bluuebunny/crossref_metadata_2025_split huggingface dataset:
1170. Invasive Fungal Infections and Colonization in Critically Ill Patients: Impact of Diagnosis and Management on Outcomes
Authors: Siudela Anthony , Khan Afshin , Bateman Marjorie E 
Published: January 2021

Abstract

Background
Invasive fungal infections (IFIs), though uncommon, are on the rise and have a high mortality rate. Fungal colonization is common, but its clinical significance is unclear. Our study aims to characterize the impact of these diagnoses and their management on outcomes in a large ICU population.

Methods
We utilized the Multiparameter Intelligent Monitoring in Intensive Care III database for this retrospective cohort study. Adults with positive fungal cultures were classified as colonized or infected using definitions from the EORTC/MSG guidelines and the Blot protocol for Aspergillus. Outcomes were compared between groups matched by age, SOFA score, admission diagnosis, culture results, and comorbidities.

Results
There were 595 hospital admissions with IFI (11.7/1000 admissions) and 5789 with colonization (114/1000 admissions). In-hospital mortality was 52% in patients with IFIs and 36% in colonized patients. Mortality post-discharge remained high and was not significantly different in the two groups.
67% of patients with IFIs had the diagnosis documented. 24% of patients with IFIs and 8% of colonized patients received antifungal therapy. Treatment did not significantly impact mortality in infected or colonized patients but was associated with increased length of hospital and ICU stay. Infectious disease (ID) consultation was performed in 39.8% of patients with IFIs and 20% of patients with colonization. In the group of IFI patients with ID consultation, in-hospital mortality was higher, but survival post-discharge increased significantly. There was a significant increase in diagnosis of IFI in the ID group and a trend toward increased treatment. In colonized patients with ID consultation, in-hospital mortality and survival post-discharge improved. Hospital and ICU length of stay were longer for patients with ID consultation.

Conclusion
Critically ill patients with IFIs have high mortality rates, which were not reduced by treatment. The prevalence of colonization was high, and colonized patients experienced significant in-hospital and post-discharge mortality. This study supports the need for additional investigation into ID consultation, which may improve outcomes in critically ill patients with fungal infection and colonization.

Disclosures
All Authors: No reported disclosures
1173. Ocular Candidiasis in Patients with Candidemia Diagnosed by Blood Culture Versus T2Candida® Assay
Authors: White Cameron , Pappas Peter , McCarty Todd P 
Published: January 2021

Abstract

Background
Ocular candidiasis (OC) is a serious complication of candidemia. Current guidelines recommend dilated fundoscopic exam (DFE) in all patients with candidemia. In this study, we examined characteristics and outcomes of patients at UAB Medical Center with candidemia diagnosed by blood culture (BC) or T2Candida® rapid diagnostic assay (T2C) who were found to have evidence of fungal disease on ophthalmologic exam.

Methods
Patients from 2016-2019 with either 1) at least one positive BC for Candida species or 2) positive T2C assay and negative or no paired BC were identified and retrospectively reviewed. Patients with additional positive BC or T2C within 60 days were excluded from the analysis. Data collected included risk factors for candidemia, causative Candida species, and whether DFE was performed after diagnosis. Patients with evidence of OC by exam were compared by type of ocular involvement (chorioretinitis vs. vitritis), whether visual symptoms were present, and whether intravitreal injection was performed.

Results
A total of 360 episodes of candidemia diagnosed by BC and 288 by T2C alone were included. Of those who underwent DFE, 33 BC patients (12.9%) had findings concerning for OC compared to 18 (8.9%) T2C patients (p=0.177) (Table 2). T2C patients with OC were younger, were more likely to have a prolonged ICU stay and to be mechanically ventilated, and were less likely to be on TPN compared to the BC group. Identification of C. parapsilosis was significantly more common in T2C patients (Table 1). There were no significant differences in presence of visual symptoms, type of ocular involvement, need for intravitreal injection, or 30-day mortality (Table 3).
Table 1. Demographics and risk factors

Table 2. Episodes of candidemia and ocular candidiasis by year

Table 3. Ocular findings and outcomes

Conclusion
The frequency of ocular disease was similar between groups. Significantly more T2C patients had candidemia due to C. parapsilosis, and the groups differed in terms of risk factors for candidemia. There were no differences in frequency of intravitreal injection, severity of eye disease, or mortality. Despite recent concerns about the necessity of DFE in asymptomatic patients with candidemia, we believe these results emphasize the importance of performing DFE in candidemic patients and also support the practice of doing so in patients with positive T2C even in the absence of positive blood cultures.

