bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Antiretroviral Resistance and Transmission in Mother–Infant Pairs Enrolled in a Large Perinatal Study
Authors: Yeganeh Nava , Kerin Tara , Ank Bonnie , Watts Heather , Camarca Margaret , Joao Esau , Pilotto Jose Henrique , Veloso Valdilea , Bryson Yvonne , Nielsen-Saines Karin 
Published: October 2017

Abstract

Background
Detection of antiretroviral (ARV) resistance in HIV-infected individuals is not uncommon and may be particularly problematic in HIV-infected pregnant women as it can lead to infant infection with resistant strains. To better evaluate the effect of drug resistance mutations (DRMs) on HIV mother-to-child transmission (MTCT), we determined the prevalence of DRMs in a subset of mother–infant pairs enrolled in a multi-center trial of infant prophylaxis among women not receiving ARVs during the current pregnancy.

Methods
A case–control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate ARV resistance as a predictor of HIV MTCT in specimens obtained from mother–infant pairs. Secondary objectives included identification of potential risk factors associated with the presence of DRMs. Viroseq HIV-1 Genotyping System was performed on mother–infant specimens to assess for mutations that might result in a substantial reduction in drug susceptibility and clinical outcome, as determined by the Stanford HIV Drug Resistance Database.

Results
One hundred and forty infants were infected. Of these, 123 HIV infected mother–infant pairs and 483 of 560 women who did not transmit HIV had amplifiable HIV nucleic acid enabling ARV resistance testing. A wide variety of DRMs were detected (Figure 1). Sixty (10%) of 606 women had clinically relevant DRMs; 12 (2%) had DRMs against more than 1 ARV class. Among 123 HIV− infected infants, 13 (11%) had clinically relevant DRMs with 3 (2%) harboring DRMs against more than 1 ARV class. Of 13 infants with DRMs, 10 (77%) were infected in utero. In univariate and multivariate analyses, DRMs in mothers were not associated with increased risk of HIV MTCT (AOR 0.79, 95% CI 0.38–1.5). Log HIV viral load was the only predictor of MTCT (OR 1.4, 95% CI 1.2−1.6). The presence of DRMs in mothers who transmitted was strongly associated with the presence of DRMs in infants (P &lt; 0.001).

Conclusion
In infected pregnant women without ARV exposure during their current gestation, the presence of pre-existing DRMs with a wide diversity was noted. DRMs do not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed they are likely to transmit resistant mutations even without selective ARV pressure, thus complicating treatment options.

Disclosures
All authors: No reported disclosures.
Improvement of Gram-negative Susceptibility to Fluoroquinolones After Implementation of a Pre-Authorization Policy for Fluoroquinolone Use: A Decade-Long Experience
Authors: Lee Rachael A , Scully Morgan , Kunz Danielle F , Jones T Aaron , Camins Bernard , McCarty Todd P , Moser Stephen , Hoesley Craig J , Pappas Peter G 
Published: October 2017

Abstract

Background
Antibiotic use is a well-known risk factor for acquisition of drug-resistant bacteria and community antibiotic prescribing can drive high rates of resistance within the hospital setting. Owing to concerns over increasing fluoroquinolone (FQ) resistance among Gram-negative organisms at UAB Hospital, our stewardship program implemented a pre-authorization policy. The goal of this study was to assess the relationship between hospital fluoroquinolone use and antibiotic resistance.

Methods
In 2006, the inpatient formulary was consolidated to only ciprofloxacin and moxifloxacin with implementation of guidelines for use to limit inpatient prescribing. Any use outside of these guidelines required approval from an infectious diseases physician. Organism-specific data were obtained from the clinical microbiology database and FQ use was obtained from the hospital database. Correlations were calculated using Pearson’s coefficient.

