bluuebunny/crossref_metadata_2025_split huggingface dataset:
1825. Optimizing β-lactam Therapy in Surgical Intensive Care Unit Patients Using Therapeutic Drug Monitoring
Authors: Al-Shaer Mohammad H , Rubido Eric , Lee Daniel , Klinker Kenneth , Peloquin Charles 
Published: October 2019

Abstract

Background
Therapeutic drug monitoring (TDM) is a powerful tool to optimize antibiotic exposure. It seldom has been used for β-lactams (BLs). We present our BL data in patients admitted to the surgical intensive care unit (SICU).

Methods
This retrospective study included SICU patients at UF Health (2016 and 2018) who received BL therapy and had TDM. Data collected included demographics, APACHE scores, platelet count, serum creatinine (Scr), infection source, cultures/susceptibilities, BL regimens, and plasma concentrations. Clinical cure was defined as resolution of infection-related symptoms at the end of therapy. Microbiologic eradication was defined as eradication of causative organism from the primary source out to 30 days after therapy. Pharmacokinetic and statistical analyses were performed on Phoenix v8.0 and JMP Pro v14.

Results
A total of 127 patients were included. Table 1 shows the baseline characteristics. The median age was 55 years, and weight was 83 kg. Eighty-three (65%) were male. P. aeruginosa was the most common isolated bacteria (n = 38). Lung was the most common source of infection (n = 50). Table 2 summarizes the median (IQR) doses, infusion times, calculated free trough concentrations (fCmin) of common BLs, and the reported minimum inhibitory concentrations (MICs). Calculated median time above the MIC (fT > MIC) for 66 (52%) patients was 100%. A total of 99 (79%) patients had clinical cure and 67 (61%) patients had microbiologic eradication. For efficacy, the Cmin/MIC ratio predicted the microbiologic eradication in wound infections only (n = 15, OR 1.09 [95% CI 1.01–1.24]). Using stepwise regression, 1-unit increase fT > MIC and APACHE score was associated with 0.84 decrease (P = 0.03) and 0.62 increase (P = 0.004) in days of therapy, respectively. For safety, Figure 2 shows the increase in Scr vs. BL free area under the concentration–time curve from time zero to end of the dosing interval (fAUC0-tau). Cefepime fAUC0-tau predicted neurotoxicity (OR per 20 unit increase 1.08 [95% CI: 1.01–1.18]).

Conclusion
In SICU patients, increase in fT > MIC was associated with shorter treatment duration, and fAUC0-tau increase was associated with an increase in Scr and incidence of neurotoxicity. TDM is warranted in this population to optimize therapy.

Disclosures
All Authors: No reported Disclosures.
1837. Considerations for a Targeted Approach to Contact Precautions for Patients with MRSA in Hospitals: A Multicenter Cohort Study to Identify High-Risk Patient Characteristics and Healthcare Personnel Interactions
Authors: O’Hara Lyndsay M , Calfee David P , Miller Loren G , Harris Lisa , Magder Laurence S , Kristie Johnson J , Morgan Daniel , Harris Anthony 
Published: October 2019

Abstract

Background
Healthcare personnel’s (HCP) gloves and gowns are frequently contaminated with antibiotic-resistant bacteria in the intensive care unit (ICU). Guidelines recommend contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA); however, this approach remains controversial. This study aimed to identify which patients are more likely to transfer MRSA to HCP gloves or gowns and to identify HCP interactions more likely to lead to glove or gown contamination.

Methods
In a multicenter cohort study of MRSA colonized patients, we observed HCP–patient interactions and cultured HCP’s gloves and gowns before doffing. We also assessed the association between bacterial burden and contamination by sampling patients’ anterior nares, perianal area, chest, and arm.

Results
We enrolled 402 MRSA-colonized patients and observed 3,982 HCP interactions. MRSA contamination of HCP gloves and gown occurred in 14.3% and 5.9% of interactions, respectively. Contamination of either gloves or gown occurred in 16.2% of interactions. Occupational/physical therapists had the highest rates of contamination (OR: 6.96 [95% CI: 3.51–13.79]), followed by respiratory therapists (OR: 5.34 [95% CI: 3.04–9.39]) when compared with the “Other” category. Touching the patient was associated with higher contamination (OR: 2.59 [95% CI: 1.04–6.51]) when compared with touching nothing in the room. Touching only the environment was not associated with glove or gown contamination (OR: 1.13 [95% CI: 0.43, 3.00]) when compared with touching nothing. Touching the endotracheal tube (OR: 1.75 [95% CI: 1.38–2.19]), bedding (OR: 1.43 [95% CI: 1.20–1.70]) and bathing a patient (OR: 1.32 [95% CI: 1.01–1.75]) increased odds of contamination when compared with not having such contacts (Figures 1 and 2). We found an association between increasing bacterial burden in the patient’s nares, perianal area, and chest skin and glove or gown contamination.

