bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested against Enterobacteriaceae and Pseudomonas aeruginosa from United States (US) Medical Centers Stratified by Infection Type (2015–2016)
Authors: Sader Helio S , Castanheira Mariana , Duncan Leonard R , Flamm Robert K
Published: October 2017

Background

We evaluated and compared the in vitro activities of ceftazidime-avibactam (CAZ-AVI) and comparators against of Enterobacteriaceae (ENT) and P. aeruginosa (PSA) from various infection types.

Methods

23,440 isolates composed of 19,249 ENT and 4,191 PSA were consecutively collected from 85 US hospitals and tested for susceptibility (S) by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial S and frequency of key resistance (R) phenotypes, such as multidrug-R (MDR) and extensively drug-R (XDR) among others, were assessed and stratified by these infection types: bloodstream (BSI; 3,434 isolates; 14.7%), pneumonia (6,439; 27.5%), skin/skin structure (SSSI; 4,134; 17.6%), intra-abdominal (IAI; 951; 4.1%), urinary tract (UTI; 7,873; 33.6%), and others combined (609; 2.6%).

Results

CAZ-AVI was active against 99.9% to 100.0% of ENT and 97.0% (pneumonia) to 99.4% (UTI) of PSA isolates. S rates were consistently lower among ENT from pneumonia compared with other infection types for β-lactams such as CAZ (82.3% vs. 87.1–90.8%), piperacillin-tazobactam (P-T; 87.5% vs. 90.2–95.6%) and meropenem (MEM; 96.8% vs. 98.4–99.4%). S to gentamicin (GEN) was also generally lower among isolates from pneumonia, whereas S to levofloxacin (LEV) and colistin (COL) were lowest among BSI and SSSI isolates, respectively. The occurrence of MDR, XDR, and carbapenem-resistant ENT (CRE) phenotypes were markedly higher among isolates from patients with pneumonia compared with other infection types (Table). Among PSA, S rates for CAZ, P-T, and GEN were lowest among isolates from pneumonia, whereas S to MEM was similar among isolates from BSI, pneumonia, and IAI (77.3–77.9%), and S to LEV was markedly lower among UTI isolates (67.1%). The frequency of PSA isolates with MDR and XDR phenotypes, as well as non-S to CAZ, MER, and P-T, were also highest among isolates from patients with pneumonia (Table).

Conclusion

Antimicrobial S rates were generally lower among ENT and PSA isolates from patients with pneumonia compared with other infections. CAZ-AVI was highly active against a large collection of contemporary ENT and PSA isolates from US hospitals (2015–2016), including MDR and XDR organisms, regardless of the infection type.

Disclosures

H. S. Sader, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant
In Vitro and In Vivo Activity of Single and Dual Antimicrobial Agents Against KPC-producing Klebsiella pneumoniae
Authors: Moussavi Farzad , Nath Sarath , Abraham Daniel , Landman David , Quale John
Published: October 2017

Background

Options for treatment of infections due to KPC-producing K. pneumoniae are limited, and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates.

Methods

Using clinically-relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime-avibactam, meropenem, rifampin, and amikacin alone and in combination. Four isolates of KPC-producing K. pneumoniae were studied, including two isolates that were resistant to polymyxin B and had ceftazidime-avibactam MICs of 8 µg/mL. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam.

Results

Two isolates that were resistant to polymyxin B and with ceftazidime-avibactam MICs of 8 µg/mL were also resistant to amikacin and meropenem. When ceftazidime-avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival with the in vivo model. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower MICs of ceftazidime-avibactam. At concentrations four times the MIC, ceftazidime-avibactam had bactericidal activity in vitro; at one fourth the MIC, synergy was observed when combined with meropenem. Improved survival rates were observed with therapy with ceftazidime-avibactam, particularly when combined with a second agent for one isolate. In the in vivo model, polymyxin B with or without rifampin or meropenem, was ineffective against polymyxin B resistant strains.

Conclusion

Pending clinical studies, combining ceftazidime-avibactam with another agent (e.g., a carbapenem) should be encouraged when treating serious infections due to these pathogens, especially for isolates with ceftazidime-avibactam MICs near the susceptibility breakpoint.

Disclosures

All authors: No reported disclosures.
Socioeconomic Status Factors Associated with Increased Incidence of Community-Associated Clostridium difficile Infection
Authors: Skrobarcek Kimberly , Mu Yi , Winston Lisa G , Brousseau Geoff , Lyons Carol , Farley Monica , Perlmutter Rebecca , Holzbauer Stacy , Phipps Erin C , Dumyati Ghinwa , Beldavs Zintars G , Kainer Marion , Guh Alice
Published: October 2017

Background

Traditionally a hospital-acquired pathogen, Clostridium difficile is increasingly recognized as an important cause of diarrhea in community settings. Health disparities in C. difficileinfection (CDI) have been reported, but little is known about the social determinants of health that influence community-associated (CA) CDI incidence. We sought to identify socioeconomic status (SES) factors associated with increased CA-CDI incidence.

Methods

Population-based CDI surveillance is conducted in 35 U.S. counties through the Centers for Disease Control and Prevention’s Emerging Infections Program. A CA-CDI case is defined as a positive C. difficile stool specimen collected as an outpatient or within three days of hospitalization in a person aged ≥ 1 year who did not have a positive test in the prior 8 weeks or an overnight stay in a healthcare facility in the prior 12 weeks. ArcGIS software was used to geocode 2014–2015 CA-CDI case addresses to a 2010 census tract (CT). Incidence rate was calculated using 2010 Census population denominators. CT-level SES factors were obtained from the 2011–2015 American Community Survey 5-year estimates and divided into deciles. To account for CT-level clustering effects, separate generalized linear mixed models with negative binomial distribution were used to evaluate the association between each SES factor and CA-CDI incidence, adjusted by age, sex and race.

