bluuebunny/crossref_metadata_2025_split huggingface dataset:
1522. Clinical and Molecular Epidemiology of Invasive Haemophilus influenzae Serotype a Infections in Utah Children
Authors: Crandall Hillary , Christiansen Jennifer E , Varghese Alyssa , Russon Adam K , Korgenski Kent , Dickey Mandy , Killpack Jarrett , Knackstedt Elizabeth , Daly Judy , Ampofo Krow , Pavia Andrew , Bonkowsky Anne 
Published: October 2019

Abstract

Background
Following widespread use of the Haemophilus influenzaeserotype b (Hib) vaccine,H. influenzae serotype a (Hia) has emerged as an important pathogen in children. Rates of Hia disease are particularly high in Utah. We describe the clinical features and molecular epidemiology of invasive Hia disease in children in Utah over 11 years.

Methods
Cases of invasive Hia disease in children less than 18 years were identified through electronic clinical and microbiology records. Demographic data and clinical outcomes were abstracted from the medical record for all cases. Available Hia isolates were collected for molecular analysis. Isolates were genotyped by multi-locus sequence typing (MLST) and clonal division was determined using sodC PCR. Presence or absence of the putative virulence-associated IS1016-bexA duplication-deletion was evaluated.

Results
We identified 51 children with invasive Hia between 2007 and 2017. Median age was 11.3 months. The average annual incidence was 1.7 cases per 100,000 children aged <5 years (95% CI 1.2–2.2). Incidence was highest among children less than one year of age (4.8/100,000; 95% CI 3.1–6.9). Incidence rates were similar by race and ethnicity, although the confidence intervals were wide. The annual number of cases was similar over the 11-year study period (figure). The most common clinical manifestation was meningitis (54%; half had intracranial complications, 25% suffered hearing loss), followed by pneumonia (14%), and arthritis (14%). Twenty-two children (44%) required ICU care and one child died. Twenty-eight isolates (56%) were available for molecular analysis. ST62, clonal division II isolates caused 75% (21/28) of disease. No isolates contained the virulence-associated IS1016-bexA duplication-deletion.

Conclusion
Hia is an important cause of severe invasive bacterial infection in Utah. Molecular analyses revealed that a majority of infections were caused by ST62 isolates, a clonal division II Hia type lacking the IS1016-bexA duplication-deletion. Hia ST62 has not been commonly reported in other settings, suggesting a unique molecular epidemiology in our population.

Disclosures
All authors: No reported disclosures.
1548. Characterizing Cefepime Neurotoxicity: Experience from a Tertiary Care Center Performing β-lactam Therapeutic Drug Monitoring
Authors: Nys Cara , Hurst Natalie , Liu Jiajun , Cherabuddi Kartikeya , Iovine Nicole M , Scheetz Marc H , Rhodes Nathaniel J , Klinker Kenneth , Veena Venugopalan 
Published: October 2019

Abstract

Background
Based on prior studies, elderly patients and those with renal dysfunction are prone to cefepime (CFP) toxicity. The toxicokinetics and toxicodynamics for CFP are not well established. Lamoth et al. reported a 50% probability of CFP neurotoxicity at a serum trough concentration of ≥22 mg/L, whereas Huwyler et al. observed CFP neurotoxicity when concentrations exceeded 35 mg/L. The objectives of this study were to quantify the incidence of CFP neurotoxicity and to assess the association between CFP concentrations and neurotoxicity.

Methods
We conducted a retrospective review between March 2016 and May 2018, of adult patients with serum CFP trough concentrations ≥25 mg/L. To be considered a CFP neurotoxicity case, patients were required to fulfill at least two of the NCI criteria for neurological toxicity such as, presence of new-onset confusion, delirium, or drowsiness. Following this, cases were classified as (1) high likelihood of toxicity (HLT) if they either had a neurology consult or EEG findings consistent with CFP toxicity and if their symptoms improved after discontinuation of CFP, (2) possible toxicity (PT) if neurology consult or EEG was absent or if we were unable to assess improvement after CFP was discontinued, or (3) nontoxicity (NT). Cases were independently reviewed by an ID pharmacist and physician. Additional data such as comorbidities, renal function, and use of anti-epileptics were collected.