Conclusion
Contamination of HCP gloves and gowns with MRSA occurs frequently when caring for ICU patients. We identified interactions that are high-risk for transmission. Hospitals may consider optimizing contact precautions by using less precautions for low-risk interactions and more precautions for high-risk interactions.

Disclosures
All Authors: No reported Disclosures.
1895. Serious Antibiotic-Related Adverse Effects Following Unnecessary Dental Prophylaxis in the United States
Authors: Gross Alan E , Suda Katie J , Zhou Jifang , Calip Gregory , Rowan Susan A , Hershow Ronald , Perez Rose , Evans Charlesnika T , McGregor Jessina C 
Published: October 2019

Abstract

Background
Dentists prescribe 10% of outpatient antibiotics in the United States, with a significant portion of these being for prophylaxis. We previously found that 80% of prescriptions for prophylaxis prescribed prior to dental visits are unnecessary; however, the sequelae of these unnecessary antibiotics have not been characterized. Our objective was to assess the harms of unnecessary antibiotic prophylaxis using Truven, a national health claims database.

Methods
This was a retrospective cohort study of patients with dental visits from 2011 to 2015 linked to medical and prescription claims. Patients with commercial dental insurance without a hospitalization or extra-oral infection 14 days prior to antibiotic prophylaxis (≤2 days supply dispensed within 7 days before a dental visit) were assessed for inclusion. Patients with unnecessary antibiotic prophylaxis (defined as antibiotic prophylaxis in patients who both did not undergo a procedure that manipulated the gingiva/tooth periapex and did not have an appropriate cardiac diagnosis) were included and assessed for serious antibiotic-related adverse effects (AAE). The primary endpoint was the cumulative incidence of any AAE within 14 days post-prescription (composite of allergy, anaphylaxis, C. difficile infection, or ED visit). The secondary analyses were the cumulative incidence of each individual AAE and the risk difference of the primary endpoint between amoxicillin and clindamycin.

Results
Of the 168,420 dental visits with antibiotic prophylaxis, 136,177 (80%) were unnecessary and included for analysis. 3.8% of unnecessary prescriptions were associated with an AAE; primary and secondary endpoints are listed in the Table. ED visits (1.2%) and new allergies (2.9%) were most frequent. Clindamycin was associated with more AAE than amoxicillin (risk difference 322.1 per 1000 person-years, 95% CI: 238.5 - 405.8).

Conclusion
Even though antibiotic prophylaxis is prescribed for a short duration (≤2 days), it is not without risk. Since most AAE are diagnosed in medical settings, dentists may not be aware of these adverse effects. These data provide further impetus to decrease unnecessary prescribing of antibiotic prophylaxis prior to dental procedures.

Disclosures
All Authors: No reported Disclosures.
1947. Educational Impact of a Hybrid Infectious Diseases Rotation for Internal Medicine Residents
Authors: Cutrell James B , Cutrell James B , Le Binh-Minh , Wolfe Heather R , King Helen , Arasaratnam Reuben J , Nijhawan Ank E , Nijhawan Ank E , McKenna Megan , Lee Francesca 
Published: October 2019

Abstract

Background
Traditional infectious diseases (ID) rotations for internal medicine (IM) residents focus on inpatient consultation, potentially skewing trainees’ perspectives on ID. We report our experience with a hybrid inpatient–outpatient ID rotation which provides broader ID clinical exposure and an effective venue for educational innovation.

Methods
We included all IM residents completing an assigned ID rotation in the UT Southwestern IM residency since July 2013. From July 2013 to June 2017, a 4-week ambulatory ID (Amb ID) rotation, consisting of general and subspecialty ID clinics and weekly teaching sessions focused on ID board review, was offered in parallel to traditional inpatient ID consult rotations. From July 2017 to present, all assigned residents complete up to a 4-week ID hybrid rotation, consisting of 2 weeks of ambulatory ID and 2 weeks of inpatient ID consults, with all residents receiving weekly teaching sessions; in some cases, the 4 weeks were not completed sequentially. Data were collected on resident numbers and training level, quantitative and qualitative course evaluations, and program in-training examination scores in ID content areas.

