bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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.
2841. A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate (TZD) and Linezolid (LZD) for Treatment of Ventilated Gram-Positive (G+) Nosocomial Pneumonia
Authors: Wunderink Richard G , Roquilly Antoine , Croce Martin , Rodriguez Gonzalez Daniel , Fujimi Satoshi , Butterton Joan R , Broyde Natasha , Popejoy Myra W , Kim Jason Y , De Anda Carisa S
Published: October 2019

Background

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are frequently caused by G+ cocci; TZD has potent in vitro activity against these pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The VITAL study compared the efficacy and safety of TZD vs. LZD for the treatment of ventilated patients with G+ HAP/VAP.

Methods

Randomized, double-blind, double-dummy, global, phase 3 study in mechanically ventilated adult patients with presumed G+ HAP/VAP (clinicaltrials.gov NCT02019420). Patients were stratified by region, age, and trauma/nontrauma, then randomized 1:1 to intravenous (IV) TZD 200 mg once daily for 7 days or IV LZD 600 mg every 12 h for 10 d (patients with concurrent G+ bacteremia received 14 d of treatment). The primary efficacy endpoint was day 28 all-cause mortality (ACM) in the intent to treat (ITT) population (all randomized patients; noninferiority [NI] margin, 10%). Secondary endpoints included investigator-assessed clinical response at test of cure (TOC; NI margin, 12.5%).

Results

In total, 726 patients were randomized (TZD n = 366; LZD n = 360). Baseline characteristics were well balanced between arms. TZD was noninferior to LZD for day 28 ACM in the ITT (table). Noninferiority was not demonstrated for TZD vs. LZD for investigator-assessed clinical success at TOC in the ITT. Stratification factors, analysis population, baseline clinical/laboratory signs of HAP/VAP, G+ only vs. mixed G+/gram-negative (G–) HAP/VAP, adjunctive G– therapy, MRSA vs. methicillin-susceptible S. aureus, and HAP vs. VAP were evaluated, and no single factor accounted for the observed imbalance in clinical response between treatment arms. Greater than 90% of patients experienced treatment-emergent adverse events (TEAEs). Anemia, hypokalemia, and diarrhea were the most frequently reported (TEAEs) in both arms. Types and incidence rates of TEAEs overall, and of drug-related TEAEs specifically, were comparable between TZD and LZD.

Conclusion

TZD was noninferior to LZD for day 28 ACM in the treatment of ventilated G+ HAP/VAP. However, TZD was not noninferior to LZD based on the investigator-assessed clinical response at TOC. Both drugs were similarly well tolerated and TEAEs were well balanced between groups, with no new safety signals identified.

Disclosures

All Authors: No reported Disclosures.
2842. Durable Efficacy of Two-Drug Regimen (2DR) of Dolutegravir (DTG) plus Lamivudine (3TC) in Antiretroviral Treatment-Naïve Adults with HIV-1 Infection at 96 Weeks: Subgroup Analyses in the GEMINI Studies
Authors: van Wyk Jean A , Man Choy Y , Sievers Jörg , Urbaityte Rimgaile , Underwood Mark , Tenorio Allan R , Pappa Keith , Wynne Brian , Smith Kimberly , Gartland Martin
Published: October 2019

Background

At Weeks 48 and 96 in the GEMINI-1 and GEMINI-2 studies (Clinicaltrials.gov: NCT02831673 and NCT02831764), the 2DR of DTG+3TC was noninferior to the three-drug regimen of DTG + tenofovir/emtricitabine (TDF/FTC) in achieving plasma HIV-1 RNA < 50 c/mL in treatment-naïve adults.

Methods

GEMINI-1 and 2 are identical, global, double-blind, multicenter Phase III studies. Participants with screening HIV-1 RNA ≤ 500.00 c/mL were randomized to once-daily DTG+3TC or DTG+TDF/FTC, stratified by plasma HIV-1 RNA and CD4+ cell count. The primary endpoint was the proportion of participants with plasma HIV-1 RNA < 50 c/mL at Week 48 (Snapshot algorithm). We present a secondary endpoint analysis of efficacy at Week 96 by baseline disease and demographic characteristics. For the overall population, estimates and confidence intervals were based on a stratified analysis using Cochran–Mantel–Haenszel weights.

Results

In total, 714 and 719 adults were randomized and treated in GEMINI-1 and -2, respectively. Based on a 10% noninferiority margin, DTG+3TC was noninferior to DTG+TDF/FTC at Week 96 in both GEMINI-1 and -2 and in the pooled analysis. Response rates across baseline HIV-1 RNA subgroups were high and similar in both arms in the pooled analysis, including in participants with baseline HIV-1 RNA >100,000 c/mL (Table 1). Results were also generally consistent regardless of age, gender, or race. In the CD4+ ≤ 200 cells/mm3 subgroup, response rates were lower in the DTG+3TC group compared with DTG+TDF/FTC; most reasons for nonresponse were unrelated to virologic efficacy or treatment regimen. Across both studies, 11 participants on DTG+3TC and 7 on DTG+TDF/FTC met protocol-defined virologic withdrawal criteria through Week 96; none had treatment emergent integrase-strand-transfer-inhibitor or NRTI resistance mutations.

