bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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 > 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

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

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

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

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

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 > 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.
384. Assessing the Multistep Approach for Clostridioides difficile Infection Diagnosis
Authors: Mendo-Lopez Rafael , Pacheco Lauren , Villafuerte-Galvez Javier A
Published: December 2022

Background

Clostridioides difficile infection (CDI) is a spore-forming anaerobic Gram-positive bacillus and the leading cause of nosocomial infectious diarrhea. 2017 IDSA/SHEA C. difficile guidelines recommend a multistep algorithm approach for CDI diagnosis. This algorithm entails stool testing via enzyme-linked immunosorbent assay (EIA) for glutamate dehydrogenase (GDH) and C. difficile toxins A/B (Tox). Discordant samples are arbitrated by nucleic acid amplification test (NAAT) for tcdB gene. GDH EIA has sensitivities >90%, while Tox EIA has sensitivities ranging from 50-90%. We aimed to evaluate the diagnostic performance of GDH and Tox EIA using the multistep algorithm as the gold standard.

Methods

We performed a secondary analysis of an inpatient dataset collected in a tertiary community health system in the Southern US, including 9-months of the incident population from 2019 to 2020. All adults ≥ 18-years old from Princeton Baptist Medical Center (Birmingham, AL) tested for C. difficile were included. Alere TechLab C. difficile Quik Chek Complete® was used to determine GDH and Tox EIA, and Alethia C. difficile DNA Amplification Assay®, a NAAT, for discordant samples. CDI case was defined as positivity for Tox and GDH, or positivity of either Tox or GDH in addition to positive NAAT. Retesting within the same admission was allowed.

Results

Overall, 288 tests were performed. Concordant positivity for GDH & Tox was found in 29 (10.1%) tests; concordant negativity in 226 (78.5%). Discordant positivity for GDH or Tox was observed in 33 (11.5%) tests; all were tested with NAAT. Only 1 of 33 (3.03%) discordant tests was GDH negative & Tox positive, which had a positive NAAT. The remaining 32 (96.97%) discordant tests were GDH positive and Tox negative, of which 18 (56.3%) were positive for NAAT (Table 1). Performance characteristics for the above tests were calculated (Table 2). Table 1:Clostridioides difficile infection case distributions per GDH and ToxinTable 2:Test performance characteristics

Conclusion

Taking the multistep algorithm as a gold standard, the performance characteristics of GDH and Tox are concordant to previous descriptions in the literature, with GDH being highly sensitive and Tox being highly specific. A diagnostic algorithm lacking GDH and NAAT would miss over one-third of CDI cases. A diagnostic algorithm lacking Tox and NAAT could potentially overdiagnose about one-fifth of tested patients.

Disclosures

All Authors: No reported disclosures.
386. Clostridioides difficile PCR Cycle Threshold to Determine Toxin Positivity Status
Authors: Crone Andrew S , Skinner Andrew M , Wright Lorinda M , Cheknis Adam K , Johnson Stuart , Pacheco Susan M
Published: December 2022

Background

Many clinical laboratories rely on polymerase chain reaction (PCR) as the sole test for diagnosis of C. difficile infection (CDI). The objective of this study was to determine if the C. difficile (CD) PCR cycle threshold could be used to predict a positive CD toxin test.

Methods

We reviewed the characteristics and outcomes of 149 consecutive patients who tested positive for by PCR (Xpert CD, Cepheid) between October 2019 and December 2021 at one VA Hospital where reflex toxin testing (Cdiff quick check complete, Alere/TechLab) was performed after a positive PCR result. Baseline characteristics, symptoms, initial laboratory data, and treatments were compared as well as clinical outcomes. Determination of CDI or CD colonization was made for each patient after review of symptoms: including chronicity of symptoms, laboratory values, stool frequency, use of laxatives, and response to treatment. The cycle threshold for the CD-PCR results were recorded and positive stools were cultured for CD.

Results

Toxin testing was positive in 38% (57/149) of cases. The mean PCR cycle threshold value for all specimens tested was 27.89 (95% CI [27.14, 28.66]). Toxin-positive stools had lower mean PCR cycle thresholds when compared to toxin-negative stools (24.56 and 29.97, respectively p < 0.0001). Among the 149 cases reviewed, 109 were determined to be CDI (73%), 36 were colonized (24%), and 4 cases were undetermined. Among those with toxin-positive stools, 96% (54/56) patients were determined to have CDI. 98% (56/57) of all toxin-positive stools had a cycle threshold of ≤ 32.2 compared to 63% (58/92) of toxin-negative stools, resulting in a negative predictive value of 97.2% (p < 0.0001). The mean cycle threshold was lower in patients who were determined to have a CDI when compared to colonized patients (27.02 vs 30.44, p = 0.0001). [Figure] Of the patients that had CDI, 83% (91/109) had a cycle threshold of ≤ 32.2 and 58% (21/36) of colonized patients had a cycle threshold of ≤ 32.2.

