bluuebunny/crossref_metadata_2025_split huggingface dataset:
721. Effect of Gastrointestinal Pathogen Panel (GIP) in Antibiotic Management
Authors: Saling Christopher F , Seville Maria T , Patron Roberto L 
Published: January 2021

Abstract

Background
GIP offers detection via PCR for a wide array of common microbes associated with diarrheal illness. Its rapid turnaround time and high sensitivity has made GIP testing commonplace for the evaluation of diarrhea. The purpose of this study is to determine if GIP influences antibiotic management in patients hospitalized with diarrhea.

Methods
Fifty patients hospitalized at Mayo Clinic Arizona between July and December 2019 who underwent BioFire® FilmArray™ GI PCR Panel testing were randomly selected. Medical records were reviewed to capture gender, age, immunocompromised state, antibiotic use within 30 days, prior hospitalization within 3 months, history of Clostridioides difficile infection, time from admission to testing and GIP results, and to determine if GIP results directly contributed towards antibiotic management. This study was exempt from Institutional Review Board approval.

Results
Twenty-six patients were male and twenty-four were female. The average age was 61.7 years. Thirty-four patients (68%) were immunocompromised. Forty-one GIPs were ordered within 24 hours of admission. Twenty-two patients (44%) had a positive GIP result; five were positive for 2 concurrent organisms. C. difficile was the most commonly detected organism, found in 16/24 (66.7%) positive tests. Eleven patients (68.8%) with C. difficile had a recent hospitalization, antibiotics within 30 days, or a history of C. difficile infection. There were 3 cases of Enteropathogenic Escherichia coli, 2 of Enterotoxigenic Escherichia coli, 2 of adenovirus, 2 of norovirus, 1 of rotavirus, and 1 of Vibrio cholerae. Excluding C. difficile positive patients, GIP testing contributed in changing antibiotic management in 3/50 (6%) patients tested. One patient had antibiotics stopped, one received correct antibiotics, and one received inappropriate antimicrobial therapy.

Conclusion
These results suggest that except in the setting of C. difficile infection, GIP has little utility in guiding antimicrobial management, even in the immunocompromised patient. GIP testing is expensive and it may be more resourceful to screen patients hospitalized with diarrhea for C. difficile alone, especially in those with risk factors for C. difficile infection. Furthermore, GIP testing can lead to antibiotic overuse.

Disclosures
All Authors: No reported disclosures
723. Epidemiology, Risk Factors, and Treatment Considerations for Pyogenic Liver Abscess (PLA) in the Calgary Health Zone (CHZ) Revisited: A Population-Based Study
Authors: Losie Jennifer A , Parkins Michael , Lam John , Gregson Daniel 
Published: January 2021

Abstract

Background
PLA is a significant cause of morbidity and mortality. However, its epidemiology and outcomes have not been recently evaluated in the CHZ. Understanding current trends will help guide management.

Methods
In this population-based study, we evaluated epidemiology, risk factors, and treatment of patients with PLA in the CHZ. CHZ residents aged ≥ 20 years diagnosed with PLA in 2015-2017 were included. Charts were reviewed for demographics and clinical outcomes. Multivariate logistic regression was used to determine factors associated with 30-day mortality. Findings were compared to a previous assessment of PLA in the CHZ from 1999-2003 (Kaplan et al., 2004).

Results
A total of 136 patients with PLA were identified, representing an annual incidence rate of 3.7 cases per 100,000 population. Compared to 1999-2003, incidence of PLA was increased (2.3 per 100,000; p&lt; 0.01) but mortality was similar (1999-2003: 0.22 per 100,000 vs. 2015-2017: 0.26 per 100,000; p=0.6). The most common culprit organisms were Streptococcus anginosus group (40%), Klebsiella species (25%), Escherichia coli (18%), and obligate anaerobes (16%). Pathogen prevalence was similar to the prior cohort. Compared to 1999-2003, antibiotic resistant organisms were more frequent (8% vs 1%, p=0.04). In our cohort, liver aspirations were less frequent (p=0.02) but aspirate culture was more often positive (p&lt; 0.01). The median duration of intravenous antibiotic therapy was longer compared to previous (2015-2017: 23 days (IQR 9-38) vs. 1999-2003: 17 days (IQR 10-29); p=0.001). Similarly, the total duration of antibiotic therapy was longer (2015-2017: 42 days (IQR 25-65) vs. 1999-2003: 31 days (IQR 18-45); p&lt; 0.001). Thirty-day mortality from admission was 7% and did not differ amongst cohorts. Risk factors are shown in Table-1.
Table-1: Risk factors for 30-day mortality in PLA