Conclusion

In GEMINI-1 and 2, DTG+3TC was noninferior to DTG+TDF/FTC in treatment-naïve adults at Week 96, demonstrating durable efficacy. The results of subgroup analyses of efficacy at Week 96 were generally consistent with overall study results, and further demonstrate that DTG+3TC is an effective initial treatment for HIV-infected patients across a spectrum of disease characteristics and patient populations. The studies are ongoing.

Disclosures

All Authors: No reported Disclosures.
2847. Comparative Genomics and Clonal Tracking of Multi-drug-Resistant Uropathogens Implicates the Fecal Microbiome as a Potential Reservoir for Recurrent Urinary Tract Infections
Authors: Thanert Robert , Reske Kimberly , Hink Tiffany , Wallace Meghan , Wang Bin , Schwartz Drew , Burnham Carey-Ann , Seiler Sondra , Cass Candice , Dubberke Erik R , Dantas Gautam , Kwon Jennie H
Published: October 2019

Background

Multi-drug-resistant organisms (MDRO) have complicated the treatment of urinary tract infections (UTIs), especially in patients with recurrent UTIs (rUTI). The objective of this pilot prospective cohort study is to determine the role of the fecal microbiome in rUTIs.

Methods

Stool and urine specimens were prospectively collected from patients with MDRO UTIs at 6 time points during and after the UTI, and with any rUTI. Specimens underwent semi-quantitative culture on differential and selective media for MDROs, and isolates underwent phenotypic susceptibility testing and whole-genome sequencing. Comparative genomics and clonal tracking were used to detect clonal uropathogen strains in the urinary and gastrointestinal tracts. Resistance genes, resistance-plasmids, and virulence genes of MDROs were characterized in silico.

Results

A total of 110 isolates (95 Escherichia coli, 2 Klebsiella pneumoniae, 13 Proteus mirabilis) were cultured from the urine and stool of 15 patients (7 non-rUTI, 8 rUTI). Clonal uropathogens were isolated between the urinary tract and their intestinal reservoir (Figure 1). Integration of clonality information with semiquantitative culturing implicated three potential routes for recurrence of UTIs: (i) bladder colonization following an intestinal bloom of uropathogens, (ii) reinfection from an external source, and (III) bacterial persistence within the urinary tract (Figures 2 and 3). Antibiotic susceptibility testing and genomic profiling indicated that antibiotic-resistant uropathogen populations colonizing the urinary tract and intestinal reservoir at symptomatic and asymptomatic timepoints have similar resistance profiles that are largely determined via a pool of shared resistance plasmids (Figure 3).

Conclusion

This study provides the first time-resolved analysis of uropathogen persistence following UTIs, showing that clonal antibiotic-resistant uropathogens can be detected in both the urine and stool at varying time points post-initial infection. The study implicates 3 potential routes of rUTI, including uropathogen persistence within the gut microbiota, reinfection from an external source, and persistent bacteriuria. Study findings could be utilized to inform future diagnostics and therapies for treatment of rUTIs.

Disclosures

Carey-Ann Burnham, PhD, BioFire: Research Grant; bioMerieux: Research Grant; Cepheid: Research Grant; Luminex: Research Grant.
2852. Epidemiology of Emerging Carbapenemase-Producing Organisms (CPO) in Chicago, Illinois, 2013–2018
Authors: Pacilli Massimo , Adil Hira , Walblay Kelly , Xydis Shannon N , Clegg Whitney , Lin Michael Y , Valley Ann M , Tang Angela , Fealy Amy E , Kemble Sarah K , Black Stephanie R
Published: October 2019

Background

Emerging CPO in the Chicago area poses clinical and infection control challenges across the spectrum of care. Since November 2013, CPO are reportable to the Illinois’ Extensively Drug-resistant Organism (XDRO) registry. We examined trends in mechanism of resistance (MOR) among CPO reported through December 2018.

Methods

MOR reported into the XDRO registry were identified by clinical laboratories performing molecular methods on routine clinical cultures, by public health laboratories during point prevalence surveys (PPS) in response to clusters and as part of a project to assess CPO prevalence in high-risk Chicago area healthcare settings. Chicago patients with known MOR other than Klebsiella pneumoniae carbapenemase (KPC) are investigated by Chicago Department of Public Health (CDPH) to implement containment strategies and identify risk factors within 6 months of culture date.

