bluuebunny/crossref_metadata_2025 huggingface dataset:
431. Screening and Targeted Staphylococcus aureus Decolonization of Acute and Intensive Care Patients and Invasive Infections in an Academic Medical Center
Authors: DiTullio David J , Takats Courtney , Hochman Sarah
Published: December 2022

Background

Staphylococcus aureus is a common cause of healthcare associated infections and is associated with high mortality. Universal S. aureus decolonization reduces methicillin-resistant S. aureus (MRSA) and other bloodstream infections among ICU patients. However, universal decolonization in acute care settings has not shown a similar benefit. We describe a screening and targeted decolonization protocol implemented at an academic hospital across acute and intensive care settings. The goal of this study was to assess the impact of decolonization on rates of S. aureus invasive infections.

Methods

Adult Medicine, Oncology, Transplant, and ICU patients were screened by nasal swab for S. aureus colonization on admission and change in level of care. Colonized patients received 5 days of chlorhexidine 2% applied to the body and mupirocin for the nares. We compared decolonized patients with patients who received no decolonization. The primary outcome was S. aureus invasive infection from hospital day 5 until discharge, defined by positive cultures from sterile sites. Secondary outcomes included 30-day readmission and 30-day mortality.

Results

Between 2018-2020, 3,835 (23%) out of 16,467 hospitalized patients screened positive for MSSA (74%) or MRSA (26%). Among colonized patients, median age was 67 years (interquartile range [IQR] 54-79) and median LOS was 6 days (IQR 4-11). Among patients with LOS ≥ 5 days, 977 (37%) received decolonization. There were 122 invasive infections, 56 (46%) occurring in patients who received decolonization. Wound infections were most common (28; 23%), followed by bacteremia (27; 22%). In multivariate regression analysis controlling for confounding factors including comorbidities and length of stay, decolonization was not significantly associated with incident invasive infections (p = 0.395).

Conclusion

We report on a S. aureus screening and targeted decolonization program; our initial analyses do not demonstrate an association between decolonization and reduced invasive S. aureus infections. Further investigations will examine subsets of high-risk patients and transmission events to assess if specific populations may benefit from this program.

Disclosures

All Authors: No reported disclosures.
432. Ward-level Variation in Transmission of MRSA in Veterans Affairs Hospitals
Authors: Khader Karim , Stevens Vanessa W , Thomas Alun , Toth Damon , Keegan Lindsay T , Rubin Michael , Samore Matthew H
Published: December 2022

Background

In 2007, the Department of Veterans Affairs (VA) implemented the methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative nationally in acute care facilities (ACFs). Since that time, numerous publications have reported declining transmission rates and infection rates due to MRSA across the VA. Recent estimates of the impact of contact precautions (CP) on transmission suggest that the infectiousness of patients while on CP was 50% lower than patients not on CP. We extend that work by estimating the variation and trend in transmission while accounting for the estimated impact of CP on transmission.

Methods

We analyzed ten years of data from 108 VA ACFs from 1/1/2008 – 12/31/2017 using a Bayesian transmission model. The data included admission, discharge, and surveillance and clinical test results for MRSA. Data were partitioned into five 2-year analysis periods to allow for estimates of transmission to change over time, including all facilities with complete data spanning the 10-year study period. We estimated person-to-person transmission rates for each ward assuming the classic mass-action transmission framework, while accounting for the impact of CP on transmission, and used random effect models with inverse variance weights to derive pooled estimates of the transmission rates and trends across ward-types and over time.

Results

In this cohort study of 108 VA hospitals during the 10-year period, more than 2 million unique individuals had over 5.6 million admissions with more than 8.4 million MRSA surveillance tests (9.3% of which were positive). We observed a decline in the overall transmission rate over time, with the reduction driven by declining rates of transmission in the ICU setting (Figure 1). We observed that the transmission rate in medical/surgical wards remained constant during the 10-year period.

Transmission trend by ward

Conclusion

We observed that in addition to the two-fold reduction in transmission of MRSA associated with CPs, that over the study period, the transmission rate declined in VA hospitals driven largely by reductions in the ICU setting. The secular trend downward in ICUs might reflect improved hand hygiene, changes in antibiotic use, or enhancements to other infection control practices. Additional work is needed to better understand and identify these factors.

Disclosures

Karim Khader, PhD, BioFire Diagnostics: Grant/Research Support.
439. Anal Dysplasia Screening Cascade within a Single-Center Outpatient HIV Clinic
Authors: Modlin Chelsea , Rockney Danica , Cherian Jerald , Zhong Diana , Krishnan Sonya , Karanika Styliani , Jones Joyce
Published: December 2022

Background

HIV-positive men who have sex with men (MSM) are recommended to have anal Pap tests annually to screen for high-grade anal squamous intraepithelial lesions (HSIL). In this population, removal of HSIL reduces the risk of progression to anal cancer. This study aims to assess the effectiveness of the anal dysplasia screening cascade in a single-center outpatient clinic.