Results
From 1998 to 2004, FQ use peaked at 173 days of therapy (DOT)/1,000 patient-days, but has remained below 60 DOT/1,000 patient-days since restriction implementation (Figure 1). FQ susceptibility was documented for five common Gram-negative isolates, P. aeruginosa, Acinetobacter spp., Enterobacter cloacae, E. coli, and K. pneumoniae, over an 18-year period (1998–2016). Common hospital acquired pathogens, including Pseudomonas aeruginosa, Acinetobacter spp. and Enterobacter cloacae improved in their susceptibilities to fluoroquinolones. Acinetobacter went from 35% to over 50% susceptible in the preceding 10 years after the policy. Pseudomonas improved from 50% susceptible to over 70% and Enterobacter improved from less than 50% to over 90% susceptible. Interestingly this improvement was not seen for E. coli which continued to show a decline in susceptibility from over 90% to near 60% in 2016.

Conclusion
In a large academic hospital setting, FQ susceptibility for common hospital-acquired GNRS improved significantly with the introduction of a restricted use program. A continued decline in E. coli FQ susceptibility suggests resistance rates may be driven by outpatient and community antibiotic use and thus, outpatient stewardship programs are necessary to prevent further spread of FQ resistance.

Disclosures
All authors: No reported disclosures.
Inpatient plus Post-discharge Durations of Therapy to Identify Antimicrobial Stewardship Opportunities at Transitions of Care
Authors: Dyer April , Ashley Elizabeth Dodds , Anderson Deverick J , Sarubbi Christina , Wrenn Rebekah , Hicks Lauri , Srinivasan Arjun , Moehring Rebekah W 
Published: October 2017

Abstract

Background
In-hospital antimicrobial durations capture only a portion of total antimicrobial exposures attributable to that inpatient stay. Review of electronic discharge prescriptions could allow stewards to identify excessive prescribing durations.

Methods
We performed a retrospective review of inpatient and discharge antimicrobial prescribing at three hospitals from April to September 2016 using two data sources: electronic medication administrations and electronic prescription orders at discharge. Antimicrobial agents from the National Healthcare Safety Network Antimicrobial Use (NHSN AU) module were included. Durations were calculated for admissions in which patients received at least one dose of an antimicrobial agent on inpatient units. Intended post-discharge durations were captured in days duration fields or calculated from sig and quantity fields of discharge prescriptions. Post-discharge days and inpatient days were summed to calculate the total duration of therapy resulting from the admission. Descriptive statistics were used to describe inpatient, post-discharge, and total durations.

Results
Among 45,693 inpatient admissions, NHSN AU antimicrobials were given during 23,447 inpatient admissions (51%) and in electronic discharge prescriptions for 7,442 admissions (16%). Median total duration was 4 days (IQR 2–11) among all patients who received antimicrobials and 12 (IQR 9–17) among those who received discharge prescriptions. Common post-discharge durations were 5, 7, and 10 days (Figure 1). Post-discharge days accounted for 40% (78,195/196,792) of the total days of antimicrobial therapy. The most common discharge agents were ciprofloxacin (14%), amoxicillin/clavulanate (11%), and levofloxacin (8%). Most discharge prescriptions originated from medical (37.1%), surgical (15.6%), and hematology/oncology wards (14.5%).

Conclusion
Post-discharge days accounted for 40% of antimicrobial days related to inpatient admissions. Common post-discharge durations suggested clinicians were not counting inpatient days when completing discharge orders. Post-discharge days were feasibly captured through electronic prescribing records and could aid in targeting stewardship interventions at transitions of care.

Disclosures
All authors: No reported disclosures.
Prevent Antibiotic overUSE (PAUSE): Impact of a Provider Driven Antibiotic-Time out on Antibiotic Use and Prescribing
Authors: Thom Kerri , Tamma Pranita D , Harris Anthony D , Morgan Daniel , Dzintars Kathryn , Srinivasan Arjun , Avdic Edina , Li David X , Pineles Lisa , Cosgrove Sara E 
Published: October 2017

Abstract

Background
Empiric antibiotic (abx) therapy is often not readdressed after clinical progress becomes apparent and the results of diagnostic studies become available. We sought to evaluate whether an antibiotic time out (ATO) by front-line clinicians after 3–5 days of abx therapy could lead to a reduction in unnecessary abx use.