Results

Of 9686 CA-CDI cases, 9417 (97%) had addresses geocoded to a CT; of these, 62% were female, 82% were white, and 35% were aged ≥65 years. Annual CA-CDI incidence was 42.9 per 100,000 persons. After adjusting for age, sex and race, CT-level SES factors significantly associated with increased CA-CDI incidence included living under the poverty level (rate ratio [RR] 1.12; 95% confidence interval [CI] 1.09–1.53), crowding in homes (RR 1.11; 95% CI 1.01–1.21), low education (RR 1.11; 95% CI 1.07–1.15), low income (RR 1.15; 95% CI 1.12–1.17), having public health insurance (RR 1.21; 95% CI 1.18–1.24), receiving public assistance income (RR 1.69; 95% CI 1.55–1.84), and unemployment (RR 1.14; 95% CI 1.07–1.22).

Conclusion

Areas with lower SES have modestly increased CA-CDI incidence. Understanding the mechanisms by which SES factors impact CA-CDI incidence could help guide prevention efforts in these higher-risk areas.

Disclosures

All authors: No reported disclosures.
Prevalence of Clostridium difficile and Multidrug Resistant Gram-negative Rods in the Soil from Southeastern Wisconsin
Authors: Lor Angela , Tran Cathy , Jencson Annette , Cadnum Jennifer , Donskey Curtis , Munoz-Price L Silvia
Published: October 2017

Background

Preliminary data suggests that community-onset Clostridium difficile might be more common in rural areas. Thus, farms—specifically livestock farms—might be a major reservoir of C. difficile. Similarly, antibiotic exposures might predispose farm animals for colonization with multidrug resistant Gram-negative organisms. The aim of this study was to determine the prevalence of C. difficile and multidrug resistant gram-negative rods in the soil of Southeastern Wisconsin farms.

Methods

From July to September of 2016, soil samples were collected from farms with livestock animals. Soil samples were collected using gloves and sample containers. Soil samples were collected from farms specifically in or near Washington, Waukesha, and Milwaukee counties which are within the proximity of Milwaukee Metro area. Soil samples were cultured for C. difficile and Gram-negative rods on selective plates and by broth enrichment.

Results

A total of 20 farms participated in this study with a total of 40 soil samples. Out of the 40 soil samples, 20 were from an area where animals roam or where manure was used and the remaining 20 were from an area where animals are prohibited or where there was no manure. Out of the 20 soil samples where animals roam, 10 (50%), tested positive for C. difficile. Out of 20 soil samples where animals are prohibited, 13 samples (65%) tested positive for C. difficile. 2 of the 23 C. difficile isolates recovered were toxigenic. Eight (40%) of the 20 soil samples where animals roam tested positive for fluoroquinolone-resistant bacteria (FQR). While 5 (25%) of the 20 soil samples where animals are prohibited, tested positive for FQR bacteria. An Acinetobacter calcoaceticus was found to exhibit carbapenem-resistance.

Conclusion

We found soil colonization with C. difficile and FQR in 65% and 25%, respectively, where animals are prohibited. Where animals roam we found C. difficile and FQR 50% and 40%, respectively. Our study suggests that farms may be a significant community source for C. difficile and fluoroquinolone resistant organisms. Additional testing should be done to examine factors that might be increasing antibiotic resistance in farms (e.g., antibiotic exposure).

Disclosures

All authors: No reported disclosures.
Induced Human Intestinal Organoids (iHIOs) as Model Systems for Chemotherapy-associated Clostridium difficile (CD) Infections
Authors: Apewokin Senu , Pradhan Suman , Frerick Michael , Weiss Alison
Published: October 2017

Background

Patients undergoing cytotoxic chemotherapy are ten times more likely to develop Clostridium difficile infections (CDI) than the general patient population. Efforts to outline pathophysiologic mechanisms underlying this disproportionate incidence have been limited by the lack of disease-representative experimental models. We hypothesized that iHIOs could serve as toxicity models to evaluate chemotherapy-associated CDI

Methods

Intact iHIOs were exposed to cytotoxic chemotherapy (melphalan) in gut media at therapeutic doses (9 μg/mL; which is the equivalent of 140 mg/m2 human dose).

Cellular death was assessed by accumulation of the membrane permeant dye, Sytox-orange added at 5-days post treatment. iHIOs were also exposed to CD toxin A and B (TcdA and TcdB respectively) and epithelial barrier damage assessed by actin mislocalization and loss of E-cadherin. For controls iHIOs were exposed / microinjected with saline/PBS. Morphological and histological changes were then captured using light and confocal microscopy

Results

Morphologic and histologic assessments demonstrated cell death and epithelial barrier damage

Conclusion

iHIOs demonstrate cell death on exposure to CD toxins and melphalan chemotherapy. These properties could be harnessed in establishing toxicity models for evaluation of chemotherapy-associated CDI

Disclosures

S. Apewokin, T2 biosystems: Investigator, Research support Astellas: Scientific Advisor, Consulting fee
Weight Changes in Fecal Microbiota Transplant for Clostridium difficile
Authors: Hussam Dina , Drees Marci , Myerson Scott , Duffalo Chad , Mosby Danielle , Herdman Christine , Depalma Fedele , Mcgraw Patty , Bacon Alfred E
Published: October 2017

Background

Fecal microbiota transplant (FMT) for relapsing Clostridium difficile infections (CDI) allows for rapid repopulation of the colonic microbiome and may prevent future relapses. FMT is considered safe, however subsequent impact on weight and metabolism are incompletely understood. Animal studies have shown that alterations in microbiota lead to changes in weight; this is also suggested in humans, based on limited anecdotal evidence. This study explores changes in weight associated with FMT.

