bluuebunny/crossref_metadata_2025_split huggingface dataset:
1380. Effect of Absolute Body Weight on Clinical Outcomes of Obese Patients Treated with Cefepime
Authors: Wagner Jamie L , Morrison Austin R , Loper J Taylor , Barber Katie E , Stover Kayla R 
Published: November 2018

Abstract

Background
Differences in pharmacokinetic and pharmacodynamic parameters for obese (OB) patients compared with nonobese (NOB) patients are well known, but drug safety and efficacy when using package insert dosing remain unclear. The purpose of this study was to evaluate the clinical outcomes of cefepime (FEP) for OB patients vs. NOB patients.

Methods
This retrospective cohort included inpatient adults ≥18 years treated with FEP monotherapy for ≥72 hours between July 2015 and July 2017. Exclusion criteria were source control not achieved within 72 hours and polymicrobial infections requiring &gt; 1 antibiotic for definitive therapy. Additional data collected were demographics, comorbid conditions, laboratory markers, site of infection, and microbiology. The primary endpoint was clinical treatment failure, defined as change in definitive therapy at &gt;72 hours due to clinical worsening, leukocytosis (WBC &gt; 10 × 109/L) for &gt;72 hours after treatment initiation, fever (single temperature &gt;100.9°F) after &gt;72 hours of treatment initiation, or readmission within 30 days due to re-infection. Secondary outcomes were 30-day inpatient all-cause mortality and 30-day readmission.

Results
One hundred fourteen subjects were included (58 OB; 56 NOB). Median (IQR) age 58[46–66] years; 66(58%) males. Median [IQR] weight 107[95–124] kg OB patients; 75[63–84] kg NOB patients. Median Charlson score was 3[2–5] (P = 0.478). Sixty-two percent OB patients vs. 46% NOB patients experienced a respiratory infection (P = 0.094); 28% OB patients vs. 39% NOB patients experienced a urinary tract infection (P = 0.185). 62% OB patients and 59% NOB patients received FEP 1g q8h (P = 0.732). Most common minimum inhibitory concentration (MIC) in both groups was 1 mg/L (74% OB vs. 83% NOB; P = 0.289). Clinical failure occurred in 52% (67% OB vs. 36% NOB; P = 0.001). OB patients more likely to need a second antibiotic (31% vs. 14%; P = 0.033) and have persistent leukocytosis (50% vs. 30%; P = 0.033). Inpatient all-cause mortality occurred in 17% (22% OB vs. 12% NOB; P = 0.164). 72% of patients were not readmitted within 30 days of discharge.

Conclusion
OB patients experienced higher treatment failure than NOB patients. Further examination is needed to assess impact of FEP dose and organism MIC on clinical failure in OB patients.

Disclosures
All authors: No reported disclosures.
1398. β-Lactam Probability of Target Attainment (PTA) and Penetration into Epithelial Lining Fluid (ELF) Based on Multiple Bronchoalveolar Lavage (BAL) Sampling Time Points in a Swine Pneumonia Model
Authors: Motos Ana , Kuti Joseph L , Bassi Gianluigi Li , Torres Antoni , Nicolau David P 
Published: November 2018

Abstract

Background
Defining ELF concentrations is desired for antibiotics developed for pneumonia. For ethical reasons, BAL sampling in humans is routinely done at a single time point, thereby creating ambiguity in the precise ELF profile. It is unknown if additional sampling of the ELF would lead to more accurate estimates of exposure. The swine pneumonia model was used to characterize the full ELF profiles (5-BAL) of two β-lactams for comparison with models employing 1-BAL (1B) and 2-BAL (2B) sampling time points only.

