bluuebunny/crossref_metadata_2025_split huggingface dataset:
2385. Evaluating the Antibiotic Risk for Clostridioides difficile Infection (CDI): Comparing Piperacillin/Tazobactam to Cefepime and Ceftazidime
Authors: Rathod Shardul , McManus Dayna , Rivera-Vinas Jose , Topal Jeffrey E , Martinello Richard A 
Published: October 2019

Abstract

Background
Clostridioides difficile infection (CDI) is a common healthcare-associated infection (HAI). Past studies have revealed that anti-pseudomonal cephalosporins such as cefepime (FEP) and ceftazidime (CTZ) are associated with a higher CDI risk than β-lactam/β-lactamase inhibitors (BLBLI) such as piperacillin/tazobactam (PTZ). However, there is limited data evaluating the comparative healthcare-associated CDI (HA-CDI) risk associated with BLBLI and anti-pseudomonal cephalosporin therapy.

Methods
An observational cohort study was performed with patients who received PTZ, FEP, or CTZ at Yale New Haven Hospital and Bridgeport Hospital from February 1, 2013 to June 1, 2018. Patients who received ≥ 3 days of PTZ, FEP, or CTZ therapy were included. Patients under the age of 18, those admitted to oncology, transplant, or pediatric units, and those with < 2 or ≥ 120 days of hospital admission were excluded. Multivariate logistic regression models were constructed to control and to adjust for underlying comorbidities.

Results
A total of 11,909 patient encounters met the study criteria. The median patient-days of therapy for both the PTZ and FEP/CTZ groups was 4 days (Table 1). FEP/CTZ exposure was associated with a higher CDI risk than PTZ exposure (P = 0.03) (Figure 1) even with higher C. difficile testing frequency in the PTZ group (P < 0.001) (Table 1). Using a multivariate logistic regression model controlling for high-risk antibiotic therapy (ciprofloxacin, clindamycin, ertapenem, meropenem, moxifloxacin), acid suppression therapy (famotidine, lansoprazole, pantoprazole), sex, Charlson comorbidity index score, age, and duration of hospital admission, FEP/CTZ exposure was independently associated with a higher CDI risk than PTZ exposure (Table 2) (Table 3).

Conclusion
FEP/CTZ exposure was associated with a higher CDI risk than PTZ exposure. PTZ may be associated with a higher risk for non-CDI antibiotic-associated diarrhea which may lead to an increased frequency of testing for CDI. The findings from this study may justify additional antibiotic stewardship efforts to limit the use of empiric FEP/CTZ therapy.

Disclosures
All authors: No reported disclosures.
2388. High-risk antibiotics associated with Clostridioides difficile infection: a national, multicenter analysis
Authors: Young Eric H , Zeidan Amina R , Garey Kevin W , Reveles Kelly R 
Published: October 2019

Abstract

Background
Historically, antibiotics with the highest Clostridioides difficile infection (CDI) risk included clindamycin, advanced-spectrum penicillins, and cephalosporins; however, a recent CDI epidemic involving fluoroquinolone (FQ)-resistant ribotype 027-added FQs as a high-risk class. Now that the ribotype 027 strain is part of an endemic population of C. difficile strains, no contemporary analysis of high-risk antibiotics and CDI risk has been conducted. The primary objective of this study was to identify the strongest antibiotic predictors for CDI.

Methods
This was a case–control study in the national United States Veterans Health Administration (VHA). The study included patients 18–89 years old with an ICD-9-CM code for CDI (008.45), a positive stool test, and active CDI therapy between 2002 and 2014. A random sample of VHA patients without a CDI ICD-9-CM code served as the control cohort. Antibiotic use was defined as any use in the 90 days prior to inclusion. Antibiotic risk factors for CDI were evaluated in a multivariable logistic regression model that included 33 covariates. Results were validated in non-VA patients at a quaternary care medical center in Houston, TX.