Methods

We conducted a retrospective observational study of patients who underwent FMT at our 1100-bed community-based academic healthcare system. FMT protocol requires 2 documented CDI relapses and failed vancomycin taper. FMT methods include colonoscopy, EGD and oral capsules. Of note, donor stool (OpenBiome, Boston, Massachusetts) criteria include BMI <30. We conducted chart review for documented provider-measured weights pre- and post- FMT (≤ 1 year), and compared pre-FMT weights to last recorded weight within 1-year period. We also evaluated weights in a subset of patients in the acute (2–6 week post FMT) timeframe.

Results

Between Apr 2014- Oct 2016, 41 patients underwent FMT. Of these, 31 (75%) patients had adequate weight data available for review (Table). Overall patients gained an average 2.4%. During the acute phase, 20 patients (65%) had documented weights; of these 50% lost and 50% gained weight, with overall weight loss of 0.7%.

Conclusion

In this limited population, it appears FMT may predispose to weight gain, which may reflect improved health with CDI cure. However, effects of FMT on patient’s microbiomes must also be considered. As this intervention becomes more widely used we must be increasingly aware of possible metabolic side effects and ensure documentation of weight changes as part of FMT protocols.

Disclosures

All authors: No reported disclosures.
Endogenous Serum IgG Antibodies to Clostridium difficile Toxin B Are Associated with Protection against C. difficile Infection Recurrence
Authors: Kelly Ciaran P , Poxton Ian R , Shen Judong , Railkar Radha , Guris Dalya , Dorr Mary Beth
Published: October 2017

Background

MODIFY I/II were global trials of the efficacy and safety of bezlotoxumab (BEZ), a monoclonal antibody (mAb) against C. difficile toxin B, alone and with actoxumab (ACT), a mAb against C. difficile toxin A. BEZ was superior to placebo (PBO) at preventing recurrent CDI (rCDI) in patients (patients) receiving antibacterials for CDI. The addition of ACT did not improve efficacy. The aims were to explore potential biomarkers for rCDI risk in the patients receiving PBO by measuring endogenous IgG Abs against Cd toxins A and B (eAb-A and eAb-B); it was expected that patients with low eAb levels might be at increased risk of rCDI.

Methods

Serum samples were collected pre-dose (PRE), at Week 4, and Week 12 postdose. eAb titers were measured using an electrochemiluminescence immunoassay. Results were reported as <1:1000, 1:1000, 1:5000, 1:25000, and ≥1:125000. As there is no clearly defined immunological surrogate of efficacy for rCDI tied to a specific eAb-A or eAb-B level, eAb levels were arbitrarily categorized as low (≤1:1,000), medium (1:5000), or high (≥1:25000). The rCDI rate was summarized by eAb category at each time point.

Results

The proportion of patients with higher eAb-A and eAb-B titers increased following the initial CDI episode (Tables 1 and 2). There was no evident correlation between eAb-A titers and the rCDI rate at any time point. The proportion of patients who experienced rCDI within 12 weeks after randomization was highest in patients with low eAb-B titers PRE and at Week 4. rCDI rate in those with low eAb-B titer at all timepoints and in patients who had low titer only at PRE was similar.

Conclusion

The rise in eAb-A and eAb-B titers over time is consistent with a convalescent humoral immune response to toxins A and B following CDI. The lack of correlation between eAb-A titers and rCDI is consistent with the lack of efficacy of ACT in prevention of rCDI. Conversely, higher eAb-B titers are associated with lower risk for rCDI, consistent with the efficacy of BEZ. 22.1% of patients with high eAb-B titers at PRE experienced rCDI. Therefore, eAb-B titers may have marginal utility as a biomarker for rCDI risk and are not likely to improve predictive value over clinical and demographic characteristics such as advanced age, compromised immunity, and CDI history.

Disclosures

C. P. Kelly, TBD: Investigator, Speaker honorarium; J. Shen, Merck & Co., Inc.: Employee, may hold stock/hold stock options in the Company; R. Railkar, Merck & Co., Inc.: Employee, may own stock/hold stock options in the Company; D. Guris, Merck & Co., Inc.: Employee, may own stock/hold stock options in the Company; M. B. Dorr, Merck & Co., Inc.: Employee and Shareholder, may own stock/hold stock options in the Company
Epidemiology and Outcomes of Clostridium difficile Infection in Hospitalized Patients within the US Military Health Care System
Authors: Eberly Matthew , Susi Apryl , Rajnik Michael , Adams Daniel , Nylund Cade
Published: October 2017

Background

Clostridium difficile infection (CDI) has become an emerging epidemic in the healthcare community. Our study aims to characterize the epidemiology and measure the attributable cost, length of stay, and in-hospital mortality of CDI among hospitalized patients in the US military health system (MHS).

Methods

We performed a retrospective cohort study of patients with CDI using MHS database billing records. Cases included all active duty patients, their dependents, or retirees admitted to a US military treatment facility for ≥2 days from October 2008 to September 2015 with a stool sample positive for Clostridium difficile via enzyme immunoassay, tissue cytotoxin assay, toxigenic culture, or polymerase chain reaction (PCR). Patient case-mix adjusted outcomes including in-hospital mortality, length of stay, and hospitalization cost were evaluated by high-dimensional propensity score adjusted logistic regression.