Methods
Sixteen ventilated swine were infected with Pseudomonas aeruginosa to establish pneumonia and then treated for 72 hours with ceftolozane/tazobactam (C/T) 50 mg/kg q8h (n = 8) or piperacillin/tazobactam (TZP) 200 mg/kg q8h (n = 8). Plasma and BAL concentrations were measured in each swine at 1, 2, 4, 6, and 8 hours after the first dose. Urea correction was used to calculate ELF values. Ceftolozane and piperacillin plasma and ELF data were fitted to a two compartment model using the nonparametric adaptive grid program in Pmetrics. Hypothetical models were refitted after randomly selecting either 1B or 2B sampling time points from each swine. A 5,000 subject Monte-Carlo simulation was performed for each model to define PTA (60% free time above the MIC) and ELF penetration [area under the curve in ELF (AUCELF) vs. free AUCplasma]. The KS-test was used to analyze distribution differences, reporting maximum vertical deviation (D) as percent difference; D &lt; 20% was defined as negligible.

Results
Thirty-two C/T and 34 TZP plasma samples and 29 and 32 BAL samples were available for the full model, respectively; 1B and 2B sampling models used eight and 16 BAL samples. All models adequately fitted the data. C/T PTA at 4 mg/L was 94.8, 96.1, and 98.0%, for the full, 1B and 2B models. TZP PTA at 16 mg/L was 55.8, 46.8, and 46.7%, respectively. C/T median [interquartile range] penetration differences were negligible between the full (65% [25––109]) and 1B (72% [45––125], D = 15%) or 2B models (62% [32––111], D = 6%). TZP penetration differences were also minimal between the full (32% [9––67]) and 1B (17% [5––49], D = 18%) or 2B models (27% [9––44], D = 15%).

Conclusion
These data suggest that antibiotic ELF models constructed from a single BAL time point result in similar exposure estimates to full ELF profiles.

Disclosures
G. Li Bassi, MSD: Grant Investigator, Grant recipient. A. Torres, MSD: Grant Investigator, Grant recipient.
668. Clinical Spectrum of Powassan Virus Infection in Patients Presenting with Suspected Acute Tick-Borne Illness From a Lyme-Endemic Focus in the Midwest
Authors: Kehl Sue , Callister Steven , Jobe Dean , Thomm Angela , Yin Ziyan , Kim Soyoung , Pratt Phillip , Knox Konstance 
Published: November 2018

Abstract

Background
Powassan virus (POWV) is the North American member of the tick-borne encephalitis complex of viruses. The potential for concurrent transmission with other tick-borne pathogens, particularly the Lyme disease agent Borrelia burgdorferi, is under studied. To better understand the clinical spectrum of POWV infection patient health records were reviewed and laboratory studies performed to evaluate the frequency of tick-borne pathogen exposure in patients presenting with suspected acute tick-borne illness (TBI) from a Lyme-endemic focus in the Midwest.

Methods
One hundred and thirty-five samples selected from patients seen at Gundersen Health System presenting during 2016 with Lyme-like symptoms were tested for Anaplasmosis, Babesiosis, Lyme disease and POWV. PCR testing was performed for Anaplasma and Babesia. Serologic testing for B. burgdorferi was performed using two-tier serologic testing. POWV infection was confirmed by POWV-EIA/IFA (Coppe Laboratories). IRB approval was obtained.

Results
Anaplasma infection was seen in 44/88 (50%), Babesia infection in 5/67 (7.5%), Lyme disease in 45/135 (33.3%) and POWV infection in 16/132 (12.1%) patients. Co-infections were seen in 21/135 (15.5%) patients. Patients with Babesia more often presented with anemia, myalgia and decreased appetite. Patients with Anaplasma presented with fever, chills/sweats, nausea/vomiting, rash, elevated liver function tests, thrombocytopenia, leukopenia, and remembered the tick exposure. Lyme disease patients complained of fatigue, rash, chills/sweats, headache and remembered the tick exposure. Co-infection with both Lyme and Powassan virus was seen in 10/45 (23%) of patients. Patients with Lyme, Powassan virus or co-infection had no other significant difference in symptoms.

Conclusion
POWV infection is more prevalent in the Midwest than previously appreciated. Clinical data suggest that symptoms of POWV infection may be indistinguishable from those of Lyme disease, requiring laboratory testing for proper TBD diagnosis and avoidance of unnecessary antibiotic use. The high rate of POWV co-occurrence with Lyme disease may have relevance for patient outcomes and warrants further investigation.