Methods

We conducted a single-center retrospective cohort study at Johns Hopkins. All adult HIV-positive MSM patients who had in-person encounters in the Bartlett Clinic between October 1, 2019-April 30, 2021 were included. Clinical information and dates of anal pap smears and HRAs were provided via an Epic data extraction. Manual chart review was conducted for anal pap and HRA pathology results. Descriptive analysis was performed. The primary outcome was successful navigation of the institutional anal dysplasia screening cascade, defined as annual anal Pap testing and completion of HRA if pap results were abnormal. This study was IRB exempt.

Results

779 HIV-positive MSM patients were seen for in-person visits during the study period. 24% (190/779) of patients underwent at least one screening anal Pap, with 29 having multiple anal pap smears leading to a total of 219 anal pap smears done. 40% (87/219) were abnormal. Among those with an abnormal pap, 72% (63/87) had a referral for HRA placed but only 26% (23/87) underwent HRA. 39% (9/23) of HRAs identified HSIL in patients with lower-grade lesions on Pap test and one patient with HSIL on Pap had anal cancer detected on HRA. In total, 120 patients navigated the anal cancer screening cascade appropriately. This compromised 15% (120/779) of eligible MSM patients seen for at least one in-person clinic visit and 63% (120/190) of patients who underwent an anal Pap.

Conclusion

Completion of a screening cascade for anal dysplasia among HIV-positive MSM at our clinic was low. The largest gaps were seen in initiating annual anal Pap screening and scheduling referrals for HRA in surgical subspecialty clinics. Increased attention and clinic resources should be directed toward narrowing these gaps to ensure HSIL and anal cancers are detected early within this high-risk population.

Disclosures

All Authors: No reported disclosures.
470. Changing Urgent Care Patterns of Diagnosing Coccidioidomycosis in a Highly Endemic Urban Population
Authors: Pu Jie , Miranda Valerie , Minior Devin , Raynolds Shane , Rayhorn Benjamin , Galgiani John N
Published: December 2022

Background

We found previously (Pu et al. Clin Infect Dis, 2021: PubMed 32511677) that only 0.2% of ICD10 codes for coccidioidomycosis (CM) in our health care system were associated with patients (pts) managed at an urgent care (UC) visit. Since 2020, during onboarding, at quarterly meetings, and in periodic emails, UC clinicians were encouraged to test for CM in patients with pneumonia (PNA).

Methods

For 2018 through 2021, Banner Health UC System increased clinics from 41 to 48, clinicians from 89 to 193 (Nurse Practioners, 49.2% ± 2%, Physician Assistants, 39% ± 2%, MDs/DOs 13% ± 1%), and total visits from 787 to 1,290 thousand. Average visits were 1.6 per pt. All UCs used a common electronic medical record (Cerner) during the study period. Data were downloaded in January 2022 to analyze UC clinician patterns of coccidioidal serologic testing (CST, 98% were EIAs), CST results, and their relation to ICD10 codes.

Results

For the study period, CST orders increased from 8.0 to 19.0 per 10,000 UC visits (chi-squared p< 0.001). The percent of clinics testing >10 per year increased from 16% to 78%, and the percentage of clinicians testing increased from 37% to 67%. Percent positive CSTs were highest for August, November, and December (27.4%) and lowest from April through July (8.1%). PNA ICD10 codes (J18.9 or J18.1) were most frequently associated with positive CSTs (374 positive of 1,872 tested), and the ICD10 code for Erythema nodosum (EN, L52, 176 total pts) had the highest positivity rate (61.4%, 27 positive of 44 tested). Only 6 pts had both EN and PNA codes. As indicated in the table, testing of PNA pts over time increased on first visits, decreased on second visits, and increased on second visits when the first CST was negative. Testing also increased for EN pats. Despite these favorable changes, CST was still not done on over three quarters of pts where recommended.

Coccidioidal serologic testing in urgent care clinics by month for 2018-2021. Open circles are percentage of total visits that involved a test; closed squares are percentage of tests that are positive.

Conclusion

Routine quality improvement activities have significantly but only partially improved rates of testing pts with PNA or EN for CM in UC clinics located in an endemic area. Innovative strategies to change clinical practices may be needed to achieve greater success.

Disclosures

All Authors: No reported disclosures.
473. Diabetes Mellitus as a Risk Factor for Cryptococcosis — a Multicenter Research Network Study
Authors: Kung Vanessa , Henao-Martínez Andrés F , Tagawa Alex , Kennis Matthew , Franco-Paredes Carlos , Vargas Barahona Lilian , Shapiro Leland , Chastain Daniel B
Published: December 2022

Background

Diabetes mellitus type 2 (DM2) is a common medical condition that increases the risk of bacterial infections, and is often present in patients with cryptococcosis. The role of DM2 as an independent risk factor for cryptococcosis is debatable. We aim to better characterize the natural history of cryptococcosis in patients with DM2 as their only comorbidity.

Methods

We utilized TrinetX, a federal national network, to identify HIV-negative patients who had cryptococcosis without known risk factors. Demographic characteristics and outcomes were compared between patients with DM2 and those without DM2, who tested positive or had ICD based diagnoses of Cryptococcus infection within five years of diagnosis of DM2.

