bluuebunny/crossref_metadata_2025 huggingface dataset:
2274. Comparison of Clinical Outcomes in Patients with Extensively Drug-Resistant Pseudomonas aeruginosa Pneumonia Treated with Aminoglycosides vs. Ceftolozane/Tazobactam
Authors: Pervin Najwa , Tate-Nero Khandase B , Ullah Saad , Koirala Sajan , Sundareshan Vidya , Koirala Janak
Published: October 2019

Background

Extensively drug-resistant (XDR) P. aeruginosa (PA), defined as resistant to ≥ 1 agents in all classes of antibiotics except two classes, limits therapeutic options to more toxic agents such as aminoglycosides (AMG) and polymyxins. Majority of the XDR PA isolated in two of our teaching hospitals were found to be susceptible to ceftolozane–tazobactam (CT) in addition to AMG and polymyxins. Our study aims to compare treatment outcomes with traditional antibiotics vs. CT in patients with XDR PA pneumonia.

Methods

This is a retrospective case–control study of patients admitted to two local hospitals from 2013 to 2018. Patients were screened by discharge diagnosis for pneumonia. We included patients over 18 years with XDR PA in sputum cultures susceptible to ≤ 2 classes of antibiotics. Statistical analyses included ANOVA, T-test, Fisher exact and Chi-square tests.

Results

Among the 48 patients with XDR PA pneumonia, 33 patients met inclusion criteria. Their mean age was 62 years (SD ±16), 30% were female, and 18% were immunocompromised. Similarly, 85% of patients had underlying lung disease and 55% had a tracheostomy tube. Majority of these patients were either nursing home residents (55%) or hospitalized (46%) within past 3 months. Septic shock associated with XDR PA pneumonia was found in 30% of patients, and 73% required mechanical ventilation during treatment. Nineteen patients received an aminoglycoside (AMG group), 1 colistin, 9 CT (CT group), and 4 received CT plus an AMG. The average time to clinical improvement was 3.5 (±2.2) days for AMG group and 2.2 (±1.7) days for CT group (P = 0.3). Compared with CT group, AMG group had significantly longer mean duration of hospital stay (19 ± 13 vs. 32.4 ± 17 days, P < 0.05). All patients who had clinical failure to improve requiring change in antibiotics (2 patients) or who died after withdrawal of care (3 patients) were in AMG group. Clinical relapse within 30 days occurred equally in both groups (4 AMG, 2 CT, P > 0.05). Six patients who developed acute kidney injury received either an AMG (5) or colistin (1).

Conclusion

Based on our observation, CT is a safe and effective treatment for XDR PA pneumonia. Compared with CT, patients who received AMG had longer hospital stays and sustained more nephrotoxicity.

Disclosures

All authors: No reported disclosures.
2275. Novel Therapeutic Options for the Treatment of Multi-Drug-Resistant Achromobacter Respiratory Infections
Authors: Canonica Theora , Thompson Shruti , Carr Amy , Alexander Jose , Minor Sarah Brooks
Published: October 2019

Background

Respiratory infection due to Achromobacter species has been increasingly more common, especially in patients with cystic fibrosis (CF). Recurrent infections in these patients contribute to significant morbidity and mortality as well as lead to repeated antibiotic exposures with subsequent development of multi-drug-resistant (MDR) pathogens. Several recently approved antimicrobials target MDR Gram-negative pathogens, but none are FDA approved for MDR Achromobacter respiratory infections and lack susceptibility breakpoint recommendations.

Methods

This retrospective analysis evaluated hospitalized patients with MDR Achromobacter respiratory infections from August 2017 to March 2019 at AdventHealth Orlando, a 2,885-bed healthcare system including 8 campuses across Central Florida. The purpose of this descriptive study was to examine novel therapeutic agents for the treatment of respiratory infections due to MDR Achromobacter.

Results

MDR Achromobacter was isolated in 36 respiratory cultures from 18 unique patients. A. xylosoxidans (61%) and A. denitrificans (22%) were the most frequently isolated species. Mean patient age was 40 years, 56% were female, and 67% had CF. Treatment indications included CF exacerbation (38%), pneumonia (35%), post-lung transplant infection (16%), and other (11%). Twenty-four infections were polymicrobial (67%) and 23 infections included MDR pathogens. Minimum inhibitory concentrations (MIC) of the antibiotics used for treatment were available for 70% of cases. Of the 18 patients with isolated MDR Achromobacter organisms, 72% had MIC changes with 69% exhibiting higher MICs on subsequent testing. Novel agents were used in 63% of cases (Table 1) for an average duration of 10 days. Eravacycline was the most frequently used monotherapy agent (5/6 cases) and the most utilized novel antibiotic (21%). All-cause readmission rates at 30 days was 33%; 92% was due to infection. Inpatient all-cause mortality was 11%.

Conclusion

Antibiotics available to treat MDR Achromobacter infections are limited and lack standard susceptibility breakpoint recommendations. Based on this evaluation, novel agents, such as eravacycline or meropenem/vaborbactam, may be viable treatment options for patients with MDR Achromobacter respiratory infections.