Conclusion
Incidence of PLA in the CHZ is rising with more antimicrobial resistance. Diagnostic liver aspirations are less frequent. Antibiotic durations are longer with no reduction in mortality. Understanding changing trends is valuable in directing future care. Encouraging liver aspirations to obtain a microbiologic diagnosis, especially with increasing resistance, is crucial. Considering shorter antibiotic durations in light of stable mortality warrants further exploration.

Disclosures
All Authors: No reported disclosures
730. Severity Of Clostridioides difficile Infection Based On Toxin Analysis, Acid Suppressant Medications and Antibiotics
Authors: Krishnan Gayathri , Parikh Richa , Witt Anna N , Bano Kulsum , Bhattacharyya Sudeepa , Kothari Atul 
Published: January 2021

Abstract

Background
Clostridioides difficile (C difficile) infection (CDI) is a major health problem in the United States and despite updated guidelines, the laboratory diagnosis remains vexed. A multistep algorithm is recommended to diagnose CDI that includes antigen, toxin and toxin gene Nucleic Acid Amplification (NAAT) assays. This study was done to assess severity of CDI based on toxin B and NAAT statuses. The other objective was to analyze if antibiotics and PPI/H2B (Proton Pump Inhibitors and H2 blockers) affected severity of CDI.

Methods
Retrospective analysis of all adult patients admitted to a tertiary medical center with diarrhea and a positive C difficile antigen test from 01/2017- 12/2017. From more than 2000 stool samples submitted to the lab, C diff antigen was positive in 265 patients. 191 were diagnosed with CDI based on the 2-step algorithm. Clinical data was available for 168 patients. Severity of CDI was determined based on published guidelines. Fischer’s exact test was used for statistical analysis.

Results
The mean age at diagnosis was 55.96. Toxin B was detected in 34% (57/168) patients and Toxin NAAT positive in 66% (111/168) patients. 57% of CDI was health care onset compared to 43% with community onset. 42% (72/168) were classified as severe out of which 40.2% (29) were toxin B positive, and 59.8% (43) were NAAT positive. There were no significant differences in severity of CDI based on toxin B and NAAT status (50.9% vs 38.4%, p=0.14). 46% of cases from community vs 39.6% from hospitals were classified as severe CDI (p=0.415). 72% of cases had antibiotic use in the last 30 days. Use of antibiotics was significantly associated with severe CDI (82% vs 64%, p=0.015). 62.5% (105) patients had history of PPI/H2B use and severity was not significantly associated with its use (p=0.872).

Conclusion
Our study shows that the presence of toxin did not significantly impact the clinical severity of CDI. The use of antibiotics did not affect the presence of toxin although the total number of CDI cases with previous antibiotic exposure was high. Patients who had recent antibiotic exposure were more likely to have severe clinical presentation. More toxin positive cases were health care onset but the effect was not pronounced. Severity of CDI did not significantly depend on health care onset or on exposure to PPI/H2B.

Disclosures
Atul Kothari, MD, Ansun Biopharma (Consultant)
732. Evaulation of Micafungin Treatment at Pediatric Patients: A cross-sectional Study from Tertiary Pediatric Centre
Authors: Arıkan Kamile , Bayram Nuri , devrim İlker , Akaslan-Kara Ayküke 
Published: January 2021

Abstract

Background
Micafungin is one of three currently available echinocandin for treatment of candidiasis and candidemia.

Methods
Children who were treated for micafungin for possible or proven invasive Candidia infection between May 2017 and October 2019 were included.

