bluuebunny/crossref_metadata_2025_split huggingface dataset:
1504. Epidemiology and Etiology of Pyogenic Liver Abscess in the Calgary Health Zone: A Population-Based Study
Authors: Losie Jennifer A , Lam John , Gregson Dan , Parkins Michael 
Published: October 2019

Abstract

Background
Pyogenic liver abscess (PLA) is a significant cause of morbidity and mortality. Epidemiological data regarding risk factors and outcome determinants are often ascertained from referral population bases. We utilized a population-based study design to better understand PLA.

Methods
Calgary Health Zone (CHZ) residents ≥18 years of age (population ~1.3 million) who were hospitalized with PLA in 2017 were included. Charts were manually reviewed to determine demographics and clinical outcomes. Univariate and multivariate logistic regression were used to assess for factors associated with 30-day mortality using STATA 15.1 (College Stn., TX).

Results
Forty-four patients with PLA were identified (39% female, median age 61 [IQR 56–68] years) corresponding to an incidence rate of 3.7 cases per 100,000 population. Prevalent co-morbidities with PLA included; hemodialysis dependence (4.5%), cancer (25%), diabetes (23%), and cirrhosis (6.8%), each of which was significantly more common (P < 0.05) than in the general population; 85.3X, 11.2X, 3.6X, 29.9X, respectively. Rates of other comorbidities including ischemic heart disease, COPD, and rheumatoid arthritis did not differ from general populations (P > 0.05). The etiology of PLA was established in 72% of cases, of which biliary was most common (48%). Most (91%) cases had at least one organism identified via blood or liver aspirate culture. The most common organisms were Streptococcus anginosus group (12), Klebsiella pneumoniae (11), Klebsiella oxytoca (6), Escherichia coli (4), and obligate anaerobes (3). Blood cultures were positive in 25/44 (56%) cases. Thirty-day mortality from admission was 11% and had multiple risk factors (Table-1).

Conclusion
PLA in the CHZ is common and associated with high mortality. Understanding factors influencing PLA occurrence and outcome can assist in correctly identifying and optimally treating patients.

Disclosures
All authors: No reported disclosures.
1507. Pharmacodynamic Target Attainment of Daptomycin Against Staphylococcus aureus for Treatment of Pediatric Osteomyelitis
Authors: Stimes Grant , Girotto Jennifer E , Courter Joshua D 
Published: October 2019

Abstract

Background
Daptomycin (DAP) is lipopeptide that frequently is used to treat infections caused by Staphylococcus aureus in adult patients. There are limited data using daptomycin in pediatric patients for the treatment of osteomyelitis caused by S. aureus. This study’s objective is to describe pharmacodynamic (PD) target attainment of daptomycin in pediatric patients with osteomyelitis.

Methods
Medline was queried to obtain PD targets, pediatric pharmacokinetic models, and bone penetration information to build a model for DAP. A 10,000 subject Monte Carlo simulation was performed to estimate steady-state concentrations in the bone. Simulations modeled 30-minute infusions with using 12 mg/kg/dose IV q24h for patients less than 7 years and 10 mg/kg/dose IV q24h for patients 7 years and older. Goal PD targets were: AUC24: MIC of 666 μg hours/mL for log1 killing and AUC24: MIC of 1,061 for log2 killing. The CLSI breakpoint of 1 mg/L was used as a starting point and MIC’s were analyzed below that level.

Results
PD target attainment in percentages is listed for DAP below in Tables 1 and 2 and are separated by age groups of patients.

Conclusion
The studied DAP doses did not reach any PD target attainment at the CLSI breakpoint of 1 mg/L. Based on these data, DAP should not be empirically used to treat SA osteomyelitis unless the exact MIC is known. Furthermore, modern pediatric pharmacokinetic studies of DAP for pediatric osteomyelitis are warranted.

