 2). Clusters of candidemia were seen in the months of January (C. parapsilosis, 3 patients), February (C.glabrata, 3 patients), March (C.albicans, 5 patients) and April (C.glabrata, 3 patients). 33/37 (89%) had a central line prior. Lines were removed in 73% (24/33) of these patients, the remaining patients were deceased before lines could be removed. Pancreatic pathology was seen in 15/37 (40.5%) patients (Table 3). 25/37 (67.5%) had an Ophthalmology consult.
Table 1. Patient demographics

Table 2. Epidemiology of candidemia

Table 3. Pancreatic pathology in candidemia

Conclusion
It is possible that the clusters identified shared equipment or other environmental factors that caused nosocomial transmission. We plan to use Whole Genome Sequencing to determine clonality among these isolates. The association of candidemia with pancreatic pathology was curious. It is to be evaluated whether this was simply a confounder or an actual risk factor that perhaps warrants consideration of prophylaxis. Rates of Ophthalmology consults to evaluate for endophthalmitis need to be improved in our setting. We hope that this study would prove valuable for infection control efforts and help us be better prepared to tackle emerging pathogens of this genus.

Disclosures
All Authors: No reported disclosures
90. Impact of Discrepant Rapid Diagnostic Test (RDT) Results on Antimicrobial Stewardship Program (ASP) Interventions in Patients with Bloodstream Infections (BSI) due to Gram-Negative Bacilli (GNB)
Authors: Robinson Evan D , Cox Heather L , Attai April E , Donohue Lindsay , Shah Megan , Hill Brandon , Elliott Zach , Mathers Amy J , Mathers Amy J 
Published: January 2021

Abstract

Background
Implementation of the Accelerate PhenoTM Gram-negative platform (AXDX) paired with ASP intervention projects to improve time to definitive institutional-preferred antimicrobial therapy (IPT). However, few data describe the impact of discrepant RDT results from standard of care (SOC) methods on antimicrobial prescribing. Here we evaluate the prescribing outcomes for discrepant results following the first year of AXDX + ASP implementation.

Methods
Consecutive, non-duplicate blood cultures for adult inpatients with GNB BSI following combined RDT + ASP intervention were included (July 2018 – July 2019). AXDX results were emailed to the ASP in real time then released into the EMR upon ASP review and communication with the treating team. SOC identification (ID; Vitek® MS/Vitek® 2) and antimicrobial susceptibility testing (AST; Trek SensititreTM) followed RDT as the reference standard. IPT was defined as the narrowest susceptible beta-lactam, and a discrepancy was characterized when there was categorical disagreement between RDT and SOC methods. When IPT by AXDX was found to be non-susceptible on SOC, this was characterized as “false susceptible“. Conversely, “false resistance” was assessed when a narrower-spectrum agent was susceptible by SOC. Results were also deemed discrepant when the AXDX provided no/incorrect ID for on-panel organisms, no AST, or a polymicrobial specimen was missed.

Results
Sixty-nine of 250 patients (28%) had a discrepancy in organism ID or AST: false resistance (9%), false susceptible (5%), no AST (5%), no ID (4%), incorrect ID (2%), and missed polymicrobial (2%). A prescribing impact occurred in 55% of cases (Table 1), where unnecessarily broad therapy was continued most often. Erroneous escalation (7%) and de-escalation to inactive therapy (7%) occurred less frequently. In-hospital mortality occurred in 4 cases, none of which followed an inappropriate transition to inactive therapy.

Conclusion
Though the AXDX platform provides rapid ID and AST results, close coordination with Clinical Microbiology and continued ASP follow up are needed to optimize therapy. Although uncommon, the potential for erroneous ASP recommendations to de-escalate to inactive therapy following AXDX results warrants further investigation.

Disclosures
Amy J. Mathers, MD, D(ABMM), Accelerate Diagnostics (Consultant)
1164. Epidemiology of Cryptococcal Infections in Non-HIV Patients: A 20-year Single Center Experience
Authors: Kumar Rebecca Nirmal , Nam Hannah , Roberts Scott C , Penugonda Sudhir , Angarone Michael , Stosor Valentina 
Published: January 2021

Abstract

Background
Cryptococcus has a worldwide distribution, with C. neoformans and C. gattii being two of the most common species causing disease. Despite advances in therapy, disseminated infection often results in significant morbidity and mortality.

Methods
We conducted a single center retrospective cohort study over a twenty-year period spanning from January 2000 through May 2020 to determine epidemiology and outcomes of non-HIV-associated cryptococcosis at Northwestern Memorial Hospital. Cases were identified by positive culture data or positive cryptococcal antigen in the serum or cerebrospinal fluid (CSF). Epidemiology of risk factors, morbidity, and mortality was evaluated.

Results
81 cases were identified of which, 67 had Cryptococcus spp isolated from culture and the remaining patients diagnosed by cryptococcal antigen and/or histopathology. The cohort was primarily Caucasian (56.8%, n=46) and male gender (67.9%, n=55), with a median age of 59.5 (IQR: 52.75-66.25) years old. Common predisposing conditions were diabetes (37%, n=30), chronic kidney disease (34.6%, n=28), and liver disease (28.4%, n=23). Solid organ transplant recipients and use of immunosuppression accounted for, respectively, 32.1% (n=26) and 29.6% (n=24) of the cohort. Sites of infection include lung (65.4%. n=53), central nervous system (33.3%, n=27), blood (30.9%, n=25), peritoneum (6.2%, n=5), musculoskeletal (2.5%, n=2), and prostate (1.2%, n=1). Mean opening pressure on lumbar puncture was 25.3 mmHg (range: 9 -52 mmHg). In hospital mortality at time of diagnosis was 27.2% (n=22), and mortality at 12 months post diagnosis was 51.9% (n=42).

