bluuebunny/crossref_metadata_2025 huggingface dataset:
2355. The Association Between Diagnostic Testing Method and Clostridium difficile Infection Severity
Authors: Menon Anitha , Perry Donald A , Motyka Jonathan , Weiner Shayna , Standke Alexandra , Penkevich Aline , Keidan Micah , Young Vincent B , Rao Krishna
Published: October 2019

Background

The optimal diagnostic strategy for Clostridium difficile infection (CDI) is not known, and no test is shown to clearly differentiate colonization from symptomatic infection. We hypothesized that detection and/or quantification of stool toxins would associate with severe disease and adverse outcomes.

Methods

We conducted a retrospective cohort study among subjects with CDI diagnosed in 2016 at the University of Michigan. The clinical microbiology laboratory tested for glutamate dehydrogenase antigen and toxins A/B by enzyme immunoassay (EIA). Discordant results reflexed to PCR for the tcdB gene. Stool toxin levels were quantified via a modified cell cytotoxicity assay (CCA). C. difficile was isolated by anaerobic culture and ribotyped. Severe CDI was defined by the IDSA criteria: white blood cell count >15,000 cells/µL or a 1.5-fold increase in serum creatinine above baseline. The primary outcomes were all-cause 30-day mortality and a composite of colectomy, ICU admission, and/or death attributable to CDI within 30 days. Analysis included standard bivariable tests and adjusted models via logistic regression.

Results

From 565 adult patients, we obtained 646 samples; 199 (30.8%) contained toxins by EIA. Toxin positivity associated with IDSA severity (Table 1), but not our primary outcomes on unadjusted analysis. After adjustment for putative confounders, we still did not observe an association between toxin positivity and our primary outcomes. Stool toxin levels by CCA >6.4 ng/mL associated with IDSA severity (Table 1), but not the primary outcomes. Compared with the period from 2010 to 2013, the circulating ribotypes of C. difficile at our institution changed in 2016. Notably ribotype 106 newly emerged, accounting for 10.6% of strains, and ribotype 027 fell to 9.3% (Table 2). The incidence of ribotype 014-027 has remained stable at 18.9%, but this strain was associated with both IDSA severity and 30-day mortality (OR = 3.32; P = 0.001).

Conclusion

Toxin detection by EIA/CCA associated with IDSA severity, but this study was unable to confirm an association with subsequent adverse outcomes. The molecular epidemiology of C. difficile has shifted, and this may have implications for the optimal diagnostic strategy for CDI.

Disclosures

All authors: No reported disclosures.
2365. Volatile Metabolite-Based Detection of Clostridium difficile Infection (CDI)
Authors: Aloum Obadah , Thalavitiya Acharige Mahesh J , Ismail Nour , Hejazi Mohamad , Al Kateb Mohamad , Zhao Yibai , Balasubramanian Raji , Koo Sophia
Published: October 2019

Background

CDI is a frequent cause of morbidity and mortality in hospitalized patients. Despite advances in rapid CDI testing, there are often delays between the onset of symptoms and receipt of test results. We sought to test the hypothesis that the altered CDI intestinal microbiome has a unique volatile metabolite profile, distinct from the profile of patients with other causes of antibiotic-associated diarrhea, which potentially can be used to identify patients with CDI.

Methods

We prospectively collected fresh stool samples from inpatients with suspected CDI at an academic tertiary care hospital from July 2015 to November 2017, adsorbed volatile metabolites from each sample onto sorbent tubes within an hour of sample collection, and used thermal desorption-gas chromatography/tandem mass spectrometry to identify each metabolite. All patients were exposed to at least one antibiotic agent in the prior 90 days, and only patients receiving empiric CDI treatment or with formed stool samples were excluded. We used logistic regression models, adjusting for prior anti-anaerobic antibiotic therapy and CDI severity (serum albumin <3 g/dL and WBC ≥ 15,000/mm3 or abdominal tenderness) and adjusting for multiple testing using Storey’s q-value procedure (with a threshold of q ≤ 0.05), to examine the relationship between CDI, as determined by the reference standard of the cell culture cytotoxicity neutralization assay, and each metabolite.

Results

In our 565-patient cohort, median age was 61 years (IQR 50, 70) and 277 (49%) were male; 173 (31%) had abdominal pain in the 24 hours before testing, 59 (10%) had fevers in the prior 24 hours, 22 (4%) had an ileus, 74 (13%) had mental status changes in the prior 24 hours, 89 (16%) were hospitalized in the ICU at the time of testing, 45 (7%) were receiving pressors, 82 (15%) had a WBC ≥ 15,000/mm3, and 137 (24%) had a serum lactate > 1.5 mmol/L. Ultimately, 155 patients were diagnosed with CDI. Ten metabolites (Table 1, Figure 1) were differentially distributed in patients with and without CDI.

Conclusion

We identified a suite of volatile metabolites that differentiates stool from patients with and without CDI; this profile may ultimately be used to identify patients with CDI.

Disclosures

All authors: No reported disclosures.
2368. Molecular Epidemiology of Clostridioides difficile Infections in Pediatric Oncology and Transplant Patients
Authors: Barbar Ruba , Hakim Hana , Hayden Randall , Hayden Randall , Garner Cherilyn D , Brazelton de Cardenas Jessica B , Carroll Karen C , Bourdas Dimitrios , Carroll Shawna Kimberly
Published: October 2019

Background

The incidence of Clostridioides difficile infection (CDI) has been rising among children, both in the community and hospital setting. The genomic variability and molecular epidemiology of CDI in children, especially with cancer are poorly understood. We aim to evaluate the molecular epidemiology and relatedness of C. difficile isolates among inpatient and outpatient pediatric oncology and stem cell transplant patients (POTP) using whole-genome sequencing (WGS).

