bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Procalcitonin (PCT)-Guided Antibiotic Therapy on Mortality in Critically Ill Patients: A Systematic Review and Meta-Analysis of 18 Randomized Controlled Trials
Authors: Pepper Dominique , Sun Junfeng , Rhee Chanu , Welsh Judith , Powers John H , Danner Robert L , Kadri Sameer 
Published: October 2017

Abstract

Background
Procalcitonin (PCT)-guided antibiotic therapy has been shown to reduce antibiotic use in critically ill patients with suspected or proven infection, but its impact on mortality remains uncertain. Our meta-analysis examines the effect of PCT-guided antibiotic therapy on survival in critically ill patients.

Methods
We searched PubMed, the Cochrane Library, Scopus, Web of Science, EMBASE and clinicaltrials.gov electronic databases up to October 2016. The meta-analysis was restricted to randomized controlled trials (RCTs) of critically ill patients receiving PCT-guided antibiotic treatment and reporting survival or antibiotic duration. Study quality was assessed using the Cochrane risk of bias tool. Two reviewers conducted all review stages independently, and a third reviewer adjudicated any differences. Data was pooled using random-effects meta-analysis.

Results
Of the 18 RCTs selected (n = 5,183 patients; Table), 17 assessed mortality and 11 assessed antibiotic duration; 8 scored ≥3 and 10 scored ≤2 out of 6 on the risk of bias assessment. Compared with controls, PCT-guided antibiotic treatment was associated with a significant reduction in mortality (20.7% vs. 23.0%; risk ratio [RR] 0.90[95% CI, 0.81–0.99], I2=0%; Figure 1). Survival benefit was retained in the RCT subset with a lower risk of bias (score ≥ 3; RR 0.87 [95% CI, 0.77,0.98], I2=0%; Figure 2) but not with higher risk (score ≤ 2; RR 0.98 [95% CI, 0.80–1.20], I2=0%). Our analysis of the effect of PCT-guided antibiotic therapy on antibiotic duration displayed significant heterogeneity (I2=61.2%, P = 0.004), which precluded reporting on aggregate effect. Important limitations were: single center RCT (n = 9), lack of double blinding (all studies) and variable protocol non-adherence and timeframes examined for mortality.

Conclusion
In a meta-analysis of RCTs of critically ill patients with suspected or proven infection, PCT-guided antibiotic treatment was associated with a significant reduction in mortality. The observed survival benefit was weighted towards RCTs of relatively higher quality. However, the plausibility of this finding, as well as the impact of protocol non-adherence on outcome needs further study.
Funded by Intramural NIH and NCI Contract# HHSN261200800001E

Disclosures
All authors: No reported disclosures.
Biomarker-based Assessment of Urinary Tract Infection in Persons with Spinal Cord Injury
Authors: Mansouri M David , Thiagarajan Perumal , Mansouri Dena , Holmes S Ann 
Published: October 2017

Abstract

Background
Urinary tract infection (UTI) is the most common infection and the second leading cause of death in spinal cord injury (SCI) patients. However, there is currently no consensus about the clinical criteria for UTI in SCI patients and the lack of a universal definition of asymptomatic bacteriuria (ABU) make the diagnosis even more complex and the treatment recommendations problematic. Prompt diagnosis and timely treatment of UTI are important to prevent possible progression to sepsis. Elevated concentrations of some biomarkers may be correlated with infection and their serial measurements may be helpful to assess the effectiveness of antibiotic therapy.

Methods
Fifteen SCI participants were enrolled for either lower UTI, upper UTI (pyelonephritis), ABU, or control. Patients suspected of having any inflammation or infection other than UTI were excluded. Participants were monitored for their serum procalcitonin (PCT) and c-reactive protein (CRP) levels initially and every 3 days once the UTI was confirmed and antibiotics prescribed. In addition, the urine was cultured initially and every three days in patients with UTI for correlation with biomarkers. UTI/ABU was assessed by patient’s physician.