Conclusion
At our center, those with cryptococcosis commonly had risk factors such as immunosuppression either secondary to solid organ transplant or otherwise. Morbidity and mortality remain high.

Disclosures
Sudhir Penugonda, MD, MPH, AbbVie, Inc. (Employee, Other Financial or Material Support, ownership and/or investment interests) Michael Angarone, DO, Abbvie (Other Financial or Material Support, Data Safety Monitoring Board)Allergan (Speaker’s Bureau)
1167. Got Micafungin? The Incidence of Fungemia in Patients with Septic Shock
Authors: Piche Mackenzie , Campion Maureen , Adeel Alina 
Published: January 2021

Abstract

Background
Timely administration of antibiotics in patients presenting with sepsis decreases mortality, however evidence evaluating empiric antifungal coverage has been inconclusive. Recent data have shown no mortality benefit of empiric antifungal therapy in patients with ICU-acquired sepsis. Despite the lack of data, the Surviving Sepsis Campaign recommends empiric coverage for all suspected pathogens, including fungi. The purpose of this study is to determine the frequency of concomitant septic shock and fungemia at UMass Memorial Medical Center, a large tertiary care center.

Methods
This was a retrospective cohort study that included adult patients with a discharge diagnosis of severe sepsis or septic shock and/or fungemia admitted to UMMMC between October 2017 and October 2019. Patients with positive fungal blood cultures were further reviewed to identify if septic shock was present within 24 hours of blood culture collection. Additionally, risk factors for fungemia and 30-day mortality were assessed. Exclusion criteria included pregnancy, cultures from outside hospitals, incarceration, and hospice care.

Results
In the analysis period, 4,253 patients had a discharge diagnosis of severe sepsis or septic shock. There were 68 cases of fungemia. In total, 54 patients with fungemia were included after applying exclusion criteria. Of the 54 patients with fungemia, 8 patients (15.1%) met criteria for septic shock at the time of positive blood culture, while 81% met SIRS criteria. Of the 4,253 total patients, 0.19% had coexisting fungemia and septic shock. At 30 days, four patients (7.4%) with both septic shock and fungemia had expired out of 12 total deaths. Three of the four deaths had multiple risk factors for fungemia including central line in place for greater than 48 hours, parenteral nutrition, and prolonged antibiotic therapy.

Conclusion
Septic shock is a rare presentation of fungemia. Most patients with septic shock and fungemia have known risk factors. Despite recommendations by the Surviving Sepsis Campaign to initiate therapy for all likely pathogens, including fungal species, the incidence of fungemia presenting as septic shock at our academic medical center was very low and does not appear to warrant empiric coverage.

Disclosures
All Authors: No reported disclosures
1168. Higher Glycosylated Hemoglobin (A1c) Levels are Associated with Increased Mortality from Cryptococcus Infection
Authors: Archuleta Solana , Sillau Stefan , Franco-Paredes Carlos , Henao-Martinez Andres 
Published: January 2021

Abstract

Background
Diabetes mellitus is a well-established risk factor for the development of bacterial infections. However, the role of diabetes mellitus as a risk factor in the occurrence of Cryptococcosis is unknown. The aim of the study was to determine whether diabetes and A1c levels were independent risk factors for infection and mortality in Cryptococcus infection.

Methods
A retrospective hospital-based case-control study matched by age and gender (96 cases and 125 controls) was performed in patients tested for Cryptococcus infection at University of Colorado Hospital from 2001-2019 (n=221). Data was extracted through RedCap. A multivariable logistic regression model was used to identify predictors of infection and mortality.

Results
Diabetes mellitus was present in 24 cases (25.0%) and 24 controls (19.2%). In cases, the mean age was 54 years, 79% were men, and diabetes was the only known risk factor in 6 cases (6.3%) and accompanied additional risk factor in 18 cases (18.8%). Other common risk factors included: HIV (39.9%), steroid use (24.7%), malignancy (23.2%), solid organ transplant recipients (18.1%), and cirrhosis (5.2%). Cryptococcal meningitis (49.0%) followed by pulmonary infection (36.5%) were the most common sites of infection. The mean A1c value for cases vs. controls was 6.5 ± 1.5 vs. 6.2 ± 1.8 mmol/L, p=0.43. Overall mortality was 27.3% vs. 26.9% among cases and controls, respectively. Among cases, the risk of death was higher for patients with diabetes, although not significantly (39.1% vs 23.1%, p= 0.137). Adjusted for gender, age and case/control; for every 1-point increase in A1c levels, the odds of mortality increased by 40% (OR = 1.4, CI: 1.0-1.9, p= 0.045).

Conclusion
Diabetes mellitus alone is an uncommon risk factor for acquiring Cryptococcus infection. However, uncontrolled diabetes in Cryptococcosis may worsen outcomes from infection, including increased mortality. Glucose control interventions may improve clinical outcomes in patients with cryptococcal infection.

Disclosures
All Authors: No reported disclosures