Results
From July 2013 to June 2019, IM residents completed a total of 626 ID rotations, an average of 104 per year (Table 1). A sample ID hybrid schedule is shown in Table 2. Overall resident satisfaction with the ID hybrid rotation was 4.7 (std. dev. 0.7) on a 5-point Likert scale. This rotation has consistently been among the highest rated rotations by residents. In-training examination ID scores increased significantly with creation of the Amb ID rotation in 2013 and further increased since 2017 with creation of the ID hybrid, in which both inpatient and ambulatory residents receive the weekly teaching sessions (Figure 1). Pilot educational innovations through this rotation include an online web-based antibiotic stewardship curriculum (2014–2015) and a mobile app-based ID board review platform utilizing spaced interval learning (2018–2019).

Conclusion
A hybrid inpatient–outpatient ID rotation for IM residents has proven to be a highly effective platform for ID education and curriculum innovation at our institution. This concept could be exported to other institutions and increase IM resident interest and breadth of clinical exposure in ID.

Disclosures
Ank E. Nijhawan, MD, MPH, Gilead Sciences, Inc.: Research Grant.
1953. VE303, a Rationally Designed Bacterial Consortium for Prevention of Recurrent Clostridioides difficile (C. Difficile) infection (rCDI), Stably Restores the Gut Microbiota After Vancomycin (vanco)-Induced Dysbiosis in Adult Healthy Volunteers (HV)
Authors: Bobilev Dmitri , Bhattarai Shakti , Menon Rajita , Klein Brian , Reddy Shilpa , Olle Bernat , Roberts Bruce , Bucci Vanni , Norman Jason 
Published: October 2019

Abstract

Background
Gut microbiota alterations and resulting changes in metabolites involved in colonization resistance and host responses, including bile acids (BA) and short-chain fatty acids (SCFA), are hallmarks of C. difficile infection. Reduction in rCDI was shown with fecal microbiota transplants (FMT), but FMT has limitations for routine use and carries unforeseen risks. VE303 is a first-in-class drug being developed for prevention of rCDI consisting of a rationally defined bacterial consortium manufactured under GMP conditions. VE303 comprises 8 distinct species belonging to Clostridium clusters IV, XIVa, and XVII, the commensal bacteria associated with clinical response in FMT, suppress C. difficile growth in vitro and improve survival in vivo.

Methods
A first-in-human Phase 1 dose-escalation study assessed safety and tolerability of VE303 in HV after vanco-induced dysbiosis. PK (strain colonization and durability) and PD (restoration of the resident microbiota, SCFA pool, and BA pool) were evaluated by metagenomic sequencing and metabolomics analysis of fecal material.

Results
HV (N = 23) received oral vanco 125 mg QID for 5 days followed by VE303 capsules at escalating single then multiple doses (total dose range 1.6 × 109 to 1.1 × 1011 CFU). VE303-related AEs, mostly gastrointestinal, all Grade 1 and transient, were observed in 35% of HV. Colonization with VE303 strains was abundant, durable (detected at 24 weeks), and dose-dependent. VE303 rapidly expanded 10- to 100-fold and each strain was detectable within 2 days after dosing. VE303 enhanced subjects’ microbiota and metabolic recovery after vanco treatment. When compared with the vanco-only cohort (N = 5), VE303 led to earlier and more complete recovery of beneficial taxa (eg, Bacteroidetes, Firmicutes), reduction in inflammatory taxa (e.g., Proteobacteria) (Figure 1.), and recovery of the secondary BA and SCFA pools.

Conclusion
VE303, a rationally designed microbial consortium, was safe, well tolerated, and efficiently restored microbiome composition after antibiotic-induced dysbiosis in a dose-dependent manner. VE303 was associated with early recovery of key PD markers of response, including microbiota composition, bile acid, and SCFA pools. A Phase 2 study of VE303 for prevention of rCDI is underway (NCT03788434).

Disclosures
All Authors: No reported Disclosures.
1958. Assessment of Guideline-Concordant Antimicrobial Prescribing in Urgent Care Centers
Authors: Wu Janet , Rivard Kaitlyn R , Neuner Elizabeth A , Athans Vasilios , Sabella Camille , Estridge Robert , Curtis Robert , Fraser Thomas G 
Published: October 2019

Abstract

Background
In the United States in 2014, 266 million outpatient antibiotic prescriptions were dispensed. The Center for Disease Control and Prevention estimates that 30% of outpatient antibiotic prescriptions are inappropriate. These inappropriate prescriptions contribute to increased resistance, adverse events, and healthcare costs.