Disclosures

All authors: No reported disclosures.
121. Cardiac Implantable Electronic Device-Related Infective Endocarditis (CIED-IE): Clinical Features and Outcomes of Patients with Definite IE Who Fulfill Both Major Duke Criteria
Authors: Gupta Siddhi , Wierzba Thomas F , Peacock James E , Baddour Larry M , Sohail Muhammad R , Le Katherine Y , Vikram Holenarasipur R , Miró José M , Prutkin Jordan M , Greenspon Arnold J , Carrillo Roger , Danik Stephan B , Naber Christoph K , Blank Elisabeth , Tseng Chi-Hong , Uslan Daniel
Published: October 2019

Background

Cardiac implantable electronic device-related infective endocarditis (CIED-IE) comprises 10–57% of total CIED infections. Patients with definite CIED-IE who fulfill both major modified Duke criteria have not been well characterized.

Methods

Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective, multinational study of CIED infections were used to describe a subset of patients with CIED-IE who met both major Duke criteria for definite IE (bloodstream infection and intracardiac vegetations [VEG]).

Results

Of 433 patients with CIED infection, 144 (33.3%) had definite CIED-IE. The median age was 68 years and 77.1% were male. Twelve (8.3%) had past CIED infection. Seventy-seven patients (53.5%) had permanent pacemakers, 38 (26.4%) had implantable cardioverter defibrillators, and 29 (20.1%) had combination devices. The median time following the last device procedure was 550 days. CIED-IE was early in 60 patients (41.7%) and late in 84 (58.3%). Most patients presented with fever (77.8%) and sepsis (44.4%) with a median symptom duration of 7 days. On echocardiography, lead VEG was noted in 125 patients (86.8%) and valvular VEG in 54 patients (37.5%) with the tricuspid valve involved in 56.5%. On the basis of VEG location, there were 90 patients (62.5%) with isolated lead-associated IE (LAE), 19 patients (13.2%) with isolated valve-associated IE (VAE), and 35 patients (24.3%) with both (LVAE). All patients had positive blood cultures and 63/119 (52.9%) had positive lead cultures. The predominant organism in blood was Staphylococcus aureus (42.4%), followed by coagulase-negative staphylococci (20.1%). CIED removal occurred in 131 patients (91%). There were 25 deaths during the index hospitalization and 34 total deaths (24.3%) by 6 months. Mortality correlated with age >75 (P = 0.023) and sepsis on presentation (P = 0.052). Infecting organism, site of VEG, and device removal did not impact the risk of death.

Conclusion

Definite CIED-IE is relatively common. The majority of patients tend to have late-onset infection and often present with sepsis. S. aureus is the dominant organism causing definite CIED-IE. Isolated LAE occurs in 63% of patients. Older age and sepsis on admission are associated with higher mortality.

Disclosures

All authors: No reported disclosures.
2307. Risk factors for Cytomegalovirus (CMV) reactivation and Association with Clinical Outcomes in Critically Ill Adults with Sepsis: A Pooled Analysis of Prospective Studies
Authors: Imlay Hannah , Dasgupta Sayan , Boeckh Michael , Stapleton Renee D , Rubenfeld Gordon D , Chen Ying , Limaye Ajit P
Published: October 2019

Background

CMV reactivation in seropositive, non-immunosuppressed adults with sepsis has been associated with worse clinical outcomes. To inform rational design of interventional trials determining whether CMV prevention improves outcomes, it is critical to identify the independence and strength of the association of CMV reactivation measures with clinically-relevant endpoints. Identification of patient factors associated with CMV reactivation would allow for optimization of the study population.

Methods

We performed a secondary pooled analysis of two prospective cohorts with sepsis: an observational cohort of ICU patients (n = 40) and the placebo cohort from a randomized, double-blind trial of ganciclovir to prevent CMV reactivation in acute critical illness (n = 66). Personnel blinded to the PCR results assessed clinical variables; CMV DNAemia was measured by quantitative plasma PCR twice weekly. Multivariable modeling using logistic and linear methods was used to examine the associations of CMV with clinical outcomes and between baseline patient factors and measures of CMV reactivation (adjusted for age, race, gender, transfusion status, study cohort, and APACHE score).

Results

CMV reactivation occurred at any level in 38/106 (36%), at >100 IU/mL in 25/106 (24%), and at >1,000 IU/mL in 14/106 (13%). In a multivariate model, CMV reactivation at any level, >100 IU/mL, or >1,000 IU/mL was associated with fewer days alive and not requiring ventilation: mean difference of −3.5 days ([95% CI −7.0, 0], P = 0.057), −5.1 days ([−8.9, −1.2], P = 0.012), and −6.1 days ([−10.9, −1.2], P = 0.016), respectively. Multiple measures of CMV reactivation were associated with other clinically-relevant outcomes, even after adjustment for baseline factors (Table 1). The association of APACHE score with CMV reactivation measures was inconsistent and with small effect size. We did not identify other patient variables associated with subsequent CMV reactivation.

Conclusion

CMV reactivation in seropositive adults with sepsis is independently and quantitatively associated with clinically-important outcomes, including death or continued hospitalization by day 28, ventilator-, ICU-, and hospital-free days. These effect sizes provide key data to inform design parameters of future interventional trials.