Results
One hundred and forty-two patients were included in the analysis. Neurotoxicity (HLT+PT) related to CFP occurred in 18/142 (13%) patients; 67% (12/18) were considered HLT. The median age in the HLT cohort was 68 years (interquartile range [IQR], 57–74), with toxicity occurring a median of 6 days (IQR, 5–8) after starting CFP. At the time of neurotoxicity, HLT patients had diminished renal function with a median SCr of 1.6 mg/dL (IQR, 1.2–2.4) and a corresponding CrCl of 35.8 mL/minute (IQR, 19.2–50.9). The median CFP trough concentration in the HLT patients was 62 mg/L (IQR, 50–73) vs. 70mg/L (IQR, 41–115) in the PT and 42 mg/L (IQR, 31–61) in the NT groups.

Conclusion
Our data emphasize the need for careful dosing in older patients with renal insufficiency. Interestingly, our study reveals higher cefepime troughs (~3-fold higher) associated with neurotoxicity than previously reported.

Disclosures
All authors: No reported disclosures.
1569. A Translational Model to Assess the Impact of Polymyxin B Dose Fractionation on Kidney Injury
Authors: Liu Jiajun , Pais Gwendolyn M , Avedissian Sean N , Lee Andrew , Rhodes Nathaniel J , Hauser Alan R , Scheetz Marc H 
Published: October 2019

Abstract

Background
Progression of antimicrobial resistance has revived Polymyxin B (PB) use in clinical practice. Dose-dependent acute kidney injury (AKI) limits its clinical use. It is unclear whether dose fractionation of total daily dose can lessen kidney injury. We assessed the role of PB fractionation on AKI in a translational model that employs sensitive urine biomarkers qualified by the FDA.

Methods
Male Sprague–Dawley rats received 12 mg/kg/day PB subcutaneously for 3 days or equal-volume normal saline (NS). PB was administered in 3 separate fractionated daily doses: 12 mg/kg daily (QD), 6 mg/kg twice daily (BID), and 4 mg/kg thrice daily (TID). Staggered blood sampling was done on days 1 to 4 and 24 hour urine was collected at baseline, on days 1, 2, and 3. Plasma creatinine (Cr) was quantified using LCMS/MS, and 24 hour urinary biomarkers (KIM1, OPN, CLN, calbindin, GSTα, IP-10, TIMP-1, and VEGF) were assayed with MILLIPLEX Rat Kidney Toxicity Magnetic Bead Panel. Mixed-effects models were used.

Results
A total of 32 rats contributed to the study data. Mean Cr were constant across groups over time (Figure 1, P = 0.18). For NS group, all biomarkers remained at baseline throughout study. Significant differences were seen for fractionation schemes for KIM1 (P = 0.02), CLN (P = 0.03), IP-10 (0.007) and TIMP-1 (P = 0.04). The differences for KIM1, IP-10, and TIMP-1 were driven by higher observed values in TID than those of BID as early as day 1 (P < 0.04). Furthermore, CLN was elevated for TID when compared with BID at baseline (P = 0.048). Similarly, TID group had the highest (but non-significant) elevations for IP-10 and TIMP-1 compared with QD on study days. Amongst all urine biomarkers, KIM1 in TID exhibited the most rapid rise from baseline to day 2 (Figure2, P < 0.0001).

Conclusion
In this translational model in which a single total daily dose was fractionated, sensitive urinary biomarkers indicated that TID dosing was worse than BID or QD dosing; dose fractionation of PB may lead to increased AKI. In addition, KIM1 rose rapidly as an early marker for AKI. Further efforts are needed to investigate the PK-TD relationship of PB in order to decrease AKI.

Disclosures
All authors: No reported disclosures.
1570. Association Between Vancomycin Area Under the Curve (AUC) and Nephrotoxicity
Authors: Poston-Blahnik Anna , Moenster Ryan P 
Published: October 2019

Abstract

Background
It is unclear whether increased vancomycin area under the curve (AUC) contributes to acute kidney injury (AKI) risk.

Methods
This retrospective cohort study was undertaken to determine whether vancomycin AUC > 550 is associated with a higher rate of AKI than an AUC < 550. Patients treated with vancomycin for at least 4 days at the St. Louis VA from 1/1/2016–9/31/2018 were included. The primary outcome was AKI (defined as an increase in serum creatinine by 0.3 mg/dL or 50% from baseline). Secondary outcomes included length of stay, readmission, or mortality in 30 days, AKI rate with concurrent antibiotics, and AKI rate with comorbidities. The AUC was calculated as daily dose (in mg) divided by vancomycin clearance. The variables of age ≥ 70, vancomycin AUC ≥ 550, creatinine clearance (CrCl) < 50 mL/minute, concomitant antibiotic administration, vancomycin treatment ≤ 7 days, and the presence of comorbidities were included in a bivariate analysis. Variables with a P-value of <0.2 were included in a multivariate logistic regression model.