Results
A total of 85,451 VHA patients were included (26,149 CDI patients and 59,302 controls). FQs were most commonly prescribed: 24.9% (CDI group) and 7.3% (controls). Strongest predictors of CDI included carbapenems (OR 54.39, 95% CI 25.42–116.36), advanced-spectrum penicillins (OR 41.54; 95% CI 31.49–54.78), third/fourth-generation cephalosporins (OR 17.35; 95% CI 14.49–20.77), clindamycin (OR 3.63; 95% CI 3.26–4.02), and FQs (OR 1.48; 95% CI 1.40–1.57). Macrolides (OR 0.83; 95% CI 0.77–0.91) and tetracyclines (OR 0.58; 95 CI 0.51–0.66) were negatively associated with CDI risk. In a validation cohort of 68,795 patients, carbapenems (OR 2.19; 95% CI 1.86–2.57), third/fourth-generation cephalosporins (OR 1.70; 95% CI 1.50–1.93), and advanced-spectrum penicillins (OR 1.64; 95% CI 1.42–1.89) were also the strongest predictors for CDI. FQs were not significantly associated with CDI.

Conclusion
Although FQs were the most prescribed antibiotic class, carbapenems were the strongest predictor of CDI development in a national cohort of veterans and a validation cohort.

Disclosures
All authors: No reported disclosures.
2396. Clostridium difficile Infection is Children with Sickle Cell Disease: An Uncommon Entity
Authors: Lee Philip , Soma Vijaya L , Cruz Carlos , Manwani Deepa , Goldman David L 
Published: October 2019

Abstract

Background
Children with sickle cell disease (SCD) have numerous risk factors for intestinal dysbiosis, including frequent hospitalization, iron overload, antibiotic exposure including penicillin prophylaxis, hypoxia, and altered gut permeability. Many of these conditions are also established risk factors for C. difficile infection (CDI); however, the incidence of CDI in children with SCD has not been characterized.

Methods
We performed a 10-year retrospective review from 1/2008–December 2017. Patients who qualified with CDI were either admitted or within 2 weeks of discharge from our site and had a positive test. A positive test was defined as a positive glutamate dehydrogenase 1 test in conjunction with either a positive ELISA or a positive PCR for toxin. Three investigators independently reviewed if patients had active diarrhea during the time of their positivity. Patients excluded were <2 years old and patients undergoing a stem cell transplant (SCT) or irritable bowel disease (IBD) at the time of a positive test. Chi-square test with Yates correction, descriptive statistics were used when comparing groups<./p>

Results
Over a 10-year period (2008–2017), there were 5666 admissions for children with SCD, corresponding to 25,915 hospitalization days and 957 unique patients. The average age of this cohort at the time of admission was 10.6 ± 6.7 years; 51.7% were male. One patient qualified; a 12-year-old who developed diarrhea and abdominal pain after recent hospitalization for pneumonia (Figure 1). This yielded a CDI incidence of 0.39/10,000 patient-days or 0.18 cases per 1000 admissions (Table 1). There were 208 cases of CDI in non-SCD children, with an incidence of 5.53/10,000 patient-days (P < 0.001) or 2.77 cases per 1000 admissions (P < 0.001) (Table 2) during the study period. In 2015–2017, there were no cases of CDI in 957 SCD patients, of which 218 were on penicillin prophylaxis.

Conclusion
There is a very low incidence of CDI in children with SCD despite significant antibiotic exposure and other risk factors for intestinal dysbiosis. These findings are consistent with recent studies in adults (N Engl J Med 2019; 380:887–888) and suggest that sickle cell patients are somehow protected against CDI. Additional studies are needed to define the host and biome factors that confer this protection.

Disclosures
All authors: No reported disclosures.
2404. Molecular Epidemiology of Clostridioides difficile in the United States, 2017
Authors: Paulick Ashley , Adamczyk Michelle , Korhonen Lauren C , Guh Alice , Gargis Amy , Karlsson Maria 
Published: October 2019

Abstract

Background
In 2009, the Centers for Disease Control and Prevention (CDC) implemented Clostridioides difficile infection (CDI) surveillance through the Emerging Infections Program (EIP) to monitor the incidence and evolving epidemiology of CDI in the United States. Since 2012, ribotypes (RTs) 027, 106, 002, 014, and 020 have constituted the top five strain types among both US community- and healthcare-associated isolates. Here we describe the changes in molecular epidemiology of C. difficile isolates collected in the United States in 2017.