Disclosures

All authors: No reported disclosures.
2314. Burden of Respiratory Syncytial Virus (RSV) Infection Among Hospitalized Older Adults and Those with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)
Authors: Anderson Evan J , Hussaini Laila , Bristow Laurel , Tippett Ashley , Gibson Theda , Hart Mari , Salazar Luis , Gaffney Michelle , Benyeogor Ifeyinwa Kanayo , Cheng Andrew , Drobeniuc Ana , Traenkner Jessica , Fayad Danielle , Washington Wesley , Emerson Lisa , Schwartz Natalia , Greaves Kandra , Todd Sean , Stanley Corshé , Bechnak Amer , Chaaya Rody Bou , Al-Husien Zayna , Deović Rijalda , Winston Juton , Ahmed Dilshad Rafi , Li Wensheng , Le Khuong , Singh Aditya , Spencer Jennifer E , Muchinsky Amy , Zaks Kathryn , Nesheim Wendy , Stephens Kathy , Swerdlow David L , Hubler Robin , Agosti Yasmeen , Munye Mohamed , Jadhao Samadhan , Ha Binh , McCracken Courtney , Kraft Colleen , Rostad Christina A , Kao Carol , Lopman Ben , Yildirim Inci , Anderson Larry , Rouphael Nadine , Rouphael Nadine
Published: October 2019

Background

Data are limited about the burden of respiratory syncytial virus (RSV)-related hospitalizations in older adults and those with COPD or CHF.

Methods

We conducted prospective surveillance at two hospitals from October 2018 to March 2019 for adults ≥50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region in Atlanta, Georgia. Asymptomatic adults ≥50 years of age were enrolled as controls. Nasopharyngeal and oropharyngeal swabs were tested for RSV and influenza (Flu) using BioFire® FilmArray® Respiratory Viral Panel (RVP) and acute/convalescent serology was obtained for RSV antibodies detection by enzyme immunoassay against RSV lysate. Standard of care results were included for enrollees. We compare the number of RSV+, Flu+ and RSV−/Flu− cases along with demographic features and outcomes.

Results

We screened 12,453 patients to identify 1,515 eligible adults of which 617 (41%) were enrolled. The most common reasons for failing to enroll were refusal (676, 75%) and inability to obtain informed consent (221, 25%). Of the 617, 36 (6%) were RSV+ and 41 (7%) were Flu+. RSV was detected in 1/126 (0.8%) and Flu in 0/126 healthy controls. RSV+ occurred earlier in surveillance and peaked at a higher frequency (figure). Clinical characteristics and outcomes are in the table. In a convenience sample, a four-fold rise in RSV antibody titer was detected among 8/15 RSV+, 0/42 RSV−/Flu−, and 0/42 healthy controls.

Conclusion

The burden and outcomes for RSV are similar to Flu in adults admitted to the hospital with ARI, CHF, or COPD. A vaccine for RSV would be beneficial.

Disclosures

Nadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant.
2315. The Relationship of Pre-Hospital Functional Status and Clinical Outcomes in Patients with Laboratory-Confirmed RSV Infection: Active Population-Based Surveillance, 2017–2019
Authors: Branche Angela , Saiman Lisa , Walsh Edward E , Falsey Ann R , Sieling William , Zachariah Philip , Greendyke William G , Barrett Angela , Vargas Celibell , Alba Luis , Phillips Matthew R , Finelli Lyn
Published: October 2019

Background

Respiratory syncytial virus (RSV) infection is a common cause of acute respiratory infection (ARI) in adults. Prospective surveillance enables collection of representative data on demographic and clinical characteristics. Few data of this kind are available for adults hospitalized with RSV infection. We used active population-based surveillance to identify patients with laboratory-confirmed RSV infection and evaluated demographic characteristics and clinical outcomes.

Methods

Hospitalized adults ≥ 18 years old residing in a predefined catchment area with ≥ 2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018–April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. Clinical and demographic data were abstracted from the medical record. Multivariate analysis was used to evaluate the relationship of patient characteristics with clinical outcomes.

Results

8,217 hospitalized adults were screened and 9.4% positive for RSV infection. Preliminary clinical and demographic data were available for 348 patients including 14% 18–49 years, 28% 50–64 years and 58% > 65 years. Mean age was 68 years and 60% were female (Figure 1). Patients had a mean of 3 co-morbidities, with diabetes (40%), chronic obstructive pulmonary disease (30%), chronic kidney disease (28%), congestive heart failure (28%), coronary artery disease (25%) and asthma (24%) the most common co-morbidities (Figure 2). Median hospital length of stay was 6 days (IQR 4–10), 13% of patients were admitted to the ICU, 5% were mechanically ventilated and 5% died during admission and 12% within 6 months. In multivariate analysis having > 3 comorbidities, cardiac disease or a lower baseline functional status measured by activities of daily living scores was significantly associated with 6-month mortality.

Conclusion

The majority of hospitalized patients with RSV infection were older adults with ≥ 3 chronic comorbid conditions. Baseline functional status may be predictive of worse clinical outcomes in patients with RSV infection. These insights into patient characteristics and clinical outcomes will provide information for prevention programs.

Disclosures

All authors: No reported disclosures.
2324. Respiratory Viral Coinfection in a Birth Cohort of Infants in Rural Nepal
Authors: Emanuels Anne , Newman Kira L , Hawes Stephen E , Martin Emily T , Englund Janet A , Tielsch James , Kuypers Jane , Katz Joanne , Khatry Subarna , LeClerq Steven , Chu Helen Y
Published: October 2019

Background

Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the effects of coinfection on disease severity or healthcare seeking are less well-understood.

