bluuebunny/crossref_metadata_2025_split huggingface dataset:
2197. Ceftriaxone Monotherapy vs. Ceftriaxone Plus Azithromycin for the Treatment of Community-Acquired Pneumonia in Hospitalized, Non-ICU Patients
Authors: Murter Forrest , Dimond Kristin , Gilstrap Christopher , Grubbs Riley , Vowell Clark , Maldonado Cody , Jansen Jeffrey W 
Published: October 2019

Abstract

Background
Community-acquired pneumonia (CAP) is the leading infectious cause of death and severe sepsis in the United States and the fifth leading cause of death overall worldwide. Current United States guidelines for the treatment of CAP recommend empiric antibiotic therapy that covers both standard organisms as well as atypical organisms. Ceftriaxone (CTX) in combination with azithromycin (AZH) is one of the most common regimens used for the treatment of CAP; however, there are studies that show β-lactam monotherapy is as effective as a β-lactam in combination with AZH for the empiric treatment of CAP. The purpose of this study was to compare the rates of treatment failure between CTX monotherapy and CTX in combination with AZH in non-intensive care unit (ICU) inpatients.

Methods
Non-ICU hospitalized patients ≥ 18 years old admitted to Saint Vincent Healthcare with a primary or secondary ICD-10 code of pneumonia from 2013 to 2018 were included. Patients were excluded if they were pregnant, admitted within 2 weeks of a previous episode of CAP, were admitted to the ICU, had cystic fibrosis, or were given antibiotics with atypical coverage (other than azithromycin) prior to admit or within 24 hours of presentation. The primary outcome was treatment failure defined as a composite of any of the following: (1) attributable mortality, (2) in vitro resistance, and (3) change of antibiotic class. Secondary outcomes included length of stay, antibiotic duration, time to oral antibiotics, and readmission within 30 days.

Results
There were 84 and 159 patients included in the CTX and CTX+AZH groups, respectively. Baseline demographics between groups are shown in Table 1. The composite primary endpoint occurred in 22 patients (26.2%) in the CTX group and in 48 patients (30.2%) in the CTX + AZH group. After adjusting for gender, race, in hospital death, chronic obstructive pulmonary disease, length of therapy, length of stay, and systemic inflammatory response syndrome, CTX monotherapy was no less effective than CTX+AZH (aOR 0.55; 95% CI: 0.27 to 1.1; P = 0.09). The primary endpoint and secondary endpoints are shown in Tables 2 and 3, respectively.

Conclusion
There was no difference between CTX monotherapy and CTX + AZH for the empiric treatment of CAP.

Disclosures
All authors: No reported disclosures.
2200. Cost-effectiveness of Ceftolozane/Tazobactam for Treating Ventilated Nosocomial Bacterial Pneumonia
Authors: Naik Jaesh , Yang Joe , Elsea David , Critchlow Simone , Puzniak Laura 
Published: October 2019

Abstract

Background
Ventilated, hospital-acquired and ventilator-associated bacterial pneumonia (vHABP/VABP) are associated with high rates of antibiotic resistance and high morbidity and mortality in hospitalized patients. Ceftolozane/tazobactam (C/T) has shown non-inferiority to meropenem for treating HABP/VABP in a Phase III trial, ASPECT-NP. This study evaluates cost-effectiveness of C/T against meropenem in treating HABP/VABP.

Methods
We developed a model consisting of a short-term decision tree (reflecting the in-hospital period) followed by a long-term Markov structure (capturing lifetime costs and outcomes). Patient characteristics and clinical efficacy were informed by subjects in ASPECT-NP who received any dose of study drugs. Susceptibility was based on the Program to Assess C/T Susceptibility surveillance database. Second-line and salvage treatment were added to resemble real-world treatment patterns and used to calculate overall clinical cure and mortality rates based on results from a network meta-analysis. We analyzed two clinical scenarios: (1)”confirmed treatment’ in which C/T or meropenem is used after pathogen susceptibility is known; (2) ‘initial treatment’ of high-risk patients before susceptibility is known. Model outcomes include, percentage clinically cured, short-term mortality, direct medical costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Sensitivity analyses (SAs) were conducted to test the robustness of results.