Results
Two hundred patients were included in the analysis; 100 patients with an AUC ≥ 550, and 100 with an AUC < 500. Only mean vancomycin dose (1722.50 mg vs. 2361.25 mg; P < 0.05), mean AUC (465.88 vs. 696.45; P < 0.05), and peak SCr (1.22 mg/dL vs. 1.48 mg/dL; P = 0.015) were significantly different between groups; AUC < 550 vs. AUC ≥ 550, respectively. Acute kidney injury occurred in 22% (44/200) of all patients; 42% (42/100) with a calculated AUC ≥ 550 developed AKI compared with 2% (2/100) of patients with an AUC < 550 (P < 0.05). The secondary outcomes of concomitant nephrotoxic agents, length of stay, readmission at 30 days, and 30-day mortality were not significantly different between groups. Only age ≥ 70, vancomycin AUC ≥ 550, CrCl < 50 mL/minute, concomitant piperacillin–tazobactam administration, and the presence of comorbidities were included in the multivariate regression. Age ≥ 70, CrCl < 50 mL/minute, and AUC ≥ 550 [OR 49.5 (95% CI 10.1 – 242.3; P < 0.05)] were found to be independently associated with risk for developing AKI.

Conclusion
Patients with a calculated vancomycin AUC ≥ 550 were found to have a significantly higher rate of AKI compared with those with an AUC < 550.

Disclosures
All authors: No reported disclosures.
1575. Vancomycin Loading Doses and Nephrotoxicity on Medicine Teaching Services
Authors: Wagner Phillip , Arnold Jon , Sheridan Kathleen R 
Published: October 2019

Abstract

Background
IDSA guidelines recommend the usage of a loading dose when using vancomycin for seriously ill patients to rapidly achieve adequate trough concentrations. While the relationship between vancomycin and nephrotoxicity is the focus of many studies, and with the strength of that relationship still debated, few studies have examined the relationship between vancomycin loading doses and nephrotoxicity.

Methods
We performed a retrospective cohort study examining vancomycin dosing for internal medicine teaching services’ patients over the 2014–15 academic year at one academic medical center. We generated a list of all hospitalized patients aged 18–85 who received vancomycin and were admitted to a teaching service. Patient data were extracted from the inpatient EMR via manual chart review. Patients were excluded if their pretreatment calculated glomerular filtration rate (GFR) was less than 50 mL/minute, if they received less than three doses of vancomycin, or if their initial dose was subtherapeutic (<10 mg/kg). Nephrotoxicity was determined by 7-day acute kidney injury (AKI) rate. Patients in the loading dose (>20 mg/kg) cohort were compared with those in the standard dose cohort (10–20 mg/kg). Our primary modeling used multi-variable logistic regression with AKI as our outcome of interest.

Results
438 of the initial 804 patients were enrolled. The loading dose (n = 365, 83%) and standard dosing (n = 73, 17%) cohorts were not significantly different regarding demographics, GFR, nephrotoxic drug exposure, total vancomycin received, trough levels, or comorbidities, and were only significantly different regarding body mass index (BMI). The 7-day AKI rate was not significantly different between the two arms (6.3% in the standard dosing arm and 8.2% in the loading dose arm P = 0.6). AKI rate significantly increased in both arms in the setting of concurrent piperacillin–tazobactam and vancomycin administration (OR 2.5, P = .04). There was no association between BMI and AKI.

Conclusion
Few studies have examined the relationship between nephrotoxicity and vancomycin loading doses. The results of this study provide evidence that the use of loading doses is not significantly associated with increased 7-day AKI rate.

Disclosures
All authors: No reported disclosures.
1592. In Vitro Activity of Ceftolozane/Tazobactam (C/T) Against Enterobacteriaceae and Pseudomonas aeruginosa Circulating in Chile
Authors: Rivas Lina M , Martínez Jose R W , Spencer Maria , Porte Lorena , Silva Francisco , Cifuentes Marcela , Barraza Bélgica , Rojas Pamela , Araos Bralic Rafael , Tran Truc T , Miller William R , Arias Cesar A , García Patricia , Munita Jose 
Published: October 2019

Abstract

Background
The widespread dissemination of carbapenem-resistant (CR) P. aeruginosa and Enterobacteriaceae has created a major global public health crisis. C/T is a recently approved therapeutic which consists of the combination of a novel cephalosporin (ceftolozane) and tazobactam (a β-lactamase inhibitor). C/T has shown good activity against a wide range of multidrug-resistant (MDR) Gram negatives, being particularly interesting as an alternative for MDR P. aeruginosa. We aimed to determine the activity of C/T against clinical strains of Enterobacteriaceae and P. aeruginosa recovered in 4 large clinical centers from Chile.