Results

Among 1,156,672 admissions within the MHS from 2008–2015, we identified 1,640 (0.14%) patients with CDI and found a significant increase in the trend of CDI over the 7-year study period (P < 0.001). Median age (IQR) was 63 (41–76) in the CDI hospitalized group and 26 (6–46) in the non-CDI hospitalized group. Male gender was a risk factor for CDI (unadjusted odds ratio, 1.94; 95% confidence interval 1.76–2.14) and the majority of patients (84.5%) were associated with large-size medical centers. Patients hospitalized with CDI had significantly higher hospitalization cost (attributable difference [AD] $51,959, P < 0.001), prolonged hospital stay (AD 11.8 days, P < 0.001), and in-hospital mortality (case-mix adjusted odds ratio 3.28; 95% confidence interval 2.69–4.00).

Conclusion

CDI in hospitalized patients within the MHS is associated with advanced age, large medical centers, and an increased length of stay, hospital cost, and in-hospital mortality. We identified a significantly increased burden of hospitalization among patients admitted with CDI, highlighting the importance of infection control and antimicrobial stewardship initiatives aimed at decreasing the spread of this pathogen.

Disclosures

All authors: No reported disclosures.
Longitudinal Trends of Clostridium difficile Infection (CDI) within Department of Veterans Affairs (VA) Medical Centers—Acute Care and Long-term Care
Authors: Kralovic Stephen , Evans Martin , Simbartl Loretta , Roselle Gary
Published: October 2017

Background

CDI remains a significant and serious healthcare-associated infection within hospital and long-term care (LTC) settings. In 2012 VA began a CDI Prevention Initiative in its acute care (AC) facilities, which expanded to include LTC. Data were collected with regard to CDI cases and healthcare-facility associated (HCFA) status.

Methods

VA used CDC National Healthcare Safety Network (NHSN) Lab-ID Event definitions from CDI/MDRO Module with the exception that HCFA-status was called with a more stringent timeframe at 48 hours after admission. Monthly, VA Medical Centers and LTC Facilities report data to a central repository which includes number of cases meeting NHSN definitions for recurrence, hospital onset HCFA (HO-HCFA), community-onset HCFA (CO-HCFA) and community-onset non HCFA (CO-notHCFA) cases (equivalent of NSHN community-acquired [CA] cases). Data collection began from 2011 forward in AC, and from part of 2012 forward in LTC.

Results

In AC, the number of all cases reported ranged from 6313 to 6595 with no trend for increase/decrease noted from 2011 to 2016. However, when evaluating proportions of each type of CDI contributing to the overall occurrence, there is significant change over the years (P < 0.0001, Chi-Square analysis of proportions) with HO-HCFA and CO-HCFA contributing to less (24.4% and 25.2%, decreases, respectively) and CO cases (particularly CO-notHCFA) contributing to more (38.1% increase) of the cases, (Fig 1). In LTC, there were overall lesser cases ranging from 980 to 789 from 2013 through 2016 (P = 0.05, linear regression), with no significant changes over the years (P = 0.06, Chi-Square of proportions) (Fig 2).

Conclusion

Over time, HO-HCFA and CO-HCFA cases have declined within VA AC facilities. However, an increase of CO-notHCFA cases (similar to NHSN CA cases) has occurred, increasing admission prevalence of CDI at VA facilities. As CDI prevalence on admission is a contributor to risk for HCFA disease, this increased pressure indicates the success of the VA CDI Prevention Initiative in decreases of HO-HCFA is even more substantive than raw rates would indicate. However, it also highlights a group of CDI cases which need a different, focused targeting of prevention strategies.

Disclosures

All authors: No reported disclosures.
A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States
Authors: Luo Ruihong , Barlam Tamar , Weinberg Janice
Published: October 2017

Background

Many strategies reported to decrease CDI occurrence have been implemented in acute care hospitals in recent years. We assessed the change in incidence, mortality and hospital charges of CDI patients in acute care hospitals during 2005–2014. We also investigated risk factors for hospital-onset CDI (HOCDI) and predictive factors for mortality of CDI patients.

Methods

Using the Nationwide Inpatient Sample database, we identified adult patients (¡Ý 18 years) with CDI by ICD-9-CM codes. The trends of CDI incidence, mortality and hospital charges were evaluated by Poisson regression. The risk for HOCDI and factors to predict in-hospital death of CDI patients were analyzed by logistic regression.

Results

3,337,910 cases of CDI were identified out of a total of 318,703,355 hospitalizations (1.05%). Incidences of non-HOCDI and HOCDI were 0.42% and 0.63% respectively. In the 10-year study period, CDI incidence increased with an annual rate of 3.3% (P < 0.001). The annual incidences of HOCDI and non-HOCDI increased with a rate of 1.4% and 2.0% respectively (P < 0.001). After adjusting for demographics, length of hospital stay and Charlson index, transfer from long-term health facilities (OR=2.02, 95% CI 1.83–2.23) and admission to a teaching hospital (OR=1.10, 95% CI 1.05–1.15) were independent risk factors for HOCDI. The in-hospital mortality of CDI associated hospitalization decreased from 9.7% in 2005 to 6.8% in 2014 (P < 0.001). Transfer from long-term health facilities significantly predicted the risk for in-hospital death in CDI patients (OR= 1.34, 95% CI 1.32–1.36). The sum charge of all CDI hospitalizations increased with an annual rate of 2.0% (P < 0.001). The median charge per CDI hospitalization increased during 2005–2009 (P < 0.001), and then decreased during 2010–2014 (P < 0.001).