Disclosures
S. Kehl, Coppe Laboratories: Consultant, Consulting fee. A. Thomm, Coppe Laboratory: Employee, Salary. P. Pratt, Coppe Laboratory: Employee, Salary. K. Knox, Coppe Laboratory: Owner, Equity as compensation.
675. Current Physician Knowledge, Attitudes, and Clinical Practice Regarding Legionnaires’ Disease in the Aftermath of the Flint Water Crisis in Genesee County, Michigan
Authors: Alaga Katanya C , Konja Jewel M , Salim Abdulbaset , Levine Pete , Smith Sherry , Zervos Marcus J , Kilgore Paul 
Published: November 2018

Abstract

Background
Legionnaires’ disease (LD) is a respiratory illness caused by the inhalation of aerosolized water contaminated with Legionella bacteria. For reasons not yet understood, the incidence of LD has steadily increased across the United States during the past 10 years. In 2014 and 2015, the City of Flint in Genesee County (GC), Michigan underwent a change in the city’s water source, which resulted in the third largest recorded LD outbreak in American history and over 100,000 residents being exposed to contaminated water. In order to reduce the incidence of LD in at-risk populations it is imperative that we evaluate and improve LD knowledge and clinical practice among healthcare personnel.

Methods
This investigation surveyed clinicians practicing in Genesee County who are also members of the Genesee County Medical Society (GCMS). A survey was designed to assess current clinical knowledge, attitudes, and practices related to LD, in addition to measuring the uptake and utility of the LD clinical guidelines. The survey and the LD clinical guidelines were distributed to all GCMS members over a 6-month period. Prompts to complete the survey using Qualtrics programming were emailed to GCMS members and posted in the GCMS monthly bulletin. In addition, surveys were distributed to members at GCMS meetings. Completed responses were entered into Qualtrics software and exported into MS Excel and SPSS statistical software for analysis.

Results
In total, 95 healthcare personnel responded. Of those surveyed, 79.5% have been in practice for more than 10 years and 55% identified as practicing in family, internal or emergency medicine. Despite, the well-publicized LD outbreak in GC, 45% of respondents did not believe or were unsure if LD was a current public health issue, and 65% have either not received, have received but are not interested, or have received but not read the LD clinical guidelines. Despite this, 47% and 61% of respondents were able to correctly identify the symptoms and risk factors for LD, respectively. In addition, 34% of participants believe that drinking tap water is a risk factor for contracting LD.

Conclusion
This survey underscores the continuing need for comprehensive physician education to improve the clinical recognition and evaluation of patients with LD.

Disclosures
All authors: No reported disclosures.
677. Using a Multisectoral One Health Approach to Prioritize Zoonotic Diseases in the United States
Authors: Krishnasamy Vikram , Behravesh Casey Barton , Varela Kate , Goryoka Grace , Oussayef Nadia , Rooney Jane , Dutcher Tracey , Bond Elaine , Hopkins M Camille , Gibbs Samantha 
Published: November 2018

Abstract

Background
Emerging and endemic zoonoses continue to have adverse global impacts. One Health approaches promoting multisectoral, transdisciplinary collaboration are important methods to address zoonoses threats through disease surveillance, prevention, control, and response. We conducted a One Health Zoonotic Disease Prioritization (OHZDP) workshop in the United States (US) to identify zoonotic diseases of greatest national concern that should be jointly addressed by the Centers for Disease Control (CDC), US Department of Agriculture (USDA), Department of the Interior, and partners.

Methods
We used CDC’s OHZDP tool to prioritize zoonoses. Workshop participants selected criteria for prioritization, and developed questions and weights for each criterion. Questions were answered using available literature and expert opinion with subsequent scoring resulting in a ranked zoonotic disease list. After agreeing on a final prioritized disease list, participants used components of the One Health Systems Mapping and Analysis Resource Toolkit, developed by USDA and University of Minnesota, to review multidisciplinary coordination processes for the prioritized zoonotic diseases.

