bluuebunny/crossref_metadata_2025 huggingface dataset:
2367. Selecting Testing Frequency for Estimation of Incubation Periods: A Simulation Study Based on Clostridioides difficile Observations
Authors: Wilson Brigid , Ascha Mustafa S , O’Hagan Justin , Donskey Curtis
Published: October 2019

Background

Estimates of the incubation period (time between pathogen transmission and symptom onset) for an infection inform infection control and prevention measures. However, observation of the exact transmission and onset times rarely occurs and “coarse,” or doubly interval-censored, data about these exact times are typically used for estimation. The effect of coarseness on the required number of symptomatic cases and the uncertainty of the estimates is unknown, prompting a simulation study informed by data from an investigation of the incubation period of Clostridioides difficile.

Methods

We simulated incubation period data assuming a log-normal distribution, a true median incubation period of 7 days, and a standard deviation of 1 day for sample sizes of 50 to 300 symptomatic cases. For each sample size, we simulated 1000 datasets and examined the impact of testing frequencies, considering intervals between tests of 0.25 to 2 times the median incubation period (1.75 to 14 days) about both transmission and symptom onset times. With these doubly interval-censored observed values, we fit accelerated failure time models to estimate the median incubation time and its 95% confidence interval (CI). Comparing the coverage of the true median and the widths of the CIs, we summarized simulation results across sample sizes and testing frequencies.

Results

Model results from all combinations of sample sizes and testing frequencies yielded median incubation period CIs close to the target 95% coverage level (Figure 1). The width of the 95% CI about the median decreased with larger sample sizes and shorter times between tests (Figure 2). Thus, similar estimates and confidence intervals would be observed from 100 symptomatic cases with a testing frequency of 3.5 days as from 200 symptomatic cases tested every 14 days.

Conclusion

The frequency of testing is a key factor in planning studies to estimate incubation periods for infectious diseases. To achieve a desired degree of certainty in estimation, increased frequency of testing can reduce the number of symptomatic cases required. We showed that simulations can assist in planning natural history studies, and these methods could be extended to include population data (e.g., transmission incidence) and cost constraints.

Disclosures

All authors: No reported disclosures.
2371. A Multicenter Cohort Study of the Natural History of Clostridioides difficile Colonization and Infection
Authors: Curry Scott R , Hecker Michelle , O’Hagan Justin , Kutty Preeta K , Alhmidi Heba , Karen Ng Wong Y , Cadnum Jennifer , Jencson Annette , Gonzalez-Orta Melany , Saldana Carlos S , Wilson Brigid , Donskey Curtis
Published: October 2019

Background

Asymptomatic carriage of toxigenic Clostridioides difficile strains is common in healthcare settings. However, the natural history of C. difficile colonization and infection is not well understood, particularly for patients with new acquisition of carriage.

Methods

In 3 tertiary care hospitals and affiliated long-term care facilities (LTCFs), we conducted a 6-month cohort study to identify patients with new acquisition of rectal carriage of toxigenic C. difficile and determined the duration and burden of carriage. Asymptomatic carriage was defined as transient if only 1 culture was positive with negative cultures before and after or persistent if 2 or more cultures were positive; clearance was defined as 2 consecutive negative rectal cultures.

Results

Of 4180 patients with negative initial cultures, 144 (3%) acquired asymptomatic carriage of toxigenic C. difficile, and 19 (13%) of these carriers subsequently were diagnosed with CDI. Of 50 asymptomatic carriers analyzed for duration of carriage, 33 (66%) had transient carriage of toxigenic C. difficile and 17 (34%) had persistent carriage. For persistent carriers, the estimated median time to clearance of colonization was 76 days (range, 41 to 95 days from acquisition). Ten of 17 (59%) persistent carriers had a high burden of carriage (defined as > 25 colonies recovered from 1 or more swabs) vs. only 1 of 33 (3%) transient carriers (P < 0.001).

Conclusion

Acquisition of asymptomatic carriage of toxigenic C. difficile carriage was common among patients in healthcare facilities, but most carriers had transient low-level carriage. Additional studies are needed to determine whether a higher burden of carriage predicts subsequent risk of transmission.