Methods

This was a retrospective cohort study of CDI in POTP in 2016. CDI cases were identified by electronic medical record search for positive C. difficile toxin PCR tests. Retrieved residual stool specimens were cultured anaerobically using pre-reduced CCMB-TAL broth (Anaerobe Systems, Inc.), toxin-producing C. difficile isolates were determined using a cell culture cytotoxicity assay with neutralization (TechLab, Inc.), and WGS was performed, followed by core genome MLST (cgMLST). Variability of the isolates was summarized by strain type (ST), and a minimum spanning tree was constructed, defining clusters of genomically related isolates as those with < 7 alleles difference. Plausible epidemiologic links among the closely related strains such as receiving care on the same inpatient unit on the same day or on the same unit but on different days within 8 weeks before CDI were evaluated to identify potential transmission events.

Results

Among 141 CDI episodes in 89 patients; 103 stool samples were cultured, and 101 (98%) isolates were sequenced identifying 23 different strain types in 81 (80%) isolates. 34 (38%) patients had multiple episodes of CDI. 16 clusters of related isolates were identified (figure), 10 (62%) of which involved only multiple specimens from the same patient. For the 6 clusters involving multiple patients, epidemiologic investigation revealed only 2 (33%) potential transmission events.

Conclusion

WGS identified a highly diverse group of C. difficile isolates among POTP with CDI. Although WGS identified clusters of closely related isolates in multiple patients, epidemiologic investigation of shared inpatient exposures identified potential transmission in only two clusters. C. difficile transmission was uncommon.

Disclosures

Randall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board.
2370. Risk Factors for Clostridioides difficile Colonization Among Adult Inpatients: A Meta-Analysis
Authors: Brown Adam M , Anjewierden Scott , Deshpande Abhishek
Published: October 2019

Background

Clostridioides difficile is one of the most common causes of healthcare-associated infections in the United States. The prevalence of asymptomatic C. difficile colonization has been demonstrated to range from 3 to 21% for hospitalized adults. Patients colonized with C. difficile may serve as potential reservoirs for transmission of C. difficile infection (CDI) within inpatient units. The purpose of this meta-analysis was to identify the risk factors for colonization at hospital admission among adult patients, to inform strategies for infection prevention.

Methods

We searched MEDLINE, Scopus, Web of Science, and Embase from inception to 2019 for articles related to C. difficile colonization on hospital admission. Studies with multivariate analyses evaluating risk factors for asymptomatic colonization in adult inpatients were eligible. Odds ratios were pooled using a random effects model. Study quality and publication bias analyses were also conducted.

Results

Among 2,982 studies identified in the search, 21 studies met the inclusion criteria. Included studies reported 18,468 adult patients of which 1,243 were asymptomatically colonized with C.difficile. Factors associated with an increased risk of colonization were CDI in the last 3 months (OR 4.18, 95% CI 2.56–6.82, I2 = 0%), hospitalization in the last 6 months (OR 2.45, 95% CI 2.06–2.92, I2 = 0%) and use of gastric acid suppression therapy within the last 8 weeks (OR 1.46, 95% CI 1.17–1.73, I2 = 1%). Receipt of antibiotics in the last 3 months (OR 1.37, 95% CI 0.94–2.01, I2 = 48%) and use of non-steroidal anti-inflammatory drugs (OR 0.90, 95% CI 0.52–1.55, I2 = 65%) were not associated with statistically significant effects on risk of colonization. There were insufficient studies to determine the association between most antibiotic classes and the risk of colonization.

Conclusion

C.difficile colonization on hospital admission was significantly associated with previous CDI, recent hospitalization, and gastric acid suppression therapy. Recognition of these risk factors may assist in identifying potential carriers of C. difficile. These findings also emphasize the importance of judicious use of gastric acid suppression and other preventative measures in reducing C. difficile acquisition.

Disclosures

All authors: No reported disclosures.
2375. Association Between Clostridium difficile Colonization and Inflammatory Bowel Disease Activity
Authors: Morado-Aramburo Oscar , Ochoa-Hein Eric , Bobadilla-Del-Valle Miriam , Yamamoto-Furusho Jesus K , Ponce de Leon Alfredo , Sifuentes-Osornio Jose
Published: October 2019

Background

Clostridium difficile (CD) is a frequent cause of nosocomial infectious diarrhea. Despite no clear evidence has linked CD colonization (CDC) or CD infection (CDI) with inflammatory bowel disease activity (IBDA), data in our setting has suggested the contrary.

Methods

Prospective cohort study in a tertiary care hospital in Mexico City. Patients aged ≥18 years with IBD in clinical remission were included between April 2017 and April 2019. Demographic, clinical and laboratory variables, as well as three fecal samples, were collected at inclusion and during follow-up. CDC was defined as a positive GDH test without diarrhea. CDI was defined as diarrhea (as per IDSA criteria) plus positive GDH and PCR tests. IBDA was defined as bloody diarrhea plus a negative GDH test. The primary outcome was the association between CDC and IBDA. Secondary outcomes were incidence rates of CDC and CDI, including risk factors associated with CDC. Univariate and multivariable analyses were performed considering P < 0.05 as statistically significant.