Methods

A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in rural southern Nepal. Prospective weekly active household-based surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT–PCR. Coinfection was defined as the presence of two or more respiratory viruses simultaneously detected as part of the same illness episode. Maternal vaccination status, infant age, prematurity, and number of children under 5 in the household were adjusted for with multivariate logistic regression.

Results

Of 1,730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected on their primary illness episode. Coinfection status did not differ by maternal vaccination status, infant age, premature birth, and number of children under 5 in the household. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. Overall, infants with coinfection had increased occurrence of fever lasting 4 or more days overall (OR 1.4, 95% CI: 1.1, 2.0), and in the subset of infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 1.0, 1.6).

Conclusion

A high proportion of infants experiencing their first respiratory illness had multiple viruses detected. Coinfection with influenza was associated with longer duration of fever compared with children with influenza alone, but was not associated with increased illness severity by other measures.

Disclosures

All authors: No reported disclosures.
2328. Human Respiratory Syncytial Virus Subgroups among Hospitalized Infants in the United States, 2015–2016
Authors: Rha Brian , Peret Teresa C T , Wang Lijuan , Lively Joana Y , Curns Aaron , Campbell Angela P , Boom Julie A , Azimi Parvin H , Weinberg Geoffrey A , Staat Mary A , Selvarangan Rangaraj , Halasa Natasha B , Englund Janet A , Klein Eileen J , Harrison Christopher J , Stewart Laura S , Szilagyi Peter G , Nayakwadi. Singer Monica , Avadhanula Vasanthi , McNeal Monica , Figueroa-Downing Daniella , Prill Mila M , Whitaker Brett L , Payne Daniel C , Lindstrom Stephen , Thornburg Natalie J , Gerber Susan I , Langley Gayle , Langley Gayle
Published: October 2019

Background

Respiratory syncytial virus (RSV) is a major cause of severe acute respiratory illnesses (ARI) in young children. Circulation of RSV subgroups A and B can vary by season and geographic location, and may have implications for disease susceptibility, outcomes, and prevention measures. We investigated RSV subgroup distribution among samples collected in the New Vaccine Surveillance Network.

Methods

Prospective active surveillance for hospitalized ARI was conducted from November 1, 2015 to June 30, 2016 among children < 12 months of age at seven pediatric hospital sites. Mid-turbinate nasal and throat flocked swabs (combined when both available) and/or tracheal aspirates were collected and tested for RSV at each site using real-time reverse transcription polymerase chain reaction (rRT–PCR) assays; RSV A/B subgroup results were available from four sites that did their own subgroup testing (Cincinnati, Kansas City, Houston, and Oakland). At three sites (Rochester, Nashville, Seattle), approximately 50 RSV-positive specimens were sampled based on the monthly distribution for each site and 1:1 distribution by gender, and then assayed for subgroup at CDC. Patient information was obtained from medical records; chi-square tests were used to compare the distribution of A and B subgroups by site.

Results

Of 704 RSV-positive hospitalized infants, subgroup data from 586 were analyzed; 340 (58%) were RSV A and 246 (42%) were RSV B. The median age for both RSV A and RSV B patients was 2 months. Subgroup distribution varied by geographic location, with the overall proportion of RSV A ranging from 18–83% across sites (P < 0.01). Peak RSV A and B detections by month varied by site, occurring from November–February (figure).

Conclusion

During the 2015–2016 season, RSV A and B subgroups co-circulated among hospitalized infants enrolled at seven US sites. The predominance of RSV subgroup varied by geographic location. Continued surveillance and additional subgroup testing over multiple seasons should improve understanding of the epidemiologic significance of RSV infections by subgroup.

Disclosures

All authors: No reported disclosures.
2340. Diagnostic Stewardship: Survey of Urine Culturing and C. difficile Testing Practices Amongst Oregon Microbiology Labs
Authors: Villamagna Angela H , Cassidy P Maureen , Pierce Rebecca , Tran Dat , Nix Chad , Pfeiffer Christopher
Published: October 2019

Background

Testing for urinary tract infection (UTI) and Clostridiodes difficile infection (CDI) poses diagnostic and antimicrobial stewardship challenges. Both diagnoses hinge on local microbiology laboratory algorithms. For UTI testing, the definition of “abnormal” urinalysis and the use of reflex urine cultures, both of which alter the frequency of bacteriuria detection, likely differs between laboratories. For CDI, pretest probability, choice and sequence of diagnostic tests are likely variable and impact the chances of accurate diagnosis.

Methods

To understand laboratory practices and determine variations in local testing algorithms, we deployed a self-administered survey to microbiology laboratories serving Oregon healthcare facilities via SurveyMonkey in September 2018. Responses were collected through April 2019. We analyzed a subset of questions focused on UTI and CDI diagnosis.

Results

Of 51 surveyed laboratories, response rate was 86% (n = 44). 91% of respondents (n = 40) process bacterial cultures. 47.5% (n = 19) primarily perform urine culture when ordered, whereas the remainder primarily perform cultures in a reflex algorithm when ordered (n = 12; 30%) or a reflex algorithm automatically (n = 9; 22.5%) (Figure 1). The definition of an abnormal urinalysis varied widely (Figure 2). 15% (n = 6) of laboratories reported considering changes to their workflow; two cited a goal of reducing unnecessary testing. Of the 32 laboratories that perform in-house C. difficile testing, the assays and sequence in which they were implemented in testing algorithms varied substantially (Figure 3) and most commonly included NAAT testing. Seven (21.8%) laboratories reported recently changed practices; these changes did not favor any particular algorithm. 84.2% (n = 32) reported stool rejection criteria to limit unnecessary testing, but these criteria varied (Figure 4).