Methods
In 2017, CDI surveillance was conducted at 10 EIP sites (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN). A convenience sample of clinical laboratories across EIP sites submitted C. difficile-positive stool specimens to the MN Department of Health Public Health Laboratory and Hines VA Hospital (IL) for culture. Isolates were forwarded to CDC and characterized by capillary-based PCR-ribotyping and PCR detection of tcdA, tcdB, cdtA, cdtB, and deletions in tcdC.

Results
In 2017, 1,051 C. difficile isolates were submitted; the total number of isolates received from each site ranged from 11 to 286 with a median of 85.5. In total, 143 RTs were observed, with the majority of isolates harboring toxin genes tcdA and tcdB (95%) and a wild-type tcdC sequence (71%). Among 556 healthcare-associated isolates, RT 027 was the most prevalent and the top RT at 5 sites (CA, GA, MD, NM, TN). Ribotype 106 was the most prevalent among 495 community-associated CA isolates and the top RT at 6 sites (CO, CT, GA, MD, MN, TN). Ribotype 027 significantly decreased from 2012 to 2017 among both healthcare-associated (21% vs 15%; p = 0.02) and community-associated isolates (17% vs 6%; P < 0.0001). Among healthcare-associated isolates, RT 076, which was observed in 8 EIP sites, increased from 2% in 2016 to 5% in 2017 (p = 0.05) and replaced RT 020 as one of the top 5 healthcare-associated RTs in 2017.

Conclusion
Despite an overall decline since 2012, RT 027 remained the most prevalent RT among healthcare-associated isolates submitted in 2017. The increased frequency of RT 076 among healthcare-associated isolates submitted in 2017 highlights the evolving molecular epidemiology of C. difficile and the need for continued surveillance to monitor potential emerging strains.

Disclosures
All authors: No reported disclosures.
2407. Overexpression of Virulence Factors in Biofilm from Recurrent Clostridium (Clostridioides) difficile Infection Isolates.
Authors: Tijerina Laura , Villarreal-Treviño Licet , Morfin-Otero Rayo , Camacho-Ortiz Adrian , Baines Simon D , Rodríguez-Noriega Eduardo , Garza-González Elvira 
Published: October 2019

Abstract

Background
Recurrent Clostridium (Clostridioides) difficile infection (R-CDI) remains a significant healthcare problem. Our aim was to analyze virulence/colonization determinants including spore formation, and expression of quorum sensing factors and adhesion capability in C. difficile biofilms, which serve as a potential reservoir for C. difficile in R-CDI.

Methods
Isolates obtained from patients with R-CDI (n = 39) and non-recurrent CDI (NR-CDI) (n = 93) were analyzed. Isolates were identified by PCR and MALDI-TOF MS and ribotyped by 16S-RNA amplification and capillary electrophoresis.
Biofilm production in a C. difficile and in a C. difficile-microbiota (Enterococcus and Lactobacillus species) model was assessed by the crystal violet method. Spore counts were determined both in planktonic and biofilm growth.
RNA was extracted from a selection of strains from R-CDI (n = 10) and NR-CDI (n = 10) isolate biofilms and relative expression levels of: spo0A, sigH, slpA, cwp84, agrD1 and luxS were determined.

Results
All NR-CDI and R-CDI isolates were biofilm producers and most were strongly adherent (90.90%) and 027 ribotype (81.37%).
In the C. difficile biofilm model, spore formation was higher in R-CDI than in the NR-CDI isolates (P = 0.015). In the biofilm of C. difficile-microbiota, no difference was detected in spore formation between the R-CDI and NR-CDI isolates (P = 0.677).
Expression of sigH (p = 0.007), spo0A (p = 0.003), cwp84 (p = 0.001) and agrD1 (p = 0.001) was higher in R-CDI than NR-CDI isolates. No difference was shown in slpA (p = 0.066) and luxS (p = 0.400) expression between groups.

Conclusion
Our data suggest that expression of sporulating pathway genes, sigH, spo0A, the quorum sensing gene, agrD1; and adhesion-associated gene, cwp84 is higher in R-CDI isolates, in addition to elevated spore formation, which may have an impact on the recurrence of the infection.

