bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of phases in detecting three-qubit entanglement
Authors: Han Kyung Hoon , Kye Seung-Hyeok
Published: October 2017

We propose separability criteria for three-qubit states in terms of diagonal and anti-diagonal entries to detect entanglement with positive partial transposes. We report that the phases, that is, the angular parts of anti-diagonal entries, play a crucial role in determining whether a given three-qubit state is separable or entangled, and they must obey even an identity for separability in some cases. These criteria are strong enough to detect PPT (positive partial transpose) entanglement with nonzero volume. In several cases when all the entries are zero except for diagonal and anti-diagonal entries, we characterize separability using phases. These include the cases when anti-diagonal entries of such states share a common magnitude, and when ranks are less than or equal to six. We also compute the lengths of rank six cases and find three-qubit separable states with lengths 8 whose maximum ranks of partial transposes are 7.
Chiral phase transition at 180° domain walls in ferroelectric PbTiO3 driven by epitaxial compressive strains
Authors: Wang Yu-Jia , Zhu Yin-Lian , Ma Xiu-Liang
Published: October 2017

Chiral ferroelectric domain walls are theoretically predicted to be promising in novel electronic memory devices. In order to develop a chirality-based device, understanding the chiral phase transition is of great importance for chirality manipulation. In this work, we systematically studied the chiral phase transition at 180° domain walls in ferroelectric PbTiO3 (PTO) under epitaxial compressive strains by first principles calculations. It is found that with the increase of the compressive strain, the Bloch components decrease due to the coupling of polarization and strain, while the components normal to domain walls increase because of the large stress gradients. The domain wall changes from a mixed Ising-Bloch type to the Ising type. It is also found that the domain wall energy increases with the increment of compressive strain, indicating that the spacings of 180° domain walls would be large for the highly compressed PTO films. These findings may provide useful information for the development of novel ferroelectric devices.
Segregation in the Golgi complex precedes export of endolysosomal proteins in distinct transport carriers
Authors: Chen Yu , Gershlick David C. , Park Sang Yoon , Bonifacino Juan S.
Published: October 2017

Biosynthetic sorting of newly synthesized transmembrane cargos to endosomes and lysosomes is thought to occur at the TGN through recognition of sorting signals in the cytosolic tails of the cargos by adaptor proteins, leading to cargo packaging into coated vesicles destined for the endolysosomal system. Here we present evidence for a different mechanism in which two sets of endolysosomal proteins undergo early segregation to distinct domains of the Golgi complex by virtue of the proteins’ luminal and transmembrane domains. Proteins in one Golgi domain exit into predominantly vesicular carriers by interaction of sorting signals with adaptor proteins, but proteins in the other domain exit into predominantly tubular carriers shared with plasma membrane proteins, independently of signal–adaptor interactions. These findings demonstrate that sorting of endolysosomal proteins begins at an earlier stage and involves mechanisms that partly differ from those described by classical models.
Restricting irreducible characters to Sylow 𝑝-subgroups
Authors: Giannelli Eugenio , Navarro Gabriel
Published: October 2017

We restrict irreducible characters of finite groups of degree divisible by

p
p

to their Sylow

p
p

-subgroups and study the number of linear constituents.
A blow-up lemma for approximate decompositions
Authors: Kim Jaehoon , Kühn Daniela , Osthus Deryk , Tyomkyn Mykhaylo
Published: October 2017

We develop a new method for constructing approximate decompositions of dense graphs into sparse graphs and apply it to long-standing decomposition problems. For instance, our results imply the following. Let

G
G

be a quasi-random

n
n

-vertex graph and suppose

H
1

,
…
,

H
s

H_1,\dots ,H_s

are bounded degree

n
n

-vertex graphs with
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="sigma-summation Underscript i equals 1 Overscript s Endscripts e left-parenthesis upper H Subscript i Baseline right-parenthesis less-than-or-equal-to left-parenthesis 1 minus o left-parenthesis 1 right-parenthesis right-parenthesis e left-parenthesis upper G right-parenthesis">

∑

i
=
1

s

e
(

H
i

)
≤
(
1
−
o
(
1
)
)
e
(
G
)

\sum _{i=1}^{s} e(H_i) \leq (1-o(1)) e(G)

. Then

H
1

,
…
,

H
s

H_1,\dots ,H_s

can be packed edge-disjointly into

G
G

. The case when

G
G

is the complete graph

K
n

K_n

implies an approximate version of the tree packing conjecture of Gyárfás and Lehel for bounded degree trees, and of the Oberwolfach problem.