Results
In this cross-sectional study, totally 78 children with a median age of 3 months (8 days -17 years), 50 (64.1%, F/M: 0.56) male were included. Thirty four (43.6%) patients were neonate, 26 (76 %) of them were premature. Thirty seven patients (47.4%) received micafungin for candidemia and 41 (52.6%) patients received micafungin empirically for IC. Twelve (32.4%) Candida spp cultured were C. albicans, the rest twenty five (67.6%) Candida spp were non-albicans Candida spp. The most commonly cultured Candida spp was Candida parapsilosis (C. parapsilosis) (n=13) followed by C. albicans (n=12), C. glabrata (n=3), C. tropicalis (n=3), C. guilliermondii (n=3), C. krusei (n=2) respectively. Resistance rate of C. parapsilosis (n=13) isolates to fluconazole, voriconazole, amphotericin B, caspofungin, micafungin were as follows respectively; 66.7%, 100%, 69.2%, 90.9%, 37.5% respectively. Resistance rate of C. albicans (n=11) isolates to fluconazole, voriconazole, amphotericin B, caspofungin, micafungin were as follows respectively; 50%, 50%, 12.5%, 42.9%, 0% respectively. None of the C. tropicalis, C. guilliermondii and C. krusei isolates were resistant to micafungin. Culture negativity could not be achieved at the end of 14th day of micafungin treatment in the 15 (16.9%) candidemia episodes. The most commonly isolated Candida spp in patients with treatment failure was C. parapsilosis (n=7), the other species were; C. albicans (n=5), C. guilliermondii (n=1), C. tropicalis (n=1) and C. tropicalis and C. guilliermondii coinfection (n=1) respectively. Median serum AST, ALT and creatinin levels didn’t increase during and at the end of micafungin therapy. None of these patients had experienced an anormal kidney or liver function tests due to micafungin usage.
Characteristics of patients who received micafungin.and cultured Candida spp

Antifungal resistance patterns of Candida spp.

Laboratory change before and after micafungin treatment

Conclusion
Increase in fluconazole resistant Candida spp makes micafungin a reasonable and effective choice for suspected or proven invasive candidiasis

Disclosures
All Authors: No reported disclosures
737. A Descriptive Analysis of Fluconazole Utilization at Two Academic Medical Centers in the Valley Fever Corridor of Arizona
Authors: Hayes Justin , Matthias Kathryn , Villanueva Juan , Nix David 
Published: January 2021

Abstract

Background
Fluconazole (fluc) is a common antifungal used at hospitals and is an important target for antimicrobial stewardship (AS). Fluc is also used for management of coccidioidomycosis (C). The objective of our study was to describe fluc prescribing patterns at two academic centers in Arizona.

Methods
We conducted a retrospective analysis of fluc usage in adult patients. One month from each quarter in a one-year period (November 2017-November 2018) was selected (4 months in total). All adult patients that received fluc at Hospital A and Hospital B in the selected months were identified. Patient demographic information and Charlson comorbidity index (CCI) to quantify the degree of comorbidity were collected. We then analyzed patients in the study by defining the fluc usage as directed towards C management or non-C management (e.g., candidiasis). In the C management group, we characterized the initial fluc dose during the patient’s course as directed for empiric, targeted, or prophylaxis treatment. Finally, we performed further analysis of the empiric C group. The study received IRB approval from our institution.

Results
During our study period, 1239 patients were included in the analysis. Patient information is shown in Table 1. Overall, most of the fluc usage was directed towards C management (63.5%, 787/1239). A significant amount of that usage was directed towards C prophylaxis at both Hospital A and B (67.4% (234/347) and 75% (330/440), respectively). In addition, fluc usage directed towards empiric C management was higher at Hospital A versus Hospital B (18.4% (64/347) versus 9.5% (42/440), respectively). Further patient data for the empiric C group is shown in Table 2.

Conclusion
We report the results of a descriptive study that demonstrate that 63.5% of fluc usage in adults at two academic medical centers in Arizona was directed for C management. In addition to traditional fluc targets for AS, our study highlights C prophylaxis in solid organ transplant recipients and empiric C management as AS targets in endemic regions. These targets are especially important due to the risk for selection of azole-resistant Candida species and invasive molds with increased antifungal exposure.

Disclosures
All Authors: No reported disclosures
738. A Novel Molecular Diagnostic Assay for Identification of Fungal Pathogens
Authors: Matzko Michelle E , Martinsen Melanie A , Sephton-Clark Poppy , Cuomo Christina , Bhattacharyya Roby P 
Published: January 2021

Abstract

Background
A rapid and accurate diagnostic method for invasive fungal infections remains a critical clinical need. We recently reported a rapid molecular method for bacterial species identification directly from clinical samples that targets highly abundant ribosomal RNA on a multiplexed hybridization platform called NanoString. Here we report an adaptation of this assay that accurately distinguishes common fungal pathogens with limit of detection at a single yeast cell.