Conclusion

Conclusions: In a setting where a CD toxin assay is not readily available, a CD stool PCR cycle threshold could be used to predict toxin status. In our study, a cycle threshold of ≤ 32.2 predicted both toxin-positivity and CDI.

Disclosures

Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
395. Impact of Racial Disparities on Clostridioides difficile Infection (CDI) Outcomes at a Southern California Academic Teaching Hospital
Authors: Zhou Anna Y , Lee Jina M , Ortiz-Gratacos Natalie M , Student Pharmacy , Isso Almas Al , Tan Karen K , Abdul-Mutakabbir Jacinda C
Published: December 2022

Background

Infectious diseases are the second leading contributor to racial disparities in healthcare. Clostridioides difficile infection (CDI) is a common community/hospital acquired infection that can cause life-threatening colitis. Despite the influence that socioeconomic factors, insurance status, and access to care can have on CDI outcomes, there is a dearth of literature that evaluates the impact of racial differences. The objective of this study was to identify racial disparities in CDI and describe clinical outcomes among hospitalized adults.

Methods

This is an IRB approved, retrospective study of adult patients (≥ 18 years) hospitalized with initial episodes of CDI between January 2020 to June 2021. Initial CDI episodes were identified by the ICD-10 code A04.72. Medical records were reviewed for demographics, comorbid conditions, insurance, total length of stay (LOS), and need for intensive care unit (ICU) admission. Patients were dichotomized by race/ethnicity into either the racially and ethnically minoritized (REM) group or the non-Hispanic White (n-REM) group. P value of ≤ 0.05 was defined as significant.

Results

In total 220 patients (61.8% REM, 136/220; 38.2% n-REM, 84/220) with an initial CDI episode were included. Majority of the REM patients were Hispanic (38.2%) followed by Black (13.6%), and Asian (5%). Compared to the n-REM group, the REM patients were younger (60 vs 69 years, p =0.016) and were more likely to have underlying comorbidities (diabetes mellitus 33% vs 9.5%; p < 0.001 and chronic kidney disease 48.5% vs 21.3%; p < 0.001). The REM patients were more likely to present with fulminant CDI (21.3% vs 11.9%; p =0.1). The REM patients were also more likely to be admitted to the ICU during their stay (41.9% vs 26.2%; p =0.021) and have a longer hospital length of stay (LOS) (12 vs 7 days; p =0.02). Lastly, the REM patients were more likely to be under-insured with 91 patients (66.9%) having Medi-Cal insurance compared to 34 patients (40.5%) in the n-REM group (p < 0.001).

Conclusion

Despite being younger, REM patients were more likely to require an ICU admission, have underlying comorbidities, have a longer LOS, and be under-insured. There is a need for further studies to understand disparities between REM and n-REM patients regarding CDI.

Disclosures

All Authors: No reported disclosures.
397. Oral Vancomycin Versus Fidaxomicin for Clostridiodes difficile: A Comparative Retrospective Evaluation across a Large, Multi-center Healthcare System
Authors: Roemer Kaleb , Burgess Hayley , Sands Kenneth E , Hodgin Ryan
Published: December 2022

Background

The Infectious Diseases Society of America and Society for Healthcare Epidemiology of America recently published the 2021 Focused Clinical Practice Guideline Update on Management of Clostridioides difficile in Adults that recommends fidaxomicin as a preferred treatment for initial and recurrent C. difficile infection (CDI) over oral vancomycin. The aim of this study was to evaluate clinical outcomes of adult inpatients with CDI diagnosis treated with fidaxomicin versus oral or rectal vancomycin.

Methods

The patient population included adult inpatients 18 years or older admitted to a hospital within the healthcare system with CDI International Classification of Diseases, Tenth Revision (ICD-10) codes from January 1, 2017 to October 31, 2021. Data was obtained for inpatients with a discharge diagnosis of CDI and receiving fidaxomicin, oral or rectal vancomycin, or no receipt of either antibiotic. Readmission was defined as readmittance to the healthcare system within 8 weeks and a CDI diagnosis. Recurrence risk factors were defined as age 65 years or older, immunocompromised based on ICD-10 codes, and severe CDI defined as white blood cell count > 15 cells/mm3 PLUS serum creatinine > 1.5 mg/dL.

