bluuebunny/crossref_metadata_2025_split huggingface dataset:
335. Comparison of inner colony production among Escherichia coli (EC) and Klebsiella pneumoniae (KP) during fosfomycin disk diffusion (DD) testing
Authors: Bixby Morgan L , Salay Jenna , Hirsch Elizabeth B 
Published: December 2022

Abstract

Background
Recent studies have indicated the presence of IC arising within the zone of inhibition during fosfomycin DD testing. CLSI and EUCAST have contradicting recommendations for interpreting these IC; CLSI recommends considering the presence of IC when interpreting DD results while EUCAST recommends ignoring them. Although DD testing is approved only for use with EC per both organizations, it is often used for testing of non-EC organisms despite neither organization publishing non-EC Enterobacterales breakpoints (BP). We sought to compare the rates of IC production among EC and KP isolates in order to assess the applicability of fosfomycin DD for KP isolates.

Methods
A convenience sample of 128 (80 KP and 48 EC) clinical isolates with varied phenotypic profiles from 3 United States locations were included. Of these, 26% (n = 21) of KP and 29% (n =14) of EC displayed ESBL phenotypes and 19% (n = 15) of the KP were KPC producing. Fosfomycin susceptibility testing via DD was conducted in duplicate on separate days following interpretations recommended by each organization. Isolates were considered IC-producing if at least 5 IC arose during ≥ 1 replicate of DD testing.

Results
Overall, 61% (n = 78) of isolates produced IC including 75% (n = 36) of EC and 52.5% (n = 42) of KP (Table 1). Of the EC isolates that produced IC, 89% (n = 33) were susceptible per CLSI and 92% (n = 34) were susceptible per both EUCAST oral and IV BP. In contrast, only 41% (n = 17) of KP isolates with IC were susceptible per CLSI and 2% (n = 1) were susceptible per both EUCAST BP. The presence of IC did not result in significant differences of zone diameters (1-14mm, EC; 2-13mm, KP) when comparing organization procedures. Table 1.Production of IC by susceptibility categorization based on three sets of fosfomycin BP
This table compares the KP and EC collection based on three different breakpoints (CLSI, EUCAST oral, and EUCAST IV) using the entire collection and the subset that produced IC (EC: 36/48 and KP: 42/80).

Conclusion
The BP and IC interpretations from EUCAST and CLSI categorized most EC isolates, including those that produced IC, as susceptible. EUCAST’s larger zone measurements and ignoring IC produced near identical results to CLSI. EUCAST’s lower BP categorized very few KP as susceptible even when ignoring the presence of IC. CLSI BP captures a more diverse categorization of susceptibility of KP isolates consistent with the diversity of zone measurements. These findings warrant further investigation into the clinical relevance of IC and applicability of fosfomycin DD BP in KP.

Disclosures
Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.
341. GeneXpert Ultra for the Diagnosis of Extrapulmonary Lymphnode Tuberculosis – A Diagnostic Study from High Tuberculosis Burden Country
Authors: Naguthevar Santhanam , Kumar Deepak , Ravindra Akshatha , Samantaray Subhashree , Kombade Sarika P , Krishna Bohra Gopal , Shankar Meena Durga , Kumar Midha Naresh , Jain Vidhi , Garg M K , Singh Kuldeep 
Published: December 2022

Abstract

Background
Extrapulmonary tuberculosis (EPTB) is quite prevalent in India, ranging from 8.3% and 13.1%. Diagnosis of EPTB is often challenging as it resembles other granulomatous conditions pathologically. TB culture remains the gold standard for definitive diagnosis, but it takes longer time and WHO has recommended the use of GeneXpert Ultra for rapid diagnosis. This study aims the utility of GeneXpert Ultra for diagnosis of tubercular adenitis.

Methods
This prospective study included the suspected tubercular adenitis patients with lymphnode size of ≥ 20mm. Patients diagnosed with other aetiology of adenitis were excluded. Excision biopsy was performed in all patients. Tissue samples were sent for Ziehl Neelson (ZN) stain, GeneXpert Ultra, histopathology and mycobacterial culture (BACTEC). The sensitivity, specificity, positive predictive value (PPV), and Negative predictive value (NPV) of GeneXpert Ultra were analysed in comparison with culture results.