Results

Sixty patients with DM2 (as the sole risk factor) and 707 patients without DM2 had cryptococcosis. Patients with DM2 and cryptococcosis were older (61 ± 13.6 years vs. 55.8 ± 16.2 years, p=0.0219), and more likely to be Hispanic or Latino (18% vs. 9%, p=0.023). They had higher rates of hypertension (77% vs 44%, p< 0.0001), cystic fibrosis (18% vs 1%, p< 0.0001), tuberculosis (18% vs 1%, p< 0.0001), and chronic kidney disease (33% vs 18%, p=0.0026). The mean HbA1c among patients with DM2 who developed cryptococcosis was 8.16 (SD 2.62). The most common sites of cryptococcus infection were pulmonary (56% vs 55%, p=0.8930) and cerebral (36% vs 40%, p=0.5589), in both groups. The two groups had similar mortality (20% vs 25.47%, p=0.3676) (Figure 1), and hospitalization rates (20% vs 31.3%, p=0.08). The overall annual cryptococcosis risk among HIV-negative patients with DM2 without any additional risk factors was 0.001%.

Conclusion

Cryptococcosis occurs rarely in HIV-negative patients with DM2 and without additional risk factors. Hispanic or Latino ethnicity, uncontrolled hyperglycemia, and chronic kidney disease may increase the risk of cryptococcosis among patients with DM2. Cryptococcosis in patients whose only comorbidity is DM2 have as high of mortality as that seen with more established comorbitidies.

Disclosures

All Authors: No reported disclosures.
474. Differences In Clinical Manifestation, Prognostic Factors, and Outcomes Between Patients With Community-onset And Nosocomial Candidemia
Authors: Chen Yung-chun , Chang Chao-chin
Published: December 2022

Background

Candidemia is an invasive and deadly infectious disease. The associated risk factors of candidemia include immunosuppression, broad-spectrum antibiotics, catheters, glucocorticoids, critical illness, surgery, neonates, previous candida colonization, and illicit drug use. In previous studies, the characteristic of community-onset candidemia was distinct from nosocomial candidemia.

Methods

We selected patients who were admitted for equal or more than two days in Taichung Veterans General Hospital of Taiwan from 2015 to 2018 with electronic medical charts. The diagnosis of candidemia was defined as Candida species identified in blood cultures by commercial identification systems. We applied Kaplan-Meier survival curves with a log-rank test and built multivariate Cox proportional-hazards models for risk factors associated with in-hospital mortality. The purpose of this study is to investigate the difference in the characteristics, outcomes, and associated risks of death between community-onset and nosocomial candidemia.

Results

A total of 339 patients were included for analysis. The incidence was 1.50 per 1000 admission person-years. 64.60% of patients were male, and the mean age was 64.24-year-old. The characteristics of patients were similar in both groups except for the status of port-A, glucocorticoid usage, and diabetes mellitus. In the community-onset group, a higher proportion of C. glabrata and C. parapsilosis, but fewer C. albicans and C. tropicalis were identified than in the nosocomial group. The all-cause mortality rate was 55.75%. Multivariate Cox proportional-hazards model showed that nosocomial (hazard ratio; HR, 1.96; 95CI, 1.291 - 2.97 ; p =0.002), glucocorticoids within seven days before candidemia (HR, 1.68; 95CI, 1.21 -2.32, p = 0.002), and septic shock (HR, 1.85; 95CI, 1.292 - 2.641, p < 0.001) were associated with poor outcome whereas treatment with an echinocandin within two days after candidemia was a protective factor (HR, 0.65; 95CI, 0.466 - 0.911, p = 0.012).

Survival curves analysis between community-onset candidemia and nosocomial candidemia

A log-rank test was applied to assess the statistical significance, and a p-value less than 0.05 was considered statistically significant.

Conclusion

In conclusion, candidemia is a lethal disease with a better outcome noted in those with community-onset candidemia. Species diversity existed in both groups, and Early initiation of echinocandin therapy within two days could reduce 35% mortality.

Disclosures

All Authors: No reported disclosures.
481. Risk Factors and Clinical Outcomes of Candidemia Associated with Severe Coronavirus Disease 2019 (COVID-19)
Authors: Bhowmick Tanaya , Jagpal Sugeet , Varughese Tilly , Patel Purvi , Jen Polly , Maxwell Tyler , Tatem Luis , (Claudia) Choi Seohyun , Walker Amanda , Eidensohn Yehuda , Smoke Steven , McCracken James A , Cardinale-King Maria , Haribhakti Aditi , Cani Eris , Dixit Deepali
Published: December 2022

Background

COVID-19 can cause serious illness requiring multimodal treatment of the viral infection and its associated complications, including the potential for secondary infections. Studies have suggested an increased risk of fungal infections, including candidemia following severe COVID-19 though understanding of risk factors and clinical outcomes remains unclear.