Conclusion

During 2005–2014, the mortality in CDI hospitalized patients decreased, but CDI incidence in acute care hospitals increased, resulting in increased total CDI associated hospital charges. Patients transferred from long-term healthcare facilities increased the risk for HOCDI and CDI associated in-hospital mortality. They should be considered as high-risk patients for CDI surveillance when developing mitigation strategies.

Disclosures

All authors: No reported disclosures.
Differences in Clinical Characteristics and Outcomes of Patients with Community-Onset Clostridium difficile Infection who Tested Positive by EIA Compared with NAAT through a Two-Step Algorithm
Authors: Phipps Erin C , Kenslow Nicole , Belovarski Ioan , Hancock Emily B
Published: October 2017

Background

The low sensitivity of toxin enzyme immunoassay (EIA) for the diagnosis of Clostridium difficile infection (CDI) motivated many laboratories to add nucleic acid amplification tests (NAAT) to their testing protocol. However, NAAT do not distinguish between colonization and infection, and indiscriminant testing could lead to over treatment of CDI.

Methods

Active, population-based CDI surveillance has been conducted through the Emerging Infections Program in Bernalillo County, NM since 2011, with test type collected at the individual level since 2014. Community-onset (CO) CDI cases with a first positive test diagnosed by a two-step algorithm (concurrent EIA/GDH, with discordant results reflexed to NAAT) in 2014–2015 were included. We analyzed clinical characteristics and outcomes of patients EIA positive compared with NAAT positive. Demographics, risk factors, treatment, and outcomes were assessed through medical record review.

Results

Among 1,063 cases, 559 (52.6%) were EIA positive only and 504 (47.4%) were NAAT positive only. Of those with stool collected as a hospital inpatient, 57% were NAAT positive (P < 0.001); this increased from 43.4% if tested the day of admission to 61.4% when tested on day three. Conversely, 38.6% of patients with stool collected in an emergency department were NAAT positive (P = 0.004). Fewer cases with complicated outcomes were NAAT positive (40.7%, P = 0.023). Among those with no documentation of recent antibiotic use, 64.3% were NAAT positive (P < 0.001), and 67.8% of cases with no CDI treatment were NAAT positive (P = 0.005). Only 28.3% percent of cases with recurrent CDI were initially NAAT positive (P < 0.001).

Conclusion

EIA negative and NAAT positive CO-CDI cases tended to have a milder clinical presentation than those that were EIA positive. This suggests that some patients positive only by NAAT may have mild CDI or be colonized, rather than infected, with C. difficile. These individuals were less likely to have complicated outcomes, have recent documented antibiotic use, be treated for CDI, or have a recurrent CDI episode than those positive by EIA. Longer hospital stay correlated with increased proportion of testing NAAT positive. Providers may benefit from considering testing protocol and clinical correlation when assessing patients with positive C. difficile test results.

Disclosures

All authors: No reported disclosures.
Clinical Characteristics and Outcomes of Hematologic Malignancy Patients with Clostridium difficile Toxin EIA vs. PCR Positive Test Results
Authors: Ziegler Matthew , Landsburg Daniel , Pegues David , Alby Kevin , Gilmar Cheryl , Bink Kristen , Gorman Theresa , Moore Amy , Han Jennifer
Published: October 2017

Background

C. difficile infection is common in patients with hematologic malignancy. There is increasing recognition that molecular (polymerase chain reaction, PCR) based testing lacks specificity for infection, while detecting patients with colonization. The objective of our study was to evaluate characteristics of patients with toxin enzyme immunoassay (EIA) vs. PCR positive C. difficile test results.

Methods

A retrospective review of inpatients at a tertiary care academic center with hematologic malignancy and a positive C. difficile test from 1/2015 to 1/2016 was performed. Data on demographics, comorbidities, clinical features, and outcomes were collected using medical record review. Characteristics were compared between patients with EIA vs. PCR positive test results using chi-squared or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables.

Results

A total of 130 patients were included: 51% and 49% had a PCR positive and EIA positive result, respectively. Diagnoses included AML (42%), multiple myeloma (22%), and Non-Hodgkin’s lymphoma (13%). Antibiotic exposure was similar, with a median of 4 days of anti-pseudomonal antibiotics received in the prior 30 days. There was no difference in history of a positive C. difficile test in the prior year (12% in the EIA group, 10% in the PCR group, P = 0.71).

Patients with EIA positive results were more likely to have a WBC ≥15/mm3 (18% vs. 6%, P = 0.02). However, there were no differences in presence of fever, stool frequency, or imaging evidence of colitis at the time of testing. Medications in the prior 72 hours were similar, including the use of proton pump inhibitors of ~40% and of laxatives of 28%. Clinical outcomes were also similar between patients with EIA vs. PCR positive tests: all-cause death (22% vs. 20%), recurrent CDI (9% vs. 13%), colectomy (1% vs. 4%), and megacolon (0% vs. 3%). Most patients received treatment with oral vancomycin for a median duration of 14 days.

Conclusion

In patients with hematologic malignancy, those with EIA vs. PCR positive C. difficile test results were clinically similar. These findings suggest that algorithms for testing and treatment of C. difficile in hematologic malignancy patients will need to be specifically targeted towards this immunocompromised population.

Disclosures

All authors: No reported disclosures.
Clostridium difficile (CD) Action Team (CDAT): An Intervention to Improve Care for Patients with a Positive CD PCR
Authors: Markou Theodore , Fabre Valeria , Dzintars Kathryn , Avdic Edina , Shulder Stephanie , Andonian Jennifer , Rock Clare , Cosgrove Sara E
Published: October 2017

Background

CD infections (CDI) may be viewed by healthcare workers (HCW) as an unpreventable consequence of antibiotics (abx). The purpose of CDAT was to use patient cases in real time to educate HCW on CD diagnostic, treatment and prevention practices including appropriate abx and proton-pump inhibitors (PPI) use.