Results

Out of 250 IBD patients, 101 cases met inclusion criteria and 85 completed follow-up (median = 420 days, IQR = 243–511 days). Twenty-three cases (27%) had IBDA during follow-up, eight cases had new CDC (incidence of 8.2/100 person-years), and one case developed CDI (incidence of 1.0/100 person-years). Figure 1 shows the cumulative percentage of cases without CDC during follow-up. In univariate analysis, the following were associated with CDC: decreasing age, decreasing age when IBD was diagnosed, residence in Mexico City or the State of Mexico, and hospitalization during follow-up. In Cox regression analysis, a decreasing age when IBD was diagnosed (HR = 0.92, CI95% = 0.87–0.98, p = 0.009) and residence in the State of Mexico (HR = 5.88, CI 95% = 1.21–28.60, p = 0.028) remained significantly associated with CDC. However, we did not find a statistically significant association between new CDC events and IBDA during a median follow-up period extending beyond 1 year.

Conclusion

We found no association between CDC and IBDA. Risk factors associated with CDC were residence in the State of Mexico and a decreasing age when IBD was diagnosed.

Disclosures

All authors: No reported disclosures.
2380. Fecal Collinsella Abundance is Negatively Associated with Toxin A/B Production in Cancer Patients with Clostridioides difficile
Authors: A. Francisco Denise Marie , Olvera Adilene , Zhang Liangliang , Yepez Guevara Eduardo , Garey Kevin W , Peterson Christine , Do Kim-Anh , Dillon Ryan J , Jenq Robert , Okhuysen Pablo C
Published: October 2019

Background

The detection of C. difficile (CDI) by nucleic acid amplification test (NAAT) with negative toxin enzyme immunoassay (EIA-) is difficult to interpret in cancer patients. Markers that differentiate true infection from colonization, and are associated with clinical outcomes are needed. We hypothesized that the microbiome composition and inflammatory fecal markers in EIA- patients differed from those who are EIA+ and were associated with disease severity and recurrence.

Methods

We studied the fecal microbiome composition (16s rRNA, V3) of 147 cancer patients with CDI diagnosed by a two-step testing algorithm. Clinical data, CDI bacterial quantity (BQ) by qPCR and markers of intestinal inflammation (calprotectin, lactoferrin, IL-1β and IL-8) were analyzed. Data were stratified according to cancer type [hematologic (H) n = 49, solid tumor (ST) n = 66, or stem cell transplant (SCT) n = 32].

Results

Demographic characteristics and symptoms were similar between the three groups. At baseline, species diversity by Shannon index was similar in all three groups regardless of EIA detection and did not correlate with clinical presentation, response to therapy or recurrence. Microbiome composition did not correlate with inflammatory response except in H in whom a higher diversity correlated with increased IL-8 (P = 0.021) and calprotectin (P = 0.01) levels. At the genus level across all strata and when compared with EIA- cases, EIA+ cases presented with a higher abundance of Peptoclostridium (P = 0.0008) which correlated with CDI BQ qPCR (log of BQ/mg 2.38 ± 1.49 vs 0.92 ± 1.28, P < 0.001). In contrast, EIA- cases had a higher abundance of Collinsella (P = 0.001). SCT patients carried fewer Peptoclostridium when compared with other groups, whereas all three patient groups carried similar amounts of Collinsella. The relative abundance of Peptoclostridium and Collinsella was not associated with response to therapy, or fecal markers of inflammation. Principal component analysis did not demonstrate differences between the three groups studied.

Conclusion

In this study, the presence of Collinsella, a known butyrate and bile salt hydrolase producer, was associated with the lack of CDI toxin A/B production. Loss of Collinsella may represent a novel risk factor for active CDI.

Disclosures

All authors: No reported disclosures.
2381. Epidemiology of Clostridium difficile Infection in Patients Receiving Interleukin-2 Therapy
Authors: Li Aldon , Nguyen Nga
Published: October 2019

Background

Clostridium difficile infection (CDI) has been associated with interleukin-2 (IL2) therapy, possibly leading to unnecessary testing and treatment of colonized patients receiving IL2 therapy. Since the debut of IL2 therapy for renal cell carcinoma (RCC) and metastatic melanoma (MM), only one study with 6 patients has shown a relationship between CDI and IL2 treatment, and no mortality data were reported. Because of the rising concern for appropriate testing and treatment of CDI, further studies looking at the correlation between IL2 therapy and CDI are needed. This study aims to describe CDI rates among a larger cohort of IL2 treated patients and to include mortality data.

Methods

Retrospective case series. A case of CDI was defined as (1) Bowel movements >3 or stool output >600 mL WITH, (2) positive laboratory test, either through toxin detection via ELISA prior to 2010 or molecular testing via PCR after 2010.

Results

During the study period from 2008 to 2015, 359 patients with RCC or MM receiving IL2 treatment were evaluated with a total of 294 patients undergoing Clostridium difficile testing (CDT). Median age was 52 (range 24–69), 33% female. An average IL2 dose of 27 million international units (MIU) was given in this population. 15% (45/294) had a positive CDT, but 7% (21/294) were found to have CDI. All patients with CDI had antibiotic exposure within the last 30 days of diagnosis. Of the patients who developed CDI, 24% (5/21) had a previous CDI episode within the last 90 days. None of the patients developed megacolon. Developing CDI lead to an all-cause mortality of 24% (5/21).