Results

More than 45,000 inpatients with a CDI diagnosis were evaluated. Administration rates of vancomycin, fidaxomicin, or no receipt of either was 76%, 6% and 18%, respectively. Median length of stay for vancomycin compared to fidaxomicin was 7 versus 9 days, respectively. Readmission rate was lower for total inpatients receiving vancomycin (14.6%) compared to fidaxomicin (18.5%), showing statistical significance (p < 0.0000005). Subgroup analyses were performed to evaluate inpatients with risk factors for CDI recurrence. Vancomycin had a lower readmission rate for all recurrence risk factor groups. Additionally, oral vancomycin had lower readmission rates for patients with more than one risk factor (13.4% vs. 16.1%).

Conclusion

The results of this study demonstrated that fidaxomicin did not result in a shorter length of stay or lower readmission rate compared to oral/rectal vancomycin. This study supports the continued use of oral/rectal vancomycin for CDI without preference for fidaxomicin.

Disclosures

All Authors: No reported disclosures.
399. Reducing Hospital-Onset C. diff with a Provider-Driven Emergency Department Ordering Algorithm
Authors: Holdsworth Jill , Milloy Aaron , Kaylor Jordan , Richardson Rita , Meloy Patrick
Published: December 2022

Background

Clostridoides difficile (C. diff) can cause diarrhea and inflammation of the colon. It is one of the most common causes of heathcare-associated infections (HAIs), estimated to cause almost half a million illnesses and thousands of deaths in the United States each year. Studies have estimated that this HAI costs up to $4.8 billion each year in excess healthcare costs for acute care facilities. Early identification, treatment and initiation of isolation precautions is crucial to patient care and transmission reduction, making the Emergency Department ideal partners in efforts to reduce C. diff infections.

Methods

A C. diff testing algorithm was introduced specific to the Emergency Department in March, 2021, promoting earlier testing and isolation of patients suspected of having C. diff. Emergency medicine clinicians were awarded the "Golden Spore" Award weekly when appropriately initiating the C. diff testing and isolation, provided the patients met criteria, or were clinically suspected of having a C. diff infection.

C. diff ordering algorithm

Ordering algorithms were printed and placed in the clinician's work area to facilitate increased ordering of isolation and testing of potentially infected patients.

GoldenSporeAward

The Golden Spore is awarded weekly to emergency clinicians who successfully identify and isolate C. diff patients prior to admission.

Results

As a result of the COVID-19 pandemic, there were varying degrees of challenges for implementation of the program. Emergency clinicians sent 199 C. diff tests pre-intervention (3/15/20-3/14/21) and 234 tests post-intervention (3/15/21-3/14/22). Pre-intervention, 44 patients were found to be C. diff positive prior to admission, compared to 62 post-intervention. Clinicians enjoyed the "golden spore" award and were excited to participate.

Conclusion

The program is ongoing, though the initial results are encouraging. There was an immediate increase in the testing and subsequent isolation of patients while in the ED. Infection prevention and emergency medicine clinicians worked together to boost their numbers, and the "golden spore" continues to be awarded in weekly newsletters. Clinicians indicated they enjoyed the engagement, and found that the small change in a routine process improved their baseline awareness of potential C. diff patients, leading to an increase in the number of tests and subsequent discovery of C. diff positive patients. C. diff champions were also named and the algorithm will be shared with additional emergency departments within our system to continue to improve detection and prevention of hospital associated infections.

Disclosures

All Authors: No reported disclosures.
401. Rigor and Reproducibility of Clostridioides difficile susceptibility testing
Authors: Lancaster Chris , Eubank Taryn A , Gonzales-Luna Anne J , Dureja Chetna , Hurdle Julian , Garey Kevin W
Published: December 2022

Background

The growth and susceptibility testing of anaerobic bacteria presents many unique challenges. The Clinical Laboratory Standards Institute (CLSI) recommends performing minimum inhibitory concentration (MIC) testing for C. difficile through agar dilution (AD) assay, which carries logistical and time burdens compared to broth microdilution (BMD) methods. In this project we aim to assess the intra-and inter-laboratory reproducibility of MIC testing for C. difficile.