Methods
Building on our bacterial approach, we computationally designed specific hybridization probes targeting species-specific variable regions of fungal 18S and 28S rRNA from 12 clinically relevant fungi: Aspergillus fumigatus, Cryptococcus neoformans, and 10 Candida species, including Candida auris. Following mechanical lysis of crude specimens, fungi were detected from laboratory culture or artificial cerebrospinal fluid via multiplexed hybridization on a NanoString (Seattle, WA) instrument which yielded results within 7 hours from sample collection. Assay sensitivity was probed using serial dilutions of lysed C. albicans in culture, and cell-equivalents were confirmed by plating.

Results
Our hybridization probes targeting fungal rRNA specifically recognized all species tested to date: A. fumigatus, C. neoformans, and C. albicans with no cross-reactivity (Fig 1a). Serial dilutions of C. albicans lysate demonstrated a limit of detection around 0.1 cell equivalents without rRNA amplification (Fig 1b), capitalizing on the intrinsic abundance of rRNA in fungal cells.
Figure 1.

Conclusion
We adapted a rapid, ultrasensitive hybridization-based diagnostic assay that has proven successful in bacteria, to fungi. Here we show the accurate detection of Aspergillus, Cryptococcus, and Candida species, including a computational design that will enable the distinction of 10 different Candida species, including C. auris, within hours from clinical specimen collection.

Disclosures
All Authors: No reported disclosures
742. Breakthrough Invasive Fungal Infections with Isavuconazonium Sulfate versus Voriconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia (AML) who Received Induction Chemotherapy
Authors: Singam Hareesh v , Pasikhova Yanina , Quilitz Rod , Greene John N , Baluch Aliyah 
Published: January 2021

Abstract

Background
Fungal infections in patients with hematologic malignancies are associated with high mortality. Primary antifungal prophylaxis has been shown to be a more effective strategy than treating a documented infection. This retrospective analysis aims to compare the rates of breakthrough invasive fungal infections in patients with acute myeloid leukemia (AML) who received induction chemotherapy and were prescribed voriconazole (Vori) or isavuconazonium (Isv) for primary antifungal prophylaxis.
The European Organization for Research and Treatment of Cancer/ Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to categorize incidence of breakthrough invasive fungal infections bIFI into ‘possible’, ‘probable’ or ‘definite’ groups who required treatment with liposomal amphotericin B, echinocandin, and/or different triazole.

Methods
This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML. These patients received either Vori or Isv sulfate as the primary antifungal prophylaxis at Moffitt Cancer Center between July 2017 and June 2019. Patients who were over 18 years old and received at least 10 days of uninterrupted primary antifungal prophylaxis with either Vori or Isv sulfate were included in the study. Patients with a history of stem cell or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or who received systematic antifungal, other than fluconazole, therapy within 30 days to induction chemotherapy were excluded.

Results
250 patients were screened for the study and out of which 118 patients met the above criteria. There was a 20.2% (18/89) break through rate of fungal infections in the Vori arm and 17.2% (5/29) in the Isv arm. In the Vori arm there were 15 possible bIFIs, 3 probable bIFIs and 0 definite bIFIs. In the Isv arm there are 2 possible bIFIs, 2 probable bIFIs and 1 definite bIFIs.

Conclusion
There is no significant statistical difference (Using the Fisher Exact test statistic p=1) between the Isv and Vori in patients who received these agents for primary fungal prophylaxis for induction chemotherapy for AML at Moffitt Cancer Center between July 2017 - June 2019.

Disclosures
Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)
743. Characteristics of Candidemia in a Coccidioidomycosis Endemic Region: The impact of Increased Azole Use in the Selection of Candida species
Authors: Al-Obaidi Mohanad , Marquez Jose , Afghan Abaseen , Zangeneh Tirdad 
Published: January 2021

Abstract

Background
The incidence of invasive candidiasis secondary to non-albicans Candida species is on the rise. In Arizona, azoles are used for coccidioidomycosis treatment and prophylaxis in immunosuppressed population. Therefore, we intended to describe the characteristics and outcomes of non-albicans Candidemia in our area.

Methods
We conducted an IRB approved multicenter study evaluating patients from October 1, 2017 to January 1, 2020. Patient demographics, medical history, procedures, antifungal use, and laboratory data were collected. Episode per patient was included in the statistical analysis.