Conclusion

The results of this study show a lower CDI rate (7%, 21/294) than previously reported in IL2-treated patients (66%, 4/6), but this difference is likely due to the difference in population size. In addition to CDI rate, this study adds information about mortality in IL2-treated patients with CDI, which was not previously described in the literature. Applying a clinical criterion to laboratory testing results revealed a difference in laboratory testing positivity and actual infection rates, suggesting 8% of this population maybe colonized with Clostridium difficile, providing further evidence for Antibiotic Stewardship Committees to put in place local guidelines to avoid indiscriminate CDT in this population.

Disclosures

All authors: No reported disclosures.
2384. The Relationship Between Rifaxamin Use and the Prevalence of Clostridiodes difficile and Vancomycin-Resistant Enterococcus in Patients with Advanced Liver Disease
Authors: Alberto. De Jesus Francisco , Kuper Kristi , Haider Alyzeh , Sackey Joachim , Finkel Diana
Published: October 2019

Background

Rifaximin (RFX) is a minimally absorbed antibiotic that achieves high concentrations after administration in the gut lumen. Previously, RFX showed activity against Clostridiodes difficile (C. difficile) recurrences post treatment with little overall impact on the normal fecal microbiota. Additional studies have found that while exposure to systemic antibiotics was associated with infection with multi drug-resistant organisms, such as VRE, exposure to only RFX was not. RFX has become widely used in hospitalized patients with advanced liver disease (ALD) who have refractory hepatic encephalopathy, but the impact of therapy on the occurrence of C. difficile and VRE is not well established.

Methods

ALD patients in the Vizient Clinical Database-Resource Manager (CDB-RM®) were identified based on ICD 10 and MS-DRG codes from January to December 2018. The data were further stratified based on receipt of RFX, documentation of C. difficile or VRE, and hospital type (academic medical centers, complex care medical centers or community hospitals). Wilcoxon signed-rank test was used to compare C. difficile rates while paired samples t-test was used to compare VRE. Chi-square analysis was used to evaluate differences in RFX use by hospital type.

Results

A total of 527,534 cases from 419 acute care hospitals were included in the ALD cohort. The frequency of C. difficile occurrence in patients who received RFX was lower than those who did not receive RFX (3.8% vs 4.3%, respectively, P = 0.25), However, VRE frequency was significantly lower in those that received RFX (0.43 cases per 10,000 patient-days) vs. the overall ALD population (2.3 cases per 10,000 patient-days) (P < 0.05). Percentage of ALD cases receiving RFX in the academic medical centers, complex care medical centers and community hospitals was 11.94%, 4.87%, and 8.76%, respectively (P < 0.05).

Conclusion

Patients with ALD who received RFX had a significantly lower frequency of documented VRE. There was a trend in the reduction in documented C. difficile, but this did not reach statistical significance. Utilization of RFX varied significantly by institutional type. These results support further studies on the relationship between receipt of RFX and protective effects against C. difficile and VRE in patients with ALD.

Disclosures

All authors: No reported disclosures.
2386. Mortality reduction with implementation of a standardized approach of surveillance, diagnosis and treatment of Clostridioides difficile infections.
Authors: Molina Aaron , Olmedo-Reneaum Alejandro , Garfias Yanelly , Carmona Paulette A , Constantino Andrea , Piñera Mariana
Published: October 2019

Background

Clostridioides difficile (C. difficile) infection is the main cause of nosocomial diarrhea in the world. In our hospital, there was no standardized protocol for diagnosis and treatment of this infection. The aim of this study was to measure the impact of implementing a multimodal strategy of active surveillance, diagnosis and treatment in the clinical outcome of patients with C. difficile infection.

Methods

Observational, retrospective, and analytical study that compared a multimodal strategy for the treatment of C. difficile infection against a traditional strategy, which consisted of treatment with either metronidazole or vancomycin with variable duration of therapy depending on the physician’s choice. The multimodal strategy consisted of active surveillance of cases of nosocomial diarrhea, timely diagnosis (<12 hours), and standard treatment with oral vancomycin for a minimum of 10 days (125 mg po qid in mild and moderate illness, and 250 mg qid in severe disease). Patients with a confirmed diagnosis of C. difficile infection (PCR- Gene Xpert Cepheid) and inflammatory diarrhea were included. The study was carried out in a third-level hospital, in the period between September 2017 and December 2018.

Results

In 15 month study period, 92 cases of C. difficile infection were documented. All cases were caused by strain NAP1 / B1 / 027. Twenty-three patients (25%) had mild disease, 28 (30.4%) moderate illness and 41 (44.56%) complicated illness. Thirty-four patients were evaluated with multimodal strategy and 58 according to the traditional treatment. Only 24 patients (41%) in the traditional treatment group received treatment with oral vancomycin. The clinical outcomes of patients in the multimodal strategy against patients with the tradional strategy were: clinical cure 85.3% vs 37.9% (P = 0.02), recurrence 2.9% vs 17.2% (p = < 0.05) and death 11.8% vs 44.8%(p = < 0.05), respectively.

Conclusion

Unfortunately, in our country, there are no guidelines for the management of C. difficile infection, and in many hospitals, metronidazole is the most prescribed treatment. In this study, we documented that implementing a standardized strategy of surveillance, diagnosis and adequate treatment, reduced mortality related to C. difficile infection, recurrence, and achieved greater clinical cure.