Methods

A total of 30 C. difficile isolates underwent MIC testing using AD and BMD techniques. To test intra-lab reproducibility, proficiency testing to develop a reproducible MIC testing process using 18 isolates was implemented across two multi-disciplinary labs, which was then validated in a prospective cohort of 116 isolates. MICs obtained by each method and lab were compared and essential agreement (EA) and major and minor error rates were calculated. To combat the labor and time-intensive demands of AD testing, automation with Integra Assist Plus was tested. Times for plate set up using a technician versus the Integra Assist Plus were measured twice and the average times were compared.

Results

AD and BMD yielded discordant resistant/susceptible results in 16.7% (5/30) of isolates tested. During proficiency testing, intra-lab comparison of AD MICs yielded 88.9% (16/18) EA and no disagreements occurred with more than 1 dilution difference. EA improved in the larger cohort to 93.9% (109/116), of which minor and major disagreements occurred in 17% (21/116) and 25% (29/116), respectively. A total of 10’4” minutes were saved using automation (12’44” mean) versus a technician (24’40” mean).

Conclusion

Here we present the process undertaken to ensure the rigor and reproducibility of C. difficile susceptibility testing. We developed a procedure that yields accurate results from two different labs, minimizes cost, and lowers the overall time required. Our future research will include validation with a larger sample and more academic partners.

Disclosures

Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|cidara: Advisor/Consultant|cidara: Grant/Research Support|Paratek: Grant/Research Support|Seres Health: Grant/Research Support|Summit: Grant/Research Support.
410. Characteristics of Patients with Extended-Spectrum Beta-Lactamase (ESBL) Producing Enterobacterales, Tennessee, 2019-2020
Authors: Hitchingham Erin , Muleta Daniel , Villegas Raquel , Gambrell Ashley , Bailey Cherlly , Wilson Christopher , Mounsey Jackie
Published: December 2022

Background

Currently, data on the incidence of Enterobacterales bacteria that produce extended-spectrum beta-lactamases (ESBL) within community settings is lacking. We set out to describe patient characteristics for healthcare-associated (HA) and community-associated (CA) ESBL-producing Enterobacterales in Tennessee.

Methods

ESBL cases were defined as isolation of Escherichia coli, Klebsiella pneumoniae, or Klebsiella oxytoca, resistant to cefotaxime, ceftriaxone, or ceftazidime, non-resistant to all tested carbapenems, from a normally sterile body site, or urine, within Maury, Lewis, Marshall, or Wayne Counties, with a specimen collection date from July 1st, 2019, to the end of 2020. Patient data was collected by reviewing patients’ medical records. HA cases were defined as those with previous healthcare exposures, of any kind, in the year preceding specimen collection. All analysis was performed using SAS 9.4.

Results

566 cases were included in this study. Demographically, 459 (81.1%) cases identified as white with an equal number (81.1%) of patients being female. The average age was 66.2 years. 560 (98.94%) specimens were collected from urine, 468 (85.1%) patients had a urinary tract infection (UTI), and 174 (37.2%) of those patients had a record of recurrent UTIs. 243 (49.6%) cases were identified as CA. 138 (24.4%) cases were identified as being hospitalized within 29 days of their specimen collection and 247 (50.4%) cases were determined to be HA. 142 (25.1%) patients were treated with antibiotic in the month before specimen collection. Cephalosporins (31.7%), fluroquinolones (29.6%), doxycycline (7.7%), and sulfonamides (7.7%) were the most common antibiotics used to treat the patients. Among patients prescribed these antibiotics (N=109), 19 (17.4%) patients had specimens resistant. Figure 1:Characteristics of patients with extended-spectrum beta-lactamases (ESBL) producing Enterobacterales isolated from 2019-2020Figure 2:Characteristics of patients with extended-spectrum beta-lactamases (ESBL) producing Enterobacterales isolated from 2019-2020, continued

Conclusion

Most cases were described in white women with UTIs, often recurrent, coming from private residences. With approximately 50% of cases described as CA, targeted intervention outside of healthcare facilities is necessary to reduce spread of ESBL infections. As 17.4% of cases were treated with antibiotics that the organism was resistant, there is an opportunity to improve judicial use of antibiotics based on susceptibility data.