Results

MOR was identified in 40% (1,216/3,587) of CPO-positive specimens collected from unique Chicago patients; 87% were KPC, 7% New Delhi metallo-β-lactamase (NDM), 5% Verona integron-mediated metallo-β-lactamase (VIM), 0.6% OXA-48-type carbapenemases, and 0.01% Imipenemase metallo-β-lactamase (IMP) (figure). Since 2017, 15 patients with CPO expressed more than one MOR; 14 were identified during PPS at ventilator capable skilled nursing facilities (vSNF) or long-term acute care hospitals (LTACH), and one was hospitalized in India. Among 156 patients with non-KPC CPO, the median age was 64 years (range, 20–97), 107 (69%) were identified from rectal screening and 49 (31%) were from clinical specimens, most of which were urine 23 (47%) or blood 6 (12%). Among 134 patients with risk factor history, 64% had history of tracheostomy (Table 1). Among 113 patients without documented travel outside of the United States, all stayed overnight at an Illinois healthcare facility; 62% stayed in a vSNF and 24% in an LTACH within 6 months of identification (Table 2).

Conclusion

We have increasingly detected non-KPC CPO in Chicago; however, estimates of prevalence are limited by lack of systematic surveillance and molecular testing. The high proportion of CPO patients without travel who stayed in vSNF or LTACH underscores the need for infection control training and surveillance in these settings.

Disclosures

All Authors: No reported Disclosures.
2856. Salvaging High-Value Catheters: Antifungal Lock Therapy for Candidal Central Catheter Infections in a Pediatric Cohort
Authors: Walker Lorne W , Nowalk Andrew J
Published: October 2019

Background

By IDSA guidelines, therapy for central line-associated bloodstream infections (CLABSI) due to Candida species requires catheter removal and administration of systemic antifungals. Despite this, in selected cases catheter salvage is desirable. The addition of antifungal lock therapy (ALT) has been proposed in these cases, but evidence for efficacy of this approach is limited. Here we report a retrospective analysis of ALT use for CLABSI due to Candida species at a single pediatric center.

Methods

All events of candidal CLABSI with ALT use were identified by retrospective record review between January 1, 2008 and December 31, 2018. CLABSI was defined by the growth of Candida from at least one central blood culture. Clearance was defined as a period of 48 hours with no positive cultures. Recurrence was defined as a subsequent positive blood culture with the same fungal organism either before or after line removal. Events were classified as “early removal” vs. “retained 7 days” depending on whether the line remained in place on day 7 after the first positive culture.

Results

Overall, 122 qualifying CLABSI were identified, 64 (52%) were retained 7 days or more (Table 1). Overall, 59% of CLABSI met criteria for clearance prior to line removal. Lines retained 7 days were likely to also remain in place at 28 days (72%) and had a low rate of relapse (8%) within 28 days. Lines in the early removal group had lower recurrence rates within 1 year (17% vs. 42%, P = 0.005), but this difference narrowed when considering recurrence at any time (31% vs. 47%, P = 0.1) or by Kaplan–Meier analysis (Figure 1) Additional microbiological and outcome data can be found in Tables 2 and 3.

Conclusion

This retrospective analysis is the largest described cohort of antifungal locks for line salvage in a pediatric population to our knowledge. These findings highlight the advantages of line removal, with lower recurrence at 1 year. However, when line salvage with antifungal locks is attempted, retention and recurrence rates in the first month are favorable, and recurrence rates converge in the long-term, presumably because the underlying risk factors remain. While line removal remains the standard therapy for candidal CLABSI, we find that ALT-based line salvage may be a viable alternative.

Disclosures

All Authors: No reported Disclosures.
2885. A Host Transcriptional Signature for Accurate Diagnosis of Candidemia in the Hospital Setting
Authors: Steinbrink Julie M , Hua Kaiyuan , Myers Rachel , Johnson Melissa D , Seidelman Jessica , Tsalik Ephraim L , Tsalik Ephraim L , Alexander Barbara D , McClain Micah T
Published: October 2019

Background

Candidemia is one of the most common nosocomial bloodstream infections in the United States and causes significant morbidity and mortality in hospitalized patients. Improved rapid diagnostics capable of differentiating candidemia from other causes of febrile illness in the hospitalized patient are of paramount importance. Pathogen class-specific biomarker-based diagnostics such as those focusing on host gene expression patterns in circulating leukocytes may offer a promising alternative.

Methods

RNA sequencing was performed on peripheral blood samples from 27 hospitalized patients with blood culture positive invasive candidiasis. Samples from healthy controls as well as at-risk subjects with acute febrile illness and similar clinical backgrounds but other infectious or noninfectious etiologies were used as comparator phenotypes (35 subjects with culture-proven bacterial infection, 49 with confirmed viral infection, and 17 with acute noninfectious illness). Bayesian techniques were utilized to develop infection-specific classifiers and leave one out cross-validation was used to estimate the predictive probability of each pathogen class.