Disclosures

All authors: No reported disclosures.
2387. Learning the Influence of Individual Clostridioides difficile Infections
Authors: Mu Emily , Makar Maggie , West Lauren R , Guttag John , Rosenberg David C , Shenoy Erica S
Published: October 2019

Background

Healthcare-associated Clostridioides difficile infection (C diff infection, or CDI) imposes a substantial burden on the healthcare system. The impact of an individual C diff infection on onward transmission is not well understood. We developed a model of incident infections using self-exciting stochastic processes, known as Hawkes processes. These models can be used to improve our understanding of the factors that affect the likelihood of new infections to result in additional infections.

Methods

All patients admitted to a large urban hospital between January 2013 and June 2014 were included. We used Hawkes processes to model the influence of each new CDI case (index infection) on transmission to other patients resulting in additional CDI. We developed separate Hawkes processes for each unit in the hospital to understand the differential impact of a C diff case across units. Units included both semi- and private-room wards, intensive care units, an emergency department, and specialty units such as oncology.

Results

The magnitude of influence of an index infection on additional infections in the 2 days prior to a C diff test being sent varied across units. Results for an oncology unit, the emergency department, and an all private-room unit are provided (Table 1). An index infection in the emergency department demonstrated the greatest influence, leading to the largest number of additional infections, and increasing in the days leading up to the C diff test being sent. The impact 2 days prior to sample collection was similar across all unit types, and remained constant for oncology unit patients.

Conclusion

We used Hawkes processes to model the impact of an index C diff infection on onward transmission. We identified differential impacts associated with the unit where the index patient was located in the days leading up to diagnosis. These differences, which could relate to unit-specific factors such as cleaning practices, patient turnover rates, use of portable medical equipment, antibiotic use, and other factors that vary across units, suggest that interventions aimed at controlling CDI may need to consider unit-specific approaches.

Disclosures

All authors: No reported disclosures.
2392. Identifying Associations Between Clostridium difficile Infection Incidence and Cancer Patients Receiving Chemotherapy
Authors: Louie Mendiola Vincent , Kesireddy Meghana , Suthar Krishna , Willis Maurice
Published: October 2019

Background

Clostridium difficile infection (CDI) is a known major financial burden. In the cancer population, CDI, was identified to have a peak incidence of 17.2 per 1000 patients with increased morbidity, mortality and hospital length of stay. The need to further elucidate chemotherapy (CTX) with vs. without ABX usage as risk factors among other variables in cancer patients arises since this population is already baseline immunocompromised.

Methods

A retrospective case–control study (total of 1989 cancer patients who received CTX and had diarrhea at UTMB through 1/2016–1/2018) was completed. Subjects were screened using extensive inclusion and exclusion criteria, and assigned as CASES (with symptomatic (s) diarrhea from proven CDI) and as CONTROLS (had diarrhea but not attributed to CDI). A 1:1 subject matching using age, sex and past medical histories was completed and a total of 46 patients: 23 cases and 23 controls were compared and analyzed. McNemar’s and independent t test of equal variance were used for association and comparing means/medians, respectively. Two-sided P value ≤ 0.05 was considered significant.

Results

The use of ABX (OR = 16, P = 0.0007) and having any degree of neutropenia at the time of diarrhea (OR = 12, P = 0.0055) among CTX patients had significant associations with having sCDI. Although no significant association between sCDI and # of days post CTX exposure (≥7 days (P = 0.1138) and ≥14 days post CTX (P = 0.1489) was identified, a mean of 12.83 ± 7.69 days passed before sCDI diagnosis in cases, compared with diarrhea diagnosis (7.46 ± 6.1 days) in controls (P = 0.0119). Meanwhile, receiving >1 CTX cycle (P = 1.000) and particular CTX types (P = ~ 0.0771–1.000) had no significant associations with sCDI diagnosis.

Conclusion

Any ABX usage post CTX exposure heavily predisposes to sCDI among cancer patients likely due to elimination of gut flora on an already predisposed population. Having any degree of neutropenia was also associated with having sCDI likely due to significant immunosuppression on top of being baseline cancer patients receiving CTX, and may have predictability benefits. The other variables may have not been significant due to expected limited cases because of low CDI incidence.

Disclosures

All authors: No reported disclosures.
2394. A Longitudinal Study of the Effect of Renal Failure on Readmission Rates of Patients with Clostridioides difficile
Authors: Destache Christopher J , Detweiler Brian , Vivekanandan Renuga
Published: October 2019

Background

Clostridioides difficile Infection (CDI) is a highly contagious bacterium that can be transferred from an infected surface. In this study, the Nationwide Readmissions Database was used to assess the risk of 30-, 60-, and 90-day readmissions in patients with comorbid CDI and renal failure (RF).

Methods

Using the Nationwide Inpatient Sample (NIS, 35 million hospitalizations/year) and the Nationwide Readmissions Database (NRD, 36 million/year), CDI in renal insufficient patients were identified. Years 2001–2014 of the NIS, as well as years 2010–2014 of the NRD were used for analysis. Chronic kidney disease (CKD) was based on the stage of the disease using IDC-9-CM coding (585.1–585.5). ICD-9-CM 585.6 was used for end-stage renal disease (ESRD). All analyses were done in R version 3.4.3.