Disclosures
Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Todd P. McCarty, MD, Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator)
1175. Pulmonary Aspergillosis in Critically Ill Patients with COVID-19: A Case Series
Authors: Mitaka Hayato , Perlman David C , Javaid Waleed , Salomon Nadim 
Published: January 2021

Abstract

Background
Invasive pulmonary aspergillosis (IPA) has been reported in critically ill patients without pre-existing immunocompromising conditions. However, there are scant data on pulmonary aspergillosis in patients with COVID-19.

Methods
We performed a retrospective review of pharmacy records of antifungal use during 3/21-4/22, 2020, and collect longitudinal clinical data. Cases were then classified by the clinical algorithm for IPA in the ICU (AspICU).

Results
7 out of 18 (39%) patients who received antifungal therapy had Aspergillus fumigatus in tracheal aspirate specimens while mechanically ventilated in the ICU. None of the patients had EORTC/MSG host factors. Median time from admission to the date of positive respiratory culture was 9 days (range: 2-15). High-dose glucocorticoids were started a mean of 5.6 days (range 3-8) before the positive respiratory culture in 5 and on the day of the culture in 2. Six received 583-1000 mg equivalent of prednisone. Two received Tocilizumab. By AspICU criteria, 4 had putative IPA. Radiographic abnormalities included cavitary pneumonia, opacities with dense consolidation, worsening infiltrates, and diffuse interstitial and patchy hazy opacities. Compatible signs included worsening respiratory failure in 3 and fever after 3 days of antibacterial agents in 1. Associated findings were leukocytosis in 4, &gt; 1 positive cultures in 3, high procalcitonin in 2, and positive serum galactomannan in 1. The remaining three were classified as colonization as they lacked compatible signs. One had concomitant Klebsiella aerogenes pneumonia with bacteremia, and two later developed Candidemia and Stenotrophomonas maltophilia pneumonia, respectively. All 3 had fever with leukocytosis. One had elevated procalcitonin. Six received antifungal therapy; one did not due to goals of care. All 7 patients expired despite ICU care.

Conclusion
The critically ill patients with severe COVID-19 in whom respiratory culture grew Aspergillus fumigatus showed very high mortality despite antifungal treatment. By AspICU algorithm, 4 patients had putative IPA. Further data on risk factors and clinical predictors of IPA in COVID-19 are needed.

Disclosures
All Authors: No reported disclosures
1177. Rapid, Non-invasive Detection of Invasive Mucormycosis Caused by Syncephalastrum monosporum Using Next-Generation Sequencing of Circulating Microbial Cell-free DNA in Plasma
Authors: Sanacore Melissa , Solh Melhem M , Holland H Kent , Bashey Asad , Webster Samuel , Morris Lawrence , Solomon Scott , de Vries Christiaan R 
Published: January 2021

Abstract

Background
Improving diagnostics have led to newly identified causes of invasive fungal infection (IFI) in immunocompromised hosts. Syncephalastrum spp. are Zygomycetes more commonly associated with skin infections and have only rarely been implicated as a cause of IFI(1). Next generation sequencing (NGS) for circulating microbial cell-free DNA (mcfDNA) in plasma offers a unique tool to diagnose rare causes of IFI (2,3).

Methods
Karius results were reviewed for Syncephalastrum detections with 2 identified at the same institution. McfDNA was extracted from plasma and NGS was performed by Karius, Inc. (Redwood City, California). Human sequences were removed and remaining sequences were aligned to a database of over 1,400 pathogens. Organisms present above a predefined statistical significance threshold were quantified in DNA molecules per microliter (MPM). Chart review was performed for clinical correlation.

Results
A 66 y/o male one month out of induction therapy for acute myeloblastic leukemia (AML) developed pneumonia. Although BAL was negative for mold and despite empiric antifungals, plasma NGS for mcfDNA showed S. monosporum at 562 MPM; the reference range is 0 MPM. Amphotericin was added to empiric posaconazole. The patient was discharged 10 days later and serial CT scans showed improvement. Repeat NGS mcfDNA 11 days later was negative. He underwent stem cell transplant (SCT) 4 months later.
In a second case, a 66 y/o female with acute prolymphocytic leukemia was admitted for fever with neutropenia. A CT chest showed new multifocal, bilateral, nodular opacities. Despite negative BAL fungal culture and pretreatment with fluconazole, plasma NGS mcfDNA revealed S. monosporum at 575 MPM. She was treated with micafungin, amphotericin, and posaconazole with clinical improvement. Repeat NGS mcfDNA 8 weeks later was negative. Serial CT scans showed improvement over 5 months. She proceeded to SCT.