Disclosures

All authors: No reported disclosures.
2373. Impact of a Change in Testing Strategy for Clostridioides difficile Infection on a Publicly Reported Metric and Treatment Days of Therapy
Authors: Miller Ryan , Morillas Jose A , Sitaras Joanne , Bako Jacob , Neuner Elizabeth A , Gordon Steven M , Brizendine Kyle D , Fraser Thomas G
Published: October 2019

Background

In an effort to optimize diagnostic testing for Clostridioides difficile infection (CDI) our health system changed from stand-alone PCR testing to a “2-step” approach wherein all positive PCR results reflexed to an EIA. We report the effects of this change on publicly reported CDI metrics and treatment days of therapy (DOT).

Methods

The setting includes 10 Cleveland Clinic Health System hospitals in northeast Ohio and one in Florida. On June 12, 2018, 9 NE Ohio hospitals changed from PCR alone to PCR followed by EIA. Stand-alone PCR testing remained at one and GDH / EIA / PCR for discordant for another. Testing volumes were obtained from the microbiology laboratory. C. difficile LabID event SIRs were obtained from NHSN. Public reporting interpretative categories were identified based on SIR for second half of 2018. DOT for CDI agents were obtained from an antimicrobial stewardship database.

Results

Among hospitals that changed strategy the volume of PCR testing and the percent PCR + was similar between time periods. EIA positivity ranged from 23% to 53%. 4/11 hospitals improved their public reporting category: 3/9 that changed testing strategy and 1/2 that did not (Table 1). Two of 3 that changed strategy and improved public reporting also had a decrease in DOT. DOT increased in the 2 hospitals that did not change strategy.

Conclusion

Six months after adopting a 2-step CDI testing strategy 7 of 9 hospitals had a lower SIR with 3 also demonstrating an improvement in public reporting category favorably impacting reputational and reimbursement risk for our healthcare system. CDI agent DOT was similar before and after the change. The impact of choice of test on publicly reported metrics demonstrates the difficulty of utilizing a proxy for hospital onset CDI, the CDI LabID event, as a measure of quality of care provided.

Disclosures

All authors: No reported disclosures.
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

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

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

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

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

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

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

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

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

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.
2419. Timing of Secondary Prophylaxis Against Clostridium difficile Infection After Antibiotic Exposure
Authors: Szela Joel , Hanna Angy , Sims Matthew
Published: October 2019

Background

Clostridium difficile infection (CDI) is the most common nosocomial infection, and is increasing. The major risk for CDI is antibiotic (abx) use. We have previously shown that secondary prophylaxis with vancomycin decreases CDI relapse in patients with recent CDI given abx to treat another infection. The median time to relapse after use of abx was 3 days. In an effort to further elucidate the best way to employ secondary prophylaxis against CDI, we examined all patients with CDI in our institution in 2016 and timing of relapse as related to another exposure to abx and the success of prophylaxis relative to the timing and the duration of prophylaxis.

Methods

All patients positive by PCR for C difficile at our institution in 2016 were examined for receipt of abx within 3 months of a positive PCR. The relapse rates for all patients, patients who received abx with or without secondary prophylaxis, and patients who did not receive abx were calculated. Timing of the relapse from the prior CDI and from receipt of abx were determined as was impact of prophylaxis, particularly in patients who relapsed despite prophylaxis.

Results

1748 patients were identified, representing 2181 episodes of CDI. The relapse rates and timing based on prior CDI, receipt of additional abx prior to relapse, and use of prophylaxis are shown in Table 1.

Prophylaxis decreased the overall relapse rate from 19.2% to 11.6%. Time to relapse in patients who relapsed despite prophylaxis was significantly longer indicating prophylaxis was having an effect. The failure appears dependent on when prophylaxis was started relative to abx and how long prophylaxis was given relative to abx.

Conclusion

Prophylaxis is effective in preventing relapses in patients given abx after CDI however the timing and duration of prophylaxis significantly impacts the effectiveness. The majority of CDI relapses after abx occur within 3 days and can be prevented by prophylaxis. Relapses that occur after 3 weeks appear unrelated to the use of abx and are not preventable through prophylaxis. Failures of prophylaxis within the first 1 week are likely related to starting prophylaxis too late after abx and failures that occur between 1 and 3 weeks after abx are likely related to ending prophylaxis too early.

Disclosures

All authors: No reported disclosures.
2428. Whole-genome Sequencing to Determine Clostridium difficile Transmission
Authors: Madigan Victoria M , Carter Glen , Buising Kirsty , Howden Benjamin , Marshall Caroline
Published: October 2019

Background

Clostridium difficile is a major problem in healthcare institutions due to its substantial attributable morbidity, mortality and costs. Although traditionally recognized as a nosocomial infection, there is increasing evidence that hospital-based transmission may not be as common as previously thought. Whole-genome sequencing (WGS) has superior discriminatory ability than other previously used techniques for C. difficile typing. This study aimed to investigate whether WGS could help to elucidate C. difficile transmission patterns at The Royal Melbourne Hospital (RMH).