Results

Over the 14 year period, the proportion of inpatients with CDI and RF increased from 0.004% (95% CI, 0.0038%-0.0042%) to 0.010% (95% CI, 0.0100%-0.0104%) in 2014. Inpatient RF and CDI increased a mean of 220,827 people over the 14 years. Inpatient CDI and RF prevalence is described as linearly increasing trend (Figure 1). Median age (2001–2014) for RF patients with CDI decreased 5 years to 68 (95% CI, 68–69). Using this model, expected CDI infections in RF to increase to 437,605.1 (95% CI, 427,984.2–447,380.8) hospital inpatients in 2018. In patients with CDI and CKD, ESRD is a significant predictor of 30-, 60-, and 90-day readmission.

Conclusion

Using the NIS and NRD identified ESRD patients as a significant predictor of readmission for 30-, 60-, and 90-days. CDI infections in ESRD are expected to increase substantially by 2018.

Disclosures

All authors: No reported disclosures.
2397. Effects of antimicrobial surgical prophylaxis on rates of Clostridioides difficile infection
Authors: Hayes Sarah K , Cooper Mandelin , Goldin Laurel , Fraker Sarah , Greer Nickie
Published: October 2019

Background

Studies have demonstrated short courses of antibiotics, including surgical site infection (SSI) prophylaxis, can increase the risk of Clostridioides difficile infection (CDI). The purpose of this study was to evaluate the incidence of CDI associated with antibacterial perioperative prophylaxis.

Methods

In a retrospective analysis of affiliated hospitals from a large healthcare system, aggregate data from 156 acute care facilities across the United States was analyzed for the time period of July 2017 through July 2018. Patients were included if they were 18 years and older, admitted to an inpatient unit, and underwent a surgical procedure requiring antibiotic prophylaxis. Patients were excluded if they received antibiotics more than 24 hours prior to procedure start, received antibiotics more than 72 hours after procedure stop, or had more than one procedure with antibiotic prophylaxis within 30 days. Patients were divided into three groups based on the duration of antibiotic prophylaxis received: preoperative only (Pre-op only), pre-op plus postoperative for 24 hours or less (Short Post-op), and pre-op plus post-op for 25 to 72 hours (Long Post-op). The primary outcome was the incidence of CDI within 30 days of surgical procedure. Study design was approved by the University of Tennessee Institutional Review Board.

Results

The final analysis included 230,524 patients: 68,307 Pre-op Only, 123,185 Short Post-op, and 39,032 Long Post-op. Overall, 195 cases of CDI were identified during the study period, for a rate of 0.8 cases per 1000 procedures. The highest incidence occurred in the Long Post-op group (1.3 cases per 1000 procedures). A pairwise comparison demonstrated the incidence of CDI is statistically higher in the Long Post-op group compared with both the Pre-op Only (P = 0.005) and the Short Post-op (P = 0.003) groups. There was no significant difference between the Pre-op Only and the Short Post-op groups<./p>

Conclusion

Patients who received antibiotics for more than 24 hours post-op had a higher incidence of CDI. No statistically significant difference in CDI between pre-op only and less than 24 hours post-op was found.

Disclosures

All authors: No reported disclosures.
2401. Epidemiology of Clostridium difficile Infection in Intestinal and Multivisceral Transplant Patients at a Single Transplant Center
Authors: Modi Anita R , Gonzalez Blanca E , Brizendine Kyle D
Published: October 2019

Background

Clostridium difficile infection (CDI) is the leading cause of infectious diarrhea in the healthcare setting. Solid-organ transplant (SOT) recipients are at increased risk compared with the general hospitalized population (7.4–20% vs. 0.9%). Our center recently expanded its intestinal and multivisceral transplant (IMVT) program, providing the opportunity to examine the epidemiology of CDI in this vulnerable population.

Methods

We conducted a retrospective study of all IMVT recipients between 2009 and 2018. CDI was defined as presence of diarrhea with a positive polymerase chain reaction (PCR) test for the toxin B gene. Early CDI constituted an episode of CDI within the first 6 months post-transplant. Data were collected on demographics, transplant characteristics, CDI episode, and outcomes.

Results

We identified 86 patients who underwent a total of 94 transplants: 60 (64%) isolated intestinal transplants, 21 (22%) intestine/liver/pancreas, 10 (11%) intestine/pancreas, two (2%) intestine/liver/pancreas/kidney, and one (1%) intestine/kidney transplant. All but three patients received perioperative metronidazole. Four patients (5%) had CDI prior to transplant, but none of them recurred in the first 6 months post-transplant. Five patients developed a total of seven mild-moderate episodes of early CDI (attack rate = 5.9%). Three patients (60%) with early CDI developed rejection, similar to the incidence (70%) in patients without CDI. Two patients with early CDI developed recurrence; both underwent intestinal re-transplantation. One-year mortality was similar among patients with and without early CDI (20% vs. 23%).

Conclusion

CDI is associated with allograft loss, rejection, and mortality in some SOT recipients. Although limited by sample size, we observed that early CDI was not associated with those outcomes in our population. Multicenter studies are merited to explore risk factors for CDI and associations with outcomes in IMVT.

Disclosures

All authors: No reported disclosures.
2402. Clinical Outcomes Associated with an Emerging Clostridioides difficile Ribotype 255 in Texas
Authors: Gonzales-Luna Anne J , Carlson Travis J , Lancaster Chris , Miranda Julie M , Garey Kevin W
Published: October 2019

Background

PCR ribotyping of Clostridioides difficile strains is commonly used to describe the epidemiology of C. difficile infection (CDI). Certain ribotypes (RT) have been associated with more severe disease and clinical outcomes, such as RT 027, while others are considered less virulent, such as RT 014-020. Texas statewide surveillance identified the emergence of a rarely-described RT 255 beginning in 2015, which now represents the fifth most common ribotype across the state. Here we describe clinical outcomes associated with an emergent RT 255 in Texas.