Conclusion
Plasma-based NGS for mcfDNA enabled rapid, non-invasive detection of pulmonary mucormycosis caused by S. monosporum despite antifungal pretreatment and unrevealing invasive procedures in 2 patients with leukemia. The rapid identification of the specific etiology of IFI enabled targeted anti-fungal therapy and resumption of definitive oncological care including SCT.
Table 1: Clinical Parameters

Disclosures
Christiaan R. de Vries, MD, PhD, Karius (Consultant, Independent Contractor)Stanford University (Employee)
1178. Risk factors for death among patients with Candida endocarditis: An observational study in US academic medical centers
Authors: Huggins Jonathan , David Michael Z , Hohmann Samuel F 
Published: January 2021

Abstract

Background
Candida endocarditis is a rare, sometimes fatal complication candidemia. Our understanding of this condition is limited to findings from case series and small observational studies. Using the Vizient clinical database, a repository for clinical and administrative data from 117 academic medical centers and more than 300 affiliated hospitals, we assembled the largest cohort of Candida endocarditis patients to date, reporting patient characteristics and risk factors for death.

Methods
Using ICD-10 code B37.6 (Candidal Endocarditis) we identified 703 inpatients at 179 United States hospitals from October 2015 through April 2019. We examined demographic, diagnostic, and procedural data from each patient’s initial encounter. With univariate and multivariate logistic regression analyses we identified predictors of in-hospital mortality.

Results
Of 703 patients, 402 (57.2%) were male, 421 (59.9%) used tobacco, 213 (30.3%) had documented opiate abuse, 128 (18.2%) had other illicit drug abuse documented, and 190 (27.0%) had documented hepatitis C infection. Among the 703 patients, 114 (16.2%) died during the index encounter. On multivariate analysis, liver failure was the strongest predictor of death (OR 8.4, 95% CI 4.4 – 15.9), and female sex (OR 1.8, 95% CI 1.1 – 2.9), transfer from an outside facility (OR 1.7, 95% CI 1.1 – 2.7), underlying aortic valve pathology (OR 2.8, 95% CI 1.5 – 4.9), hemodialysis (OR 2.0, 95% CI 1.0 – 3.8), cerebrovascular disease (OR 2.2, 95% CI 1.2 – 3.8), neutropenia (OR 2.5, 95% CI 1.3 – 4.7) and alcohol abuse (OR 2.9, 95% CI 1.3 – 6.7) were also associated with higher odds of in-hospital death. In the same analysis, opiate abuse was associated with a lower odds of in-hospital death (OR 0.4, 95% CI 0.2 – 0.8).
Table 1. Characteristics of 703 patients with Candida endocarditis

Table 2. Factors associated with in-hospital death in multivariate regression analysis

Conclusion
We found that for patients Candida endocarditis inpatient mortality was 16.2% and liver failure was associated with a high risk of death while opiate abuse was protective. Further investigation is necessary to better understand these associations.

Disclosures
Michael Z. David, MD PhD, GSK (Consultant)
1179. Septic shock in Coccidioides immitis Infection
Authors: Wisniewski Piotr , Ewers Evan C , Maves Ryan C 
Published: January 2021

Abstract

Background
Coccidiodes can cause severe or disseminated disease in a minority of patients, but coccidioidomycosis resulting in septic shock is rare. We describe a case of fulminant C. immitis infection whose diagnosis was delayed by a markedly elevated serum procalcitonin. We review the published literature of coccidioidomycosis complicated by septic shock.
Case Report
A 74-year-old man presented with cough, fever, and three weeks of progressive decline. He was febrile at 39.1°C, tachycardic, and tachypneic with crackles in the left lung; an initial procalcitonin (PCT) was 1.73 ng/mL. Broad-spectrum antibacterials were administered. His condition worsened on the 2nd day, requiring vasopressors, endotracheal intubation, and hemodialysis. PCT rose to &gt; 400 ng/mL. Respiratory cultures grew fungi consistent with Coccidioides. Liposomal amphotericin B (AmB) was initiated. His shock progressed, and he died on hospital day 6.

Methods
We performed a MEDLINE and Google Scholar search using the terms “coccidioidomycosis”, “Coccidioides”, “sepsis”, and “septic shock”. Indexed articles and conference abstracts were included if the patient had confirmed coccidioidomycosis and vasopressor-dependent shock with no alternate cause. Data on age, sex, ethnicity, comorbidities, antifungal therapy, and outcome were tabulated.