Methods

From 7/17/16 to 5/6/17, Johns Hopkins abx stewardship team reviewed positive CD PCRs in inpatient to determine whether they had CDI or colonization (no diarrhea or an alternate cause) and if prevention and management was optimal. Included in this time are 2 surveillance periods (SP) (SP1: 7/17–9/27/16 and SP2: 12/18/16–3/30/17). During SP1, there was no contact with HCW. SP2 followed the intervention, and allowed assessment of sustained practice changes. During the intervention periods (IP) (IP1: 10/9–12/17/16 and IP2: 3/31–5/6/17), teaching points for optimizing care for each case were shared and discussed in person with the HCW team, including prescribers and nursing. Compliance with recommendations at 48 hours was assessed. Chi-square test was used to compare sub-optimal management for each variable in different time periods.

Results

We assessed 217 cases in the SPs and 96 cases in the IPs. 75 of 96 cases reviewed in the IPs required intervention. CDAT spoke to 74 teams, which led to a change in the care of patients in 49 cases (65%). Compliance with recommendations were as follows: 1) stop or modify CDI therapy, 53%, (39 cases); 2) stop PPI therapy, 52% (15 cases); 3) stop laxatives, 53% (9 cases); 4) stop or modify non-CDI abx, 46% (16 cases); and 5) improve BM documentation, 58% (11 cases). The Figure shows proportions of patients with suboptimal CD management without (SPs) or before (IPs) CDAT intervention in each period. There were no changes in practice between the SP1 and IP1. Between the SP1 and IP2, significant improvement in BM documentation was seen (P = 0.007). No differences were observed for other variables, although there was a trend towards improved CD therapy (P = 0.09).

Conclusion

Overall, prescribers did not independently change practice as a result of daily contact with CDAT; however, they were responsive to CDAT recommendations. BM documentation, the only nursing intervention, improved significantly.

Disclosures

All authors: No reported disclosures.
Know When to Test: Optimizing Diagnostic Practices for Clostridium difficile Infection (CDI) Among Patients at a Tertiary-Care Cancer Center
Authors: Aslam Anoshé , Eagan Janet , Kaplan Janice , Robilotti Elizabeth , McMillen Tracy , Kamalska-Cyganik Monika , Kelson Suzanne , Nevrekar Reshma , Narain Wazim , Stetson Peter , Kamboj Mini , Babady N Esther
Published: October 2017

Background

Polymerase chain reaction (PCR) based diagnostic testing for the detection of toxigenic Clostridium difficile infection (CDI) does not distinguish between carriers and patients with true CDI. As a result, CDI is over-diagnosed in hospitalized patients with diarrhea. Unnecessary testing generates false positives and several downstream sequelae.

Aim: The aim of this study was to reduce unnecessary testing for CDI through an electronic alert, targeted education, and implementation of evidence-based laboratory testing policy.

Methods

In order to quickly identify laxative induced diarrhea and avoid CDI testing, an electronic alert was created in the electronic medical record (EMR) system. The alert was built on a logic that identified patients who had received laxatives within 48 hours of a CDI PCR test order. The alert additionally provided the rationale for avoiding testing in patients on laxatives and guidance on appropriate testing for CDI. The following steps were taken simultaneously to complement these efforts: 1) Infection Control conducted hospital-wide education for licensed independent practitioners on a CDI testing algorithm 2) Laboratory based policy was instated to reject all formed stools (Bristol Stool Chart types 1 through 4) for CDI testing.

Results

In the 6 month pre-intervention period, there were 29 CDI tests per 1000 patient-days. In the post-intervention period, CDI tests decreased to 19 per 1000 patient-days, a 35% decrease (P < 0.0001). The decline in testing has been sustained for 7 months. The following observations were also made: 1) HAI rate reduction of 28%; 2) decrease in oral vancomycin use.

Conclusion

Decreasing inappropriate testing has several distinct advantages, including reducing excessive and unnecessary antibiotic use, avoiding misclassification of carriers as CDI cases, normalizing healthcare-associated CDI rates, and diminishing healthcare costs associated with preventable tests. Laboratories that use PCR only testing for CDI diagnosis should follow stringent policies to ensure that only patients with high pretest probability are tested. EMR systems are a useful and effective resource to achieve this for patients with laxative induced diarrhea.

Disclosures

All authors: No reported disclosures.
Enzyme Immunoassay for C. difficile Toxin Reduces Lab ID Events but Fails to Detect Clinically Significant C. difficile Infection
Authors: Ridgway Jessica P , Murillo Cynthia , Marrs Rachel , Garcia-Houchins Sylvia , Harper Clinitka , Bartlett Allison H , Landon Emily
Published: October 2017

Background

The National Health Safety Network (NHSN) requires reporting of Lab ID events for C. difficile infection (CDI) including all positive clinical tests after day three of hospitalization. Nucleic acid amplification tests (NAAT) that detect genes for toxins A and/or B may be overly sensitive, in some cases detecting C. difficile colonization. Some have advocated for two-stage testing, with positive NAAT tests followed by confirmatory enzyme immunoassay (EIA) to detect the presence of toxin and minimize the downside of false positives (i.e. additional NHSN reports or overuse of antibiotics). We aimed to better understand clinical characteristics of patients with positive NAAT and/or EIA tests.