Methods
A quasi-experimental study to evaluate the impact of an ATO on decreasing abx use was performed over a 6-month base period and 9-month intervention period in 11 units across 6 hospitals in the greater Maryland region was conducted. Patients who received abx for at least 3 calendar days were eligible for study inclusion. Outcomes included days of abx therapy (DOT) per admission to cohort as well as percent of patients with a change in abx regimen on day 3–5 and appropriateness of abx regimens on days 3–5. Appropriateness of abx therapy was adjudicated by infectious diseases (ID) clinicians using prespecified criteria. Regression analysis was used to compare outcomes between the base and intervention periods.

Results
A total of 3,448 abx courses were reviewed, including 1,541 during the base and 1,907 during the intervention period. Overall DOT per cohort admission was similar between the two periods (12.7 vs. 12.2 hospital DOT per admission in the base and intervention periods, respectively, and was not statistically significant after controlling for unit and season (P = 0.18). After adjusting for season, unit, ID consultation, and comorbidities, there was a 36% increase in the odds of changing or discontinuing abx on days 3–5 in the intervention period compared with the base period (48% vs. 54%, P &lt; 0.05). Similarly, there was an 89% increase in the odds of receiving an appropriate abx regimen on days 3–5 in the intervention period compared with the base period (53% vs. 68%, P &lt; 0.01). There was no difference in the rate of Clostridium difficile lab-events in the two study periods.

Conclusion
In this multicenter study, we found that performance of an ATO by front-line providers was effective at improving the appropriateness of abx therapy 3–5 days after initiation, but did not change the amount of abx use, suggesting that additional interventions, perhaps later during hospitalization or at discharge, are needed to impact duration of abx therapy.

Disclosures
All authors: No reported disclosures.
Perinatal Case Fatality Rate Related to Congenital Zika Syndrome in Brazil: a Cross-Sectional Study
Authors: Queiroz Igor Thiago , Da Silva Maia Jessika Thais , Rosa Gleysson , Mendes Tatyana Vidal , Vidal S Jayne Alves , Lins Maria Goretti , Zacarkim Marcelo Rodrigues , Aronoff David , Labeaud A Desiree , Mendes Neto Nilson N 
Published: October 2017

Abstract

Background
Many studies have demonstrated a causal link between Zika virus (ZIKV) infection, microcephaly (MCP), and other congenital abnormalities (CA). This study aimed to determine perinatal case fatality rate in cases of Congenital Zika Syndrome (CZS) in the Rio Grande do Norte State (RN), a Brazilian Northeast State highly impacted by the Zika virus outbreak.

Methods
A cross-sectional study was conducted using data obtained through the State Health Department (SHD) for cases of MCP and CA in Rio Grande do Norte from April 2015 to February 5, 2016. Definition of perinatal period: commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth.

Results
During the study period, there were 486 cases of MCP and others CA notified in RN, of which 142 were confirmed and 108 remain under investigation. The remaining 236 cases have been ruled out by presenting normal examinations or due to presenting microcephaly by noninfectious causes. Of the total confirmed cases, 26.7% (38/142) died after birth or during pregnancy. 15.78% (06/38) of confirmed deaths had ZIKV infection during pregnancy and 2.63% (01/38) had a positive TORCH blood test. The six cases related to ZIKV were confirmed by RT–PCR and/or IgM/IgG antibodies against ZIKV. The remaining cases of deaths remain either under investigation or have been ruled out.

Conclusion
This study highlights a high rate of perinatal lethality (15.78%) in cases of CZS. Despite the growing number of CZS cases, the real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). Due to the high rate of lethality and the ongoing uncontrolled ZIKV outbreak, this study predicts an increase in the infant mortality rate in Brazil and highlights the need for developing public health programs to control the ZIKV outbreak.