Results

Candidemia triggers a unique, robust and conserved transcriptomic response in human hosts with 1,170 genes differentially upregulated compared with healthy controls. Based on this strength of signal, we developed a transcriptomic classifier that was capable of identifying candidemia, viral, or bacterial infection with a high degree of accuracy (auROC for Candida 0.93, Bacterial 0.98, Viral 0.99). The Candida component of this classifier (29-genes) was able to diagnose candidemia with a sensitivity of 88% and specificity of 100%.

Conclusion

The host transcriptomic response during candidemia in hospitalized adults is highly conserved and unique from the genomic responses to acute viral and bacterial infection. This approach shows promise for the development of host response-based classifiers capable of differentiating multiple types of clinical illnesses at once in at-risk febrile patients.

Disclosures

Ephraim L. Tsalik, MD MHS PhD, Immunexpress: Consultant; Predigen, Inc.: Officer or Board Member, Research Grant.
2889. Skin Niche Conditions Trigger C. auris to Form Robust Biofilms That Resist Desiccation
Authors: Nett Jeniel E , Patel Tarika , Johnson Chad , Kernien John
Published: October 2019

Background

Emerging pathogen Candida auris, the first fungus to be labeled as a public health threat, causes nosocomial outbreaks of invasive candidiasis with mortality as high as 60%. Little is known about the pathogenesis of this species that has newly arisen in the last 10 years. It is unclear why this species readily colonizes the skin and transmits efficiently in healthcare settings. We considered the possibility that C. auris may proliferate in conditions of the skin niche.

Methods

We analyzed the growth of C. auris (B11203) in synthetic sweat media that was designed to mimic human axillary sweat. We included C. albicans SC5314 as a comparison. To simulate sweat evaporation, we examined fungal growth in sweat media that had been concentrated up to 2.5-fold. We utilized OD600 readings to quantify planktonic and biofilm growth. Biofilm architecture was assessed by scanning electron microscopy. To determine the resilience of biofilms, biofilm viability was assessed by viable burden following desiccation.

Results

In the various concentrations of sweat media, C. auris formed biofilms that were 3.5- to 5-fold greater that those observed for C. albicans (A). In contrast, C. auris biofilms formed in RPMI-MOPS were approximately half the density of the C. albicans biofilms. During planktonic growth in synthetic sweat media, C. auris and C. albicans replicated similarly, including in media that had been concentrated 2.5-fold. This suggests that the various media conditions differently trigger biofilm formation for the two species. The C. auris biofilm formed in sweat media was approximately 100-fold more resistant to 1 week of desiccation (B).

Conclusion

Skin niche conditions trigger C. auris to form resilient biofilms that resist desiccation. We propose that this unique characteristic may account for the propensity of this species to colonize the skin and for its capacity to persist on the surface of contaminated medical devices.

Disclosures

All Authors: No reported Disclosures.
2904. Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice
Authors: Jagger Brett W , Dowd Kimberly A , Chen Rita , Desai Pritesh , Himansu Sunny , Graham Barney S , Pierson Theodore C , Diamond Michael S
Published: October 2019

Background

Zika virus (ZIKV) caused an epidemic of microcephaly and congenital malformations in 2015–2016, prompting the development of ZIKV vaccines. Plasmid DNA and modified mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccines were among the first to reach human clinical trials, where their evaluation is ongoing. Few studies have evaluated vaccine efficacy in the setting of infection during pregnancy, and there is an open question around antibody-dependent enhancement (ADE) of flaviviral disease due to cross-reactive fusion loop epitope (FLE) antibodies.

Methods

Female C57BL/6J mice and human STAT2 knock-in (hSTAT2-KI) mice were immunized with plasmid DNA (VRC5283) or mRNA-LNP (Moderna Inc.) vaccines encoding the ZIKV prM-E genes. Antibody responses were assayed, and immunized mice were mated and WT mice were transiently immunocompromised by administration of interferon blocking antibody, followed by ZIKV challenge. 1 week post-infection, ZIKV burden was measured via qRT-PCR. ZIKV-specific memory B cell (MBC), long-lived plasma cell (LLPC), and CD8+ T cell vaccine responses were also assayed.

Results

VRC5283 and mRNA-LNP vaccines were highly immunogenic, eliciting serum neutralizing EC50 responses >1:10,000, and markedly reduced placental ZIKV burden and fetal transmission. An improved mRNA-LNP construct with higher immunogenicity correlated with reduced placental viral burden. Significantly, an FLE-mutant mRNA-LNP vaccine yielded comparable EC50 responses without compromising vaccine efficacy; sera from these mice did not enhance dengue virus infection in vitro. Both VRC5283 and mRNA-LNP vaccines elicited MBC, LLPC, and CD8+ T cell responses, although MBC and LLPC responses were greater after mRNA-LNP immunization. Surprisingly, low-level ZIKV infection of the placenta and a minority of fetal heads were observed despite robust neutralizing antibody responses, which was not seen in the immunocompetent hSTAT2-KI model.