Methods

A multi-center, case-control study of patients with severe COVID-19 was conducted to evaluate risk factors and clinical outcomes in patients who developed candidemia between August 2020 to August 2021. Risk factors associated with candidemia and mortality were characterized using multivariate analyses.

Results

A total of 275 patients were enrolled in the study, including 91 patients with severe COVID-19 and subsequent candidemia and 184 patients with severe COVID-19 without candidemia. Most patients received antibiotics prior to candidemia episode (93%), while approximately one-quarter of all patients received biologic for COVID-19. In-hospital mortality was significantly higher in the case group compared to the control group (68% vs 40%, P < 0.01). Multivariable logistic regression revealed that the use of central lines, biologic and paralytic therapy were independent risk factors for candidemia. The presence of candidemia, older age, central line use, and intensive care unit admission were significantly associated with mortality.

Demographics and Baseline Characteristics of Study Patients with SARS-CoV-2 Positive With or Without Candidemia

Hospitalization Details and Outcomes

Conclusion

Clinicians should be aware of the possibility of development of candidemia in hospitalized older patients with severe COVID-19 and should closely monitor those patients at risk. Risk factors for developing candidemia in the setting of COVID-19 are largely consistent with classic risk factors previously identified.

Disclosures

Tanaya Bhowmick, MD, Gilead: Grant/Research Support|Shinogi: Advisor/Consultant Steven Smoke, PharmD, BCPS, BCIDP, Karius: Advisor/Consultant|Shionogi: Advisor/Consultant.
484. Vaginal Candida albicans: High Frequency of In-vitro Fluconazole Resistance in a Select Clinical Population.
Authors: Agrawal Pranjal , Yazdy Golsa M , Ghanem Khalil G , Handa Victoria L , Sobel Jack D , Zhang Sean , Tuddenham Susan
Published: December 2022

Background

In vitro fluconazole resistance in vaginal C. albicans has rarely been reported in the U.S. Little is known about the characteristics of patients who demonstrate fluconazole resistance vs. sensitivity, or how likely resistant strains are to persist over time. Hence we sought to describe patterns of fluconazole resistance in clinician ordered vaginal cultures positive for C. albicans at our center. We compared patient characteristics between those with fluconazole sensitive versus resistant isolates.

Methods

We conducted a chart review of patients with clinician ordered vaginal cultures positive for C. albicans undergoing fluconazole susceptibility testing in our medical center’s clinical mycology lab from January 2017 to April 2021. Patient characteristics were compared using chi-square and ANOVA tests and correlated to fluconazole resistance with logistic regression models.

Results

Of N=92 patients with vaginal C. albicans, 3.3% were sensitive dose-dependent (SDD: minimal inhibitory concentration (MIC) =4) to fluconazole, and 30.4% were resistant (R: MIC > =8). Amongst those with at least 2 previous episodes of vulvovaginal candidiasis (VVC) in the past 6 months (N=45), 50% had R and 6.5% had SDD isolates. Compared to those with sensitive (S: MIC < =2) isolates, patients with SDD or R were younger and more likely to have the following characteristics: Black race, bacterial vaginosis (BV) in the past year, high or multi-dose azole treatment, fluconazole suppressive therapy in the past 6 months, and more VVC and BV episodes in the previous 6 months (Table 1). Of N=10 patients who had a follow-up culture with initial R isolates, 28.6% had a sensitive C. albicans vaginal isolate.

Conclusion

The frequency of C. albicans vaginal isolates with in vitro resistance to fluconazole in this study was high. Our findings highlight the importance of obtaining cultures and sensitivity testing in patients with recurrent or refractory VVC. However, resistant vaginal strains may not necessarily persist over time. Future, larger studies on those with recurrent VVC are needed to verify factors associated with fluconazole resistance, how frequently azole-resistant strains persist over time, and how well in vitro resistance correlates to in vivo treatment response.

Disclosures

Susan Tuddenham, MD, MPH, Luca Biologics: Advisor/Consultant|Medscape/WebMD: Honoraria|UpToDate: Royalties.
495. Enterovirus Genotype Specific Immune Response in Cerebrospinal Fluid of Infected Infants
Authors: Shore Kayla , Sasidharan Anjana , Lee Brian R , Hassan Wail M , Harrison Christopher J , Selvarangan Rangaraj
Published: December 2022

Background

Non-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF.

Methods

Salvaged standard of care CSF samples from ≤6 month olds (real time EV PCR(+) or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27).

Results

Data from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987.

Conclusion

Preliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes.

Disclosures

Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.
503. Lack of coronary aneurysms during Kawasaki Disease (KD) correlates with higher levels of autoantibodies to both full form and spliced variant of immune regulator EDIL-3 (Del-1)
Authors: Ross Welliver R , Prakash Aviraag Vijaya , Hicar Mark D
Published: December 2022

Background

Kawasaki disease is a rare multisystem inflammatory condition that mainly affects children under the age of 5 years. Current theory of the pathogenesis is that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to EDIL3 (also known as DEL-1) in children with KD. EDIL3 is an extracellular matrix protein which is expressed both in macrophages and vascular endothelium. EDIL3, has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against EDIL3 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation.