Methods

Our hospital uses Xpert C. difficile assay (Cepheid), a NAAT method utilizing polymerase chain reaction (PCR), to diagnose CDI on unformed stool only. As part of a 6 month quality initiative, we pilot tested the C.DIFF QUIK CHEK COMPLETE® test (Alere), an EIA that tests for C. difficileantigen (Ag) and toxin, on all specimens that tested positive by NAAT. We abstracted clinical data from the medical record for a subset of patients who underwent EIA testing.

Results

Over 6 months, 294 patients had a positive test by NAAT. Of these, 258 (87.8%) underwent EIA testing. 67 (26.0%) were Ag+/toxin+, 173 (67.1%) were Ag+/toxin-, and 18 (6.8%) were Ag-/toxin-. Mortality rates were as follows: Ag+/toxin+, 17.9% (12/67); Ag+/toxin-, 13.9% (24/173); Ag-/toxin-, 27.8% (5/18), P = 0.27. Among the EIA toxin negative patients who underwent chart review, 81% had 3 or more loose stools within 24 hours, 62% had abdominal pain, nausea, or vomiting, and 27% had a WBC > 15.

Conclusion

The majority of patients testing positive for CDI by NAAT had a negative EIA test for toxin. There was no significant difference in mortality between EIA toxin positive and negative. Those with negative EIA toxin tests often had clinically significant symptoms of CDI. A two-stage CDI testing algorithm with NAAT followed by EIA for toxin may exclude patients with clinically significant CDI but would have resulted in a 75% reduction in reported NHSN LabID events.

Disclosures

All authors: No reported disclosures.
Clostridium difficile Laboratory Identification Event Reporting – A Need for Diagnostic Stewardship
Authors: Rock Clare , Pana Zoi , Leekha Surbhi , Trexler Polly , Andonian Jennifer , Gadala Avi , Carroll Karen C , Maragakis Lisa L
Published: October 2017

Background

Clostridium difficile LabID event reporting uses electronic laboratory results without chart review. Nucleic acid amplification testing is common in the US. A positive result may represent colonization or C. diff infection (CDI). We review C.difflabID events to ascertain if Hospital-Onest CDI (HO CDI). For non-HO CDI, we identify reason and use a matrix to prioritize clinical areas for intervention efforts.

Methods

Each C. difflab ID event from Jan 2015 to June 2016 at academic center had chart review for HO CDI; defined significant diarrhea, not present on admission, with no laxatives in prior 48 hours. For non HO-CDI events, reason and receipt of antibiotic treatment within 14 days of the positive test were retrospectively noted.

A prioritization matrix, where clinical services were ranked according to number of lab ID events (service’s contribution to the facility C. diffLabID), was multiplied by a rank based on percent of inappropriate tests giving an overall prioritization score for where intervention resources could potentially best be used.

Results

There were 490 C difficile LabID events; 284 (58%) were HO-CDI; 206 (42%) were inappropriate or delayed testing. Of the 190 with available medical records at time of retrospective review, reasons for not meeting the HO-CDI included laxative use within the previous 48 hours (41%), no clinically significant diarrhea (49.5%); delayed testing (9.5%). See figure. Of 172 patients with inappropriate testing, 159 (92%) were treated for CDI. Medicine and psychiatry ranked first and second on prioritization matrix. See table.

Conclusion

Nearly half of C. diff LabID events were not true HO CDI, but inappropriate or delayed tests. Prioritization matrix identified medicine and psychiatry as areas where diagnostic stewardship interventions could affect most on facility C. diff LabID.

Disclosures

K. C. Carroll, GenePOC, Inc.: Grant Investigator, Grant recipient
Association of Acid Suppression and Antimicrobial Use with Clostridium difficile Infection in Children
Authors: Huynh Hoang A , Wisdom Christy , Maples Holly D
Published: October 2017

Background

Clostridium difficileinfections (CDIs) can cause severe diarrhea and be potentially life-threatening, especially in children. Possible risk factors include age, being immunocompromised, prior antibiotic exposure, the use of antacids, and diseases that alter intestinal microbiota. Data in adults are vast while limited data is available in children. The objectives of this study are to identify pediatric risk factors and determine if an association between acid suppression and CDI’s in children exists.

Methods

A retrospective study was conducted between November 1, 2013 and October 31, 2016 at Arkansas Children’s Hospital. Children ages 1 – 18 years with a positive C. diff PCR test and ≥3 loose stools documented were included. Cases were excluded if previous positive PCR was within 60 days. Data collection included age, sex, encounter type (inpatient or outpatient), acid suppressing agents, previous antimicrobials within last 90 days and comorbidities including transplant, chronic pulmonary, hematology/oncology, and GI tract diseases. Statistical methods included descriptive analyses, χ2test, and Kruskal–Wallis test.

Results

A total of 139 cases of CDI among 123 patients were evaluated. Of these cases, the median (IQR) age is 8 years (3–13) with 77 (55.4%) being male and 86 (61.9%) of CDI cases identified inpatient of which 75 came from outpatient. Pediatric risk factors identified in C. diff cases included exposure to acid suppressing agents [61 (43.9%)] and antimicrobials [98 (70.5%)] with 90 (64.7%) having ≥1 comorbidities. Cases having ≥1 comorbidities were found to be associated with previous antacid exposure (P < 0.0005) while antimicrobial(s) use was associated with CDI hospitalization (P = 0.001). Similarly, exposure to either antacid suppression or antimicrobials or both with comorbidities were found to have a significant association (P < 0.0005) and associated with CDI hospitalization (P = 0.001).