Disclosures

All Authors: No reported disclosures.
412. Clinical and demographic features associated with beta-lactamase producing Enterobacterales in an academic medical center in Loma Linda, CA
Authors: Liu Eugene W , Pappas James
Published: December 2022

Background

Emergence of antibiotic resistant bacteria is a threat to public health. The aim of this study is to identify clinical and demographic features associated with beta-lactamase producing Enterobacterales, specifically extended spectrum beta-lactamase producing (ESBL) and carbapenem-resistant Enterobacterales (CRE), in patients at Loma Linda University Health, an academic medical center in Loma Linda, California.

Methods

This retrospective case control study compared patients with/without beta-lactamase producing Enterobacterales. Cases and controls were identified from microbiology records with Enterobacterales isolated between January 1, 2020, and December 31, 2021. Case subjects were individuals with ≥1 CRE isolate (confirmed by nuclear amplification testing, NAT) and control subjects were those with ≥1 isolate that were all non-CRE. We identified isolates of interest, defined as the first CRE isolate in cases and the first non-CRE isolate for controls. For each isolate of interest and corresponding specimen collection date, we extracted electronic medical record data including inpatient antibiotics received in the preceding 6 months, specimen type, patient sex and age. We performed similar analysis with ESBL-producing Enterobacterales confirmed by NAT.

Results

On multiple logistic regression, age (OR, 1.02; 95%CI, 1.01-1.04), isolation of klebsiella (10.75; 4.59-25.21), providentia (20.86; 2.47-176.17), and serratia (8.01; 1.59-40.40), receipt of non-carbapenem beta-lactams (1.06; 1.03-1.10), carbapenems (1.19; 1.12-1.27), doxycycline (1.26; 1.04-1.52), and tetracycline (1.89; 1.08-3.29), were independently associated with increased odds of CRE infection. Similarly, gender (2.59; 2.07-3.24), age (1.01; 1.01-1.02), isolation of proteus (1.47; 1.01-2.13), receipt of non-carbapenem beta-lactams (1.08; 1.06-1.11), carbapenems (1.33; 1.23-1.44), and vancomycin (1.07; 1.03-1.12) were associated with increased odds of infection with ESBL-producing Enterobacterales.

Conclusion

Age and receipt of beta-lactams (including carbapenems) were associated with odds of infection with both CRE and ESBL-producing Enterobacterales in an academic medical center in Southern California, highlighting the importance of antibiotic stewardship.

Disclosures

All Authors: No reported disclosures.
418. Fosfomycin Dosing Regimens for The Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Receiving Continuous Renal Replacement Therapy: a Monte Carlo Simulation
Authors: Kanchanasurakit Sukrit , Srisawat Chansinee , McPherson Charles E , Saelim Weerayuth , Siriplabpla Wuttikorn , Suthumpoung Pornsinee , Santimaleeworagun Wichai
Published: December 2022

Background

To predict the appropriate dosing of intravenous fosfomycin for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in continuous renal replacement therapy (CRRT) patients.

Methods

Minimum inhibitory concentration (MIC) values of all isolates were determined by E-test method. Population pharmacokinetic parameters were obtained from a previously published study. The percentages of a 24-hour period in which the drug concentration exceeded the MIC (%T >MIC) were defined to be 70% T >MIC and 100% T >MIC, respectively. In addition, the 24-hour area under the unbound concentration-time curve over the MIC (AUC0-24/MIC) of 45 mg·h/L was used as a target value. All dosing regimens were estimated for the probability of target attainment (PTA) using a Monte Carlo simulation.

Results

For the effluent rate of 20 mL/kg/h, the PTA for reaching 70% T >MIC, 100% T >MIC, and AUC0-24/MIC of 45 mg·h/L was achieved in pathogens with a MIC of 24 mg/L, 12 mg/L, and 24 mg/L in all regimens, respectively. Meanwhile for the effluent rate of 25 mL/kg/h, the PTA for reaching 70% T >MIC, 100% T >MIC, and AUC0-24/MIC of 45 mg·h/L was achieved in organisms with a MIC of 16 mg/L, 12 mg/L and 24 mg/L in all regimens, respectively.

Conclusion

The appropriate fosfomycin dosing regimens for CRE infections in critically ill patients receiving CRRT were suggested based on pharmacokinetic/pharmacodynamic targets, MIC values, and effluent rates. Clinical validation is warranted.