Results
In the confirmed treatment setting, C/T had a higher cure rate (5.0 percentage points, the same below), lower short-term mortality (−5.1%), cost more ($2,728), and yielded higher lifetime QALYs (0.61) than meropenem ($4,472/QALY gained). In the initial treatment setting, C/T sustained a better clinical performance (9.5% more cure, −6.8% mortality, 1.16 more QALYs), yet cost less than meropenem (−$5,662) due to better susceptibility. The response and mortality rates from ASPECT-NP had the greatest impact on results. SAs showed that the result of C/T being cost-effective over meropenem was generally robust.

Conclusion
The results indicate that, compared with meropenem, C/T could be a cost-effective option for patients with vHABP/VABP in the US setting.

Disclosures
All authors: No reported disclosures.
115. Evaluation of the Clinical Impact of the T2MR for the Diagnosis of Bloodstream Infections
Authors: Seitz Tamara , Baumgartner Sebastian , Wenisch Christoph , Zoufaly Alexander 
Published: October 2019

Abstract

Background
The EK-189 study evaluates the clinical impact of T2 magnetic resonance (T2MR) for rapid detection of bloodstream infections (BSI) caused by ESKAPE-pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli) compared with blood culture (BC). Here we present preliminary results from this ongoing study.

Methods
Patients newly admitted to an infectious diseases department with suspected blood stream infection with ESKAPE pathogens (based on predefined criteria) are included and randomized into BSI diagnosis with (a) T2MR and blood culture or (b) blood culture alone. Routine diagnostic workup including chest X-ray, complete laboratory workup (including blood count, C-reactive protein, interleukin-6) is performed in all patients. Antibiotic regimens are selected empirically based on suspected pathogens and are switched to targeted therapy at the discretion of the treating physician once a pathogen is detected. Outcome parameters include time to targeted (predefined) antibiotic therapy and time to discharge. Test characteristics of the T2MR compared with BC are also assessed.

Results
So far 44 patients were included (22 in each group). In 9/22 patients (41%) in the T2MR-group a pathogen was detected (4 Escherichia coli, 2 Klebsiella pneumoniae, 1 Staphylococcus aureus, 1 Pseudomonas aeruginosa and 1 Acinetobacter baumanii) and in 3/22 (14%) patients in the BC-group (all E. coli). The comparison of T2MR vs. BC is depicted in Table 1. Sensitivity and specificity of T2MR in comparison to BC were 100% and 64.7%. All positive results in T2MR were considered true positive results. The days until clinical improvement, the need for admission at ICU and the in-hospital mortality were similar in both groups.

Conclusion
The results from this preliminary analysis show that in patients with suspected BSI with ESKAPE pathogens, T2MR detects more pathogens than BC and potentially provides a quicker detection and shorter time to targeted therapy. Further analyses of this ongoing study with a larger sample size are needed to evaluate the impact of the use of T2MR on patient’s outcome

Disclosures
All authors: No reported disclosures.
2223. Real-time Prediction of Respiratory Pathogen Infection Based on Machine Learning Decision Support Tool
Authors: Nir-Paz Ran , Almogy Gal , Keren Arie , Livne Guy , Amit Sharon , Wolf Dana , Moses Allon E 
Published: October 2019

Abstract

Background
Respiratory pathogens are a common cause of disease. Currently there is not a practical tool to predict the putative etiology of each case with an inexpensive, fast point-of-care assay. Here, we describe a decision support tool that enables the prediction of both bacterial and viral respiratory pathogen infections in a single patient, using a Machine Learning model.

Methods
The data were obtained from the Hadassah-Hebrew University Medical Center during a period of 10 years beginning from 2007 and contained more than 40,000 patients from a 1,000,000-population community for whom specimens were tested by either PCR or culture. The pathogens included were, H. influenzae; M. catarrhalis; S. pneumoniae; M. pneumoniae; Adenovirus; Human metapneumovirus; Influenza H1N1, A, B; parainfluenza 1,2 and 3; and RSV. We then created a Machine-Learning algorithm to simulate the spread of infection in the entire Jerusalem area. We defined transmission areas based on geographical distances of patients’ home-addresses. Then we prospectively tested the tool accuracy over a 4-month period, in addition to real-time improvement of the model.