Disclosures
All authors: No reported disclosures.
Fetal and Postnatal Brain Imaging for the Detection of ZIKV Encephalopathy in the Fetus/Newborn
Authors: Mulkey Sarah , Vezina Gilbert , Fourzali Yamil , Bulas Dorothy , Arroyave-Wessel Margarita , Cristante Caitlin , Swisher Christopher , Kousa Youssef , Cure Carlos , DeBiasi Roberta , Plessis Adre Du 
Published: October 2017

Abstract

Background
Up to 15% of pregnancies complicated by maternal ZIKV infection result in Zika-virus associated brain abnormalities in the fetus/newborn. Fetal ultrasound (feUS) is the standard imaging modality for the evaluation of fetal anatomy and for brain changes from congenital infection. Fetal MRI (feMRI) may be a useful adjunct.

Methods
We performed a prospective longitudinal neuroimaging study of fetuses/newborns of pregnant women with clinical and/or lab confirmed (RT-PCR and/or IgM/PRNT) diagnosis of Zika infection in Barranquilla, Colombia (endemic) and in Washington, DC, USA (travel-related). Gestational age (GA) at exposure and timing between ZIKV exposure/symptoms and imaging was documented. Subjects had one to two feMRIs and feUS, depending upon GA at enrollment. The feMRI and feUS protocols were standardized between sites and studies were centrally interpreted at Children’s National. Postnatally, infants received an unsedated brain MRI and head US.

Results
Forty-eight, ZIKV exposed/infected in first or second trimester pregnant women were enrolled (46 Colombia, 2 USA). Subjects had symptoms of ZIKV infection at mean of 8.4±5.7 week GA. The first feMRI and feUS were performed at 25.1±6.3 week GA. Thirty-six infants had a second feMRI and feUS at 31.1±4.2 week GA. Three of 48 (6%) cases had an abnormal feMRI: (1) heterotopias and abnormal cortical indent; (2) parietal encephalocele and Chiari II; (3) thin corpus callosum, dysplastic brainstem, temporal cysts, subependymal heterotopias, and generalized cerebral/cerebellar atrophy. FeUS in these three cases found (1) normal study; (2) parietal encephalocele and Chiari II; (3) significant ventriculomegaly with decreasing percentiles of head circumference from 32 to 36 week GA (38% to 3.6%). Postnatal head US revealed findings not seen on feUS: choroid plexus or germinal matrix cysts in nine infants and lenticulostriate vasculopathy in one infant.

Conclusion
FeMRI and feUS provide complimentary information in the assessment of fetal brain changes in ZIKV. In cases of abnormal brain structure, feMRI reveals more extensive areas of brain damage than is seen by US. Further studies are needed to determine whether cystic changes on postnatal head US are related to ZIKV infection, or are incidental findings.

Disclosures
All authors: No reported disclosures.
Maternal Immunization with a Single-Cycle Herpes Simplex Virus (HSV) Candidate Vaccine, ΔgD-2, Protects Neonatal Mice from Lethal Viral Challenge
Authors: Kao Carol , Burn Clare , Jacobs William R , Herold Betsy C 
Published: October 2017

Abstract

Background
Perinatal HSV is associated with ~60% mortality if untreated and with substantial morbidity even with appropriate therapy. We recently engineered a single-cycle virus deleted in glycoprotein-D (ΔgD-2) that induces high-titer antibodies (Abs) that are non-neutralizing but activate the Fc receptor (FcR) to elicit antibody-dependent cellular cytotoxicity (ADCC). Immunization with ΔgD-2 completely protects adult mice from HSV-1 and HSV-2 disease following vaginal, skin, intraocular, or intranasal challenge and prevents the establishment of latency (ELife, 2014, JCI Insight, 2016). Thus we hypothesize that maternal immunization with ΔgD-2 and/or passive transfer of immune serum will protect neonates from HSV.