Results
Both mean initial PCT and CRP were significantly higher in patients with lower UTI (P = 0.027 and P = 0.001, respectively) and those with upper UTI (P = 0.044 and P &lt; 0.0001, respectively) compared with control and ABU participants. PCT and CRP were generally reduced to the normal levels gradually during the course of antibiotic therapy for those patients with UTI that were placed on antibiotic therapy. Mean bacterial colonies grown from initial urine cultures in patients with upper or lower UTI were &gt;100,000 CFU/mL. Control participants had urine cultures of ≤1,000 CFU/mL). Generally, cultures from UTI patients placed on antibiotics were negative for the organism(s) treated for during or after the completion of antibiotic therapy.

Conclusion
Serum concentrations of CRP and PCT may be used to aid in the early assessment of UTI in SCI patients in the absence of other sources of inflammation and/or infection. In general, CRP measurements are more pronounced than PCT measurements in patients with ABU or lower UTI. However, PCT levels elevate conspicuously in patient with pyelonephritis.

Disclosures
All authors: No reported disclosures.
Serum Procalcitonin as a Marker for Infection in Patients with Acute Myocardial Infarction
Authors: Vitkon-Barkay Itzhak , Lazarovitch Tsilia , Marchaim Dror , Segaloff Hannah , Zaidenstein Ronit , Minha Sa’ar 
Published: October 2017

Abstract

Background
Significant proportion of patients with acute myocardial infarction (AMI) also present with systemic inflammatory response syndrome (SIRS). Thus it is difficult to determine in certain situations, whether empiric antibiotic treatment is warranted. Serum procalcitonin (PCT) is known to be elevated in bacterial infections, but its performances in predicting bacterial infection among patients with AMI, who might benefit from appropriate empiric management, is unknown.

Methods
A prospective observational study was conducted at Assaf Harofeh Medical Center, Israel. Serum PCT was collected within 48 hours from patients presenting with AMI. Demographic, clinical, and laboratory data, were collected prospectively. Two experienced Infectious Diseases (ID) specialists who were blinded to the PCT results, independently determined the gold standard for infection in every patient. By utilizing sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the ROC curve (AUC), the performance of PCT, fever, white-blood cells (WBC) count and C-reactive protein (CRP) for infection diagnosis was calculated.

Results
The analysis included 230 AMI patients (age 63.0 ± 13.0 years), of which 36 (15.6%) were determined to be infected. The best cutoff for PCT as a differentiating marker between infected and non-infected patients was achieved at 0.09ng/dl (sensitivity 94.4%, specificity 85.1%, AUC ROC 0.94). This test outperformed CRP, WBC, and fever, for infection diagnosis (figure).

Conclusion
PCT should be utilized for ruling out infection in AMI patients by utilizing serum PCT&gt;0.09ng/dl (i.e., ≥0.1ng/dl) as a cutoff.

Disclosures
All authors: No reported disclosures.
Impact of a Pharmacist-Driven Respiratory Viral Panel Stewardship Program on Antibiotic Exposure Within a Multicenter Community Health System
Authors: Cubillos Ashley , Estrada Sandy , Bachmeier Harrison , Turner Edgar 
Published: October 2017

Abstract

Background
Strategies to ensure optimal use of multiplex polymerase chain reaction (mPCR) testing results for antimicrobial stewardship in acute respiratory infections remain to be elucidated. This study sought to assess the impact of pharmacist intervention (by means of prospective feedback to prescribers) on overall antibiotic exposure in patients with viral-positive mPCR Respiratory Viral Panel (RVP) laboratory test results.

Methods
This retrospective cohort study included patients ≥18 years of age admitted to an acute care hospital with a viral-positive nasopharyngeal FilmArray Respiratory Panel test result receiving antibiotics for a suspected respiratory tract infection. Immunocompromised patients, patients with RVP samples from bronchiolar lavage, patients in the intensive care unit when samples were obtained, and patients receiving antibiotics for non-respiratory infections were excluded. Antibiotic exposure days, antibiotic discontinuation at 72 hours, and culture-positive bacterial superinfection were compared in two cohorts of patients, before and after the rollout of an educational pharmacist RVP stewardship initiative.