Conclusion

Wide variation exists in laboratory workflows for UTI and CDI diagnoses in Oregon, suggesting lack of consensus on optimal practices. Encouragingly, multiple labs described recently implemented or planned interventions to reduce unnecessary testing for both infections. This snapshot will inform statewide education and interventions to optimize testing and help prevent patient and population harm.

Disclosures

All authors: No reported disclosures.
2358. Understanding the Clinical Implications of Clostridium difficile Detection in the Molecular Age: Colonization vs. Infection in Children Less Than 3 Years of Age
Authors: Hecht Shaina , Wang Huanyu , Everhart Kathy , Watson Joshua , Leber Amy
Published: October 2019

Background

Infants have a high rate of asymptomatic Clostridium difficile (CD) colonization (up to 37%) but can rarely develop true CD infection (CDI). However, currently available polymerase chain reaction (PCR) and enzyme immunoassays (EIA) have suboptimal sensitivity/specificity to distinguish CDI from colonization. Recent data from adults showed that lower cycle threshold (Ct) values of a semi-quantitative CD toxin B gene (tcdB) PCR assay in stool correlated with detection of free CD toxin in stool and poor clinical outcomes. We hypothesized that a tcdB PCR assay may be utilized to distinguish CDI from colonization in patients < 3 years old.

Methods

Symptomatic patients < 3 years old with CD detected by the BioFire FilmArray Gastrointestinal Panel (FGP) were enrolled 2/2018–3/2019. We performed CD tcdB PCR and toxin A/B/GDH EIA on frozen aliquots of stool in Cary Blair. CDI was defined among those that were tcdB PCR positive as (1) a consistent clinical syndrome (diarrhea + no current laxative use), (2) CD EIA toxin+, (3) symptomatic improvement with CDI-directed treatment, and (4) no alternative etiology of diarrhea identified. Patients who did not meet criteria for CDI were considered colonized. We compared median tcdB PCR Ct values between the CDI and colonized groups using the Mann–Whitney test.

Results

Of 193 FGP CD+ patient samples with charts available for review, 37 (19%) samples were EIA GDH+/toxin+, 121 (63%) were GDH+/toxin− and 35 (18%) were EIA−. 150 (78%) samples had detectable tcdB by PCR. Six (4%) patients met criteria for CDI and 144 (96%) for colonization. Median (interquartile range) tcdB PCR Ct values were 23.8 (22.0–29.5) and 30.5 (26.3–35.8) in patients with CDI and colonization, respectively (P = 0.03).

Conclusion

Using a strict clinical and laboratory definition, 4% of evaluable patients < 3 years old met criteria for CDI and had significantly lower tcdB PCR Ct values than colonized patients. A combination of clinical and laboratory criteria, including semi-quantitative tcdB PCR, may help differentiate colonization from CDI in this patient population.

Disclosures

All authors: No reported disclosures.
2359. Prospective Feasibility Study for Novel Ultrasensitive Multiplexed Immunoassay for Clostridiodes difficile Toxins A and B
Authors: Watson Lauren , Zimbric Michele L , Shaughnessy Catherine , Kale Shraddha , Debad Jeff , Navaratnam Manjula , Safdar Nasia
Published: October 2019

Background

The diagnosis of Clostridiodes difficile infection is challenging. A wide array of diagnostic tests are used in practice; however, each available test has important limitations. We examined the feasibility and analytical performance of a novel ultrasensitive multiplexed immunoassay designed by Meso Scale Diagnostics (MSD) compared with five current diagnostic assays for detection of C. difficile toxin A and B.

Methods

Stool, serum and urine samples from 44 admitted inpatients were collected within 72 hours of a standard of care nucleic acid amplification test (NAAT) result (23 positive, 21 negative). These specimens underwent five standard diagnostic assays: enzyme immunoassay for toxins A and B (EIA), cytotoxin cell assay, bacterial culture isolation, and two different NAATs to determine presence of viable C. difficile cells, toxins, and toxin-encoding genes (Table 1). The concentration (fg/mL) of toxin A and toxin B in all stool samples was then quantified using MSD’s multiplexed immunoassay (Table 1).

Results

At least one of the five standard diagnostic tests for C. difficile was positive in 16 of the 23 clinically positive patients. The MSD multiplex immunoassay detected toxin A and/or toxin B in 15 of these 16 samples and quantified low levels of toxin A in one clinically positive sample that was negative for all other tests. In contrast, only 2 of the 16 positive samples were positive by EIA, demonstrating the benefits of the ultrasensitive assay over standard immunoassay methods. All clinically negative specimens were negative in all tests. Toxin detection in urine and serum samples was negligible. In stool samples, the MSD test had an estimated sensitivity of 93% (95% CI: 70–99%) and specificity of 93% (95% CI: 78–98%) compared with the clinically used NAAT.

Conclusion

The MSD multiplex toxin assay is a feasible test to move forward for further evaluation. Ultimately, future studies should examine the performance of this test compared with standard of care in a prospective randomized trial assessing clinical outcomes.