Conclusion

Nucleic acid vaccines were highly immunogenic and protective against vertical ZIKV transmission during pregnancy in mice. These data support and inform the ongoing clinical development of these vaccines in humans.

Disclosures

All Authors: No reported Disclosures.
2905. Long-term Immunological Persistence of the Adjuvanted Recombinant Zoster Vaccine: Clinical Data and Mathematical Modeling
Authors: Bastidas Adriana , Catteau Grégory , Volpe Stéphanie , Mrkvan Tomas , Enemuo Adaora , Smetana Jan , Schwarz Tino , Rombo Lars , Pauksens Karlis , Berengier Estelle , Hervé Caroline , Oostvogels Lidia , Schuind Anne
Published: October 2019

Background

The adjuvanted recombinant zoster vaccine (RZV, GSK), administered to adults ≥ 50 years of age (YOA) demonstrated ≥ 90% efficacy against herpes zoster across all age cohorts. Vaccine-specific immune responses elicited by two RZV doses in adults ≥ 60 YOA have been shown to persist above pre-vaccination levels at least up to 9 years after initial vaccination. Here we present persistence of the humoral and cellular immunity and safety up to 10 years after initial vaccination as well as data from mathematical modeling, performed to predict immune persistence up to 15 years.

Methods

This phase IIIB, open-label extension trial (NCT02735915) included 70 participants who had received two RZV doses in the initial trial (NCT00434577) and builds on a previous extension trial (NCT01295320). Cellular and humoral immune responses up to year 10 after an initial 2-dose vaccination schedule are presented here. Additionally, prediction of immunological persistence at year 15 was assessed by mathematical modeling (Piecewise, Power-law, Fraser), using the individual subject values for available data up to year 10.

Results

The median frequency of varicella-zoster virus glycoprotein E (gE)-specific CD4+ T-cells expressing ≥ 2 activation markers plateaued at 3.3-fold above pre-vaccination levels starting around year 4 up to year 10 post-initial vaccination. Anti-gE antibody concentrations plateaued starting around year 3 up to year 10 post-initial vaccination.Ten years after initial vaccination, humoral responses remained 5.9-fold higher as compared with pre-initial vaccination levels (Figure 1). No relevant safety events were identified during the study (year 9–10 post-initial vaccination). In line with previous modeling data, the year 10 analysis predicts that both cellular and humoral immune responses will remain above pre-vaccination levels for at least 15 years after initial vaccination (Figures 2 and 3).

Conclusion

In adults vaccinated when ≥ 60 YOA, humoral and cellular immune responses induced by two RZV doses persist above pre-vaccination levels for at least 10 years post-initial vaccination. Mathematical modeling predicts a maintained vaccine-related immune response for at least 15 years after initial vaccination.

Funding. GlaxoSmithKline Biologicals SA.

Disclosures

All Authors: No reported Disclosures.
1140. Evaluation of Neonatal Sepsis Guidelines in a Neonatal Intensive Care Unit
Authors: Patel Priya V , Nash Colleen B , Vu Betty N
Published: October 2019

Background

Clinical practice surrounding neonatal sepsis varies significantly among physicians. In efforts to confront the challenge of inappropriate and overuse of antimicrobials in our Neonatal Intensive Care Unit (NICU), a multidisciplinary team developed a guideline for the evaluation and management of suspected and proven sepsis within the NICU in preterm infants. We evaluated the antimicrobial utilization before and after the implementation of our guideline, developed in July 2018.

Methods

All infants <37 gestational weeks born in July and August of 2016, 2017, and 2018 were retrospectively reviewed and compared before and after implementation of the guideline. The primary outcome was the percentage of antibiotic-free days per admission. Secondary outcomes include percentage of directive treatment courses and percentage of antibiotic days for culture-negative sepsis. Chi-square and Mann–Whitney U tests were performed, as appropriate.

Results

A total of 75 and 37 patients were included for preliminary data analysis in the pre- and post-implementation periods, respectively. Chi-square and Mann–Whitney U tests were performed, as appropriate. The percentage of antibiotic-free days per admission per patient born in the pre-implementation period was lower (84.4% vs. 86.5%, P = 0.028). There is no statistical difference in the percentage of directive treatment between the two groups. The percentages of culture-negative antibiotic days were not statistically significant (69.2% vs. 80.5%, P = 0.296). The average birth weights were lower (1,719.7 grams vs. 1,420.7 grams, P = 0.02) and gestational ages were younger (31.4 weeks vs. 29 weeks, P = 0.001) in the post-implementation period.