Disclosures
All authors: No reported disclosures.
2409. External Validation and Comparison of Clostridioides difficile Severity Scoring Systems
Authors: Perry Donald A , Shirley Daniel , Micic Dejan , Putler Rosemary K B , Patel Pratish , Menon Anitha , Higgins Peter , Young Vincent B , Rao Krishna 
Published: October 2019

Abstract

Background
Annually in the US alone, Clostridioides difficile infection (CDI) afflicts nearly 500,000 patients causing 29,000 deaths. Since early and aggressive interventions could save lives but are not optimally deployed in all patients, numerous studies have published predictive models for adverse outcomes. These models are usually developed at a single institution, and largely are not externally validated. This aim of this study was to validate the predictability for severe CDI with previously published risk scores in a multicenter cohort of patients with CDI.

Methods
We conducted a retrospective study on four separate inpatient cohorts with CDI from three distinct sites: the Universities of Michigan (2010–2012 and 2016), Chicago (2012), and Wisconsin (2012). The primary composite outcome was admission to an intensive care unit, colectomy, and/or death attributed to CDI within 30 days of positive test. Structured query and manual chart review abstracted data from the medical record at each site. Published CDI severity scores were assessed and compared with each other and the IDSA guideline definition of severe CDI. Sensitivity, specificity, area under the receiver operator characteristic curve (AuROC), precision-recall curves, and net reclassification index (NRI) were calculated to compare models.

Results
We included 3,775 patients from the four cohorts (Table 1) and evaluated eight severity scores (Table 2). The IDSA (baseline comparator) model showed poor performance across cohorts(Table 3). Of the binary classification models, including those that were most predictive of the primary composite outcome, Jardin, performed poorly with minimal to no NRI improvement compared with IDSA. The continuous score models, Toro and ATLAS, performed better, but the AuROC varied by site by up to 17% (Table 3). The Gujja model varied the most: from most predictive in the University of Michigan 2010–2012 cohort to having no predictive value in the 2016 cohort (Table 3).

Conclusion
No published CDI severity score showed stable, acceptable predictive ability across multiple cohorts/institutions. To maximize performance and clinical utility, future efforts should focus on a multicenter-derived and validated scoring system, and/or incorporate novel biomarkers.

Disclosures
All authors: No reported disclosures.
134. A Comparison of Lyme Carditis in Children and Adults, a Case Series
Authors: Shen Richard V , McCarthy Carol A , Smith Robert P 
Published: October 2019

Abstract

Background
Lyme disease is a common entity in Maine, and Lyme carditis is an uncommon manifestation of this disease. This case series describes and compares the presentation, management, and outcomes of Lyme carditis in pediatric and adult populations.

Methods
Charts of pediatric and adult patients with heart block and positive Lyme serologies hospitalized in Portland, Maine between January 2010 and December 2018 were analyzed. Data on medical history, presentation, treatment, and outcomes are described.

Results
Ten children (range 7–17, mean 12.4 years) and 20 adults (range 22–81, mean 41.4 years) were admitted for Lyme carditis in the examined period. All cases presented between June and October. Twenty-seven (90%) were male, and 26 (87%) had no prior cardiac history. Of the adults, 1 (5%) reported using cocaine, 4 (20%) opioids, and 6 (30%) marijuana. Seventeen (57%) had outpatient evaluation prior to admission. Ten patients (59%) were not recognized as having Lyme disease. One case suspected to have Lyme was not initially treated with doxycycline. The most common alternative diagnoses were a viral illness and erythema multiforme. No coinfections were noted. Proportionately more children than adults had disseminated erythema migrans (40% vs. 20%) and fever (60% vs. 35%). First degree heart block was more prevalent in children (40%), and Mobitz type 2 heart block was more prevalent in adults (55%). Ten patients (30%) presented with syncope. More adults than children needed temporary pacing, 9 (45%) vs. 2 (20%). Children had shorter antibiotic durations compared with adults (mean 19.8 days vs. 23.6 days) Twenty-seven (90%) had improved heart block. Three adult patients (10%) required a pacemaker following hospitalization. Nine (90%) children and 14 (70%) adults were discharged with a PR 200-300ms. There was a single death in this series, which occurred after discharge to another state.

Conclusion
Cases tended to be in younger patients with male predominance. Most patients still had some degree of heart block on discharge. The majority of patients were evaluated prior to hospitalization but Lyme disease was suspected in only 41%. Improved recognition of early Lyme disease and more prompt treatment may lead to decreased complications of Lyme carditis.