Methods
This was a retrospective study of patients presenting to 22 urgent care centers within a large healthcare system between September 1, 2018 and February 28, 2019. Data were collected from a dashboard designed to track antimicrobial prescribing data by indication, location, and provider. ICD-9 and -10 codes associated with otitis media, pharyngitis, sinusitis, cystitis, and upper respiratory infections (URI) were included. Guideline-concordant antimicrobial prescribing was determined based on compliance with national guideline recommendations, after taking patient allergies into account. The URI category includes disease states in which antimicrobials are rarely appropriate (e.g., acute rhinitis, nasopharyngitis, and acute bronchitis).

Results
A total of 57,799 encounters were included in this analysis (19,242 pediatric and 38,557 adult) and 60% of patients received an antibiotic prescription. Overall antimicrobial guideline concordance was higher in pediatrics (84%) than adults (62%). Rates of guideline-concordant antimicrobial selection are shown in Table 1. The most common guideline-discordant prescriptions were tetracyclines (39%), amoxicillin/clavulanate (26%), and macrolides (17%) in adult patients with sinusitis, pharyngitis, or otitis media. In pediatric patients, the most common discordant prescriptions were macrolides (32%), third-generation cephalosporins (30%), and amoxicillin/clavulanate (19%). Unnecessary antimicrobial prescribing for URI occurred in 23% of pediatric patients and 36% of adult patients.

Conclusion
Guideline-discordant antimicrobial prescribing is common in urgent care centers, particularly in adult patients. In addition to encouraging utilization of order sets, emphasis on education and feedback may be important to improve and sustain guideline-concordant prescribing rates and reduce prescribing for URI.

Disclosures
All Authors: No reported Disclosures.
1959. Parent Satisfaction and Antibiotic Prescribing for Pediatric Respiratory Infections by Telemedicine
Authors: Foster Charles B , Kathryn Martinez , Sabella Camille , Weaver Gregory , Rothberg Michael 
Published: October 2019

Abstract

Background
Respiratory tract infections (RTIs) are a common reason for direct-to-consumer (DTC) telemedicine consultation. Antibiotic prescribing during video-only DTC telemedicine consults was explored for pediatric RTIs, focusing on correlates with visit duration and patient satisfaction.

Methods
Data on pediatric (age less than 19 years) RTI consults were obtained from a large DTC nationwide telemedicine platform and included patient, physician, and encounter characteristics. Mixed-effects regression was used to assess variation in antibiotic receipt by patient and physician factors, as well as the association between antibiotic receipt and visit length or patient satisfaction.

Results
Of 12,842 RTI visits with 560 physicians, 55% of patients received an antibiotic prescription. Antibiotic prescribing rates among telemedicine providers were high: sinusitis (92.1%), otitis media (96.0%), pharyngitis (76.7%), and bronchitis/bronchiolitis (62.0%). A provider was more likely to receive a 5-star satisfaction rating from the parent when the child was provided a prescription for an antibiotic (OR 3.38; 95% CI 2.84–4.02), an antiviral (OR 2.56; 95% CI 1.81–3.64) or a nonantibiotic (OR 1.93; 95% CI 1.58–2.36). Visit length (mean 6.4 minute) was associated with higher satisfaction only when no antibiotic was prescribed (OR 1.03 per 6 seconds; 95% CI 1.01–1.06). Compared with nonpediatricians, pediatric providers were less likely to prescribe antibiotics (OR 0.44; 95% CI 0.29–0.68); however, patients of pediatricians were more likely to be highly satisfied (OR 1.50; 95% CI 1.11–2.03).

Conclusion
During DTC telemedicine video consultations for RTIs, pediatric patients were frequently prescribed antibiotics, which correlated with visit satisfaction. Although pediatricians prescribed antibiotics at a lower rate than other physicians, their satisfaction scores were higher. Especially problematic, adherence to guideline-concordant criteria for diagnosing acute otitis media and streptococcal pharyngitis, which, respectively, require otoscopy and throat culture, is not possible during a video-only telemedicine consult. High rates of antibiotic prescribing to children with RTIs suggest a need for antimicrobial stewardship efforts during video-only telemedicine consultation.