Results
In the study period, there were 145 patients with 151 candidemia episodes. For the episode-per-patient, median age was 51 (IQR 37-62), 45% were female, and 86% were Caucasian. 10% had a history of transplantation (40% HSCT and 60% SOT), and 22.5% had a history of cancer. 78% had another concomitant systemic infection. 4/80 (5%) and 12/102 (12%) had infective endocarditis. Only 5 (3.3%) had a history of coccidioidomycosis and 37 (24.5%) had exposure to azole therapy in the prior 3 months. 60% of the candidemia episodes were due to non-albicans Candida species, 27/37 (73%) had a prior history of azole therapy, 12/15 (80%) were transplant recipients, and 23/34 (80%) had cancer. The majority (71%) of patients initially received an echinocandin without a significant difference in mortality. Of all the admission episodes, there were 45/151 (29%) deaths and 7/151 (4.5%) were discharged to hospice. Not removing central catheters was associated with 60% of deaths (P=0.002). Infectious diseases consult was associated with lower mortality (OR 0.25, 95% CI 0.087-0 .70) and higher rates of catheter removal (OR 8, 95% 2.2-29.5). There was no difference in mortality between non-albicans versus albicans Candidemia (28.6% vs. 32%, P=0.7).

Conclusion
Our study found higher rates of non-albicans Candidemia that are more eminent in transplant recipients and those with prior azole use, but this was not statistically significant. The removal of the central line and ID consultations was associated with a significant reduction in mortality. In Coccidioidomycosis endemic regions, the risk of non-albicans candida infections can be higher with the use of azoles; however, further studies are recommended.

Disclosures
All Authors: No reported disclosures
744. Clinical Performance of Real-time PCR in the Diagnosis of Pneumocystis jirovecii Pneumonia compared with Immunofluorescence Assay
Authors: Veintimilla Cristina , Alvarez-Uria Ana , Martin-Rabadan Pablo , Alcala Luis , Muñoz Patricia , Marin Mercedes 
Published: January 2021

Abstract

Background
The laboratory diagnosis of Pneumocystis jirovecii pneumonia (PJP) has been traditionally based on microscopy techniques, which have suboptimal sensitivity and depends on the experience and skills of the microbiologist. Molecular detection assays based in PCR (Polymerase chain reaction) could improve sensitivity.
Our aim was to evaluate the utility of real-time PCR in the diagnosis of PJP compared with IFA (Immunofluorescence assay) performed in different respiratory samples of patients with PJP suspicion for routine use in a clinical laboratory setting.

Methods
From September 2015 to April 2018, we studied by a real-time PCR targeting the large subunit of rRNA gene of P. jirovecii (PJ-PCR RealCycler PJIR kit Progenie Molecular) and Immunofluorescence assay (MONOFLUO P. carinii IFA BioRad) in all respiratory samples received for microbiological diagnosis of PJP. The definite clinical diagnosis of PJP was established by infectious disease physicians considering symptoms, radiological and laboratory findings.

Results
Overall, 302 samples were included (182 bronchoalveolar lavage, 67 sputum, 53 tracheal aspirates). PJ-PCR was positive in 51 (16.9%) and IFA in 11 (3.6%) of the patients with PJP. There were not IFA positive/PCR negative samples. Sensitivity, specificity, PPV and NPV for IFA were 26% (95%CI 15.9-39.6%), 100% (95%CI 98.5-100%), 100% (95% CI 77.2-100%) and 87.2% (95% CI 82.6-90.6%). Whereas, sensitivity, specificity, PPV and NPV for PCR was 92% (95%CI 81.2-96.8%), 98% (95% CI 95.4-99.2%), 90.2% (95% CI 79.0-95.7%) and 98.4% (95% CI 96.0-99.4%).
PJ-PCR had sensitivity &gt; 80% and specificity &gt; 90% in all type of samples included.
A definitive diagnosis of PJP was considered in 50 (16.6%) patients, including 4 (1.3%) cases with negative PJ-PCR. Five cases (9.8%) with positive PJ-PCR were considered as colonization.

Conclusion
P. jirovecii PCR improves the sensitivity and NPV of PJP diagnosis respecting to IFA, regardless of respiratory sample type. Our results suggest that Microbiology laboratories should use PCR techniques to diagnose PJP better than IFA.

Disclosures
All Authors: No reported disclosures