Conclusion

Our preliminary data did not show a significant decline in the percentage of antibiotic-free days or culture-negative antibiotic days after the implementation of our guideline; however, this may be confounded by the differences noted in our patient populations and is based on preliminary data. Implementation of this guideline is feasible and may reduce the inappropriate use of antimicrobials. Further data collection is ongoing to fully assess the impact of this guideline.

Disclosures

All authors: No reported disclosures.
1141. Implementation of a Pediatric Handshake Antimicrobial Stewardship Program to Improve Antimicrobial Utilization
Authors: Hughes Amanda P , Beganovic Maya , Oram Ronda , Wieczorkiewicz Sarah , Chiang Anthony
Published: October 2019

Background

Antimicrobial stewardship (AMS) programs emerged in response to rising rates of resistance and adverse effects associated with inappropriate antimicrobial utilization. Optimal metrics and strategies (e.g., preauthorization, prospective audit and feedback) for AMS remain to be elucidated. This study evaluated the impact of a multidisciplinary, rounding-based AMS strategy (i.e., Handshake Stewardship) on antimicrobial utilization and prescribing practices at a pediatric hospital.

Methods

This was a single-center, retrospective quality improvement study at a community, teaching children’s hospital. All pediatric and neonatal inpatients with active antimicrobial orders between July 2018 and March 2019 were included in the study, and endpoints were compared with data from July 2017- March 2018. Antimicrobial courses were prospectively audited by a multidisciplinary AMS team, and feedback was provided to the primary teams during Handshake Stewardship rounds. The primary endpoint was a number of interventions made and the corresponding acceptance rates. The secondary endpoint was days of therapy (DOT) per 1000 patient-days. Descriptive statistics were performed on all continuous and categorical data as appropriate.

Results

Of 2238 antimicrobial courses reviewed, 710 (32%) required intervention, and 86% of the interventions made were accepted. The top 3 indications evaluated were respiratory (n = 522, 23%), sepsis/bacteremia (n = 351, 16%), and surgical prophylaxis (n = 266, 12%). Of the respiratory courses reviewed, there were 228 opportunities for antimicrobial optimization. The most common interventions were: bug-drug optimization (n = 208, 29%), discontinuation of anti-infective (n = 136, 19%), and dose optimization (n = 120, 17%). No significant difference was observed for overall, ceftriaxone, meropenem, and vancomycin DOT pre- and post-implementation of Handshake Stewardship. However, a statistically significant reduction in DOTs was observed for piperacillin–tazobactam (15.2 vs. 7.4, P = 0.004) and a nonsignificant reduction in meropenem (9.5 vs. 6.2).

Conclusion

Rounding-based, Handshake AMS was associated with overall high intervention acceptance rates and a reduction in commonly utilized broad-spectrum antimicrobials.

Disclosures

All authors: No reported disclosures.
1144. Evaluation of Nafcillin vs. Vancomycin as Empiric Therapy for Late-Onset Sepsis in the Neonatal Intensive Care Unit
Authors: Magers Jacqueline , Prusakov Pavel , Sanchez Pablo J
Published: October 2019

Background

Empiric therapy for possible late-onset sepsis (LOS) due to Gram-positive bacteria in the neonatal intensive care unit (NICU) has included vancomycin to cover, among other pathogens, coagulase-negative staphylococci (CoNS) which are the most frequent cause of bloodstream infections (BSI). In 2015, Nationwide Children’s Hospital (NCH) neonatal antimicrobial stewardship (nASP) team recommended nafcillin rather than vancomycin, in combination with gentamicin, as the preferred agent for empiric therapy of LOS in infants not colonized with methicillin-resistant Staphylococcus aureus, irrespective of presence of a central venous catheter. The NCH nASP team provides oversight for 6 Columbus NICUs, and Our objective was to evaluate the impact of the vancomycin reduction program, with secondary objectives including duration of therapy, recurrence of BSI within 14 days of completion of therapy, and mortality.

Methods

The pharmacy database at NCH was queried with respect to all nafcillin and vancomycin use from 2013–2018. Pertinent clinical and laboratory data were obtained from the electronic health record (EHR) on all infants who had nafcillin or vancomycin therapy initiated, with each initiation defined as an antibiotic “course.”

Results

From 1/2013 to December 2014 (pre-vancomycin reduction), there was an average of 112 vancomycin and 42 nafcillin courses provided to infants each year. From 1/2015 to December 2018, the use of nafcillin increased to an average of 90 courses while vancomycin decreased to 55 courses per year (P < 0.01). Since the institution of the vancomycin reduction program, preliminary EHR review of 50 infants has shown that 9 had a positive blood culture (7 CoNS; 2 methicillin-susceptible S. aureus; 1 Escherichia coli). All CoNS isolates were resistant to nafcillin, and all infants sterilized the blood culture within 24 hours of vancomycin. The overall median length of therapy was 3 days with nafcillin or vancomycin. However, when excluding rule outs, the median duration of therapy was 9.5 days. There was no BSI recurrence or infection-related death.