Results
Initial model was created based on gender, age, home addresses and the diagnostics test results. We then reconstructed a putative spread pattern for each of the pathogens that can be correlated to potential “transmission routes.” The initial prediction tool had an AUC for most pathogens around 0.85. It ranged from 0.75 to 0.8 for the bacterial and 0.82 to 0.89 for the viral pathogens. In almost all pathogens the NPV was 0.98–0.99. We then tested the decision support tool prospectively over four consecutive months (January to April 2019—1,700 patients with respiratory complaints from whom samples were sent to the lab). While the AUC in the prospective cohort was 0.81 on average, the NPV remained high on 0.98.

Conclusion
The implementation of the decision support tool on respiratory pathogen diagnostics enables better prediction of patients not infected with either viral or bacterial pathogens. The use of such a tool can save more than 50% of diagnostic tests expenses as well as real-time mapping of disease spread. Improvement of the Machine Learning protocol may further promote the optimization of positive predictive values.

Disclosures
All authors: No reported disclosures.
119. Nocardia Bacteremia Is Almost Always Associated with Immune Compromise or an Intravascular Device: Single-Center Case Series and Systematic Review of the Literature
Authors: Williams Eloise , Jenney Adam W , Spelman Denis W 
Published: October 2019

Abstract

Background
Nocardia bacteremia is a rare but important phenomenon, with previous studies describing a 50% mortality rate. We undertake a single-center review and the largest systematic review of Nocardia bacteremia performed over the past 20 years.

Methods
A single-center review of cases of Nocardia bacteremia was performed using hospital microbiology records from January 1, 2010 to December 31, 2017. A systematic literature review was also performed to identify cases of Nocardia bacteremia described in the English language literature between January 1, 1999 and December 31, 2018 using the NCBI PubMed database and snowballing from citations of relevant publications.

Results
Single-center case series: Four cases of Nocardia bacteremia are described. Three patients had an intravascular device in situ prior to the onset of Nocardia bacteremia and three patients were immunocompromised; one patient had both risk factors. Systematic literature review: A systematic review identified 50 publications that described 85 cases with sufficient patient data to be reviewed in detail. Including the 4 cases described in our institution, 89 cases of Nocardia bacteremia were included in the analysis. The median age was 57 years [interquartile range (IQR) 42–68] and 69% were male. Eighty-two percent of cases were immunocompromised and 38% had endovascular devices. Pulmonary infection was the most common concurrent site of clinical disease (66%), followed by central nervous system (25%), pleural (17%) disease, and endocarditis (11%). Blood cultures were the only positive microbiological specimen that isolated Nocardia in 45% of cases. Median incubation time to blood culture positivity was 4 days [IQR 3–6]. Thirty-day all-cause mortality was 24% and overall all-cause mortality was 42%.

Conclusion
Four new cases of Nocardia bacteremia are described. Isolation of Nocardia from blood cultures is rare but represents serious infection with high associated overall mortality. Nocardia bacteremia is most frequently identified in immunocompromised patients and those with intravascular devices.

Disclosures
All authors: No reported disclosures.
2263. Fosfomycin Trometerol Use for Complicated UTIs Including Pyelonephritis, a 1-year Review of Outcomes and Prescribing Habits
Authors: Hatlen Timothy J , Flor Richard , Nguyen Megan , Miller Loren G 
Published: October 2019

Abstract

Background
Treatment of complicated urinary tract infections (UTI) caused by multidrug-resistant organisms (MDROs) is increasingly problematic given limited oral antibiotic options. In these situations, fosfomycin is increasingly used. However, there are limited outcome and pharmacokinetic data to support fosfomycin use for complicated UTIs (cUTI), especially in the upper tract. We describe fosfomycin use for complicated cUTI in our healthcare system.

Methods
We performed a retrospective review of all fosfomycin prescriptions between 1/1-December 31/17 in the Los Angeles Department of Health Service system, which consists of 4 medical centers and 19 clinics that provide care to >600,000 patients annually. In our system, fosfomycin use requires ID approval. We collected demographics, clinical characteristics, adverse effects, and 30-day success rates. Subsequent urine cultures up to December 31/18 were examined for fosfomycin susceptibility.