We provide a more general version of the above approximate decomposition result which can be applied to super-regular graphs and thus can be combined with Szemerédi’s regularity lemma. In particular our result can be viewed as an extension of the classical blow-up lemma of Komlós, Sárkőzy, and Szemerédi to the setting of approximate decompositions.
Approximate linear minimum variance filters for continuous-discrete state space models: convergence and practical adaptive algorithms
Authors: Jimenez Juan Carlos
Published: October 2017

In this article, approximate linear minimum variance (LMV) filters for continuous-discrete state space models are introduced. The filters are derived from a wide class of recursive approximations to the predictions for the first two conditional moments of the state equation between each pair of consecutive observations. The convergence of the approximate filters to the exact LMV filter is proved when the error between the predictions and their approximations decreases no matter the time distance between observations. As particular instance, the order-$\beta$ local linearization filters are presented and expounded in detail. Practical adaptive algorithms are also provided and their performance in simulation is illustrated with various examples. The proposed filters are intended for the recurrent practical situation where a stochastic dynamical system should be identified from a reduced number of partial and noisy observations distant in time.
Impact of an Automatic Hospital Probiotic Protocol on Clostridium difficile Infection Rates and Antibiotic Usage Patterns
Authors: Slain Douglas , Georgulis Amy , Dermitt Ronald , Morris Laura , Colodny Stephen
Published: October 2017

Background

The use of probiotics in hospitalized patients ordered antibiotics has been associated with a preventative effect against Clostridium difficile infection (CDI) in a few small studies and meta-analyses. Starting in 2014, all adult patients admitted to our 330-bed community hospital who were started on an antibiotic automatically received a course of the probiotic Saccharomyces boulardii (SB). Our study provides a much larger experience with which to assess the preventative use of SB in patients receiving concomitant antibiotics.

Methods

Rates of CDI were compared during the 3-year periods before and after the automatic SB protocol implementation. CDI infection rates using ICD-9 code and CDC hospital-associated infection (HAI) definitions were compared. The use of CDI treatment agents (oral vancomycin and oral metronidazole) expressed in DDD/1,000 patient-days, and rates of SB infections/cultures were also assessed. All rates were standardized per hospital census. Clostridium difficile laboratory detection was performed by PCR analysis throughout the study period.

Results

Case rates of CDI using ICD-9 or CDC HAI definitions did not differ before and after protocol implementation (P = 0.165 and P = 0.521, respectively). The use of CDI treatment antibiotics were also similar; oral metronidazole (P = 0.269), oral vancomycin (P = 0.938), total CDI agents (P = 0.633). Positive specimen cultures for SB where identified in two patients prior to protocol and in 27 patients during the protocol years. Actual SB infections from sterile body sites were identified in five patients during the protocol vs. only one case in the pre-protocol years (P = 0.035). The average yearly cost of SB prophylaxis was $63,000.

Conclusion

In our global assessment of this data, the use of an automatic SB protocol at our community hospital was not associated with a protective effect against CDI. The use of SB was associated with an increased risk of SB infections. Further study of SB and other probiotic formulations for CDI prevention are warranted.

Disclosures

All authors: No reported disclosures.
Comparative Effectiveness of β-lactams Vs Azithromycin for Treatment of Outpatient Pediatric Community-acquired Pneumonia
Authors: Handy Lori , Gerber Jeffrey S , Bryan Matthew , Zaoutis Theoklis , Feemster Kristen
Published: October 2017

Background

Guidelines recommend amoxicillin as first-line therapy for mild, community-acquired pneumonia (CAP) in healthy, immunized children because of its effectiveness against S. pneumoniae. However, macrolides, which have inferior anti-pneumococcal activity, are the most commonly prescribed class of antibiotics for outpatient CAP. We aimed to determine the comparative effectiveness of β-lactam vs. macrolide antibiotics for the treatment of CAP.

Methods

We conducted a retrospective cohort study in 31 pediatric primary care practices. Patients 3 months to 18 years of age with CAP diagnosed between January 1, 2009 and December 31, 2013 were identified by ICD-9-CM codes. Clinical data were abstracted electronically. Treatment failure was defined as change in antibiotic by the pediatrician, emergency department (ED) visit, or hospitalization for pneumonia in the 2 weeks following diagnosis. Multivariable logistic regression models including children prescribed monotherapy of amoxicillin, broad-spectrum β-lactam antibiotics, or macrolides were built to determine the association of each class with treatment failure, adjusting for clinical and demographic characteristics.