Conclusion

An empiric antibiotic regimen that includes nafcillin rather than vancomycin for possible LOS in high-risk infants in the NICU effectively and safely reduced overall vancomycin use.

Disclosures

All authors: No reported disclosures.
1150. Evaluating the Impact of Antibiotic Prophylaxis on the Microbiology and Incidence of Ventriculitis in Patients with External Ventricular Drains
Authors: McCormick Jack , McManus Dayna , Ammar Abdalla A , Topal Jeffrey E
Published: October 2019

Background

External ventricular drains (EVDs) are frequently used in acute brain injuries for continuous intracranial pressure monitoring and cerebrospinal (CSF) fluid diversion. EVDs are associated with a 0–22% risk of ventriculitis. The evidence for antibiotic prophylaxis (AP) for ventriculitis prevention is not robust. This study aimed to delineate the incidence of EVD-related ventriculitis and causative organisms in patients receiving AP.

Methods

A retrospective chart review from 2013 to 2018 at Yale New Haven Hospital was performed. Patients were included if ≥18 years of age, admitted to the neurosciences intensive care unit (ICU), and had AP with cefazolin, vancomycin, sulfamethoxazole/trimethoprim, or clindamycin. Patients were excluded if they had a diagnosis of meningitis or ventriculitis prior to EVD placement, on multiple agents for AP, on antibiotics for indications other than AP, CSF leak, or skull fracture. The primary endpoint was the incidence of ventriculitis per 1,000 EVD-days. Secondary endpoints were causative organisms of ventriculitis, EVD duration, ICU length of stay (LOS), hospital LOS, and 30-day mortality.

Results

Five hundred ninety-nine patients were reviewed and 249 patients were included. Baseline demographics are noted in Table 1. Cefazolin was the most common agent for AP (98%). There were 7 cases of ventriculitis with an incidence rate of 2.8% (4 infections per 1000 EVD-days). All of the causative organisms were resistant to the prophylactic agents administered (Table 2). Patients with ventriculitis had a significantly longer duration of EVD placement (10 ± 3 vs. 7 ± 6 days, P = 0.03), hospital LOS (30 ± 19 days vs. 15 ± 12, P = 0.04), ICU LOS (22 ± 14 vs. 10 ± 7, P = 0.03). Two patients with ventriculitis (28%) died within 30 days of admission compared with 46 patients without ventriculitis (19%, P = 0.53) (Table 3).

Conclusion

The rate of ventriculitis in our study was similar to previous studies that did not utilize AP. All of the causative organisms were resistant to the prophylactic agent. Patients who had ventriculitis had a longer duration of EVD placement, hospital LOS, and ICU LOS; however, 30-day mortality was not impacted. Based on our findings, the use of AP to prevent EVD-related ventriculitis should be reconsidered.

Disclosures

All authors: No reported disclosures.
1160. CAUTIs are the Most Common Type of Healthcare-Associated Infection. In an Effort to Decrease CAUTI Rates Through Proactive Prevention, We Sought to Develop a Weighted Model of CAUTI Risk Factors. The Final Set of Risk Factors Jointly Predicting CAUTI Were ADL Dependent, CVA, Catheter Replacement Within 7 days, and Catheterization Duration ≥5. We Have Defined Contemporary Weighted Risk Factors for CAUTI and Intend to Utilize These to Deploy a Tiered Approach Where Patients with Risk Factors Will Receive Advanced in Addition to Basic Preventive Efforts
Authors: Nanda Neha , Aleksanyan Meline
Published: October 2019

Background

Catheter-associated urinary tract infections (CAUTI) are the most common type of healthcare-associated infection. In an effort to decrease CAUTI rates through proactive prevention, we sought to develop a weighted model of CAUTI risk factors in our patient population.

Methods

A retrospective case–control study was conducted to identify potential CAUTI risk factors in a 401-bed, acute care, tertiary academic facility. Data were collected through chart review of CAUTI cases between January 2014 and June 2018. Controls were catheterized patients who did not develop a CAUTI, and were selected based on the corresponding case event date (±7 days) and location. The case to control ratio was 1:2. A multivariable logistic regression was used to identify CAUTI risk factors by stepwise selection. All tests were 2-sided at a 0.05 significance level. All statistical analyses were performed using SAS 9.4.

Results

We reviewed 501 patients. The mean age was 62.7 years and 51% were female. The most common organisms in CAUTI cases (n = 167) were Escherichia coli (28.7%) and Pseudomonas aeruginosa (18.6%). Median catheterization duration for cases and controls was 8 and 5 days, respectively. Univariate logistic regression analyses revealed the following statistically significant risk factors: female, catheterization duration ≥5 days, ADL-dependent, cerebrovascular disease (CVA), nonoperating room procedure, catheter placement in operating room and history of malignancy. The final set of risk factors jointly predicting CAUTI included ADL-dependent (OR 1.69), CVA (OR 7.3), catheter replacement within 7 days (OR 1.85), and catheterization duration ≥5 (OR 2.1). The final model’s AUC was 0.72. Risk factors were scored using β coefficient from the final model. The highest score attainable was 20 with CVA receiving the maximum weight. The risk score’s ability to classify infection was measured by AUC of 0.60.