Results
A total of 156 patients received fosfomycin; 21 (13%) had lower UTI, 39 (25%) had lower tract cUTI, 24 (15%) had upper tract not pyelonephritis, and 37 (24%) had pyelonephritis. The majority (n = 98, 63%) were female, 82 (53%) had urological or functional abnormalities, 67 (43%) had diabetes, 26 (17%) were immunocompromised and most (n = 135, 87%) presented from the community. E.coli was the predominant pathogen (n = 123, 79%), 112 (91%) of these produced ESBL. For cUTI (n = 100), dosing interval was q24h (3%), q48h (51%) and q72h (46%). Among patients with 30-day outcomes (n = 100, 64%), success was seen in 84 (84%), and was 79% (14/64) among those with cUTI. Failure was associated with male gender (p = 0.005), urological abnormalities (p = 0.047), and non-E. coli UTIs (p = 0.03). Only 1 adverse effect at 30 days was described. Fosfomycin-resistant E. coli were found in 9/64 (14%) of patients with follow-up urine cultures > 30 days after initial treatment (mean 5.7 ± 4.03 mo.).

Conclusion
Despite the lack of data supporting its use, we found that most patients receiving fosfomycin for complicated upper UTIs had clinical success. However, emergence of subsequent resistance warrants caution. Further studies should be done to better understand optimal use of fosfomycin for complicated UTIs.

Disclosures
All authors: No reported disclosures.
2264. An Evaluation of Empiric Treatment Patterns for Adult Patients with Community-Onset (CO) “Low-Risk” (LR) Complicated Intra-Abdominal Infections (cIAI) Across US Hospitals
Authors: Lodise Thomas , Izmailyan Sergey , Olesky Melanie , Lawrence Kenneth , Tsai Larry 
Published: October 2019

Abstract

Background
Current cIAI guidelines recommend that broad-spectrum antibiotics (abs) like anti-pseudomonal β-lactams should be reserved for “high-risk” CO cIAI patients. Fluoroquinolone (FQ) use is also discouraged in geographic areas with a high incidence of FQ-resistance. Compliance with these recommendations are unclear as there are limited data on empiric treatment (tx) patterns for adult patients with cIAI across US hospitals. This study sought to evaluate empiric tx patterns for patients with CO LR cIAI and assess compliance with cIAI guideline recommendations.

Methods
A retrospective multi-center study using data from the Premier Research Database (October 2015–December 2017) was performed. Inclusion criteria: age ≥ 18 years; hospitalized; primary cIAI diagnosis and a cIAI surgical procedure or a secondary cIAI diagnosis and cIAI surgical procedure within 5 days of admission; and received an ab within first 4 hospital days. For patients with multiple cIAI admissions, only the first cIAI was considered. Apt was classified as high-risk (HR) if they met any one of the following criteria: sepsis, severe sepsis, septic shock; ≥3 components of sepsis; or ≥2 two physiologic risk factors (age ≥ 70 years, malignancy, kidney dysfunction, hepatic dysfunction, hypoalbuminemia, and significant cardiovascular compromise). Empiric tx was abs received during the first 4 hospital days. Incidence of empiric tx regimen including one of the following abs was determined among LR patients: piperacillin/tazobactam (TZP), meropenem (MER), cefepime (CFP), and FQ.

Results
Overall, 70,275 patients met study criteria; 11,382 (16%) were HR and 58,893 (84%) were LR. Among LR CO cIAI patients, the mean (SD) age was 54.3 (18.1), 52% were male, and the median (IQR) for Charlson Comorbidity Index was 0 (0–1). The most common diagnosis among LR patients was acute appendicitis with peritonitis (53%). The 10 most common empiric antibiotics administered are shown in table. Among LR patients, 52% received TZP, 3% received MER, 3% received CFP, and 20% received a FQ; 8% received ≥2 of these agents.

Conclusion
Overuse of non-guideline concordant broad-spectrum abs was commonplace among CO cIAI patients classified as LR. These findings can serve as the basis for an antimicrobial stewardship initiative in hospitals aspiring to reduce the use of broad-spectrum antibiotics.

Disclosures
All authors: No reported disclosures.
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

Abstract

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

Abstract

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.