Results
Participants selected epidemic or pandemic potential, disease severity, economic impact, introduction or increased transmission potential, and national security as criteria to prioritize 56 zoonoses. The eight prioritized zoonotic diseases for the US were zoonotic influenzas, salmonellosis, West Nile virus, plague, emerging coronaviruses (e.g., SARS, MERS), rabies, brucellosis, and Lyme disease. Agencies then discussed recommendations to enhance One Health approaches to surveillance, response, prevention, and control of the prioritized zoonoses. Key themes and next steps for further implementation of One Health approaches were identified.

Conclusion
This OHZDP workshop represents the first use of a One Health approach to zoonotic disease prioritization in the United States. It is a critical step forward in US government agency collaboration using One Health approaches. Further, the workshop created a foundation for future US government One Health systems strengthening for the prioritized zoonoses.

Disclosures
All authors: No reported disclosures.
681. Epidemiology and Outcomes of Patients with Carbapenem-Resistant Bloodstream Infection in United States Hospitals, 2010–2015
Authors: Echols Roger , Corvino Frank , Cai Bin , Lodise Thomas P 
Published: November 2018

Abstract

Background
Carbapenem resistance (CR) in patients with Gram-negative (GN) bloodstream infections (BSI) presents a mounting therapeutic challenge. To gain a better understanding of CR among patients in US hospitals, we explored their characteristics and outcomes.

Methods
We performed a retrospective cohort analysis of consecutive adult patients (age ≥18 years) with a positive blood culture for GN pathogens (11 most prevalent pathogens reported in ~53,811 study patient samples), hospitalized in one of 181 institutions contributing microbiology data to the Premier Healthcare Database (October 2010–September 2015). We compared patients with CR vs. carbapenem-susceptible (CS) BSIs based on their characteristics and outcomes. Primary outcome was mortality, and secondary outcomes included post-index culture hospital and ICU lengths of stay (LOS), and likelihood of being discharged home.

Results
Of the ~53,811 study patient samples, 46,381 patients had a GN BSI, with the prevalence of CR occurring at 3.5% (n = 1,602). Compared with patients with CS, those with CR were younger (mean/SD 60.4/17.1 vs. 67.4/16.4 years, P &lt; 0.01), more likely to be male (52.8% vs. 45.9%, P &lt; 0.01), black (22.7% vs. 17.7%, P &lt; 0.01), and had Medicaid as a payor (18.1% vs. 10.9%, P &lt; 0.01). The mean/SD Charlson Comorbidity Index was higher in CR than CS group (2.9/2.5 vs. 2.3/2.5, P &lt; 0.01). Crude mortality was also higher (20.6% vs. 9.7%, P &lt; 0.01) in the setting of CR than CS, as were unadjusted median (IQR) post-index culture hospital (9 [6, 15] vs. 7 [5, 10] days, P &lt; 0.01), and ICU (5 [2, 11] vs. 3 [2, 6] days, P &lt; 0.01) LOS. Patients with CR BSI were less likely to be discharged home than those with CS (32.7% vs. 53.8%, P &lt; 0.001).

Conclusion
Patients with CR BSIs have lower likelihood of surviving hospitalization or being discharged home, and longer post-index culture hospital and ICU LOS, compared with those with CS BSIs. This highlights the need for better and more preventive and therapeutic strategies aimed at combating GN CR.