Results
A total of 85 patients Lymph node were included, of which 60% (n=51) had cervical LN, 15%(n=13) abdominal LN, 12%(n=11) mediastinal LN, and 15%(n=11) others. Most of the patients (97%) HPE findings of granulomatous inflammation of which only 20%(n=17) were ZN stain Positive. TB culture showed positivity of 56.47%(n=48) . Mycobacterial tuberculosis was detected in 69%(n=59) of patients by GeneXpert Ultra & none of them showed Rifampicin resistance. The Sensitivity, specificity, PPV & NPV for GeneXpert Ultra were found 85.4%, 51.3%, 25.06% and 94.8%, respectively.

Conclusion
GeneXpert Ultra showed excellent sensitivity and negative predictive value for the diagnosis of TB Lymphadenitis. Further this method detects Rifampin sensitivity which is crucial for initiation of appropriate antitubercular drugs.

Disclosures
All Authors: No reported disclosures.
346. Aspergillosis in COVID-19 era in Dominican Republic
Authors: Rojas-Fermin Rita A , Sanchez-Marmolejos Ann S , Acra-Tolari Ricardo , Guzman-Marte Anel E , Suero Irina 
Published: December 2022

Abstract

Background
COVID-19-associated Pulmonary Aspergillosis (CAPA) and Invasive Pulmonary Aspergillosis (IPA) represent a difficult diagnostic challenge to the clinician. Moreover, during the COVID-19 pandemic, as airway invasive procedures were limited due to fear of contamination, these diagnoses were even harder to make, as one of the most useful diagnosis tools, bronchoscopies, were postponed. The aim of this study was to describe the epidemiology and risks factors of Aspergillosis and CAPA in a Dominican tertiary health care facility during the COVID-19 pandemic. Table 1
Characteristics of patients with COVID-19-associated Pulmonary Aspergillosis (CAPA) and Invasive Pulmonary Aspergillosis (IPA)

Methods
A retrospective, cross-sectional, case-series study was carried out were all patients during the COVID-19 pandemic from March 2020 - March 2022 in HGPS who had a galactomannan (GM) test were analyzed. Using E-records patients with positive galactomannan (GM) tests were identified, and the following variables were evaluated: demographics, laboratories, risk factors, comorbidities, CT scans and prognosis. Cases were classified as CAPA (Probable, possible or proven according to classification ECMM/ISHAM), or IPA.

Results
Out of 77 patients who underwent a GM test, 10 had a positive result; 40% of these were probable CAPA and 60% were IPA. 7 were co-infected with multidrug-resistant pathogens from which 71.4% died; overall median age was 56.9 years (minimum 29 – maximum 71), and only one patient was female. The overall mortality rate was 60% and 50% for the probable CAPA group. Most radiological findings from the probable CAPA group were classified as typical invasive pulmonary aspergillosis. Major documented risk factors and comorbidities were lymphopenia, prolonged steroids use, hypertension, diabetes mellitus and mechanical ventilation.

Conclusion
An increase in both CAPA and IPA screening is needed in patients who present risk factors such as mechanical ventilation, prolonged use of steroids, or renal replacement therapy. Screening for GM in bronchoalveolar lavage, mycologic cultures and histopathologic tests, are needed for an improvement in the diagnostic classification as well as the clinical outcome of these patients.

Disclosures
Rita A. Rojas-Fermin, MD, Gilead: Advisor/Consultant|MSD: Expert Testimony|MSD: Honoraria|Pfizer: Advisor/Consultant.
354. Invasive fungal disease in patients with severe COVID-19 infection at a midwestern academic medical center
Authors: Maurer Stephen M , Linder Kathleen A , Miceli Marisa H 
Published: December 2022

Abstract

Background
Invasive fungal diseases (IFD) have been described in patients (pts) with severe coronavirus disease 2019 (COVID), albeit with geographic variability in rates.

Methods
We performed a retrospective study to determine rates of & risk factors for IFD occurring within 30 days (d) of COVID diagnosis (dx) in adults requiring critical care for severe COVID between 5/11/20 & 2/7/21. Mortality was assessed at 90 d following COVID dx and at 84 d after IFD dx, if applicable. ECMM/ISHAM criteria were used for COVID-associated pulmonary aspergillosis (CAPA) and EORTC/MSGERC criteria were used for other IFD and treatment response.