Methods

All C. difficile isolates (N = 138) identified in patients admitted to RMH from November 1, 2015 to October 31, 2016 had molecular typing performed by WGS, multilocus sequence typing (MLST) and PCR ribotyping. Clinical epidemiological data were collected for each episode so that patient locations could be examined together with molecular typing information to determine putative transmissions in the hospital.

Results

After combining molecular and clinical epidemiology, a picture of diverse C. difficile emerged. Only 7 (6%) of isolates appeared to have been transmitted from other hospital patients, according to combined WGS and patient location data. However, both PCR ribotyping (33%) and MLST (44%) had significantly higher proportions of putative transmissions in this cohort.

Conclusion

This finding has significant implications for the Infection Prevention team as efforts toward prevention of C. difficile infection may need to be redirected away from the current focus on prevention of nosocomial transmission. Future studies are needed to broaden understanding of C. difficile transmission dynamics so that other sources can be identified and targeted for intervention.

Disclosures

All authors: No reported disclosures.
2429. Whole-genome Sequencing of Healthcare-Onset C. difficile Infection (HO-CDI) Cases Shows Widespread Presence of Antimicrobial Resistance Genes
Authors: Hyun Shin Jae , Viana da Silva Costa Deiziane , Parikh Hardik , Barry Katie E , Mathers Amy J , Warren Cirle
Published: October 2019

Background

Clostridioides difficile infection (CDI) is the most common pathogen to cause healthcare-associated infections. Unlike some other bacterial pathogens antimicrobial treatment is seldom based on culture with susceptibility testing with infrequent surveillance for antimicrobial resistance. We have evaluated healthcare-onset CDI (HO-CDI) for both transmission and antimicrobial resistance emergence.

Methods

We identified cases of HO-CDI diagnosed by PCR within a 3 month period (October 1/2018–December 31/2018) at University of Virginia Health System with overlapping stays in the same inpatient units with other HO-CDI. Chart review of all cases was performed. C. difficile was cultured from stool, then DNA was extracted and underwent sequencing on Illumina Miseq platform. Antimicrobial resistance genes were screened using NCBI’s AMRFinder tool from the de-novo assembled contigs using SPAdes. All the C. difficile isolates underwent antibiotic susceptibility testing.

Results

Eleven patients were identified with overlapping stays from 5 units. Mean age was 64 years and 63.6% were female. 36.3% of cases were severe CDI with one case of fulminant CDI. There was one recurrence within 90 days (9.1%). Patients were treated with PO vancomycin (72.7%) or IV metronidazole and PO vancomycin (27.3%), none were treated with metronidazole alone. None of the hospital strains were genetically related. There were two isolates with binary toxin gene (cdtB), one ribotype 027 (CD196) and one ribotype 078 (M120). Ninety-one percent of isolates had vanG-like gene cluster and vanZ1 originally identified in Enterococcus sp. erm(B), tet(M), and cfr(C) genes were also detected in several strains. All isolates were susceptible to vancomycin, metronidazole, and tigecycline. There was one strain with moxifloxacin resistance associated with the presence of erm(B) gene. None of the isolates were susceptible to clindamycin.

Conclusion

There were no widely circulating clones or direct transmissions found in this small sample of HO-CDI cases at our hospital. Like others have we demonstrate carriage of many vanG/Z genes without conferring phenotypic resistance to vancomycin. The origin and function of Van genes in C. difficile could be an area of future research.

Disclosures

All authors: No reported disclosures.
136. Factors Associated with Reduced Vancomycin Susceptibility in Pediatric Staphylococcus aureus Bacteremia
Authors: Ericson Jessica E , Curley Tara E , Canty Ethan A , Ansusinha Emily , Hamdy Rana F
Published: October 2019

Background

Vancomycin is often used empirically for treatment of pediatric Staphylococcus aureus bacteremia while susceptibility testing is being performed. Reduced vancomycin susceptibility (RVS) occurs when the minimum inhibitory concentration (MIC) for vancomycin is elevated, potentially resulting in decreased efficacy. Patient factors associated with RVS in pediatric S. aureus infections have not been well studied.