Disclosures
A. F. Shorr, Astellas: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium
Cidara: Consultant, Consulting fee. Merck & Co.: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee.
682. The Changing Epidemiology of Bacterial Meningitis During 2015–2017 in Turkey: A Hospital-Based Prospective Surveillance Study
Authors: Ceyhan Mehmet , Ozsurekci Yasemin , Bayhan Cihangül , Gurler Nezahat , Sali Enes , Emiroglu Melike Keser , Öz Fatma Nur , Camcioglu Yıldız , Salman Nuran , Kurugol Zafer , Akisoglu Havva Ozlem Altay , Tuygun Nilden , Belet Nursen , Ulusoy Emel , Dinleyici Ener Cagri , Tezer Hasan , Parlakay Aslınur , Karbuz Adem , Aktar Fesih , Hacimustafaoglu Mustafa , Basaranoglu Sevgen Tanır , Aykac Kubra , Kocabas Emine , Gundeslioglu Ozlem Ozgur , Hatipoglu Nevin , Hatipoglu Sadık Sami , Şensoy Gülnar , Oncel Eda Karadag , Solmaz Mehmet Ali , Kara Soner Sertan , Çelebi Solmaz , Çelik Ümit , Metin Özge , Bozdemir Şefika , Devrim Ilker , Kara Ahu , Sütçü Murat 
Published: November 2018

Abstract

Background
The etiology of bacterial meningitis in Turkey has been changed after the implementation of conjugated vaccines against Streptococcus pneumonia and Haemophilus influenzae type b (Hib) in Turkish national immunization schedule. Methods. This prospective study was conducted in 25 hospitals located seven regions of Turkey (representing 30% of Turkey population) and children aged between 1 month and 18 years with suspected meningitis and hospitalized were included. Cerebrospinal fluid samples were collected and bacterial identification was made according to the multiplex PCR assay results. Results. During the study period, 927 children were hospitalized for suspected meningitis and Hib (n:1), S. pneumonia (n:17) and Neisseria meningitidis (n:59) were detected in 77 samples (Figure 1, Table 1). During 2015–2016, N. meningitidis serogroup W, B, A, Y, X frequencies were as 5 (13.9%), 16 (44.4%), 1 (2.8%), 1 (2.8%), 1 (2.8%), respectively. There were 12 nongroupable N. meningitidis samples and serogroup C was not detected. In 2017, of meningococcal meningitis serogroup B, W, A, Y and X were identified in two (8.7%), 15 (65.2%), two (8.7%), 1 (4.3%) and 1 (4.3%) cases, respectively (Figure 2). There were four deaths in this study period, all of them were caused by N. meningitidis serogroup B and three of them were under 1 year old. Conclusion. The epidemiology of meningococcal diseases has been varied in time with or without any apparent reasons. Hajj is a well-known cause for serogroup W epidemics and serogorup W was the most common cause of meningitis in Turkey during 2009–2014 as in other Middle East countries. After the impact of serogroup W epidemics related to Hajj seen in 2010’s was diminished, serogroup B has been leading cause of childhood meningitis since 2015. In countries affected from Hajj like Turkey, vaccination of children with serogroup B meningococcal vaccine as well as quadrivalentconjugated vaccine seems to be very important. It should be kept in mind that meningococcal epidemiology is dynamic and needed to be closely monitored to detect changes in years

Disclosures
All authors: No reported disclosures.
705. Four Superbugs Isolated From a Single Patient in the United States: E. coli (EC) and K. pneumoniae (KP) Harboring NDM-5, P. aeruginosa (PA) Harboring NDM-1 and Candida auris
Authors: Khan Ayesha , Hanson Blake , Dinh An , Wanger Audrey , Ostrosky-Zeichner Luis , Miller William , Arias Cesar 
Published: November 2018

Abstract

Background
The spread of carbapenem resistance in Enterobacteriacae (CRE) and PA is an urgent public health concern. Candida auris (CA) is also an emerging threat, with the epicenter of US cases on the East Coast. Transcontinental spread of multi-drug-resistant (MDR) organisms has the potential to change local susceptibility patterns via dissemination of resistance determinants or high-risk clones. Here, we report and characterize MDR-isolates of EC, KP, PA and CA, all isolated from a single patient admitted to an ICU in Houston, Texas after complications from plastic surgery in India.