Disclosures
All authors: No reported disclosures.
2413. Assessment of compliance with Clostridioides difficile prophylaxis guideline and its efficacy on secondary prophylaxis and reducing hospital-onset Clostridioides difficile infections.
Authors: Vyas Nikunj M , Hou Cindy , Levin Todd P 
Published: October 2019

Abstract

Background
One of the complications of Clostridium difficile infection (CDI) is the risk of recurrence, particularly in high-risk patients who are exposed to broad-spectrum antibiotics (BSA). Antimicrobial stewardship program at our institution developed Clostridium difficile prophylaxis (CDP) guidelines. Purpose of this study was to evaluate the compliance to this guideline and evaluate the efficacy of it preventing recurrent CDI.

Methods
This was an IRB approved retrospective study performed at a 607-bed community health system between 2014–2016. Patients were included if they were ≥18 years old and admitted for > 24 hours on BSA with history of CDI in last 6 months. CDI prophylaxis was provided with oral vancomycin 125 PO BID. Patients were excluded if they had active CDI receiving metronidazole or treatment doses of oral vancomycin. Patients were compared in two cohorts: Study group which was patients in CDP group which were matched to control group. The primary objective of the study was to evaluate the compliance of CDP guidelines and incidence of hospital-onset CDI (HO-CDI) between CDP group and control group. The secondary objective focused on all-cause inpatient mortality and 30-day readmission between two groups.

Results
There were total of 72 patients reviewed and 47 patients met the inclusion criteria for CDP group which were matched with control group. Most common type of infection and BSA were pnuemonia (26%) and broad-spectrum cephalosporins (31%), respectively. CDP guidelines compliance was measured at 65%. The incidence of HO-CDI/10000 patient-days during the admission was lower in CDP group compared with control group (2.02 vs 5.4 per 10,000 PD, P = 0.03). No differences were seen in all-cause inpatient mortality and 30-day readmission between two groups. Forty-five percent of patients suffered from CDI < 3 months prior to admission. The most common dose of oral vancomycin was 125 mg PO BID.

Conclusion
Patients in CDP group had a lower incidence of developing HO-CDI compared with control group. Overall compliance with CDP guidelines was higher than expected. No difference was seen in all-cause inpatient mortality and 30-day readmission between two groups. Oral vancomycin 125 mg PO BID shows promising results as a secondary prophylaxis in patients receiving BSA.

Disclosures
All authors: No reported disclosures.
2418. Determining the Impact of Visitor Contact Precautions on Hospital-Onset Clostridioides difficile Infection Rates: An Agent-Based Simulation Modeling Approach
Authors: Alagoz Oguzhan , Scaria Elizabeth , Barker Anna K , Safdar Nasia 
Published: October 2019

Abstract

Background
Visitor contact precautions (VCP) have been suggested to reduce the transmission of Clostridiodes difficile at healthcare institutions. However, there are no data describing the impact of VCP on hospital-acquired C. difficile infection (HO-CDI) rates. Enforcing VCP for CDI control is also controversial, as VCP are poorly implemented and highly variable.

Methods
We developed an agent-based simulation model of C. difficile transmission at a model 200-bed acute-care adult hospital. Our agent-based simulation model represented interactions among the physicians, nurses, patients, visitors, and physical environment. We used the agent-based simulation model to evaluate the impact of VCP on reducing HO-CDI considering many different hospital settings and various assumptions on patient susceptibility, adherence rates to other infection control practices, interactions between healthcare workers and patients.

Results
VCP did not reduce the CDC-defined HO-CDI rates by more than 1% in any of the tested scenarios and hospital settings. Increasing the adherence of hand hygiene of healthcare workers to 56% from a baseline estimate of 55%, or compliance to room cleaning to 50% from a baseline estimate of 47% have led to higher rates of reduction in CDI compared with VCP.

Conclusion
This is the first mathematical model to quantify the reduction in HO-CDI with VCP. The agent-based simulation model suggests that the impact of VCP on hospital-onset CDI is minimal and hospitals can achieve a higher rate of reduction for HO-CDI by implementing other interventions such as healthcare worker hand hygiene, environmental cleaning and healthcare worker contact precautions. Further studies are needed to evaluate the impact of VCP on C. difficile colonization in community.

Disclosures
All authors: No reported disclosures.