Methods
We analyzed 434 isolates of Enterobacteriaceae (347 E. coli, 66 K. pneumoniae, 21 Enterobacter cloacae complex) and 57 P. aeruginosa collected during 2017 from 4 tertiary care institutions in Santiago, Chile. Identification was performed as per each local clinical microbiology lab. Susceptibility testing was performed by broth microdilution using customized Sensititre plates (Trek). Carba-NP was performed to screen for carbapenemase production. Susceptibilities were analyzed as per 2019 CLSI breakpoints.

Results
The MIC50/90 for C/T against Enterobacteriaceae and P. aeruginosa were 1/4 μg/mL and 2/16 μg/mL, respectively. In Enterobacteriaceae, susceptibility to C/T reached 92% in E. coli (Figure 1A), 91% in E. cloacae complex (Figure 1B) and 70% in K. pneumoniae (Figure 1C). Remarkably, C/T remained active against 58% (33/57) of CR Enterobacteriaceae (Figure 2A). Among Carba-NP-negative CR isolates (46%, 26/57), susceptibility to C/T was 54% (Figure 3 A–C). In P. aeruginosa, the overall susceptibility to C/T was 81% (Figure 1D), maintaining activity against 69% (25/36) of CR strains (Figure 2B). Importantly, susceptibility to C/T in CR P. aeruginosa isolates with a negative Carba-NP (67%, 24/36) was 83% (20/24) (Figure 3D).

Conclusion
In this multicenter study, we observed that C/T was highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa. Of note, C/T remained active against a large proportion of CR clinical strains. Moreover, the activity of C/T was particularly high against CR P. aeruginosa isolates with a negative Carba-NP.

Disclosures
All authors: No reported disclosures.
1616. Confronting Measles: The View from a New York City Health System at the Center of the Outbreak
Authors: Lighter Jennifer , Sterling Stephanie , McKinney Kelly , Medefindt Judith , Hochman Sarah , Stachel Anna , Pham Vinh , Phillips Michael S 
Published: October 2019

Abstract

Background
A measles outbreak was identified in NYC in October, 2018. Over 430 cases have been confirmed to date, mostly in under-vaccinated children. Due to referral patterns, our health system provided care to a large number of these patients in the ambulatory, Emergency Department and inpatient settings, placing significant pressure on Infection Prevention and Control efforts. Our response utilized the engineering, administrative, protective equipment and educational hierarchy of controls to prevent transmission to patients, visitors and staff.

Methods
Patients residing from outbreak zip codes were flagged in our electronic medical record. Screening for symptoms, measles exposure, vaccine opportunities and education were provided when patients presented for care. Enhanced controls for premature infants and immunocompromised patients were enacted. Automated emails to providers caring for patients from the outbreak area served as reminders to consider measles in differential diagnosis. As most cases of measles occurred in children, special effort was taken to prevent transmissions in pediatrics. Patient rooms on multiple inpatient floors were converted to negative pressure with respect to corridor, as admitted patients developed symptomatic (contagious) illness while hospitalized. We limited all nonimmune visitors <5 years from entering inpatient units. Patients were contacted prior to ambulatory visits, procedures, and surgery to ensure patients from outbreak zip codes were triaged appropriately. Automated alerts to Infection Control when measles testing was ordered allowed timely implementation of prevention measures and surveillance. Finally, educational materials for patients and visitors were translated into 7 languages and shared with other NYC hospitals.

Results
To date, 95 patients with suspect measles presented to our system, with 20 patients (16 pediatric and 4 adult) laboratory-confirmed cases requiring hospital admission due to measles pneumonia, hepatitis, and encephalitis. There was no evidence of transmission within the hospital and ambulatory setting to patients or staff.

Conclusion
A coordinated response involving engineering and administrative controls, PPE training and education is necessary when confronting a large urban measles outbreak.