Results
218 pts were included; median age was 62 (19 – 91) & 63% were men. Underlying conditions included solid organ transplant (Tx) (16; 7%), allogenic stem cell Tx (3; 1%), malignancy (21; 10%), & exposure to either high-dose steroids (HDS) (11; 5%) or T- or B-cell suppressants (29; 13%) within 90 d prior to COVID dx. 209 (96%) pts had respiratory failure & 127 (58%) required mechanical ventilation. 15 (7%) required extracorporeal membrane oxygenation. COVID treatment consisted of corticosteroids in 205 (96%) & tocilizumab in 10 (5%).
12 (6%) pts developed IFD. 6 pts had CAPA (2 probable, 4 possible); 50% were men, median age 64.5 (48 – 83). Mean time to CAPA dx from COVID dx was 17 d (± 14d). All pts had received corticosteroids for COVID but only 1 pt received &gt; 30d of HDS by the time of IFD dx. Mortality at 84 d from CAPA dx was 67%. 5 (2%) pts had central venous catheter associated candidemia; 80% were men & median age 61 (55 – 77). Mean time from COVID to candidemia dx was 29 d (±12 d). All pts with Candida infection had received steroids for COVID. Mortality at 84 d from candidemia dx was 60%.
A 35-year-old man with prolonged exposure to HDS had Paecilomyces pneumonia; he was alive at 84 d after IFD dx. No cases of mucormycosis were identified.
All-cause mortality in the entire cohort was 38% at 90 d after COVID dx. Mortality among pts who developed IFD was 58% at the same time point.

Conclusion
Rates of IFD in pts with severe COVID were low and most pts with IFD after COVID had CAPA or catheter-associated candidemia. All but one pt with CAPA had no risk factors for IFD. In pts with severe COVID, mortality was higher among pts who developed IFD than those who did not.

Disclosures
Marisa H. Miceli, MD, Astellas: Advisor/Consultant|F2G: Grant/Research Support|Miravista: Advisor/Consultant|PSI: Advisor/Consultant|Scynaxis: Advisor/Consultant|Scynaxis: Grant/Research Support.
359. The Clinical Utility of the GenMark Dx ePlex® Fungal Blood Culture Identification Panel
Authors: Carmona Stefania , Meeder Jeremy , Moates Derek , McCarty Todd P , Lee Rachael A , Leal Sixto M 
Published: December 2022

Abstract

Background
The GenMark ePlex® Fungal Blood Culture Identification (BCID) Panel utilizes electrowetting technology to detect 15 most common causes of fungemia. Rapid identification of fungal species and innate resistance patterns enable improved antifungal stewardship.

Methods
In this prospective study, aliquots of the initial diagnostic blood culture bottle with fungal organisms detected on Gram Stain (n=61) received standard of care (SOC) fungal identification in two study periods. MALDI-TOF MS was utilized in both phases. BCID-FP results were not reported to treating clinicians during the pre-implementation phase. After 35 isolates, BCID-FP results became part of the SOC for all bloodstream infections (implementation phase) with results available to providers. Chart reviews were performed to assess risk factors for candidemia and evaluate the potential then actual impact of the BCID-FP on the time to organism identification, treatment, and patient outcomes.

Results
A total of 61 patients were included in the final analysis, 35 in the pre-implementation phase and 26 in the post-implementation phase (Table 1). C. albicans was most common, followed by C. glabrata and C. parapsilosis. The cohort includes two cases of Cryptococcus as well as two rare yeasts unable to be identified by BCID-FP and requiring the state lab identification (Table 2). Overall outcomes and differences between groups are seen in Table 3. The BCID-FP identified species 1.4 days faster compared to SOC methods across all patients, 1.12 days in the pre-implementation phase vs. 1.81 days in the post-implementation phase. In 32 patients (52%), the BCID-FP allowed for an earlier change in antifungal therapy for species with known low risk of fluconazole resistance.

Conclusion
The BCID-FP enabled earlier fungal identification compared to SOC identification. Earlier identification allows for earlier antifungal stewardship as well as better empiric therapy for non-Candida­ fungal pathogens. Empiric therapy rates were low with high mortality rates, indicative of an ongoing need for improving the care of patients with fungemia.

Disclosures
Todd P. McCarty, MD, GenMark Dx: Grant/Research Support|GenMark Dx: Honoraria Sixto M. Leal, Jr., MD, PhD, GenMark Dx: Grant/Research Support|GenMark Dx: Honoraria.
360. The diagnostic sensitivity of beta-D-glucan assay in patients with chronic disseminated candidiasis
Authors: Son Hyo-Ju 
Published: December 2022

Abstract

Background
Chronic disseminated candidiasis (CDC) is a specific syndrome in patients with hematologic malignancies which usually occurs after the recovery of neutrophils due to previous chemotherapy. The beta-D-glucan (BDG) assay has been proposed as an adjunct test for diagnosing invasive fungal infection. However, data on BDG assay in patients with CDC are scare. We aimed to investigate the diagnostic sensitivity of BDG assay in patients with CDC.