Disclosures

All Authors: No reported disclosures.
427. Trends in Hospital-onset Escherichia coli Infections Resistant to Fluoroquinolones and Extended-spectrum Cephalosporins, 2012-2020
Authors: Hood Nicole , Wolford Hannah , Olubajo Babatunde , Rose Ashley , Baggs James , Reddy Sujan
Published: December 2022

Background

Inpatient and outpatient fluoroquinolone (FQ) use has decreased substantially in the last decade; however, the impact of this trend on FQ resistance is less clear. During this period, extended-spectrum β-lactamase (ESBL) Escherichia coli infections have increased. We examined hospital-onset (HO) E. coli clinical culture trends and resistance patterns among hospitalized adult patients in the United States.

Methods

We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of hospitals submitting data to the Premier Healthcare Database from 2012-2020. We included E. coli cultures with susceptibility testing to FQs or extended-spectrum cephalosporins (ESC). ESC resistance was defined as non-susceptibility to cefotaxime, ceftriaxone, ceftazidime, or cefepime and FQ resistance as resistance to ciprofloxacin, levofloxacin, or moxifloxacin. Co-resistance was defined as both ESC and FQ resistance in the same E. coli isolate. Isolates were classified as FQ resistant only (and not ESC), ESC resistant only (and not FQ), co-resistant, or neither FQ nor ESC resistant.

Results

The overall proportion of HO E. coli with any FQ resistance decreased 12.3% (from 36.7% in 2012 to 32.2% in 2020). The proportion of HO E. coli with only FQ resistance decreased by 39.8% (from 27.9% in 2012 to 16.8% in 2020); the proportion with only ESC resistance increased by 112.5% (from 2.4% to 5.1%), and co-resistance increased by 75.0% (from 8.8% to 15.4%) (Figure). Figure.Proportion of hospital-onset E. coli infections with selected antibiotic resistance patterns, 2012-2020

Conclusion

These results suggest that declining FQ use has been accompanied by declining FQ resistance in E. coli. Increases in FQ and ESC co-resistance may be due to factors including increases in the use of non-FQ antibiotics such as cephalosporins and increased transmission of E. coli strains such as ST131 in which co-resistance is prevalent. Antibiotic stewardship across multiple antibiotic classes combined with infection control measures are likely necessary to reduce multidrug resistant E. coli infections.

Disclosures

All Authors: No reported disclosures.
428. Deep-Learning Based Predictive Model for Patients with Positive MRSA Cultures Using Time-Series Electronic Health Records
Authors: Nigo Masayuki , Rasmy Laila , Xie Ziqian , Septimus Edward J , Zhi Degui
Published: December 2022

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the common pathogens leading to significant morbidity and mortality in the hospital. This pathogen requires specific empirical antibiotics. Hence, identifying the personalized risks of this pathogen likely optimizes the usage of those antibiotics. Deep-learning based (DL) models are shown to be useful for modeling time-series electronic health record (EHR) data, and thus offering potential for predicting individualized risk for MRSA infection.

Methods

Longitudinal data were retrospectively retrieved from EHR in Memorial Hermann System, Houston, Tx. Patient encounters, demographics, diagnostic & procedure codes, antibiotics use, and microbiology data were extracted between 1/2018 and 4/2021. Inpatient and outpatient data were included. We randomly identified roughly equal numbers of patients with positive culture (Cx) for MRSA, MSSA, other pathogens, and negative Cx. We set a 2-week window for the prediction, and any first culture within the window was used as an index Cx. Some patients had multiple predictions over time and were included into both MRSA vs. non-MRSA groups. Our team developed a DL model platform (Pyorch_EHR) for clinical outcomes predictions using structured EHR data. In this project, the outcome is MRSA positivity taken within 2 weeks from the index Cx. Datasets are split into 50, 30, and 20% for training, validation, and test, respectively. Other machine learning models; logistic regression (LR) and light GBM (LGBM) were used for comparison. Pytorch ver. 1.7.1 and Sklearn ver. 0.24.2 are used.

Results

A total of 8164 patients and 22,563 patients were identified as MRSA and non-MRSA groups, respectively. Table 1 summarizes the key features of the patient’s characteristics. After model training using train and validation datasets, our model achieved an AUC of 91.8 in test dataset, whereas AUC of 86.0 and 88.2 in LR and LGBM, respectively. Figure 1 shows the cumulative incidence of 2 week MRSA positivity. Our model precisely stratified the risks. Figure 1:Cumulative Incidence of Positive MRSA Cultures Based on Risk Stratificationa

Conclusion

Our DL based model exhibited excellent performance in the prediction of 2 week MRSA positivity. Our model precisely categorized patients into low, medium, and high-risk. This work should be validated with other data sources and high-risk subgroups.

Disclosures

All Authors: No reported disclosures.