Disclosures
All authors: No reported disclosures.
1512. Treatment of Staphylococcus aureus Bacteremia in a Pediatric Population: A Retrospective Cohort Analysis
Authors: Gunter Sarah G , Stover Kayla R , Barber Katie , Wagner Jamie , Joyce Wingler Mary , Cretella David A 
Published: October 2019

Abstract

Background
Staphylococcus aureus bacteremia (SAB) is a well-known cause of morbidity in pediatric patients; however, limited data are available regarding optimal antimicrobial therapy. The purpose of this study was to assess treatment outcomes associated with intravenous (IV) vs. oral (PO) stepdown treatment of SAB in a pediatric population.

Methods
This study evaluated patients who were admitted between July 2012 and August 2018, between the ages of 3 months and 18 years, had a blood culture positive for S. aureus, and received at least 72 hours of inpatient treatment. Exclusion criteria were as follows: pregnancy, death within 72 hours of initial culture, hospice/palliative care, polymicrobial bacteremia, and previous SAB within the study period. The primary endpoint was 30-day readmission rates. Secondary endpoints included hospital length of stay and all-cause inpatient mortality.

Results
In total, 101 patients were included (43 IV therapy alone; 58 PO stepdown). The median age was 7.9 years (IQR, 3.0, 12.2; range 4 months to 16.7 years), and 52.5% were male. The most common primary foci of infection were osteomyelitis (n = 32), device-associated infections (n = 23), and skin/soft-tissue infections (n = 8). Most patients (56.4%) had no comorbidities. There were no significant differences in comorbidities between groups except the IV group had significantly more immunosuppressed patients (30.2% vs. 1.7%; P < 0.001). Methicillin resistance was noted in 56.4% of patients (62.8% IV group vs. 51.7% PO stepdown; P = 0.313). The most common IV agents were vancomycin (n = 51) and anti-Staphylococcal penicillins (n = 21), while the most common PO agents were clindamycin (n = 29) and cephalexin (n = 20). Thirty-day readmission occurred in 25.6% (n = 10) of patients receiving full-course IV therapy and 5.3% (n = 3) in the PO stepdown group among survivors (P = 0.006; n = 96). Median length of stay was 11.0 days (IQR, 8.0, 21.0) in the IV group and 7.0 days (IQR, 5.0, 11.0) in the PO stepdown group (P = 0.001). All-cause inpatient mortality occurred in four patients (9.3%) in the IV group compared with one (1.7%) in the PO stepdown group (P = 0.160).

Conclusion
Patients in the PO stepdown group had a low rate of 30-day readmissions and had a significantly shorter hospital length of stay than patients who received a full IV course.

Disclosures
All authors: No reported disclosures.
1513. Management of Children with Blood Cultures (BC) Positive for Nonpathogenic Organisms After the Introduction of Polymerase Chain Reaction (PCR) Technology
Authors: Hughes Julianne , Barone Stephen 
Published: October 2019

Abstract

Background
Traditionally, clinicians would wait for the absence of growth in BC for 48 hours to consider a BC negative. A BC with a positive gram stain necessitated a repeat BC and antibiotics prior to final identification. Blood culture identification (BCID) PCR has the potential to shorten this time course, particularly with pathogens that are considered “contaminants.” There is no published data which addresses the clinical significance of more rapidly identifying contaminants.

Methods
This is a retrospective chart review of data collected from children (ages 2 months- 18 years) treated at Cohen Children’s Medical Center, who had a positive BC deemed a contaminant. A 2.5-year period prior to and after implementation of PCR technology was observed (September 2015–November 2018). A contaminant was defined as bacteria that is not considered virulent in an immunocompetent patient. Patients with indwelling catheters, those who have undergone corrective cardiac surgery or are immunocompromised were excluded from analysis. Data collected included length of stay, antibiotic duration and whether a patient received a repeat BC.

Results
136 patients during this time (49% (n = 67) pre-PCR and 51% (n = 69) post-PCR) had positive BC for nonvirulent bacteria. Patients in the pre-PCR period received BC only, while those in the post-PCR period received both BC and PCR, with all BC and PCR results being concordant. The proportion of patients who did not receive antibiotics was greater in the post-PCR group (70%, 48 of 69) compared with the pre-PCR group (45%, 30 of 67), P < 0.01. Of those who received antibiotics, the proportion of patients who received more than 1 dose was significantly lower in the post-PCR group (43%, 9 of 21) compared with the pre-PCR group (73%, 27 of 37), P < 0.025. The proportion of patients who had a repeat BC was significantly lower in the post-PCR group (58%, 40 of 69), compared with the pre-PCR group (82%, 55 of 67), P = 0.0022. The proportion of patients who were asked to return to the emergency department was significantly lower in the post-PCR group (59%, 16 of 27), compared with the pre-PCR group (88%, 23 of 26), P = 0.016.