Methods
All adult patients who were diagnosed as CDC in a tertiary hospital in Seoul, South Korea, from January 2017 to December 2019 and underwent BDG assay (Gold Mountain River Tech Development, Beijing, China) were retrospectively reviewed. CDC was defined by the demonstration of small, target-like abscesses in liver or spleen (bull’s-eye lesions) or in the brain at the time of neutrophil recovery after a prolonged phase of neutropenia. The values for BDG over 80 pg/mL was classified as positive.

Results
A total of 20 patients were enrolled. The median age was 51 years (Interquartile range 39 – 64). Of these, 13 patients had acute myeloid leukemia, 3 acute lymphoid leukemia, 2 myelodysplastic syndrome, and 1 aplastic anemia. Candida spp. were isolated in 6 patients; 3 were C. tropicalis, 2 C. glabrata, and 1 C. krusei. Of the 20 patients, 10 (50%) revealed positive BDG results. The median BDG value was 174 pg/dL (IQR 137–402). More CDC patients with previous candidemia had positive BDG assay than those without candidemia, but with no statistical significance (4/5 (80%) vs. 6/15 (40%), P = 0.30). In the 7 patients with BDG assay-positive CDC, for whom follow-up BDG results were available, the BDG remained high in 6 patients (86%) for more than 4 weeks after adequate antifungal therapy. All 4 patients who died had a positive BDG assay, and 3 of them showed an increasing trend of BDG values during treatment.

Conclusion
Negative BDG assay appears to be not useful to rule out CDC. BDG assay decreased slowly during the adequate treatment of CDC.

Disclosures
All Authors: No reported disclosures.
361. Think Fungus! – Clinical profile, Risk factors and Diagnostic Utility of Galactomannan in diagnosis of Invasive Aspergillosis in Non-Neutropenic patients – A Prospective Study from India
Authors: Ravindra Akshatha , Kumar Deepak , Krishna Bohra Gopal , Neetha T R , Khatod Yash , Shankar Meena Durga , Kumar Midha Naresh , Jain Vidhi , Singh Kuldeep , Chauhan Nishant Kumar , Sharma Ankur 
Published: December 2022

Abstract

Background
Invasive aspergillosis(IA) is known to occur in immunocompromised patients including neutropenic patients. But there has been a trend of increasing cases in non-neutropenic host with the emergence of newer risk factors like DM, cirrhosis etc.
The aim of this study was to evaluate the clinical features & risk factors of IA in non-neutropenic patients & to look at the clinical utility of galactomannan in diagnosis of IA.

Methods
This was a prospective observational study which included the suspected cases of IA, based on the clinical & radiological criteria. Patients with haematological & solid organ malignancy were excluded. In patients with suspected Invasive pulmonary aspergillosis (IPA), serum & BAL, while in patients with suspected CNS IA CSF & serum samples were sent for galactomannan analysis (Platelia ELISA). The clinical features, risk factors, outcomes were analysed.

Results
We screened 243 patients with suspected IA, of which 49 non-neutropenic patients with IA (16 Proven & 33 Probable cases) were included. The mean age was 47.8 years. Of all IA cases 69.5% (n=34) were IPA, 20.4% (n=10) were CNS aspergillosis & 10.2% (n=5) showed disseminated form of IA. The common symptoms included Fever (71.4%), cough (71.3%), expectoration (44.7%) & dyspnoea (59.1%) in IPA, while in CNS aspergillosis, presented with fever (73.3%), altered sensorium (53%).The predominant risk factor included previous TB, DM, COVID-19. The radiological manifestations in IPA included the typical cavity (40.4%, n=17), Centrilobular nodules with tree in bud appearance in 56.5% (n=23). The CNS aspergillosis was associated with ring enhancing lesion (41.6%, n=5) with leptomeningeal enhancement (50%, n=6), while cerebral abscess was seen in 16.6% (n=2) patients. The positivity of galactomannan were 24.4%, 91.3% & 87.5% in serum, BALF & CSF respectively. Culture positivity & Direct smear positivity was 18.3% & 28.5% respectively. The overall mortality was 20.4%. Complete response in 3 months follow-up period was seen in 69.3% patients.

Conclusion
The clinical manifestations of IA in non-neutropenic are diverse & nonspecific. Also, culture & direct microscopy lack sensitivity, hence diagnostic markers like Galactomannan can be used for early diagnosis of IA in patients with newer emerging risk factors.