Methods

A retrospective cohort study was conducted including patients from two tertiary care centers in Houston, Texas. Patients infected with C. difficile strains of either RT 255, 014-020, or 027 between 2016–18 were included. The primary outcome was disease severity as classified by the 2017 IDSA guidelines. Multivariable logistic regression analysis was done to control for other patient factors. Results were significant at P < 0.05, and all statistical analyses were completed using SPSS, version 25.

Results

A total of 150 patients were included (50 patients infected with each RT). Overall, 53% of the patients had severe or fulminant disease most commonly due to RT 027 (80%) followed by RT 014-020 (40%) and RT 255 (38%). Patients infected with RT 255 or 014-020 had a 75% relative reduction in the odds of severe disease compared with RT 027 after controlling for patient age and serum albumin level (OR, 0.25; 95% CI, 0.86–0.74; P = 0.12;). No differences were seen in the rates of 30- or 90-day recurrence between RTs.

Conclusion

Although RT 255 is becoming increasingly common across Texas, it does not appear to be associated with more severe disease when compared with other common ribotypes. Further studies are warranted to determine contributing factors for its increasing prevalence.

Disclosures

All authors: No reported disclosures.
2420. Reduced hospital-onset Clostridium difficile infection incidence following Saccharomyces boulardii co-administration with broad-spectrum antibiotics during hospitalization.
Authors: Wombwell Eric , Patterson Mark E , Bransteitter Bridget , Gillen Lisa
Published: October 2019

Background

Conflicting evidence in smaller randomized trials and meta-analyses regarding the protective effects of probiotics against Clostridium difficile infection underscore the need for further study. Our objective was to evaluate the effect of a single probiotic strain, Saccharomyces boulardii, at a standardized dose on hospital-onset C. difficile (HO-CDI) rates within hospitalizations administered broad-spectrum antibiotics.

Methods

Retrospective cohort study merging hospital prescribing data with C. difficile case data from the National Health Safety Network at a 220-bed level-2 trauma center nonacademic hospital. A convenience sample of 8,763 hospital admissions administrated at least one dose of a fluoroquinolone, clindamycin, or β-lactam class antibiotic during hospitalization was assessed. Hospitalizations were categorized by whether antibiotics were administered alone (control) or in conjunction with S. boulardii 20 billion colony-forming units daily (intervention). Associations between S. boulardii administration and HO-CDI incidence was evaluated by multivariate logistic regression. A sub-group analysis evaluated the extent to which administering S. boulardii within or after 24-hours of antibiotic start changed the effect. Propensity scores incorporated to account for selection bias.

Results

Hospitalizations where S. boulardii was co-administered with antibiotics had a reduced likelihood of HO-CDI (OR = 0.56, 95% CI 0.32 – 0.93) compared with control hospitalizations. S. boulardii administered within 24-hours of antibiotic start had a reduced likelihood of HO-CDI (OR = 0.40, 95% CI 0.21 – 0.75). No effect observed if S. boulardii administered after 24-hours (OR = 0.86, 95% CI 0.45 – 1.64). Post-hoc analysis for disease latency, the average number of days to HO-CDI onset was 5.6, 6.4, and 8.0 days for antibiotic only, S. boulardii after 24-hours, and S. boulardii within 24-hours of antibiotic, respectively (P < 0.04).

Conclusion

Co-administering S. boulardii with broad-spectrum antibiotics is associated with a reduced risk of C. difficile in hospitalized patients, especially if started within 24-hours of antibiotic initiation. S. boulardii should be considered as preventative intervention to reduce the risk of HO-CDI.

Disclosures

All authors: No reported disclosures.
2424. Shedding of Viable Clostridiodes difficile in Patients Admitted to a Medical Intensive Care Unit
Authors: Young Vincent B , Keidan Micah , Yelin Rachel D , Dangana Thelma E , Bell Pamela B , Rao Krishna , Hayden Mary K
Published: October 2019

Background

Hospitalized patients are at risk of colonization with a range of healthcare-associated bacterial pathogens, including C. difficile. In patients admitted to intensive care units (ICUs), in whom C. difficile infection (CDI) is associated with increased morbidity and mortality. To understand the risk for acquisition of C. difficile and development of CDI, we monitored ICU patients daily for shedding of C. difficile by culture.

Methods

We conducted a secondary analysis of daily rectal/fecal swab samples collected from medical ICU patients of a 720-bed academic medical center in Chicago, IL. Selective culture for C. difficile was performed on swab samples from patients who had 2 or more samples obtained using selective media. Confirmation of putative C. difficile isolates was done by specific PCR assays for the 16S rRNA-encoding gene and the toxin genes tcdA, tcdB, cdtA and cdtB. Clinical testing for CDI was performed using the Xpert® C. difficile PCR assay (Cepheid). Clinical and demographic metadata were collected at bedside and by electronic medical record review.

Results

Culture was attempted on 2106 swab samples from 451 patients (486 ICU admissions) (Figure 1). A mean of 4.33 samples was obtained from each patient. C. difficile was isolated from 211 (10%) samples from 79 patients (Table 1). The first sample was positive by culture for 48 (9.9%) of patient admissions to the ICU. 31 (6.4%) patients who were initially negative by culture had a subsequent sample from which C. difficile was isolated. Persistence of culture-positivity varied from patient to patient (Figure 2). Of 80 patients who were tested for CDI based on physician suspicion, 12 patients had a positive Cepheid PCR test; 9 had diarrhea and were treated for CDI.