Conclusion

Exposure to acid suppression in patients with comorbidities was associated with increased risk of CDI. Antimicrobial usage was associated with increased risk for hospitalization due to CDI. As pediatric outpatient antimicrobial stewardship evolves, improving CDI rates can center on improving antimicrobial and acid suppressive agents usage.

Disclosures

All authors: No reported disclosures.
A Randomized Trial of High-dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients
Authors: Natori Yoichiro , Humar Atul , Shiotsuka Mika , Slomovic Jaclyn , Hoschler Katja , Ferreira Victor , Ashton Peter , Rotstein Coleman , Lilly Les , Schiff Jeffrey , Singer Lianne , Kumar Deepali
Published: October 2017

Background

The annual influenza vaccine is recommended for solid-organ transplant recipients (SOTR) although studies have shown suboptimal immunogenicity. Influenza vaccine containing higher dose antigen may lead to greater immunogenicity in this population.

Method

We conducted a randomized, observer-blind trial comparing the safety and immunogenicity of high dose (HD; FluzoneHD, Sanofi) vs. standard dose (SD; Fluviral, GSK) influenza vaccine in adult SOTR. Patients were randomized 1:1 to receive the 2016–2017 influenza vaccine. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay for the three vaccine strains and an additional B strain not included in the vaccine.

Result

We randomized 172 patients and 161 (84 HD; 77 SD) were eligible for analysis. Median age was 57 years (range 18–86) and time from transplant was 38 (range 3–1402) months. Types of transplant were kidney 67 (39.0%), liver 38 (22.1%), lung 25 (14.5%), heart 23 (13.3%), and combined 19 (11.0%). Seroconversion to at least one of the three vaccine antigens (primary outcome) was present in 78.6% vs. 55.8% in HD vs. SD vaccine, respectively (P < 0.001). Seroconversion to A/H1N1, A/H3N2, and B strains were 40.5% vs. 20.5%, 57.1% vs. 32.5%, and 58.3% vs. 41.6% in HD vs. SD vaccine (P = 0.006, 0.002, 0.028, respectively). Postimmunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group  (P = 0.007, 0.002, 0.033). Independent factors associated with seroconversion to at least one vaccine strain were the use of HD vaccine and being on mycophenolate doses less than 2 g daily (P = 0.003, 0.013, respectively). Seroconversion rate to the B strain not included in the trivalent study vaccine was also higher in the HD vaccine group (33.3% vs. 14.1%, P = 0.004). Local and systemic adverse events were similar for the two vaccines. Biopsy-proven rejection was seen in 3.4% vs. 1.2% in HD vs. SD groups, respectively (P = 0.62). Two patients in the SD vaccine group and one in the HD group developed influenza infection during the follow-up.

Conclusion

High-dose vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population.

Disclosures

D. Kumar, Sanofi: Speaker’s Bureau, Speaker honorarium. Pfizer: Speaker’s Bureau, Speaker honorarium. GSK: Grant Investigator, Grant recipient.
The SEP-SEQ Trial: Clinical Validation of the Karius Plasma Next-Generation Sequencing Test for Pathogen Detection in Sepsis
Authors: Thair Simone , Seng Hon , Hollemon Desiree , Hong David , Blauwkamp Timothy , Kertesz Mickey , Ho Carine , Mann Rosen , Quinn James , Yang Samuel
Published: October 2017

Background

Sepsis is a leading cause of death and can be caused by a wide range of potential pathogens. In up to 40% of cases, a causative pathogen is never identified. There is a need for improved diagnostic tests that can accurately identify the breadth of potential pathogens to inform effective antimicrobial therapy.

Methods

We enrolled a prospective cohort of patients presenting to the hospital with signs and symptoms of sepsis. Plasma samples were collected for NGS testing at time of initial blood culture. Extracted plasma cell-free DNA was sequenced, human sequences removed and remaining reads aligned against a pathogen database consisting of viruses, bacteria, and eukaryotic pathogens. Relative abundance was estimated; pathogens present at high statistical significance were identified. NGS results were compared with a composite reference standard of all microbiology testing performed within 7 days of admission and clinical diagnosis.

Results

Of 286 patients enrolled, plasma NGS identified potential pathogens in 60.1% (172 of 286) of septic subjects including DNA viruses, bacteria (including fastidious/unculturable bacteria like Mycobacterium tuberculosis), and fungi. In contrast, 15.7% (45 of 286) subjects had a positive initial blood culture and 38.1% (109 of 286) had a potential infectious etiology identified using a composite microbiology laboratory standard. The NGS plasma assay had a positive agreement of 86.7% (39 of 45) and 79.5% (78 of 98) compared with initial blood culture (after excluding contaminants) and the composite laboratory reference standard, respectively. After clinical adjudication, 81.4% (140 of 172) of the positive plasma NGS results were deemed to be consistent with the septic event. Of the remaining 32 subjects, 15 had NGS results that were plausible causes of sepsis but clinical were insufficient to confirm this.

Conclusions

With a single blood draw, the Karius plasma NGS assay identified a broad range of pathogens in septic patients three times more often than blood culture and more often than all microbiology tests combined. This plasma NGS test can identify a viruses, bacteria, and eukaryotic pathogens which can provide valuable information to help clinicians better target antimicrobial therapy for patients with sepsis.

Disclosures

H. Seng, Karius, Inc.: Employee, Salary. D. Hollemon, Karius, Inc.: Employee, Salary. D. Hong, Karius, Inc.: Employee, Salary. T. Blauwkamp, Karius, Inc.: Employee, Salary. M. Kertesz, Karius, Inc.: Employee, Salary. S. Yang, Karius, Inc.: Research Contractor, Research grant.