Results
Median antibiotic exposure days did not differ between the pre- and post-intervention groups (6 days vs. 7 days, P = 0.20). Antibiotic discontinuation at 72 hours was significantly lower in the post-intervention group (38% vs. 25%, P = 0.02). More patients in the post-intervention group had positive bacterial respiratory cultures (2.7% vs. 10%, P = 0.007) and chest radiographs suggestive of pneumonia (34.7% vs. 46%, P = 0.05). Patients with peak serum procalcitonin levels &lt;0.25 ng/mL were more likely to have antibiotics discontinued at 72 hours than those with peak levels ≥0.25 ng/mL (36% vs. 0%, P = 0.02).

Conclusion
An antimicrobial stewardship initiative by pharmacists among patients with viral-positive RVP results did not appear to impact antibiotic exposure days. Serum procalcitonin levels appeared to influence antibiotic discontinuation decisions. Alternative strategies for maximizing the antimicrobial stewardship impact of RVP testing should be explored.

Disclosures
All authors: No reported disclosures.
Multidisciplinary Approach to Improve Utilization and Cost Savings of Multiplex Polymerase chain reaction (PCR) Respiratory Pathogen Testing in a Large Community Hospital
Authors: Hassoun Ali , Edwards Jonathan 
Published: October 2017

Abstract

Background
PCR technology can be used for precise detection of infectious agents and improves antibiotic stewardship through: Accelerated de-escalation of therapy Rapid identification of pathogens Detection of resistance genes. In our center, basic respiratory Panel detect 11 targets and cost $100 while Complete panel detect 31 targets and cost $230.The purpose of the study is to improve utilization of these panel testing in a large community hospital.

Methods
Retrospective chart review of all patients with an order for a complete or basic panel and excluding Patients discharged or deceased prior to result reporting or insufficient specimen quantity to perform. Each patient was evaluated for appropriate respiratory panel collection site and antibiotic regimen changes within 48 hours of results. The preintervention period conducted from 10/2015- 12/2015, evaluated how respiratory panels were being utilized in antibiotic decision-making. Three primary interventions were enacted: Eliminated nasal swabs as a source option for respiratory panels in the clinical information system, restricted complete panel ordering to ID physicians and Eliminated PCR ordering options from all order sets. The postintervention period conducted from 5/2016 – 8/2016, re-evaluated the utilization and costs of respiratory panels.

Results
270 tests ordered preintervention (13% basic and 87% complete) and 196 postintervention (84% basic and 16% complete), nasal swab was done in 78% in preintervention vs. 8% in postintervention, action was taken in 51 vs. 44 in pre-vs. post intervention. cost in preintervention period was 57,420 in preintervention vs. 23,660 in post intervension. No difference between ID vs. non-ID specialist in utilization of PCR.

Conclusion
Nasal swab collections for PCR decreased post-intervention from 78% to 8%. Appropriate sources for PCR specimen, such as sputum, were utilized during the post-intervention period. Post-intervention utilization of the panel results was comparable to pre-intervention period. Elimination of PCR respiratory panels from order sets and restrictions of complete respiratory panel ordering to ID physicians resulted in $33,760 saved.

Disclosures
All authors: No reported disclosures.
Enteropathogen Identification by Multiplex PCR in Guatemalan Children with Acute, Non-bloody Diarrhea
Authors: Melgar Mario , Lamb Molly , Calvimontes Diva M , Asturias Edwin J , Contreras-Roldan Ingrid , Dominguez Samuel , Robinson Christine C , Berman Stephen , Gaensbauer James 
Published: October 2017

Abstract

Background
Diarrhea is a leading cause of morbidity and mortality in children in low and middle income countries (LMICs). Assessing diarrhea etiology in LMICs is of great importance in order to better develop both therapeutic and public health strategies, but is hampered by the complexity of potential diarrheal pathogens, and diverse methodology needed for pathogen identification

Methods
Subjects 6 to 35 months old with acute, moderate severity, non-bloody diarrhea were enrolled in a diarrheal treatment trial, conducted at one rural (N = 172) and two urban sites (N = 144) in Guatemala. Diarrheal pathogens were determined in stool by multiplex PCR (FilmArray GI® Biofire) which allows simultaneous identification of 23 bacterial, viral, parasitic pathogens. Descriptive statistics on demographics, pathogen load, and differences in pathogen occurrence by site were performed; differences were assessed with t-test and chi2 test