Conclusion

Surveillance for shedding of C. difficile by daily culture reveals that patients admitted to the ICU can shed the pathogen intermittently without attributable disease. This can be in the form patients who are admitted carrying the organism as well as those who appear to acquire the organism during their stay. It is unclear whether patient or microbiome factors underlie the differences seen in patterns of shedding. Furthermore, intermittent shedding may reflect multiple episodes of exposure to C. difficile spores and asymptomatic shedding without stable colonization.

Disclosures

All authors: No reported disclosures.
2426. Performance of Statistical Process Control Charts for Detecting Clinically-Significant Increases in Clostridium difficile Infection Rates
Authors: Nehls Nicole , Bilantuono Anthony , Etherton Christian , Ilieş Iulian , Benneyan James C , Baker Arthur W , Anderson Deverick J
Published: October 2019

Background

Clostridium difficile infections (CDIs) are the most common type of healthcare-associated infection in the United States, with an estimated annual incidence of 500,000 cases and excess healthcare costs of $5 billion per year. The prevalence and severity of CDIs have been increasing in recent years, making it of vital importance to detect outbreaks sufficiently early to minimize negative health outcomes. Statistical process control (SPC) methods have proven to be a versatile tool in healthcare, enabling near real-time monitoring of adverse events rates and thereby improving patients’ health. The aim of this study was to investigate the performance of SPC in detecting clinically significant increases in CDI rates.

Methods

We retrospectively analyzed monthly CDI rates at 6 community hospitals in the Duke Infection Control Outreach Network from 2009–2017. Detected CDIs were stratified by surveillance system (LabID or traditional), infection source, recurrence type, and diagnostic test (nucleic acid amplification or enzyme-linked immunosorbent assay). Recurrent and community-associated CDIs were excluded from all analyses. Several variations of Shewhart and exponentially-weighted moving average (EWMA) u-charts were applied to each hospital (Figure 1), including using different baseline types (global, fixed, or rolling) and baseline data streams (hospital or network-wide). To help assess chart performance, epidemiologists determined the clinical relevance (yes/no) of 167 statistical signals generated using earlier iterations of these charts. Performance was quantified via sensitivity, specificity, and accuracy.

Results

EWMA u-charts with global network-wide baselines performed the best (Figure 2), detecting the largest number of clinically relevant signals (56% sensitivity) with high specificity (96%). Charts utilizing network-wide baselines were generally more accurate than those using local hospital data for that purpose (accuracy of 46–72% vs. 43–45%). Similarly, charts with fixed baselines performed better than those with rolling ones (accuracy of 43–62% vs. 43–47%).

Conclusion

SPC charts are easily applicable to CDI surveillance; however, their parameters would need to be optimized to maximize utility.

Disclosures

All authors: No reported disclosures.
2431. When More is Less – Recognizing More Community-onset Clostridium difficile Infections Helps to Dramatically Lower C diff Standardized Infection Ratio (SIR)
Authors: Parada Jorge P , Green Melissa , Wright Dominique , Parilla Deborah , Hedlund Heather , Harrington Amanda , Smith Kevin R
Published: October 2019

Background

It is essential to recognize the true burden of community-onset (CO) Clostridium difficile infection (CDI) in hospital, not only because it prevents late recognition of CO CDI as being classified as a hospital-onset (HO) event, but also to assure appropriate contact precautions and therapeutic measures are deployed in a timely fashion. We recognized that our timely diagnosis of CO-CDI was suboptimal and sought to improve early recognition of CO-CDI.

Methods

We developed an automated daily report for all patients during their first 3 days of hospitalization who had loose stools documented in the nursing flow sheets and no stool sample sent to the lab. This report was automatically pushed out to the unit nurse managers, as well as reviewed by the infection preventionists (IP). Nurse managers alerted staff to acquire a stool sample to send to the lab. If stool testing still was not sent at the time of IP review of these symptomatic cases, then the IP called the nurse caring for the patient to encourage that a stool sample be sent ASAP and before the third hospital day was completed.

Results

We increased early appropriate stool testing for patients with documented loose stools during the first 3 days of hospitalization. Improved early diagnosis and better lab stewardship was associated with a marked increase in CO-CDI (15.6/month in 2015 vs 58.7/month in the last year), as well as a decrease in HO-CDI (22.8/month in 2015 vs 7.4/month last year) (Figure 1). In turn, we saw a remarkable drop in our CDI SIR (2 year pre-intervention SIR = 1.49 vs post-intervention SIR for the last 1.5 years = 0.41) (Figure 2).

Conclusion

After several years of our CDI SIR remaining stubbornly around 1.5, we developed a system of enhanced recognition of patients who had loose stools early in their hospitalization. This aided in better recognition of CDI present on admission, substantially increasing our detection of CO-CDI. We also noted decreases in HO-CDI, presumably secondary to no longer diagnosing patients later in their hospitalization as HO-CDI cases who actually had been admitted with CO-CDI. Better early recognition and isolation of patients with CDI also helped to decrease inadvertent C. difficile transmission in hospital, contributing to decreases in HO-CDI. In turn, we noted a remarkable decrease in our CDI SIR.

Disclosures

All authors: No reported disclosures.