Methods
CRE were isolated from the urine, PA from respiratory cultures and CA from wound cultures. Antimicrobial susceptibility testing was performed on Vitek 2 or by Etest. Synergy testing was done by Aztreonam (ATM) E-test on Mueller-Hinton agar supplemented with 2.2 µg/mL avibactam. Bacterial isolates underwent whole genome sequencing on an Illumina MiSeq, and resistance determinants (Abricate using CARD), plasmid replicon types (PlasmidFinder 1.3) and sequence type (Tseemann MLSTtool) were identified. Genes were verified by PCR.

Results
The CRE were resistant to all β-lactams, including ceftazidime/avibactam (CZA) and ceftolozane/tazobactam. Synergy testing with CZA+ATM reduced the ATM MICs of the EC from &gt;256 to 0.5 µg/mL and the KP from &gt;256 to .094 µg/mL, while the PA ATM MIC was 4 µg/mL irrespective of the presence of avibactam. WGS indicated that the EC and KP shared the blaNDM-5, blaTEM-4, and blaCTX-M-15 β-lactamase genes, as well as IncFII and IncX3 plasmid replicon types. In addition, the EC harbored blaCMY-59, blaOXA-181, qnrS1 and two additional IncB and IncY plasmid replicon types. The PA isolate harbored blaNDM-1, qnrVC1, several aminoglycoside resistance genes and a type 1 integrase. The CA isolate had a fluconazole MIC of &gt;256 µg/mL and a micafungin MIC of 0.125 µg/mL.

Conclusion
Here we report the identification of 4 MDR organisms, including the first reported isolate of CA in Houston, in one patient. The pattern of resistance determinants suggests horizontal transmission of blaNDM-5 between the CRE isolates. Prompt recognition of MDR organisms is imperative to prevent healthcare-associated spread.

Disclosures
W. Miller, Merck: Investigator, Research support. C. Arias, Merck & Co., Inc.: Grant Investigator, Research support. MeMed: Grant Investigator, Research support. Allergan: Grant Investigator, Research support.
722. Normal Clinical Signs and Duration of Antibiotics in Hospitalized Patients with Pneumonia
Authors: Ochoa Aileen , Ji Wenjing , Smith Cara , Rhee Chanu , Klompas Michael 
Published: November 2018

Abstract

Background
The most common reason for antibiotic prescribing in hospitalized patients is suspected respiratory tract infection. In many cases, however, antibiotics may be started when the diagnosis is unclear and continued for a fixed course regardless of patients’ clinical trajectories. We sought to characterize the distribution of clinical signs in patients started on antibiotics for possible pneumonia, number of days to normalization of clinical signs, and duration of antibiotics beyond when signs normalized.

Methods
We performed a retrospective analysis on 43,820 consecutive adults admitted to Brigham and Women’s Hospital from May 2017 to January 2018. We identified all nonventilated patients started on antibiotics for pneumonia using clinicians’ stated indications in their medication orders. We analyzed the distribution of clinical signs indicative of pneumonia (maximum temperature, maximum white blood cell count, median respiratory rate, and supplemental oxygen need) on the first day of antibiotics. We then calculated median days to normalization for each sign, total days of antibiotics for pneumonia, and duration of antibiotics beyond when all signs normalized.

Results
We identified 2,754 nonventilated patients started on antibiotics for pneumonia. On the first day of antibiotics, 38%had oxygen saturations ≥95% without supplemental oxygen, 78% had normal temperatures, 63% had normal white blood cell counts, and 79% had median respiratory rates &lt;22 breaths/minute. All signs were normal in 25% of patients. Amongst those with at least one abnormal clinical sign on the first day of antibiotics, all signs returned to normal within a median of 3 days (IQR 2–7 days). Antibiotics were nonetheless continued for ≥3 more days in 33% of these patients.

Conclusion
Pneumonia is a major driver of antibiotic utilization in hospitalized patients but we found 25% of cases lacked the cardinal clinical signs of pneumonia and antibiotics were continued for ≥3 days after all clinical signs normalized in a third of the 75% of patients who did have signs of pneumonia. These findings suggest substantial opportunities to improve antibiotic prescribing for suspected respiratory tract infections in hospitalized patients.

Disclosures
All authors: No reported disclosures.