Results
Nearly all (96.8%) subjects had pathogens identified, and most had multiple potential pathogens identified (mean pathogen count: 2.7 urban and 4.8 rural; P &lt; 0.001 (Figure 1). Notable pathogen differences were observed between rural and urban populations. Bacteria (particularly E.coli pathotypes and Campylobacter) and protozoa (particularly giardia) were more common in the rural population (Figure2). Viral pathogens were either similar or more common (norovirus; P = 0.04) in the urban population; rotavirus was uncommon in both sites (10 rural and 12 urban cases). A similar pattern of pathogen evolution with patient age was noted in both settings, with a decrease in the relative number of viral and increase in parasitic pathogens (Figure 3). Important demographic and socioeconomic differences between rural and urban were noted: rural subjects had poorer nutritional status, underdeveloped water and sanitation facilities and more domestic animal exposure

Conclusion
Acute diarrheal episodes in Guatemalan children were associated with a complex spectrum of pathogens when determined by multiplex PCR, with distinct patterns in rural and urban populations. Future studies to precisely determine diarrheal etiologies in LMICs will need to incorporate controls to sort causative organisms from those colonizing the intestine.

Disclosures
All authors: No reported disclosures.
Appropriateness of a Rapid Multiplex Gastrointestinal Panel in the Investigation of Suspected Infectious Diarrhea After Implementation at an Academic Medical Center
Authors: Beatty Norman , Nix David , August Jessica , Swazo Roberto , Kottey Janame , Mckeown Kyle , Alshibani Mohannad , Petty Wanda , Matthias Kathryn , Al Mohajer Mayar 
Published: October 2017

Abstract

Background
The BioFire FilmArray™ Gastrointestinal (GI) Panel is a 1 hour multiplex real-time PCR test that can detect the presence of 22 GI pathogens (viral, bacterial, and parasitic) known to cause infectious diarrhea. Our tertiary-care academic medical center implemented the GI Panel for all cases of suspected infectious diarrhea replacing the previous conventional testing once utilized to detect GI pathogens. Since its implementation we have not had any criteria for ordering this test to aid healthcare providers.

Methods
The aim of this IRB approved, retrospective investigation was to determine the appropriateness of ordering the GI panel at our academic institution. Cases were randomly selected, stratified by age group and result (specific pathogens or negative result) from May 2015 through April 2016 in the post-implementation period (n = 400 of 1117 total tests). We developed appropriateness criteria for ordering the GI panel which included: passage of at least 3 unformed stools in 24 hours plus one or more enteric symptom (nausea, vomiting, abdominal pain/cramps, tenesmus, fecal urgency, moderate to severe flatulence), and one of the following: grossly bloody diarrhea (dysenteric), persistent diarrhea (14 – 30 days), worsening or relapsing diarrhea, fever ≥ 101 F°, severe diarrhea &gt; 10 bouts in 24hrs, immunosuppression, pregnancy, food handler, infant &lt; 1 year and their care takers, age ≥ 65 years old, concern for disseminated GI infection, with no previous GI panel testing in the past 30 days.

Results
Overall appropriateness of GI panel testing based off our generated criteria was 36% (n = 144/400). This included all tests ordered in the outpatient clinics, emergency department, inpatient medical/surgical wards, and intensive care units.

Conclusion
Currently there is not a well-established standard criteria for ordering the GI panel for investigating suspected infectious diarrhea. After implementation at our academic tertiary-care medical center the GI panel was used inappropriately in most cases without a criteria for ordering in place to aid clinicians. Educating healthcare providers about appropriate testing indications is being performed. Further studies are needed to assess if our generated criteria will lead to decreased costs and unnecessary testing.

Disclosures
All authors: No reported disclosures.
Risk Factors and Clinical Outcomes of Cancer Patients with Clostridium difficile Associated Diarrhea Co-infected with a Second Enteropathogen
Authors: Yalamanchili Harika , Chao Andrew , Guevara Eduardo Yepez , Aitken Samuel L , Bhatti Micah , Okhuysen Pablo C 
Published: October 2017

Abstract

Background
Cancer patients are at an increased risk for C. difficile infection (CDI) which is often identified along with other enteropathogens. The impact of co-infections on outcomes has not been established in this population. We compared the risk factors and clinical characteristics of patients with CDI monoinfection (CDIM) and patients coinfected with bacterial (CDIB) or viral (CDIV) enteropathogens.