Conclusion
With the addition of PCR technology, patients with BC positive for nonpathogenic bacteria have received less antibiotics, less repeat BCs and were less frequently asked to return for evaluation.#8232;

Disclosures
All authors: No reported disclosures.
1518. The Microbiology of Osteoarticular Infections in Patients with Sickle Hemoglobinopathies at Texas Children’s Hospital, 2011–2018
Authors: Ikeda Saki , Kaplan Julika , McNeil Jonathon C , Kaplan Sheldon L , Vallejo Jesus G 
Published: October 2019

Abstract

Background
Osteoarticular infections (OAI) are common in patients with major sickle hemoglobinopathies (Hemoglobin [Hgb] SS, Hgb SC, and Hgb Sβ thalassemia). Although Salmonella spp. cause a substantial number of OAIs in these patients, contemporary data regarding the most common etiology in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) are lacking. This introduces challenges for selecting empiric antimicrobial therapy. We evaluated the microbiology and management of OAI in children with sickle hemoglobinopathies.

Methods
Children with sickle hemoglobinopathies admitted to Texas Children’s Hospital with acute hematogenous OAI from 2011 to 2018 were identified based on ICD10 codes and the consult database of the pediatric infectious diseases service. Culture-negative cases were included if treated for OAI. Medical records were reviewed. Statistical analyses were conducted with STATA ver. 13.

Results
36 patients met inclusion criteria; 53% were diagnosed with isolated osteomyelitis and 47% with osteomyelitis and septic arthritis. In 42% a microbial etiology was identified (Figure 1) with Salmonella spp. being the most common (n = 7, 47%) followed by S. aureus (n = 5, 33%).11 (31%) patients had subperiosteal or intraosseous abscesses and 26 (72%) underwent diagnostic and/or therapeutic surgical procedures; 36% had positive blood cultures. Children with Salmonella spp. infections had a longer duration of fever (median-5, range: 4–9 days) compared with those caused by other pathogens (median-2, range: 0–6 days; P = 0.04). The median duration of IV therapy was longer in culture-positive than culture-negative cases (30 vs.10 days, P = 0.009); the total duration of therapy was similar for all cases (32 days, IQR: 28–42). No patients were readmitted due to OAI.

Conclusion
At our institution, Salmonella spp. were the most common cause of OAI among children with sickle hemoglobinopathies. Subperiosteal/intraosseous abscess formation and the need for surgical procedures were common. The role of oral antibiotics for the treatment of Salmonella OAI in patients with sickle hemoglobinopathies warrants further study.

Disclosures
All authors: No reported disclosures.
1526. Epidemiology of and Risk Factors for Nontyphoidal Salmonella Bacteremia in Children: A 20-Year Retrospective Cohort
Authors: Greenhow Tara L 
Published: October 2019

Abstract

Background
Nontyphoidal Salmonella (NTS) infections are the most common culture-confirmed foodborne illness in the United States. One to five percent of enteric infections due to NTS result in bloodstream infection (BSI). Host risk factors for NTS BSI include extremes of age and chronic or immunosuppressing conditions.

Methods
This was a retrospective review of the electronic health records (EHRs) of all blood cultures collected from January 1, 1999 to December 31, 2018 at Kaiser Permanente Northern California (KPNC) positive for Salmonella spp. The speciation and group of all Salmonella spp. were extracted from the microbiology records. Using KPNC population data, the incidence rate of NTS BSI by age and year of infection was calculated. Using a test for trend, the trend in rates of NTS BSI was determined. Risk factors for complicated NTS BSI using clinical and laboratory data were calculated.