Disclosures

All authors: No reported disclosures.
129. Antimicrobial Activity of Ceftazidime–avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017–2018)
Authors: Carvalhaes Cecilia G , Castanheira Mariana , Mendes Rodrigo E , Sader Helio S
Published: October 2019

Background

We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals.

Methods

A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype).

Results

The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA.

Conclusion

CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals.

Disclosures

All authors: No reported disclosures.
2369. Prescribing Choices and C. difficile Infection Risk: A Longitudinal Cohort Study of Nursing Home Residents in Ontario, Canada
Authors: Antoine. Brown Kevin , Schwartz Kevin , Langford Bradley , Diong Christina , Garber Gary , Daneman Nick
Published: October 2019

Background

Antibiotics are the primary modifiable risk factor for C. difficile infection (CDI). However, the comparative risks of different prescribing choices are not known. Our objective was to quantify the benefits of: (1) preventing antibiotic initiation, (2) substituting high-risk antibiotics for low-risk antibiotics, (3) reducing antibiotic duration.

Methods

We conducted a cohort study of residents of over 600 Ontario nursing homes in the 2014 to 2017 period. All non-acute care hospital antibiotic exposures were identified from the Ontario Drug Benefit database, while CDI was identified using outpatient billings and/or hospital ICD-10 codes. Logistic regression models were used to examine the risk of CDI as a function of time-varying antibiotic exposures, while controlling for 14 different risk factors. Based on the models, we estimated the comparative risks of specific antibiotic regimens.

Results

We identified 1,944 cases of CDI, for an incidence of 1.60 per 100,000 person-days. The 90-day risk among residents without antibiotics was 0.84 per 1,000 residents (‰), compared with 1.85‰ in those with a 7-day course of antibiotics. Preventing a 7-day course reduced CDI risk by 45% (see table, adjusted relative risk [RR] = 0.55, 95% confidence interval [CI] = 0.50, 0.60). The antibiotics conferring the highest risks were clindamycin at 4.1‰, moxifloxacin at 3.2‰, and amoxiclav at 3.0‰. Comparing 7-day courses of antibiotics with similar indications: nitrofurantoin engendered 37% less risk than ciprofloxacin, amoxicillin resulted in 31% less risk than amoxicillin-clavulanate, and cephalexin had 51% less risk than clindamycin. Reduced antibiotic durations were associated with less C. difficile risk. Compared with a 10-day course, a 7-day course was associated with 12% less risk, while a 5-day course was associated with 21% less risk.

Conclusion

We have quantified, using a real-world population-based cohort of nursing home residents, the reduction in CDI risk incurred by preventing unnecessary antibiotic initiations, preferring low-risk agents over high-risk agents, and reducing duration. These figures will help clinicians compare risks and benefits of different prescribing choices with regards to CDI prevention.

Disclosures

All authors: No reported disclosures.
2382. Recurrent Clostridioides difficile Infection (CDI) Worsens Anxiety-Related Patient-Reported Quality of Life
Authors: Garey Kevin W , Schroeder Claudia P , Hardin Thomas C , Hengel Richard L , Ritter Timothy E , Nathan Ramesh V , Dillon Ryan J , Van Anglen Lucinda J
Published: October 2019

Background

The Health-Related Quality of life (HR-QOL) instrument, the Cdiff32, allows studies on QOL changes associated with recurrent CDI. An ongoing real-world study of bezlotoxumab (BEZ) provided a unique opportunity to study anxiety-related HR-QOL in patients at high risk for recurrent CDI using the anxiety sub-domain of Cdiff32. The aims of this study were to assess baseline anxiety-related HR-QOL based on the number of prior episodes of CDI and to evaluate changes in patients with or without recurrence.

Methods

Patients at high risk for recurrent CDI given BEZ were administered the anxiety sub-domain questions of the Cdiff32 prior to infusion and at approximately 90 days after administration (0 = worst anxiety; 100 = no anxiety). The number of prior episodes of CDI were collected, along with demographics and co-morbid conditions. Patients were followed for 90 days for CDI recurrence, which was defined as new onset of diarrhea requiring CDI-active antibiotics.

Results

There were 107 patients evaluated, aged 68 ± 14 years (mean ± SD) with multiple co-morbid conditions (mean Charlson: 4 ± 3) and multiple previous CDI episodes (3 ± 1 episodes). Fourteen patients (13%) experienced a further CDI recurrence within 90 days following BEZ. Overall, baseline anxiety HR-QOL was 29 ± 22. Risk factors for lower baseline anxiety-related HR-QOL included immunocompromised conditions (P < 0.046) and receipt of a proton pump inhibitor (P < 0.018). Compared with patients with primary CDI disease (Score: 35 ± 20), baseline anxiety HR-QOL was worse with subsequent prior recurrences (Score: 26 ± 23) for CDI episodes 2–4, and then improved for subsequent episodes (Score: 38 ± 22). Anxiety-related HR-QOL improved by a mean of 32 ± 25 points compared with patients that experienced a further recurrence where HR-QOL declined (P < 0.0001). Results were confirmed in a multivariate model controlling for Charlson score and chronic renal failure.

Conclusion

Poor anxiety-related HR-QOL was observed at baseline in all patients regardless of number of prior episodes. QOL improved 90 days after BEZ infusion in patients without further recurrences of CDIs and worsened in patients with a subsequent recurrence.