Disclosures
All Authors: No reported disclosures.
378. Utility of CMV Quantitative PCR in Tissue Biopsy for the Diagnosis of CMV Gastrointestinal Disease among Solid Organ Transplant Recipients
Authors: Baldassarre Lucila , Vernooy Camille Pelletier , Luong Me-Linh 
Published: December 2022

Abstract

Background
Cytomegalovirus (CMV) infection is an important cause of morbidity after solid organ transplantation (SOT). Rapid and accurate diagnosis of gastrointestinal (GI) CMV disease is central to the early initiation of appropriate therapy. Currently, the diagnosis mainly relies on histopathology on formalin-fixed GI tissue biopsy. CMV diagnosis by quantitative polymerase chain reaction (qPCR) on tissue biopsy is not routinely performed for the diagnosis of tissue invasive disease, but potentially holds many practical advantages over the gold standard including a rapid turnaround time and providing a quantitative objective result.

Methods
We compared the performance of CMV qPCR on fresh GI biopsy with tissue biopsy histopathology for the diagnosis of GI CMV disease.

Results
A total of 62 SOT patients with GI symptoms underwent endoscopic assessment with GI biopsy analyses for both histopathology and tissue CMV qPCR. Twelve patients (19.4%) had proven CMV disease on histopathology. Among them, all had a positive qPCR on biopsy (median value of log 7.7 and 5.4 x107 copies/mL), and all had a positive serum CMV PCR (median value of log 4.5 and 3.4 x104 copies/mL). Of the 49 remaining patients with negative histopathology, 26 (53%) had CMV qPCR positive tissue biopsy specimens with a median log 4.3 and 2.0 x104 copies/mL. Of these 26 patients with histopathology negative/CMV qPCR positive tissue biopsies, 10 had positive serum CMV qPCR. Twenty-four patients were negative for all three tests: histopathology, CMV qPCR on tissue biopsy, and CMV viremia. ROC analysis for optimal threshold value for CMV qPCR on tissue biopsy for diagnosis of confirmed CMV GI disease is 104 824 copies/mL (sensitivity 100%, specificity 82%, area under ROC 0.91).

Conclusion
Our study shows that tissue biopsy CMV qPCR is highly sensitive (sensitivity of 100%) for the diagnosis of CMV GI disease. As such, tissue CMV qPCR may be a useful adjunctive diagnostic tool for the rapid diagnosis of CMV GI disease.

Disclosures
All Authors: No reported disclosures.
383. Assessing the 2021 IDSA Treatment Clostridioides difficile Guidelines in a Small, Community Hospital
Authors: Barner Amanda , Maiullari Michael , Yu Shirley , Yu Shirley , Regan Mary 
Published: December 2022

Abstract

Background
Cambridge Health Alliance (CHA) is an academic healthcare system in the greater Boston area that includes two acute care, community hospitals. Oral vancomycin has been the first line treatment option for initial C. difficile infection (CDI). In 2021, IDSA updated its guidelines to recommend fidaxomicin as the preferred treatment for initial episodes. At our institution, fidaxomicin is restricted to infectious diseases approval.The objective of this evaluation was to assess CDI recurrence rate and to identify a target population within our organization who may benefit from fidaxomicin as initial CDI treatment.

Methods
A retrospective chart review of all inpatients ordered for oral vancomycin or fidaxomicin from January 2021 to February 2022 was conducted to assess treatment success, failure, and 60 day recurrence rate of CDI at two community teaching hospitals. Treatment success was defined as resolution of diarrhea or absence of diarrhea for two consecutive days after completion of therapy. Treatment failure was defined as continuation of symptoms for greater than 6 days after treatment initiation. Risk factors for recurrence evaluated were age &gt; 65 years, immunocompromised status, fulminant infection, and use of vancomycin versus fidaxomicin.

Results
A total of 47 patients administered oral vancomycin or fidaxomicin for CDI treatment between January 2021 and February 2022 were included in the analysis. Only one patient received fidaxomicin. The median age was 66 years and 55.3% female. Four patients were immunocompromised. Only one immunocompromised patient over 65 years had CDI recurrence. In our population, oral vancomycin had a treatment success rate of 85.1% and a recurrence rate of 2%. The one patient who received fidaxomicin did not have recurrence. Given the low recurrence rate, we were unable to identify significant risk factors associated with CDI recurrence in our population.

Conclusion
In our population, oral vancomycin had a high treatment success rate, which correlates with current literature. Limitations of our analysis include its retrospective design, small sample size, and inclusion of few immunocompromised patients. Oral vancomycin remains the preferred treatment for an initial CDI episode in our population, as recurrence rate is low.

Disclosures
All Authors: No reported disclosures.