Results
We identified 18 reports describing 31 patients with vasopressor-dependent septic shock due to Coccidioides since 1993 (table 1). Of these cases, 23/31 (74.2%) died. Of those with reported race/ethnicity, 20/23 were Latino, 4/23 of African descent, 5/23 Asian-Pacific Islander, and 3/23 white. 27/31 (87.1%) were male. All but two were adults (median age 51.5 years). 21/31 (67.7%) had reported comorbid conditions. 20/31 patients (64.5%) and all of the survivors received AmB-based therapy.
Table 1 - Published cases of coccidioidomycosis complicated by septic shock. All ages are in years. Abbreviations: HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome; CAD = coronary artery disease; COPD = chronic obstructive pulmonary disease; ESRD = End stage renal disease; SLE = Systemic Lupus Erythematosus; APC = recombinant human activated protein C (drotrecogin alfa).

Conclusion
Coccidioidomycosis is an elusive diagnosis in critically-ill patients due to its rarity, the lack of rapid diagnostics, and its propensity to mimic other infections. Mortality is high, potentially due to delays in diagnosis. The marked elevation in PCT has not been previously noted in coccidioidomycosis and may further confound diagnosis. Improved diagnostics and the rapid institution of AmB may reduce mortality in patients with coccidioidal sepsis.

Disclosures
All Authors: No reported disclosures
1184. Activity of anti-pseudomonal antibiotics among all Pseudomonas aeruginosa (PSA) at an academic medical health system, including β-lactam, multi-drug (MDR) and extensively drug resistant (XDR) strains
Authors: Rose Warren , Heikkinen Benjamin , Radaatz Janet , Puzniak Laura A , Dillon Ryan J , Schulz Lucas 
Published: January 2021

Abstract

Background
PSA with MDR and XDR are a growing threat, and appropriate initial treatment of this organism is critical. C/T is a novel antibiotic with broad gram-negative in vitro susceptibility among surveillance studies. However comprehensive susceptibility analyses of C/T among PSA clinical isolates in comparison with other anti-PSA antibiotics remain limited, since routine clinical C/T susceptibility testing is not typically performed.

Methods
This study assessed all adult inpatient cultures positive for PSA from 32 months at an academic health system. Antimicrobial susceptibility was prospectively performed using Kirby Bower disk diffusion and interpreted by BIOMIC V3 during routine clinical care. Initial susceptibility testing included C/T along with amikacin, aztreonam, cefepime, ciprofloxacin, doripenem, gentamicin, imipenem, meropenem, piperacillin/tazobactam, and tobramycin. MDR and XDR isolates were identified using established definitions. The primary outcome was to quantify C/T resistant PSA (includes intermediate and resistant strains). Secondary outcomes were to determine resistance to other anti-PSA antibiotics and to identify C/T activity among isolates with MDR, XDR and pan-β-lactam resistance (PBLR = all β-lactams except C/T).

Results
A total of 2990 PSA isolates from 2339 cultures in 1311 individual patients were collected. Most cultures were from the lung (45%), followed by urine (30%), and body fluids (10%). For the primary outcome, 121/2990 (4%) of PSA isolates were C/T resistant. All PSA blood cultures were susceptible to C/T. Table 1 summarizes in vitro activity of all anti-PSA agents evaluated. C/T had the greatest percent susceptibility across all culture locations including MDR/XDR PSA isolates with median MICs of 8 µg/mL. For PBLR strains 35/66 (53%) were susceptible to C/T with a median MIC of 8 µg/mL.
Table 1

Conclusion
C/T susceptibility testing during routine care over a 2.5-year period revealed 96% susceptibility among PSA. C/T showed the highest susceptibility among all anti-PSA antibiotics for all culture locations and for MDR and XDR isolates. Given the high rates of resistance to traditional anti-PSA agents, the value of new agents with high rates of in vitro susceptibility in the gram-negative armamentarium is high.

Disclosures
Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support) Janet Radaatz, PharmD, Merck (Employee) Laura A. Puzniak, PhD, Merck (Employee) Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee)
1186. Cefazolin inoculum effect predicts reduced susceptibility to other antibiotics and patient outcomes in MSSA endovascular infections
Authors: Smelter Dan , McCrone Sue , Rose Warren 
Published: January 2021

Abstract

Background
MSSA Infective endocarditis (IE) is inherently a high-burden infection with up to a 30% mortality rate. Cefazolin is an appealing treatment option for IE with low toxicity and a favorable dosing scheme. However, cefazolin has been associated with treatment failure in IE, attributed to an inoculum effect. The specific mechanism underlying the cefazolin inoculum effect (CIE) remains undetermined, but CIE has been linked to both blaZ expression and agr dysfunction. This study aims to determine whether CIE is linked to reduced susceptibility to other antibiotics and worse outcomes regardless of therapy in MSSA endovascular infections.