Disclosures
All authors: No reported disclosures.
1618. Public Health at the United States/Mexico Border: Evaluation of the County of San Diego Health and Human Services Agency’s Health Screening Assessment of Asylum-Seeking Families at the San Diego Rapid Response Network Shelter
Authors: Horton Lucy E , Graves Susannah , Fischer Kathleen , Fleming-Magit Gina , Romero Camila , Thorne Christine , McDonald Eric , Murto Christine , Koenig Kristi L , Tuteur Jennifer M , Hill Linda 
Published: October 2019

Abstract

Background
Many families arrive at the United States–Mexico border seeking asylum. Jewish Family Service and the San Diego Rapid Response Network operate a shelter in San Diego that provides shelter, food, clothing, legal services and travel coordination for asylum-seeking families. Two local federally qualified health centers provide on-site urgent care.

Methods
In late December 2018, the County of San Diego expanded public health efforts by conducting health screenings of guests upon entry to the shelter with the goal of identifying health issues requiring urgent or emergent evaluation and preventing the spread of communicable disease. University of California San Diego Health physicians contracted by the County of San Diego Health and Human Services Agency (HHSA) nurses and ancillary staff provide daily on-site services to all shelter entrants including: health screening for diseases of public health significance, treatment and/or referral of urgent conditions, and medical clearance for shelter entry or medical isolation as needed. Official tracking of screening outcomes from January 2 to April 24, 2019 were collected using standardized surveys and analyzed for program evaluation and surveillance purposes.

Results
During that time a total of 9,124 asylum-seekers were screened, averaging 81 guests daily, identifying: 42 influenza-like illness, 645 lice, 330 scabies, 8 varicella, and 0 hepatitis A cases. Chest radiography for suspected tuberculosis was performed for 29 guests. Only one chest x-ray was abnormal. Sputum specimens for acid-fast stain (n = 3) and nucleic acid testing (n = 2) were all negative and no tuberculosis cases were diagnosed. Emergency department referrals were made for <1% of guests (n = 90) for conditions including pregnancy complications, asthma, dysentery, hemoptysis and fractures. No deaths or outbreaks of communicable disease occurred.

Conclusion
Coordination among local partner agencies resulted in early identification of communicable and acute health conditions prior to shelter entry allowing evaluation, treatment and off-site isolation, and minimizing stress on the emergency medical services system. This approach provides a successful model for health screening of asylum-seeking families arriving at the United States–Mexico border.

Disclosures
All authors: No reported disclosures.
1641. A Comparison of Human Papilloma Virus Infection Prevalence Trends Pre- and Post-HPV Vaccine Implementation
Authors: Ovie. Fueta Patrick , Greg Chido-Amajuoyi Onyema 
Published: October 2019

Abstract

Background
Human papilloma virus (HPV) is the most common sexually transmitted infection in the United States, with an annual incidence rate of approximately 14 million people. The HPV vaccine has been demonstrated to be highly effective in the prevention of HPV infection and HPV-associated diseases. This study aims to evaluate the impact of HPV vaccine on the prevalence of HPV infection in the United States and evaluate the trends of disease prevalence pre- and post-HPV vaccine implementation.

Methods
We conducted a secondary data analysis of the National Health and Education Survey (NHANES) for trends in HPV infection from 2003 to 2016. The analysis was grouped into a pre-HPV vaccine implementation (2003–2006) cohort including 4064 females, aged 18–59 years; and a post-HPV vaccine implementation (2007–2016) cohort which included 10718 females, aged 18–59 years. Further analysis of HPV infection prevalence, pre- and post-HPV vaccine implementation, stratified by sociodemographic characteristics were conducted.

Results
The prevalence of HPV infection prior to HPV vaccine implementation was 43.98% (95 CI 42.71%–46.58%) compared with 40.55% (95 C.I 40.55%–40.56%) in the post-HPV vaccine implementation era. Among females with HPV infections in the post-HPV vaccine implementation cohort 82.6 (95% CI 80.41%–83.42%) were unvaccinated. In both cohorts, black females had a significantly higher prevalence of HPV with a prevalence rate of 18.56% (95% CI 18.23%–20.56%) in the pre-HPV vaccine implementation cohort, and 15.61% (95% CI 14.82 – 19.4%) in the post-HPV vaccine implementation cohort. Females with less than high school education had a higher prevalence of HPV in the pre and post- HPV vaccine implementation cohorts with prevalence rates of 25.77% (95% CI 23.44%–28.72%) and 24.96% (95% CI 23.41%–25.67%), respectively.

Conclusion
The results suggest that HPV infection prevalence has declined since the implementation of HPV vaccine to US national immunization program. Our findings highlight disparities in HPV infection prevalence by race and educational status, and these patterns are in keeping with HPV-associated disease such as warts and HPV-associated cancers.

Disclosures
All authors: No reported disclosures.