Methods
Four- to 6-week-old C57Bl/6 female mice were primed and boosted at 3-week intervals with ΔgD-2 or an equal volume of uninfected cell lysates (VD60 cells). Two weeks post-boost, mice were mated and pups were challenged with a lethal dose of HSV-1 (Bx31.1) at day 7 of birth. To differentiate the contribution of transplacental vs. colostrum Abs, mothers were switched at birth. Alternatively, 7-day-old mice born to nonimmunized mothers received a single dose of immune serum (400 μg total Ab) intraperitoneally at time of intranasal challenge.

Results
Thirty-eight of 47 (81%) of the pups born to and nursed by ΔgD-2-immunized mothers survived, exhibited little or no signs of disease and were protected from latency as measured by quantifying HSV DNA by PCR in neuronal tissue. In contrast, 12/14 (86%) of pups born to control vaccinated and nursed mice developed neurological signs of disease and died (P &lt; 0.0001, Fisher’s exact test). Survival was associated with increased ADCC Abs in the serum of neonatal mice. In contrast, passive transfer of immune serum, which consistently protects adult mice from infection, did not protect neonates. If newborns born to immunized mice suckled with control mice, protection was partially abrogated (11/19, 58% survival), suggesting that both systemic and mucosal Abs are required for complete protection.

Conclusion
Maternal vaccination with ΔgD-2 provides significant protection against intranasal neonatal challenge but may require exposure to systemic and mucosal Abs.

Disclosures
W. R. Jacobs Jr., xvax: Scientific Advisor, Research support; B. C. Herold, X-vax: Grant Investigator, Research grant and Research support
Evidence for Cross-species Influenza A Virus Transmission within Swine Farms, China
Authors: Ma Mai-Juan , Wang Guo-Lin , Anderson Benjamin , Bi Zhen-Qiang , Lu Bing , Wang Xian-Jun , Wang Chuang-Xin , Chen Shan-Hui , Qian Yan-Hua , Song Shao-Xia , Li Min , Lednicky John A , Zhao Teng , Wu Meng-Na , Cao Wu-Chun , Gray Gregory 
Published: October 2017

Abstract

Background
Our understanding of the risk factors for swine influenza A virus transmission between humans and pigs is sparse.

Methods
Beginning in 2015, we used a One Health approach and serial sampling to prospectively study 299 swine workers and 100 controls, their 9000 pigs, and six pig farm environments in China for influenza A viruses (IAVs) using molecular, culture, and immunological techniques. Study subjects were closely monitored for influenza-like illness (ILI) events.

Results
Upon enrollment, swine workers had higher serum neutralizing antibody titers against swine H1N1 and higher nasal wash total IgA and specific IgA titers against swine H1N1 and H3N2 viruses. Over a period of 12 months, IAVs were detected by qRT-PCR in 52 (12%) of 432 environmental swabs, 275 (7.6%) of 3600 pig oral secretion, 25 (5.8%) of 432 water, 24 (5.5%) of 432 aerosol, and 20 (4.6%) of 432 fecal-slurry specimens. Five (15.6%) of 32 subjects with ILI events had nasopharyngeal swab specimens that were positive for IAV and 17 (53%) demonstrated 4-fold rises in neutralization titers against a swine virus. Reassorted Eurasian avian-like swine H1N1, pdm09(H1N1)-like virus, and swine-like H3N2 viruses were identified in pig farms. The H1N1 viruses were nearly genetically identical with the human H1N1 viruses isolated from the subjects with ILI.

Conclusion
There was considerable evidence of A(H1N1)pdm09-like, swine H1N1 and swine H3N2 viruses reassorting and circulating within the pig farms and crossing species. These data suggest that stronger surveillance for novel influenza virus emergence within swine farms is imperative.

Disclosures
All authors: No reported disclosures.
Vaccine waning and mumps re-emergence in the USA
Authors: Lewnard Joseph , Grad Yonatan H 
Published: October 2017

Abstract

Background
Following decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses.

Methods
We pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape.

Results
We estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination.

Conclusion
The resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination.

Disclosures
J. Lewnard, Pfier: Grant Investigator, Research grant