Methods
Sixty-four MSSA strains were collected from patients with endovascular infections not treated with cefazolin. To determine CIE phenotype, strains were cultured and MICs assayed for cefazolin, nafcillin, and vancomycin at 107 CFU/mL for high-inocula (HI) and 105 CFU/mL for standard-inocula (SI). This study defined CIE as a ≥ 4-fold increase in MIC at HI compared to SI, with at least an MIC of 4 mg/L at HI. Nitrocefin disks identified blaZ expression, and beta lysin disks were used to determine hemolysin type and agr function. Patient outcomes of mortality and bacteremia duration were assessed across cohorts.

Results
Twenty-four strains exhibit a CIE (38%), with 10 strains having an MIC of ≥ 32mg/L at HI. Nafcillin and vancomycin also had an inoculum effect, uncoupled from the CIE and occurring at a lower frequency and amplitude at HI. Presence of CIE had a greater association with blaZ expression (71% vs 25%) than agr dysfunction (38% vs 20%). 50% (9/18) of CIE infections were cleared within 48 hours while 77% (20/26) of CIE-negative infections were cleared within 48 hours (P=0.106). However, presence of CIE was not associated with increased mortality (25% CIE-positive vs 35%; P=0.578)

Conclusion
Previous studies for CIE failed to enrich for isolates from endovascular sources, where inocula are known to be high. This study presents one of the largest endovascular source cohorts for CIE evaluation. It identifies that CIE prevalence (38%) is higher than reports from diverse infection sources (10-36%). CIE appears to predict bacteremia duration with other MSSA treatment options, suggesting mechanisms independent of blaZ and agr function for this phenomenon.

Disclosures
Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support)
1189. Correlation of BK polyomavirus (BKPyV)-specific Immunity and BKPyV Viruria within 6 months after Kidney Transplantation: A Prospective Cohort Study
Authors: Siripoon Tanaya , Kantachuvesiri Surasak , Apiwattanakul Nopporn , Bruminhent Jackrapong 
Published: January 2021

Abstract

Background
Since viral-specific immunity has been shown to be correlated with viral containment in solid organ transplant recipients, we investigated an association of BK polyomavirus (BKPyV)-specific immunity and BKPyV viruria in kidney transplant (KT) recipients.

Methods
A prospective cohort study of all adult KT recipients between January and August 2019 was conducted. High-level BKPyV viruria was defined as the presence of BKPyV viral load in urine &gt; 7log10 copies/mL. BKPyV-specific immunity was measured by an intracellular cytokine assay measuring the percentage of IFN-γ-producing CD4+, CD8+, NK, and NKT cells, after stimulation with large-T antigen (LT) and viral capsid protein 1 (VP1). The incidence of high-level BKPyV viruria within 6 months after KT was estimated by the Kaplan-Meier method. Clinical and immunological factors were analyzed using Cox proportional hazard model. BKPyV-specific immune responses prior to and at 1 month after KT were compared using a mixed-linear regression test.

Results
Among 90 evaluable patients, 37% were female with a mean age + SD of 42 + 12 years. Sixty-four and 68 % received deceased-donor KT and induction immunosuppressive therapy, respectively. The cumulative incidence of BKPyV viruria within 6 months was 20%. In multivariate analysis, pre-transplant factors which were independently associated with BKPyV viruria were panel-reactive antibody of 11-50 % (HR 13.35; 95%CI, 1.926-92.590; P = 0.009), %natural killer (NK) cells (HR 1.26; 95%CI, 1.077-1.469; P = 0.004), and %VP1-specific NK cells (HR 1.25; 95%CI, 1.088-1.433; P = 0.002). Among those with BKPyV viruria, the mean %NK, %VP1-specific NK cells and %NKT cells at 1-month post-KT were significantly increased over time as compared to pre-KT (coefficient: 1.202; 95%CI, 0.033-2.371; P = 0.04), (coefficient: 2.602; 95%CI, 1.083-4.121; P = 0.001), and (coefficient: 0.199; 95%CI, 0.051-0.348; P = 0.008), respectively.

Conclusion
A presence and increasing proportion of NK, VP1-specific NK and NKT cells were observed among KT recipients who developed early and clinically significant BKPyV viruria in our cohort. Quantification of BKPyV-specific NK and NKT cell immune monitoring could potentially stratify those at risk of BKPyV viruria among KT recipients.

Disclosures
All Authors: No reported disclosures