Methods

Children aged <18 years admitted from 2012 to 2016 to two tertiary care children’s hospitals with a blood culture positive for S. aureus were identified. Demographics, presence of comorbidities, hospitalizations in the year prior to the infection, surgical procedures in the 30 days prior to the infection, presence of a central venous catheter at diagnosis and methicillin-resistant (MRSA) vs. methicillin-susceptible S. aureus (MSSA) were abstracted from the electronic medical record using a structured data collection form. RVS was defined as a MIC >1 µg/mL as reported by the clinical microbiology laboratory. Wilcoxon rank-sum and Fisher’s exact test to compare continuous and categorical variables, respectively. A multivariable logistic regression model was used to evaluate the association of RVS with patient factors, MRSA vs. MSSA, admitting hospital, and year.

Results

We identified 221 S. aureus bloodstream infections. Most (84%) had RVS though there were differences by the hospital, 74% vs. 87%, P = 0.037. Bloodstream infections in the setting of a musculoskeletal infection were most common (36%), followed by central line-associated bloodstream infections (22%). The median age was similar between RVS and non-RVS infections, 3 (25th, 75th %tiles: 0, 9) vs. 5 (0, 12) but, when adjusted for patient factors, younger children were more likely to have RVS infections than older children, aOR: 0.92 (0.85, 0.99). Black children were more likely to have RVS than white children on both univariate and adjusted analyses (table).

Conclusion

RVS is common among pediatric S. aureus bloodstream infections and appears to be influenced by patient age and race but not by the source of the infection or other clinical factors.

Disclosures

All authors: No reported disclosures.
2433. Oral Vancomycin Plus Intravenous Metronidazole for Severe Clostridioides difficile Infection in Critically Ill Patients
Authors: Vega Ana D , Kristie Johnson J , Heil Emily , Blackman Alison L , Banoub Mary , Hopkins Teri , Leekha Surbhi , Claeys Kimberly C
Published: October 2019

Background

Molecular strain 027/NAP1/BI (NAP1) is a common cause of Clostridioides difficile infections (CDI). Despite high morbidity and mortality, optimal therapy remains elusive. There is also a paucity of data regarding optimal treatment of critically ill patients with severe CDI. We aimed to determine the impact of combination therapy (intravenous metronidazole [IV MTZ] plus oral vancomycin [PO VAN]) on clinical outcomes in critically ill patients with severe CDI, including those with NAP1 CDI.

Methods

Retrospective cohort of adult patients admitted to an intensive care unit (ICU) from April 2016 to October 2018 with a positive C. difficile PCR and an order for PO VAN. Patients with an order for IV MTZ for at least 72 hours formed the combination therapy group. A subset of patients had stool samples collected for NAP1 identification via GeneXpert C. difficile Epi molecular assay. The primary outcome was 30-day in-hospital mortality. A subgroup was matched using Acute Physiology and Chronic Health Evaluation (APACHE) II Scores. Cox regression was conducted to identify variables associated with time to mortality.

Results

138 patients were included; 60 (43.5%) received IV MTZ. Patients with IV MTZ had a higher median WBC count at diagnosis (20.9 vs 15.9, P = 0.0002) and were more likely to receive a higher dose of PO VAN (31.7% vs 12.9%, P = 0.008). 42 patients had NAP1 testing, 11 were positive (26.2%). There was no difference in probability of receiving IV MTZ based on APACHE II, however, NAP1+ were more likely to receive IV MTZ (50% vs 16.7%, P = 0.049). Clinical success was higher in the monotherapy group (46.8% vs 16.7%, P = 0.002). There was no difference in mortality (20% vs 14.1%, P = 0.368). In a subgroup of patients matched by APACHE II (n = 96), mortality remained non-significantly different (18.8% vs 14.6%, P = 0.785). Adjusted for IV MTZ, APACHE II (aHR = 1.06, 95% CI 1–1.12) and number of severity criteria (aHR = 2.08, 95% CI 1.40 – 2.97) were associated with mortality. There was no difference in mortality (9.1% vs 3.2% P = 0.459) or clinical success (18.2% vs 33.7%, P = 0.283) among NAP1+ vs. NAP- patients.

Conclusion

Our data questions the utility of IV MTZ with PO VAN for ICU patients with severe CDI, including NAP1 infections. There remains a possibility for confounding by indication in our analysis.