Conclusion

In our study, we have defined contemporary weighted risk factors associated with CAUTI. We intend to utilize these findings to deploy a tiered approach where patients with risk factors will receive ‘advanced’ in addition to ‘basic’ preventive efforts. Additionally, our risk score model will allow for prioritizing efforts.

Disclosures

All authors: No reported disclosures.
1164. In vitro Antimicrobial Efficacy of Novel Antimicrobial Dacron Vascular Grafts in the Inhibition of Multidrug-Resistant Gram-Negative Biofilm
Authors: Vargas-Cruz Nylev , Rosenblatt Joel , Reitzel Ruth A , Khalil Kamal , Raad Issam I
Published: October 2019

Background

Vascular graft infections can be a devastating complication in vascular reconstructive surgery. Management of these infections is highly invasive and includes excision of the graft, debridement of infected material, and in situ reconstruction. There is a need for additional strategies for infection prevention in graft surgeries. The minocycline + rifampin + chlorhexidine (MRCH) triple combination had been previously demonstrated to be effective against biofilm formation in central venous catheters. In this study, we evaluated in vitro effectiveness and durability of MRCH coated Dacron vascular grafts in inhibiting multidrug-resistant Gram-negative biofilm formation.

Methods

Dacron vascular grafts were coated with MRCH based on a proprietary method. Antimicrobial efficacy at baseline and 3-week durability was assessed using a well-established in vitro biofilm colonization model. Multidrug-resistant Gram-negative pathogens tested include CRE Escherichia coli (EC), MDR Pseudomonas aeruginosa (PS) and CRE Klebsiella pneumoniae (KB). Antimicrobial durability was assessed for grafts that had been eluting in serum for 3 weeks prior to testing. Baseline and 3-week grafts were quantitatively culture to enumerate any biofilm viable biofilm colonization. Uncoated Dacron grafts were used as controls.

Results

At baseline and 3 weeks MRCH vascular grafts completely inhibited biofilm formation resulting in an 8-log10 reduction in bacterial colonization compared with uncoated grafts.

Conclusion

MRCH coated Dacron vascular grafts demonstrated in vitro effectiveness for at least 3 weeks in preventing biofilm colonization by multidrug-resistant Gram-negative pathogens. Further in vivo testing is warranted.

Disclosures

All authors: No reported disclosures.
1170. A Quality Improvement Study to Assess the Effectiveness of a Meaningful Use Protocol in the Reduction of PICC Line Use and Complications
Authors: Dillon William P , Szpunar Susan , Sharma Mamta
Published: October 2019

Background

The use of peripherally-inserted central catheters (PICC) has grown substantially over time because of their ease of insertion, cost-effectiveness and relative safety. With increased use; however, there are increased complications including catheter-related bloodstream infections (CLABSI) and PICC line-associated deep vein thrombosis (DVT). To help decrease complications a meaningful use protocol was implemented based on the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) to define appropriate indications for PICC line use. The objectives of this study were (1) to determine the rate of PICC line use at our hospital; (2) to determine rates of complications associated with PICC lines, including CLABSI and DVT; and (3) to compare the metrics listed above before and after implementation of the meaningful use protocol.

Methods

We performed a retrospective chart review of all inpatient admissions before (June 1, 2017 to September 1, 2017) and after the implementation of the meaningful use protocol (June 1, 2018 to September 1, 2018). Patients who had a PICC line inserted at another institution or in the outpatient setting were excluded. We compared the rate of insertion, patient demographics, characteristics of the use of PICC lines and complications from the two periods. Data were analyzed using the chi-squared test, Student’s t-test, the Mann–Whitney U test and the z test for proportions.

Results

We reviewed 281 patient charts, 166 before the implementation of the meaningful use protocol and 115 after implementation. Overall, the mean age was 55.8 ± 17.9 years, 58.7% male and 54.1% white. There were no significant differences between groups with respect to demographics, comorbidities, source of admission, or complications. Post-implementation there was a significant reduction in lines used for unknown reasons as well as lines used for multiple blood draws (P <0.0001). The overall rate of PICC line use decreased from 23 per 1,000 admissions to 17.2 per 1,000 admissions after the intervention (P = 0.007).

Conclusion

Implementation of a meaningful use protocol reduced the rate of PICC line use at our institution by 25%. The proportion of lines used for unknown reasons decreased as well. Widespread implementation could have a significant impact on the reduction of PICC line use.

Disclosures

All authors: No reported disclosures.