Methods

We assessed plasma samples from a cohort of febrile children, including Kawasaki disease with ELISA assay using recombinant EDIL3 using ELISAs.

Results

Time course samples of KD (pre-IVIG, post-IVIG and convalescent) from two different patient cohorts showed that there is increased autoantibody levels against EDIL3 in the post-IVIG samples, which is consistent with the commonality of antibodies. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not higher in children with Kd. Correlation with signs of cardiac inflammation showed lower autoantibody levels.

Conclusion

Auto-antibodies to EDIL3 are common in febrile children and, like other autoantibodies, are seen in IVIG formulation. Lower levels of these may be a susceptibility marker for KD or may be sequestered during aneurysm formation.

Disclosures

All Authors: No reported disclosures.
512. The relationship of Clostridioides difficile in-vitro antibiotic resistance, prior exposure to antibiotics and ribotype: A single center study
Authors: Alsoubani Majd , Thorpe Cheleste M , Walk Seth , McDermott Laura A , Snydman David R
Published: December 2022

Background

Antibiotic exposure is the most important risk factor for Clostridioides difficile associated diarrhea (CDAD). Little information has been reported on the relationship between prior antibiotic exposure, antibiotic resistance of C. difficile, and isolate ribotype.

Methods

C. difficile isolates were collected from the stools of patients with CDAD. Isolates were ribotyped by PCR-based fragment analysis. Susceptibility testing was performed using Clinical & Laboratory Standards Institute (CLSI) recommended methods. MIC results were interpreted using European Committee on Antimicrobial Susceptibility Testing (EUCAST) epidemiologic cut off values or the CLSI breakpoints. Demographic data and antibiotic exposure in the 30 days period prior to C. difficile isolation were collected via retrospective chart review.

Results

Of a total of 490 C. difficile isolates, 335 (67.3%) isolates were resistant to one or more antibiotics (Table 1). Patients who had higher Charlson Comorbidity Score (CCI) and who had hospital associated CDAD were more likely to receive antibiotics (Table 2). Moxifloxacin resistance was significantly associated with prior fluoroquinolone exposure (OR 2.5, CI 95% 1.5-4.1). Fluoroquinolone use was associated with vancomycin resistance (OR 2.7, CI 95% 1.3-5.6) and rifampin resistance (OR 1.9, CI 95% 1.2-3). Infection with a clindamycin resistant isolate was more likely to be hospital acquired (p = 0.006). We identified 54 different ribotypes (Figure 1). Prior treatment with aminopenicillins increased the odds of acquiring ribotype 053-163 (OR 2.9, 95% CI 1.0-8.2) and ribotype 002 (OR 3.2; CI 95% 1.0-10) (Table 3). .Prior treatment with cephalosporins had an increased risk of 014-020 (OR 2.0, CI 95% 1.2-3.3); prior treatment with carbapenems was associated with ribotype 106 (OR 2.3, CI 95% 1.2-4.4). Isolation of ribotype 027 following prior treatment to fluroquinolones was marginally significant (p = 0.054).

Conclusion

Specific antibiotic exposure may select for infection by specific C. difficile ribotypes, which can often lead to infection with resistant strains. Prior fluoroquinolone treatment, in particular, was associated with an increased risk of isolating multi-drug resistant strains.

Disclosures

Cheleste M. Thorpe, MD, Actelion: Grant/Research Support|Deinove: Advisor/Consultant|General Mills: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Summit: Advisor/Consultant|Summit: Grant/Research Support David R. Snydman, MD, Merck: Advisor/Consultant|Merck and Company: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres: Advisor/Consultant|Seres Health: Grant/Research Support|Summit Plc: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Visterra: Advisor/Consultant.
518. Characterization of colistin-resistant (COL-R) Acinetobacter baumannii calcoaceticus complex (ABC) isolates from a recent, global Phase 3 trial (ATTACK)
Authors: Moussa Samir , McLeod Sarah , Miller Alita
Published: December 2022

Background

Due to the lack of effective therapies, last-resort agents such as colistin are more frequently being used to treat drug-resistant ABC infections. Consequently, COL-R ABC is becoming more common, with some countries such as Greece reporting rates of >50%1. The efficacy and safety of sulbactam-durlobactam (SUL-DUR) was recently compared to COL, both on a background of imipenem/cilastatin therapy, in patients with ABC infections, including those caused by multidrug-resistant strains. SUL-DUR was non-inferior to colistin with respect to 28-day all-cause mortality (19 vs. 32.3%). SUL-DUR therapy resulted in higher clinical cure rates and significantly improved safety compared to COL. Here, we describe COL-R ABC in ATTACK.

Methods

Antibiotic susceptibility was determined by broth microdilution according to CLSI guidelines at IHMA, Inc. COL-R was defined as MIC ≥ 4 µg/ml. Next generation sequencing was performed using Nextera® libraries on an Illumina MiSeq system (San Diego, CA) at JMI Laboratories. Assembly and analysis were performed using CLC Genomics Workbench.