Results

Of 10,470 children who received antibiotics for pneumonia, 4252 (40.6%) received amoxicillin, 4459 (42.6%) received macrolides, and 1759 (16.8%) received broad-spectrum β-lactams. The groups differed by age category, proportion of black patients, insurance type, documented fever, ordering of a chest X-ray, and prior antibiotic exposure. Treatment failure occurred in 633 children (6.1%); 418 required a change in antibiotic by the pediatrician, 169 required an ED visit, and 47 required hospitalization. In the adjusted model, macrolide prescribing was associated with a decreased odds of treatment failure in children <5 years old (aOR = 0.52, 95% CI 0.34, 0.78) and in children ≥5 years old (aOR = 0.32, 95% CI 0.25, 0.41). In practices with the lowest macrolide use, this relationship persisted (OR 0.46; 95% CI 0.23, 0.92).

Conclusion

While rates of treatment failure in children diagnosed with CAP in the outpatient setting were low, macrolides were associated with a lower failure rate than treatment with β-lactams. This may be due to residual confounding by indication or changing epidemiology of outpatient pneumonia.

Disclosures

T. Zaoutis, Astellas: Consultant, Consulting fee; Merck: Grant Investigator, Research grant; nabriva: Consultant, Consulting fee.
Comprehensive Detection of Pathogens in Immunocompromised Children with Bloodstream Infections by Next-generation Sequencing
Authors: Horiba Kazuhiro , Kawada Jun-Ichi , Okuno Yusuke , Tetsuka Nobuyuki , Suzuki Takako , Ando Shotaro , Kamiya Yasuko , Torii Yuka , Yagi Tetsuya , Takahashi Yoshiyuki , Ito Yoshinori
Published: October 2017

Background

Bloodstream infection (BSI) is a severe complication in immunocompromised patients. Prompt identification of causative microorganisms would improve the outcome of BSI due to optimization of antimicrobial treatment. Next-generation sequencing (NGS) allows us to analyze comprehensively and quantitatively all microorganisms present in a clinical sample in comparison with blood culture. However, there are currently no established methods to identify causative pathogens by NGS.

Methods

BSI was defined by the following criteria: (i) pathogen isolated from blood culture and (ii) fever ≥38.0°C or C-reactive protein >1.0mg/dl. Thirty-five pediatric patients (12 with BSI and 23 with suspected BSI/negative blood culture) were enrolled. Plasma/serum samples were used for sequencing and the results were compared with those from blood culture. The bacterial reads per million reads of the sequence depth (BR) and relative importance values of the dominant bacteria (P1) were applied to identify causative pathogens.

Results

Sequencing reads of bacteria isolated in blood culture were identified by NGS in all plasma/serum samples at the onset of BSI. Additionally, bacteria isolated in blood culture were identical to the dominant bacteria by NGS in 8 of 12 patients with BSI. Causative microorganisms were detected when the NGS results fulfilled the criteria of BR >200 and P1 >0.5. In two patients with catheter-related BSI, causative bacteria were detected in the plasma/serum at 7 days before disease onset. Causative pathogens (Tatlockia micdadei, Escherichia coli, and human adenovirus 2) were identified in three of 23 patients in the suspected BSI group. A total of 62 resistance genes were detected in nine patients with sequences covering 5–100% of references.

Conclusion

An NGS-based approach has great potential for analysis of causative microorganisms in BSI and may help to diagnose a disease before disease onset. Antimicrobial resistance genes can also be found through sequence data processing.

Disclosures

All authors: No reported disclosures.
Passive Immunization with Anti-Pertussis Toxin Humanized Monoclonal Antibody Mitigates Clinical Signs of Pertussis Infection in Newborn Baboons
Authors: Maynard Jennifer , Nguyen Annalee , Wolf Roman , Papin James , Connelly Sheila , Kaleko Michael
Published: October 2017

Background

Pertussis is a significant mortality risk in the developing world, killing up to 200,000 infants annually. Maternal vaccination as a strategy to protect newborns has shown some success, but is unlikely to capture all eligible mothers. Hu1B7 is a monoclonal antibody (mAb) that potently neutralizes pertussis toxin. Hu1B7, when administered as part of a binary mAb cocktail, demonstrated therapeutic efficacy in pertussis-infected weanling baboons. Here, the prophylactic potential of hu1B7 to protect infants during their first few months, when mortality risk is highest, was evaluated.

Methods

Neonatal baboons of normal gestational age (180 days ± 10), normal birth weight (~1.0kg), and anti-Fha titer < 5 IU/ml (verifying no prior exposure to Bordetella species) were recruited into the study. At 2 days of age, treated baboons received hu1B7 (40mg/kg, IV), while control animals were untreated. Serum levels of hu1B7 were followed for 5 weeks, at which time the animals were infected with 108 cfu of B. pertussis strain D420. Animals were monitored for clinical signs of disease.