Disclosures

All authors: No reported disclosures.
2389. Assessing the Time Course of Proton Pump Inhibitor Use and Clostridioides difficile Infection
Authors: Panagos Katherine , Blanco Natalia , Leekha Surbhi , von Rosenvinge Erik , Heil Emily
Published: October 2019

Background

Proton pump inhibitors (PPIs) are a known risk factor for Clostridioides difficile infection (CDI) and recurrence, even in the absence of antibiotic use. No studies have specifically assessed the increased risk for CDI based on PPI duration, given that PPIs are frequently newly prescribed during hospitalizations and infrequently discontinued, even when CDI has occurred. The aim of this project was to assess the time course of PPI utilization and risk of CDI.

Methods

We conducted a retrospective matched case–control study comparing patients who developed CDI (cases) with patients who did not develop CDI (controls, matched on age, gender, date of admission and hospital location) from a cohort of patients with a C.difficile PCR test order from an academic medical center. Patient charts were reviewed for PPI use prior to the date of the positive test and whether the PPI was started in the hospital or as a home medication (>30d, 30–90d, 90–180d, >180d). The primary comparison was odds of PPI use between cases and controls using conditional logistic regression adjusted for antibiotic exposure (SAS 9.4, Cary, NC).

Results

A total of 348 patients were included in the study, 174 cases and 174 matched controls. 65% of patients in the study received a PPI, 85% a PPI or H2 blocker and 95% of patients received antibiotics during their admission. Patients on PPIs as home medications were not at an increased risk of CDI (OR = 1.08 (95% CI 0.60–1.93)) compared with those not on PPIs. Patients whose PPIs were initiated in the hospital were at increased risk of CDI compared with those not on PPIs (OR = 1.4 (95% CI 0.81–2.41)). No significant difference was observed across time periods of PPI use prior to admission and development of CDI.

Conclusion

Patients who started PPIs during inpatient stays were at a higher risk of developing CDI than patients not exposed to PPIs. However, PPI use was not found to be significantly associated with CDI in this analysis, regardless of the time or duration of PPI prescription. The results may be confounded by the high frequency of PPI use and concomitant antibiotic use in both cases and controls. Further study is needed to evaluate the impact of short-course PPI prescriptions in inpatient settings on CDI.

Disclosures

All authors: No reported disclosures.
2390. Acquisition of Clostridium difficile Infection Following Exposure from Roommate Defined by Concordance on Genotyping
Authors: Aslam Anoshé , McMillen Tracy , Wills Jonathan , Bayoumi Nagla , Usiak Shauna , Kamboj Mini
Published: October 2019

Background

Observational studies have identified same room occupancy with a hospital-onset Clostridium difficile infection (HO-CDI) case as a risk factor for subsequent CDI diagnosis. Despite this, the risk remains poorly characterized in endemic settings. Furthermore, genotyping techniques have not been applied to examine concordance between infecting strains in index patients and exposed roommates who eventually develop CDI. The study seeks to quantify transmission of C. difficile from an index case to their roommates and identify if concordance was present among strain types by the application of multi-locus sequence typing (MLST).

Methods

Laboratory-identified cases of hospital onset C. difficile infection (CDI) from October 1, 2017 through March 31, 2018, were included in the study. Patients with HO-CDI are placed in private room once diagnosis is established. Roommates who were in the same room as cases for at least 24 hours prior to diagnosis, regardless of duration of overlap, were identified through of the hospital patient tracking database to establish spatial link. Next, all exposed roommates who developed CDI within 3 months after exposure (defined as date of CDI diagnosis of index case) were identified. Strain types of linked cases was examined by MLST.

Results

During the 6-month period, 279 cases of CDI were diagnosed. Of these cases, 156 were hospitalized at the time of diagnosis including 83 (53%) in a room with shared occupancy. These 83 patients had 109 roommates that met exposure criteria. Four (3.7%) roommates developed CDI over a 90-day follow-up period. None of the examined pairs were genetically concordant.

Conclusion

Indirect patient to patient transmission of C. difficile from newly diagnosed CDI cases to roommates is not common despite the spatial proximity with shared occupancy.

Disclosures

All authors: No reported disclosures.
2391. Increased Risk of Systemic Infections with Multidrug-Resistant Organisms in Patients with Severe Clostridioides difficile Infection
Authors: Dotson Kierra M , Gonzales-Luna Anne J , McPherson Jacob , Lancaster Chris , Endres Bradley T , Zasowski Evan J , Begum Khurshida , Alam M Jahangir , Garey Kevin W
Published: October 2019

Background

The gut microbiota is a defense mechanism against colonization of multidrug-resistant organisms (MDROs), including carbapenem-resistant Enterobacteriacae (CRE). Gut dysbiosis caused by broad-spectrum antibiotics favors MDRO colonization and increased susceptibility of intestinal infections, including C. difficile infection (CDI). Increased CDI severity may increase the risk of bacterial translocation due to damage to colonic epithelial layer. The aim of this study was to assess CDI disease severity and subsequent risk for MDRO systemic infection.