Disclosures

All authors: No reported disclosures.
2434. Proton Pump Inhibitor Use on Efficacy of Fecal Microbiota Transplant Administered by Trans-Oral Routes for Clostridioides Difficile Infection: A Systematic Review and Analysis
Authors: Hong Annie S , Yuan Yu Wen , Hong Jenny M , Azab Mohamed , Ohning Gordon V , Jayaraj Mahendran
Published: October 2019

Background

Current guidelines include fecal microbiota transplantation (FMT) in the management of recurrent Clostridioides difficile infections (CDI). However, FMT protocols are often facility dependent, and one variable is whether proton pump inhibitors (PPI) are given during preparation. Theoretically, PPIs reduce acidity and protects the transplanted microbiome for the most potent dose. On the other hand, PPIs have also been shown to negatively alter the microbiome and increase the risk of CDI. We conducted a systematic review of the literature to study PPI use on the efficacy of FMT delivered by the trans-oral route.

Methods

We searched PubMed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16th, 2018 using variations of keywords “fecal microbiota transplant” and “Clostridium difficile infection” with 4210 results. Two independent authors reviewed and excluded studies with unrelated topics, abstracts, case reports, or a low level of evidence. Studies with data on trans-oral FMT, PPI use, and the success rate were included. Final review yielded 11 studies including randomized controlled, case–control, cohort, retrospective and prospective trials. The primary outcome was the rate of FMT failure, defined as recurrence of symptoms with positive CDI testing at follow-up.

Results

Out of 233 included patients, 131 received a PPI per FMT protocol resulting in 27 cases of treatment failure. There were 23 cases of recurrence out of 102 patients who did not receive pre-FMT PPI. The primary outcome occurred in 20.6% in the group with PPI use vs. 22.6% in the group without (RR 0.91; CI 0.56 - 1.50). Limitations include the lack of studies directly comparing outcomes with respect to PPI use, and inability to control possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.

Conclusion

We did not find a significant difference in efficacy between FMT protocols with regard to PPI use. It is possible that the theoretical benefit from increased survival of transplanted microbiota is offset by negative effects associated with PPIs. We suggest that routine use of PPIs in FMT be reconsidered in the absence of clear benefit. Further investigation is needed to optimize protocols for safety and efficacy.

Disclosures

All authors: No reported disclosures.
2435. The Impact of Treatment Strategy and Toxin Status on Outcomes of Patients with Clostridioides difficile Infections
Authors: Friedman Daniel , Zurek Karen , Asadi Leyla , Lee Mao-Cheng , Hoang Holly
Published: October 2019

Background

Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality and management continues to evolve. For laboratories that diagnose by detection of toxin gene, it is unclear whether reporting toxin production is additive to patient care. Furthermore, is there still a role for metronidazole (MNZ) given treatment guidelines now recommend vancomycin (VAN) as first-line therapy for non-severe cases? We analyzed cases of CDI in our hospital to assess outcomes of patients on MNZ vs. VAN and with or without toxin production.

Methods

A retrospective chart review of inpatients with CDI (based on detection of C. difficile toxin gene by PCR) was conducted between November 2017 and August 2018. Comparison of demographics and outcomes was performed in a) cases that were toxin-positive by enzyme immunoassay vs. negative and b) non-severe cases initially managed with MNZ vs. VAN.

Results

76 patients were included (46 toxin-positive, 30 toxin-negative). Toxin-positive patients were older (mean age 77 vs. 62, p = 0.002) but had similar disease severity and initial treatment. A CDI recurrence occurred in 22% vs 0% in the toxin-positive cases (p = 0.006). Any CDI-related complication occurred in 23% of toxin-negative and 35% of toxin-positive cases (ns). After adjusting for toxin-status, age, and severity, the odds ratio of the composite outcome of any complication with toxin-positive CDI was not significant (OR 1.45 95% CI 0.45 -4.6, p = 0.52).

There were 37 (49%) patients with non-severe CDI (27 MNZ, 10 VAN). Patients treated with VAN had higher stooling/day (6.3 vs 4.4, p = 0.04) and heart rate (p = 0.02). Initial MNZ use was associated with treatment escalation in 48% of cases compared with 10% in those treated with VAN alone (p = 0.03). CDI-associated mortality was higher in the VAN group (2/10 vs 0/27, p = 0.017). The rate of other complications was not significantly different.

Conclusion

Although no difference in the composite outcome of any CDI-related complication was detected between toxin positive vs negative patients, toxin-positivity may predict patients at risk for subsequent recurrence. Patients with non-severe CDI did not have increased risk of complications when managed with MNZ; however, they were more likely to require treatment escalation.

Disclosures

All authors: No reported disclosures.