Results
From 1999 to 2018, there were 212 cases of NTS BSI and 104 cases of Salmonella typhi and paratyphi BSI. The average number of cases per year was 10.6 (range 3–25). There were 14,952,802 evaluable children over the 20 years, with an average of 747,640 per year. The incident rate of NTS bacteremia was 1.4 per 100,000 children per year. The trend to increasing cases was not statistically significant (Figure 1). The distribution of NTS BSI cases were 114 (54%) Group B, 33 (15.5%) Group C, 31 (14.5%) Group D, 19 (9%) Groups E or G and 15 (7%) other/nonspecified. The predominant NTS pathogen was Salmonella heidelberg occurring in 37 (17.5%) cases. Forty-five percent of children were female. (Table 1) Forty-two percent of children were less than 3 years old with a steady rate after age 3. Two (0.9%) children had an underlying immunodeficiency, three (1.4%) additional with a malignancy and 16 (7.5%) with underlying non-immunosuppressing comorbidities.

Conclusion
Despite improvements in food safety, the rates of NTS bacteremia have not decreased over the last two decades. The rate of NTS was 1.4 per 100,000 children per year with the highest proportion in children less than 3 years. Two percent had underlying immunosuppressing comorbidities. Although only 10% had underlying comorbidities, this was substantially higher than the population at KPNC.

Disclosures
All authors: No reported disclosures.
1534. Polymyxin Antimicrobial Susceptibility (AST) Testing and Breakpoints for P. aeruginosa, A. baumannii, and Enterobacteriaceae: Recommendations from the United States Committee on Antimicrobial Susceptibility Testing (USCAST)
Authors: Pogue Jason M , Jones Ronald N , Bradley John S , Andes David , Bhavnani Sujata M , Dudley Michael , Flamm Robert K , Rodvold Keith A , Ambrose Paul G 
Published: October 2019

Abstract

Background
Polymyxins are important antimicrobial agents for the treatment of infections due to carbapenem-resistant and other multidrug-resistant organisms. Recently, the CLSI and EUCAST have set breakpoints for colistin (EUCAST and CLSI) and polymyxin B (CLSI) with slight differences in recommendations. However, there are issues unique to the polymyxin class that warrant additional guidances. Herein, we assess data related to breakpoint setting and make additional recommendations for polymyxin AST interpretive criteria.

Methods
Data sources included longitudinal (2011–2017) US surveillance reference broth microdilution (BMD) MIC distributions (128,573 isolates) for colistin and polymyxin B (PB), published data on accuracy of various AST methodologies, in vivo pharmacokinetic/pharmacodynamic (PK-PD) models, prior polymyxin guidelines and agency package insert dosing recommendations, and population PK-PD and toxicodynamic (TD) data. Epidemiological cut-off, PK-PD (and TD), and clinical data were all considered for susceptible (S) breakpoint determinations.

Results
Data demonstrate that the most commonly utilized AST methodologies (disk diffusion, Etest, and automated MIC susceptibility panels), as well as agar dilution testing cannot reliably detect resistance; and BMD is the preferred AST. Importantly, colistin S is a reliable surrogate for PB S with cross-S accuracy at > 99% of isolates in each pathogen group. Breakpoint recommendations can be found in the Table with emphasis on applying combination therapy. Key recommendations include an S breakpoint of ≤2 mg/L for each pathogen (both colistin and PB). However, based on a lack of preclinical efficacy in murine pneumonia models, PK/PD concerns, and poor clinical outcome data, we strongly suggest that no breakpoints are applied for pneumonia and that alternative therapies should be used where available. Additionally, due to a lack of significant renal excretion, PB will also have no S breakpoint recommendation for lower urinary tract infections.

Conclusion
The polymyxins have compromising characteristics that make them suboptimal antimicrobials when used alone, and additional caveats are required for AST breakpoint interpretive criteria and stewardship programs.

Disclosures
All authors: No reported disclosures.
1540. A Population Pharmacokinetic Model for Vancomycin in Korean Patients Receiving Extracorporeal Membrane Oxygenation Therapy: A Prospective Study
Authors: Jung Younghee , Lee Dong-Hwan , Soo Kim Hyoung 
Published: October 2019

Abstract

Background
There is no literature on population pharmacokinetics (PK) of vancomycin in Korean patients receiving extracorporeal membrane oxygenation (ECMO) therapy. The aim of this study was to develop a population PK model for vancomycin in Korean ECMO patients.