Methods

This was a prospective, observational study of adult hospitalized patients tested for CDI at a large, university-affiliated tertiary care hospital. Patients with a history of systemic MDRO infection in the past 90-days of stool testing were excluded. Patients were stratified by test positivity (CDI vs. antibiotic-associated diarrhea (AAD)), as well as, CDI disease severity and followed for 30-days for subsequent MDRO infections defined as presence of MDRO cultures from systemic, normally sterile sites (blood, urine, cerebrospinal fluid). Stool samples were collected and grown for MDRO colonization.

Results

A total of 335 CDI-positive and 135 antibiotic-associated diarrhea (AAD) hospitalized patients were included. No differences were found in rates of MDRO colonization by test positivity or disease severity (overall 68% VRE, 53% Candida spp., 30.4% MRSA, and 1.8% CRE). Significantly more patients with severe CDI had higher rates of developing systemic MDROs compared with mild-moderate CDI and AAD (23.2%, n = 112 vs. 8.1%, n = 223 P < 0.001; vs. 11.9%, p = 0.018). Severe CDI was found to be an independent risk factor for subsequent systemic MDRO infection via logistic regression.

Conclusion

Severe CDI disease is associated with an increased risk of systemic MDRO infections.

Disclosures

All authors: No reported disclosures.
2395. Analysis of Countywide Clostridium difficile Infection using Descriptive Statistics and Geographic Information Systems Mapping
Authors: Li Jeanne , Mwenda Kevin , Stanfield Leslie , Beswick Richard
Published: October 2019

Background

Clostridium difficile infection (CDI) is now the most common pathogen causing nosocomial infectious diarrhea in the United States, and more than 500,000 people are estimated to have either healthcare-associated (HA) or community acquired (CA) CDI. The epidemiology of CDI is incompletely understood with more than 50% of all CDI cases occurring in the outpatient community and growing at a pace that is greater than HA-CDI.

Methods

Patients with CDI within Santa Barbara County, California were identified via three types of tests: Clostridium difficile PCR, gastrointestinal panel by PCR, and enzyme immunoassay (EIA) via local laboratory. Basic patient characteristics were analyzed using descriptive statistics. Changes with CA-CDI incidence were examined on a quarterly basis to identify and compare quarterly trends in CA-CDI incidence. Geographic Information Systems (GIS) mapping was utilized to provide better spatial understanding of disease distribution across communities.

Results

Over 2,000 unique patients with CDI were identified between January 1, 2013 and January 31, 2019. Median age of these patients was 64 years (interquartile range: 45 – 78) and 60% were female. Hot spots of CDI within Santa Barbara County were localized to three major cities: Santa Barbara, Goleta, and Lompoc. Our results show that based on seasonal quarterly data CDI occurred most frequently in winter months.

Conclusion

In conclusion, CDI hot spots occurred most frequently during winter months and could possibly be associated with increased antibiotic treatment during flu season. Using the results from this study, we believe that by utilizing spatial and seasonal trends associated with CDI, physicians may be able to identify, diagnose and treat patients with CDI more promptly in Santa Barbara County.

Disclosures

All authors: No reported disclosures.
2399. Ribotype Diversity of Clostridioides difficile strains obtained during screening tests
Authors: Munoz-Price L Silvia , Ledeboer Nathan A , Tickler Isabella A , Johnson Rebecca L , Park Taylor , Goering Richard , Oppenheim Beryl , Tenover Fred C
Published: October 2019

Background

Clostridioides difficile is an organism acquired not only in healthcare settings but also in community settings. For the past several years our hospital has performed screening tests to detect asymptomatic carriage of C. difficile. We now aim to better understand the ribotypes and degree of diversity among these C. difficile strains obtained in a systematic screening.

Methods

This study was performed at a 600 bed teaching affiliated hospital in Milwaukee, WI, where surveillance testing is performed in selected units upon admission and weekly thereafter using nucleic acid amplification test (NAAT; Xpert® C. difficile; Cepheid, Sunnyvale, CA). Screening tests are obtained regardless of symptoms. NAAT positive samples underwent anaerobic cultures in C. difficile selective broth (CCMB-TAL) for 24–48 hr and then to Brucella blood agar plates (BA) for 48–72 hr to conﬁrm C. difficile presence. PCR-ribotyping was performed as previously described by Stubbs et al. with minor modifications. The results were compared with a database containing >3,000 clinical isolates including C. difficile reference strains from the Cardiff ribotype collection.

Results

A total of 104 strains belonging to 93 unique patients were processed. Patients had a mean age of 60 years (range: 18 - 89) and 49% were females. Most patients were hospitalized in the hematology oncology units (55.7%) or in the solid-organ transplant step down unit (9.6%). A total of 25 different ribotypes were identified. The most common ribotype was 014/020 (23; 22%), followed by ribotype 56 (13; 12.5%), 106 (12; 11.5%), 027 (11; 10.5%), 002 (6; 5.7%), and 078/126 (5; 4.81).

Regarding the timing of admission, 70 strains were obtained within 4 days from hospital admission and the remaining 34 were obtained afterwards. Both groups had ribotype 014/020 as the most frequently detected ribotype but 027 were the second most commonly detected at the time of admission (table). A total of 7 patients had more than one stool sample processed and 5 of them had discordant ribotypes at different time points.

Conclusion

Systematic screening tests for C. difficile carriage in a single center showed a large heterogeneity of ribotypes with the majority not being 027. Additionally, most patients tested more than once carried different ribotypes.

Disclosures

All authors: No reported disclosures.