Results

17% (30 of 175) baseline ABC isolates from m-MITT (microbiologically modified Intent-to-Treat) patients were COL-R. All were extensively drug-resistant2 and 26 were pan-drug resistant (PDR). Two additional ABC isolates became COL-R in patients with pneumonia who received COL therapy; neither patient survived to 28 days. Most came from 5 clinical sites: Hungary (N = 9), Russia (N = 7), Greece (N = 6), Israel (N = 4) and Turkey (N = 2). No COL-R ABC was found in China or the Americas. Sequencing analysis on selected isolates suggested sites in Hungary and Russia had clonal outbreaks, whereas others were non-clonal but closely related ( >99%). SUL-DUR was highly active in vitro against COL-R ABC isolates, with an MIC50/90 of 2/4 µg/ml. Of the 22 patients with COL-R ABC infections treated with SUL-DUR, 17 (77%) survived to 28 days with clinical and microbiological cure at test-of-cure (TOC).

Conclusion

A notable number of ABC infections in ATTACK were COL-R, most of which were PDR but susceptible to SUL-DUR at ≤ 4 µg/ml. If approved, SUL-DUR could be an effective treatment for patients with these types of infections.

1. Nowak (2017) JAC, 72, 3277–3282

2. Magiorakis (2012) CMI,18, 268-81

Disclosures

Samir Moussa, PhD, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Sarah McLeod, PhD, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Alita Miller, PhD, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.
530. Characterization of the Proteomic Changes via SARS-CoV-2 Infection or Vaccination in the COVID-19 Community Research Partnership (CCRP)
Authors: DeWitt Michael E , Herrington David M , Williamson John C , Seals Austin L , Wierzba Thomas F , Binek Aleksandra , Van Eyk Jennifer , Sanders John W
Published: December 2022

Background

There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome.

Methods

The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naïve) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of < 0.05 and log2 fold change (L2FC) >0.2.

Results

We found 11 and 12 proteins differentially expressed proteins in the naïve/infected and naïve/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24; p < 0.001) only in those who were infected while fibrillarin (L2FC -0.24; p< 0.001) and lambda-crystallin homolog (L2FC -0.29, p < 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes.

Conclusion

We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings.

Disclosures

All Authors: No reported disclosures.
536. Evaluation of the Clinical Utility of Universal Polymerase Chain Reaction Testing
Authors: Donkin Joshua D , Emery Rebecca P , Polega James , Behenna Curtis J , Caulfield Adam J , Simeunovic Gordana
Published: December 2022

Background

Despite advances in microbiologic techniques, for patients with complex infections it often remains a challenge to identify the causative infectious pathogen. Traditional cultures (Cx) may fail to grow microorganisms due to inadequate sampling, prior antibiotic use, or the inherent insensitivity of culture methods for fastidious pathogens. Molecular tests allow for the detection of microbial nucleic acids directly from clinical specimens and do not require the presence of viable organisms for identification. Universal polymerase chain reaction testing (UPCR) is offered though the University of Washington Department of Laboratory Medicine and Pathology as a metagenomic approach using broad-range PCR primers followed by sequencing to hypothetically identify any pathogen present. The testing is composed of 3 separate tests for bacterial (BUPCR), fungal (FUPCR), and acid-fast (AFUPCR) organisms. The utility of UPCR has not been formally evaluated. Our objective is to describe the diagnostic utility of UPCR by comparing Cx and UPCR results, and their impact on management. Figure 1:Introduction - Types of Universal PCR Testing

Methods

We retrospectively collected data on UPCR and culture results and changes in antimicrobial therapy based on UPCR results for all patients with at least 1 UPCR test done during the 2-year study period.

Results

367 UPCR tests were performed over 24 months on 155 patients. From 367 tests, 119 were FUPCR, 111 AFUPCR, and 137 BUPCR.

32/155 (20.6%) patients had positive UPCR. 25/32 were BUPCR and 7/32 were FUPCR. No AFUPCR was positive.

In 8/155 (5.2%) patients management was changed based on UPCR results: Positive UPCR results directed treatment in 5 patients: 4 patients had positive UPCR and negative culture, and 1 had both UPCR and Cx positive but for different organisms. In all 5 therapy was changed in favor of UPCR result. All 5 tests were BUPCR.Negative UPCR led to antimicrobial discontinuation in 3 patients.

11/155 (7.1%) patients had negative UPCR and positive Cx, 10 of which were BUPCR and 1 AFUPCR. These results did not change management. Figure 2:Results – Type of Tissue and Test ResultsFigure 3:Results – Universal PCR Test Type and ResultsFigure 4:Results - Summary

Conclusion

Based on the real-world experience, UPCR results have limited impact on antimicrobial management in our institution. Further studies may try to identify clinical scenarios where UPCR may be of better clinical utility.