Disclosures
All Authors: No reported Disclosures.
1964. Predictive Factors for HIV Seroconversion Among Women Attending an Urban Health Clinic in the South: A Matched Case–control Study in Atlanta, GA
Authors: Harrington Pauline , Onwubiko Udodirim , Qi Mingli , Holland David , Wortley Pascale , Chamberlain Allison 
Published: October 2019

Abstract

Background
In 2019, Fulton County, GA was named one of 48 priority “hotspots” to target in renewed efforts to end the HIV epidemic in the United States. To more accurately predict women at greatest risk for HIV, we conducted an individually matched case–control study among women who attended a Fulton County health clinic to identify risk factors associated with HIV seroconversion.

Methods
We obtained data about women who sought care at Fulton County Board of Health Sexual Health Clinic (SHC) between 2011 and 2016. Cases were women with at least one clinician-assisted visit (CAV) at the SHC prior to HIV diagnosis date. Controls were women who visited the clinic in this same period but remained HIV negative. Controls were individually matched to cases in a 2:1 matching ratio on race, age at first CAV, and date of first CAV. Conditional logistic regression was used to develop a model for predicting probability of and identifying risk factors for HIV seroconversion.

Results
Of 18,281 women who were HIV negative at their first visit to the SHC between 2011 and 2016, 110 (0.6%) seroconverted before 2018. Of these, 80 (73%) had a CAV prior to HIV diagnosis. Using these 80 cases and 160 matched controls, having a history of gonorrhea, multiple gonorrhea episodes, a history of syphilis, a greater number of sex partners in the past 2 months, anal sex, history of injection drug or crack cocaine use, a history of exchanging drugs/money for sex, and heterosexual sex with more than one sex partner in the last month were associated with HIV seroconversion in bivariate analyses. After conducting backward selection from a fully adjusted model, predictors remaining were: having a history of syphilis (OR = 4.9, 95% CI: 1.4, 16.9), anal sex (OR = 2.9, 95% CI: 1.0, 8.3), and injection drug or crack cocaine use (OR = 34.8, 95% CI: 3.7, 328.1). Women having all three risk factors were six times more likely to seroconvert compared with matched controls without these risk factors.

Conclusion
Our results offer clinical insights into which women are most at-risk for HIV and are therefore best candidates for initiating HIV prevention interventions like pre-exposure prophylaxis (PrEP) within a HIV “hotspot” in the South.

Disclosures
All Authors: No reported Disclosures.
2838. Safety and Immunogenicity of a gp120-CD4 Chimeric Subunit Vaccine: A Phase 1a Randomized Controlled Trial
Authors: Chua Joel V , Davis Charles , Nelson Amy , Lam Ka Wing J , Mutumbi Lydiah , Stafford Kristen A , Gilliam Bruce , DeVico Anthony L , Lewis George K , Sajadi Mohammad M 
Published: October 2019

Abstract

Background
A primary challenge for HIV vaccine development is to raise antiviral antibodies capable of recognizing highly variable viral antigens. The full-length single chain (FLSC) gp120-CD4 chimeric protein was designed to present a highly conserved CD4-induced HIV-1 envelope structure that evokes cross-reactive humoral responses (Figure 1). IHV01 is an FLSC subunit vaccine formulated in alum adjuvant. The safety and immunogenicity of IHV01 was evaluated in this first-in-human phase 1a trial.

Methods
This randomized, double-blind placebo-controlled study involved three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Eligible participants were HIV-1 uninfected healthy volunteers aged 18 to 45 years. Participants in each cohort were block randomized in groups of four in a 3:1 ratio to receive either vaccine or placebo. Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. Crossreactive antibody binding titers against diverse HIV envelopes and antigens and specific CD4i epitopes on gp120 were assessed.

Results
Sixty-five volunteers were enrolled—49 vaccine and 16 placebo. Majority (81%) of vaccinations with IHV01 produced no localized or systemic reactions; no different from the control group. The overall incidence of adverse events (AEs) was not significantly different between groups. Majority (89%) of vaccine-related AEs were mild in severity. The most common vaccine-related AEs were injection site pain (31%), pruritus (10%), and headache (10%). There were no vaccine-related serious AE, discontinuation due to AE, or intercurrent HIV infection. By the final vaccination, all subjects in all cohorts had developed antibodies against IHV01; all placebo recipients were negative. The antibodies induced by IHV01 reacted with envelope antigens from diverse HIV-1 strains (Figure 2).

Conclusion
IHV01 vaccine was safe, well tolerated, and immunogenic in all doses tested. The vaccine raised broadly reactive humoral responses against multiple gp120 domains, transition state structures, and CD4i epitopes.

Disclosures
All Authors: No reported Disclosures.