Methods
Adult patients presenting with primary or recurrent CDI (n = 88) identified on a two-step GI multiplex assay (Biofire) followed by toxin A/B EIA, were classified into CDIM (n = 66), CDIB (n = 12), and CDIV (n = 10) groups. Demographic and clinical data were collected and risk factors and outcomes compared by Fisher’s exact test, ANOVA, and the Kruskal–Wallis test. CDI severity was determined using Zar’s criteria, presence of bacteremia, and ICU stay.

Results
During the study period, 2,017 diarrheal samples were submitted to the microbiology laboratory. An enteric pathogen was identified in 311 (15%) patients. CDI was identified in 88 cases of which 22 (25%) had a second pathogen. CDIM was found in 66 (21%), CDIB in 12 (4%), and CDIV in 10 (3%) subjects. The most common co-pathogens identified were diarrheagenic E. coli in the CDIB group (9/12, 75%) and norovirus in the CDIV group (8/10, 80%). Groups were similar in terms of demographics, number of recurrences, health care acquisition, co-morbidities, disease severity, serum creatinine at presentation, presence of toxin by EIA, and mortality. Patients with CDIM were more likely to have a recent hospitalization than the CDIB group (44/66 67% vs.. 3/12 25%, P = 0.01). Clinical symptoms at presentation were similar for the three groups except for nausea which was more common in the CDIV group when compared with CDIM (8/10, 80% vs. 25/66, 38%; P = 0.02). The use of proton pump inhibitors was similar in the three groups. There was however, a higher proportion of patients taking GABA-like drugs within 90 days among the CDIB patients (10/12, 83%) than the group with CDIM (26/66, 40%) P = 0.01.

Conclusion
In CDI cancer patients, co-infection with other enteropathogens is common. Patients with CDIB were less likely to have a recent admission to a health care facility. The use of GABA-like drugs was associated with a higher risk of bacterial co-infection.

Disclosures
All authors: No reported disclosures.
Genetic Variation in Shiga Toxin-producing Escherichia coli Recovered from Patients in Michigan and Connecticut
Authors: Selheimer Heather , Mosci Rebekah , Rudrik James , Manning Shannon 
Published: October 2017

Abstract

Background
Shiga toxin-producing Escherichia coli (STEC) is a gram-negative foodborne pathogen that causes approximately 265,000 illnesses in the US annually. STEC O157 and six non-O157 STEC serotypes are most commonly associated with illness, though variation exists in the ability of different STEC types to cause disease. Consequently, we sought to examine genetic variation in virulence genes and clustered regularly interspaced repeat (CRISPR) loci among clinical strains of diverse lineages from different geographic locations.

Methods
Isolates were collected from a sentinel surveillance in 2000–2006 by the Michigan Department of Health and Human Services (n = 44) and Connecticut Department of Public Health (n = 115). Whole genome sequencing was performed and genes for O-antigen (serotype), multilocus sequence typing (MLST) and virulence factors were extracted. CRISPRFinder and Geneious were used for CRISPR loci.

Results
A phylogenetic tree based on MLST found no geographic clustering of the strains. Similarly, no difference was observed for stx1 (MI: 89.6%, CT: 83.5%), stx2 (MI: 6.9%, CT: 7.1%), stx1/stx2 (MI: 3.4%, CT: 9.4%), ehxA (MI: 80.0%, CT: 81.2%) and eae (MI: 86.7%, CT: 94.1%) frequencies across geographical locations. Although the CRISPR loci were similar within related STs, which was independent of serotype, some variation was detected between locations.

Conclusion
These data highlight the circulation of common non-O157 STEC lineages capable of causing disease in different populations. Strains had similar virulence gene profiles, though the diversity of the CRISPR loci varied across strains. The latter could be impacted by varying selective pressures that could affect disease frequencies and symptom severity. Continued surveillance of non-O157 STEC is needed to elucidate the genetic characteristics that are most important for disease severity.

Disclosures
All authors: No reported disclosures.