Disclosures

All Authors: No reported disclosures.
540. Impact on Clinical Decision Making of Microbial Broad Range Metagenomic Cell-Free DNA at a Single Academic Medical Center, a Retrospective Study
Authors: Olthoff Michael C , Kobayashi Takaaki , Parsons Meredith , Ford Bradley A , Prasidthrathsint Kunatum , Non Lemuel R , Diekema Daniel , Ince Dilek , Salinas Jorge
Published: December 2022

Background

Broad-range metagenomic cell-free DNA testing (Karius®) can identify a variety of pathogens from a single blood sample to help in diagnosis of deep seated and bloodstream infections. Few studies have evaluated the impact of Karius testing on clinical decision making when compared to more conventional diagnostic methods.

Methods

We performed a retrospective cohort study of adult patients who had Karius tests at University of Iowa Hospitals and Clinics between 01/2020 and 10/2021. Chart review was conducted to obtain patient characteristics and clinical course including patient age, immunocompromising conditions, involvement of Infectious Disease (ID) consultant, reason for the test, and final diagnosis. Results of the Karius tests and conventional tests were compared for concordance. Clinical impact and change in management due to Karius testing were determined using previously established criteria outlined by Hogan et al.(Clin Infect Dis. 2021 Jan 27;72(2):239-245)

Results

Out of 26 patients who had Karius testing, 20 patients (77%) had an immunocompromising condition, the most common of which was hematologic malignancy (17 patients, 65%). Twenty-four patients (92%) had received a formal ID consultation prior to the test. The most common finding prior to testing was the presence of pulmonary infiltrates on imaging (20 patients, 77%). Karius testing was positive in 18/26 cases (69%). Organisms detected by Karius and conventional testing were concordant in 9/18 cases (50%). Karius test result had a positive clinical impact in 3 cases (12%), an indeterminant impact in 1 case (3%) and no impact in 22 cases (85%). Reasons for a positive impact are as follows: 1 case with initiation of antituberculosis therapy due to earlier diagnosis of tuberculosis, 1 case with de-escalation of antifungal therapy based on negative Karius results, and 1 case of clearance for urgent lung transplantation based on negative Karius results in the setting of mobile echo density on echocardiogram in the absence of other stigmata of endocarditis.

Conclusion

The impact of Karius testing on patient management appears limited. Further studies will be needed to identify patient populations or disease factors in which this testing have clinical impact.

Disclosures

All Authors: No reported disclosures.
545. Real-world use of a novel host-response test to aid physicians in distinguishing between bacterial and viral infections at outpatient urgent care centers
Authors: Ben David Shirley Shapiro , Rahamim-Cohen Daniella , Kalmovich Boaz
Published: December 2022

Background

Uncertainty in the diagnostic process of an acute infection may cause antibiotic overuse and underuse. MeMed BV® (BV) is an FDA cleared test designed to differentiate between bacterial and viral infections based on computational integration of the blood levels of three proteins (TRAIL, IP-10, CRP) into a score. Here we describe the impact of its real-world use on the uncertainty physicians face in the diagnostic process.

Methods

A retrospective study was conducted at three Maccabi Healthcare Services outpatient urgent care centers in Israel between December 2020 and May 2021. Physicians could use BV in real time whenever they felt uncertain regarding the cause of the infection -bacterial or viral. The BV result is based on pre-defined score thresholds: 0 ≤ score < 35 viral (or other non-bacterial) infection, 35 ≤ score ≤ 65 equivocal and 65 < score ≤ 100 bacterial infection (or co-infection). Physicians were asked to answer a questionnaire composed of two parts: The first part included the suspected etiology and likelihood of prescribing antibiotic (AB) treatment before ordering the test. The second part included questions regarding the tool's impact on their decision-making process, completed after receiving the BV results.

Results

A total of 152 questionnaires were filled out. Of them, 58% of the patients were children under the age of 18, and 51% were female. The average number of days from fever onset was three in children and 2.3 in adults. Out of the 131 cases with either bacterial or viral scores, in 86 (66%) of the questionnaires the physicians confirmed that the BV result supported their overall impression and management. In 28 (21%) cases the BV results altered their decision. In 39 (30%) cases the physicians marked high likelihood for prescribing ABs, of them 22 (50%) received a viral score and in 8 (36%) of them physicians altered their decision and withheld ABs. In 63 (41%) cases the physicians marked low likelihood for prescribing ABs of which 8 (15%) received a bacterial score and in 6 (75%) cases physicians altered their decision and prescribed ABs.

Conclusion

BV contributed greatly to physicians’ decision-making process in the management of patients with acute infection. These preliminary results demonstrate the test’s clinical utility with regard to AB overuse and underuse.

Disclosures

Shirley Shapiro Ben David, MD, pfizer: Grant/Research Support.
546. Resolution of a Cluster of Travel-Associated Leptospira santarosai Infection in Four Adolescents by Plasma Microbial Cell-Free DNA Detection with the Karius Test®
Authors: Nguyen-Tran Hai D , Erdem Guliz , Laufer Marcelo , Patterson Lori , Ahmed Asim A , Bower William A , Galloway Renee , Saporta-Keating Sara
Published: December 2022

Background

Leptospira can cause severe infections but their diagnosis can be challenging. Diagnosis is limited by nonspecific, protean clinical symptoms; the fastidious nature of Leptospira; and poor specificity, sensitivity, and long turnaround times of serologic testing. Given these limitations, identifying epidemiological clusters of leptospirosis can be challenging. Rapid, non-invasive diagnosis of leptospirosis by microbial cell-free DNA (mcfDNA) next-generation sequencing (NGS) of plasma offers a means to overcome these limitations in individual diagnosis and public health epidemiological surveillance.