Methods
We prospectively enrolled adult patients who were undergoing ECMO and receiving vancomycin from July 2018 to April 2019. After initial dose of vancomycin was administrated, serial blood samples (seven to nine times per patient) were drawn before the next dose. A population PK model for vancomycin was developed using a nonlinear mixed-effect modeling. Age, sex, creatinine clearance, and body weight were tested as potential covariates in the model. Model selection was based on log-likelihood test, model diagnostic plots, and clinical plausibility.

Results
Fourteen patients were included over the period. Ten received venovenous, three venoarterial, and one both type ECMO. Eleven were men and the median age was 54 (interquartile range 45–66.3). Mean estimated glomerular filtration rate (eGFR) was 69 ± 46 mL/minute/1.73m2 by the modification of diet in renal disease equation. A total of 123 vancomycin concentrations from the patients were included in the analysis. The population PK of vancomycin was best described by a two-compartment model with a proportional residual error model. The typical value (%between-subject variability) for total clearance was estimated to be 4.33 L/h (21.6%), central volume of distribution was 9.22 L, the intercompartmental clearance was 10.75 L/hr (34.9%) and the peripheral volume of distribution was 19.6 L (26.6%). The proportional residual variability was 8.81%. Creatinine clearance significantly influenced vancomycin clearance (CL). The proposed equation to estimate vancomycin clearance in Korean ECMO patients was CL = 4.33 + 0.199 × (eGFR – 56).

Conclusion
A two-compartment population PK model successfully describes vancomycin PK profiles in Korean ECMO patients. The model could be used to optimize the dosing regimen if more data become available from currently ongoing clinical study.

Disclosures
All authors: No reported disclosures.
1556. Assessment of Translational In Vitro and Animal Pharmacokinetic–Pharmacodynamic Data Used to Support Drug Development of Recent Tetracycline Derivatives
Authors: Moore Jason , Pahwa Sonia , Yan Danielsen Zhixia , Colangelo Philip 
Published: October 2019

Abstract

Background
Nonclinical (animal and in vitro) models are commonly used during the development of antibacterial drugs. Pharmacokinetic (PK) and pharmacodynamic (PD) data obtained from these nonclinical models are used to generate a PK-PD target, which can then be bridged to humans in a probability of PK-PD target attainment (PTA) analysis to support selection of the dose regimen for phase 3 trials and in vitro susceptibility testing criteria (breakpoints) to guide clinical usage.

Methods
Two recently approved tetracycline antibacterial drugs, eravacycline (ERV) and omadacycline (OMD), were evaluated. PK-PD data from nonclinical models and clinical microbiological response were collected from each of the respective clinical pharmacology reviews and assessments published by FDA and EMA, respectively. The highest MICs (minimum inhibitory concentrations) reflecting 80% success in the ability of the drug to inhibit growth in the target bacteria were identified from clinical and nonclinical data and termed the MIC cutoff. The nonclinical MIC cutoff was obtained from the PTA analysis using the PK-PD targets from animal studies. The clinical MIC cutoff was obtained from microbiological response (microbiological intent-to-treat population) data from clinical trial experience. The ratios of the clinical and nonclinical MIC cutoffs were calculated and used to evaluate potential discrepancies between the animal model prediction and clinical trial experience.

Results
The drug development programs for ERV and OMD included murine infection models and in vitro models to characterize PK-PD. The clinical to nonclinical MIC cutoff ratios ranged from 4 to 32. Higher values of the MIC cutoff signify that the drug can treat larger proportions of the bacterial population; therefore, high clinical to nonclinical MIC cutoff ratios signify that the drugs had more activity in reducing the bacterial population in clinical than in nonclinical studies.

Conclusion
Thus, the nonclinical models for ERV and OMD under-predicted microbiological response and breakpoints. While nonclinical models are generally useful, more characterization of translational factors may be needed to allow nonclinical models to be more predictive of clinical trial outcomes.

Disclosures
All authors: No reported disclosures.