Methods

The Karius Test® (KT) detects and quantifies mcfDNA in molecules/µL (MPM) in plasma from a curated genomic database of >20,000 organisms reporting on >1000 pathogens through the Karius CLIA certified/CAP accredited lab (Redwood City, CA). Four KT detections of Leptospira santarosai were identified April - August 2021 across four independent United States institutions. Clinical review was performed by pediatric infectious diseases consultants.

Results

KT detected L. santarosai in four adolescents with travel to Costa Rica or Belize (Table). A broad work-up was performed in all patients. McfDNA NGS was the first test to identify L. santarosai as the diagnosis in all cases with an average time to diagnosis of 2.5+/- 0.58 days from sample collection, enabling narrowed, targeted antibiotic treatment. L. santarosai mcfDNA was positive in three patients despite pretreatment; average L. santarosai mcfDNA concentration was 173.5+/- 186.1 MPM. Leptospira serologies were confirmatory in three patients, potential epidemiological exposures were identified in all patients, and all recovered.

Conclusion

KT enabled rapid, non-invasive diagnosis of diverse manifestations of L. santarosai against a competing broad differential in four adolescent travelers returning from Costa Rica or Belize. The resolution of the etiology of this cluster of patients with leptospirosis demonstrates the potential utility of mcfDNA to quickly diagnose and support case definitions of reportable diseases and the potential importance of plasma mcfDNA NGS in public health and epidemiological surveillance.

Disclosures

Asim A. Ahmed, MD, Karius: Employee|Karius: Stocks/Bonds Sara Saporta-Keating, MS, MD, Pfizer: Co-investigator in investigator-driven study sponsored by Pfizer.
551. Antibiotic Use Among Surgical Patients in the Neonatal Intensive Care Unit (NICU): The NO-More-AntibioticS and Resistance in Surgery (NO-MAS-R-S) Study
Authors: Dixit Himangini Singh , Drews Joseph D , Nwomeh Benedict , Sanchez Pablo J , Goff Debra A , Medoro Alexandra K , Magers Jacqueline , Prusakov Pavel
Published: December 2022

Background

Although antibiotic exposure among infants in the NICU is associated with short- and long-term adverse effects, the burden of antibiotic use in neonatal surgical patients has not been well described. The pediatric surgical team at Nationwide Children’s Hospital (NCH) provides all surgical consultations for central Ohio in the level 4 outborn referral NICU at NCH. Our objective was to quantify the total use of antibiotics in surgical NICU patients and thus inform antimicrobial stewardship opportunities.

Methods

This was a prospective observational study of all infants in the NCH NICU who underwent pediatric surgical evaluation and received antibiotic therapy from 1/3/2022 to 4/29/2022. The pediatric surgery fellow informed the neonatal clinical pharmacist about all consultations and provided qualitative data on antibiotic prescribing (diagnosis, indication and reasoning for antibiotic selection, dosing, and duration) using a set questionnaire. Pertinent demographic maternal/infant data were obtained from the electronic health records.

Results

During the 4-month study period, 59 infants (median gestational age, 35 wks, IQR 28-35 wks; median birth weight, 2275 g, IQR 1085-3107 g) underwent surgical evaluation at a median postnatal age of 2 days (IQR, 1-12 d). 33 (56%) infants were male; 9 (22%) had antibiotic exposure for >48 hours before surgical consultation. Of the 59 infants, 28 (47%) had a surgical procedure performed (Figure 1) with indications for antibiotic use provided in Figure 2. 34 (58%) infants had antibiotics started by surgical team for a median treatment duration of 7 days (IQR, 5-14). Surgeons considered 74% (20/27) of antibiotic initiation courses to be evidence-based. Of the 59 infants, the most commonly used antibiotics were gentamicin (32%), ampicillin-sulbactam (29%), cefazolin (19%), and piperacillin-tazobactam (14%). The most frequent blood isolate was E. coli (n=4). Mortality was 2% (n=1) and was not infection-related. Figure 1Surgical procedures performed in 28 of 59 infants who underwent surgical evaluation.

Figure 2 Indications for antibiotic use in 59 infants who underwent surgical evaluation

Conclusion

Antibiotics were utilized in the majority of infants who had surgical consultation. Surgical prophylaxis was the main indication and may serve as a potential opportunity for ongoing surgical stewardship efforts.

(Supported by Merck & Co research grant)

Disclosures

Debra A. Goff, Pharm.D, FIDSA, FCCP, Merck Sharp & Dohme (MSD): Grant/Research Support Alexandra K. Medoro, MD, Merck: Grant/Research Support Pavel Prusakov, PharmD, Merck Sharp & Dohme: Grant/Research Support.