Results

Six controls and seven treated animals were evaluated. All animals were heavily colonized with B. pertussis during the first week after infection. Controls developed significant leukocytosis, most coughed, and three required euthanasia. In contrast, white blood cell counts for all treated animals remained within the normal range, coughing was virtually absent, and all animals maintained normal activity. As expected for a humanized mAb in a nonhuman primate, hu1B7 had an elimination half-life of 11.8±3.4 days.

Conclusion

Protection of newborn baboons from pertussis was achieved by mAb administration 5 weeks prior to pertussis infection. Hu1B7, when systemically present, mitigated the clinical signs of pertussis, including leukocytosis and coughing, but did not prevent bacterial colonization. Assuming a half-life in humans of 3 weeks, mAb administration at birth could potentially provide 4 months of prophylaxis and is a viable strategy to complement maternal vaccination. Moreover, strategies that extend the mAb half-life and lower the dose could further support developing world application.

Disclosures

J. Maynard, Synthetic Biologics, Inc.: Collaborator, Research support; A. Nguyen, Synthetic Biologics, Inc.: Collaborator, Research support; R. Wolf, Synthetic Biologics, Inc.: Collaborator, Research support;; J. Papin, Synthetic Biologics, Inc.: Collaborator, Research support; S. Connelly, Synthetic Biologics, Inc.: Employee, Salary; M. Kaleko, Synthetic Biologics, Inc.: Employee and Shareholder, Salary and stock options
Epidemiology and Trends of Pertussis among Infants: United States, 2000–2015
Authors: Bozio Catherine , Skoff Tami , Pondo Tracy , Liang Jennifer
Published: October 2017

Background

Pertussis, a cyclic respiratory disease, causes the greatest morbidity and mortality among infants, particularly those too young to be vaccinated. Following a resurgence of pertussis in the 1990s, a recommendation was made in 2012 to vaccinate during every pregnancy in order to prevent infant disease. We describe pertussis trends from 2000–2015 among U.S. infants aged <1 year.

Methods

We analyzed infant pertussis cases reported through the National Notifiable Diseases Surveillance System from 2000 to 2015. Incidence rates (cases per 100,000 population) among various age groups (<2, 2– <4, 4– <6, and 6–<12 months) were calculated using National Center for Health Statistics population estimates as denominators. Negative binomial regression was used to estimate the annual average percent change with a linear trend; P < 0.05 was significant.

Results

From 2000 to 2015, 48,909 infant pertussis cases and 255 deaths were reported; infants aged <2 months accounted for 38.7% of cases. The age distribution of infant cases was stable from 2000 to 2009 but changed from 2010 to 2015 (Fig. 1), as the proportion of cases aged 4–<12 months increased annually on average by 4.7% (P < 0.001). Annual incidence was highest among <2 month olds; however, rates increased among older infants (Fig. 2): 7% average annual increase among infants aged 4–<6 months and 11% among infants aged 6–<12 months (P < 0.001 for each). The proportion of infants hospitalized decreased over time in each age group (P < 0.001 for all) with the largest annual average declines among 4–<6 (−5.1%) and 6–<12 month (−5.9%) olds. For all age groups, hospitalization rates were relatively stable, but non-hospitalization rates increased (P < 0.05 for all). The case–fatality ratio (CFR) was highest among <2 month olds (1.6%); CFRs decreased over time among <2 and 2–< 4 month olds (P < 0.05 for each).

Conclusion

Pertussis incidence remains highest among infants aged <4 months, although the age distribution appears to be changing. Decreasing proportions of infants hospitalized may suggest a true decline in disease severity or an increase in reporting of less severe disease. Ongoing monitoring of infant pertussis is needed to better understand the impact of vaccinating pregnant women to prevent pertussis in young infants.

Disclosures

All authors: No reported disclosures.
Increased Risk of Invasive Meningococcal Disease Associated with Primary and Secondary Immunodeficiency
Authors: Lundbo Lene Fogt , Harboe Zitta Barrella , Smith-Hansen Lars , Benfield Thomas
Published: October 2017

Background

Risk of invasive meningococcal disease (IMD) is increased for persistent complement deficiency and HIV infection. However, risk associated with other primary and secondary immunodeficiency is unknown.

Methods

Nationwide case–control study of adults aged >18 years. Cases and matched controls were identified by registry linkage. Primary and secondary immunodeficiencies diagnosed prior to IMD were based on International Classification of Disease (ICD), eight or tenth revision. Odds ratios (OR) with 95% confidence intervals (CI) were estimated by conditional logistic regression after adjustment for sex, age, and the year of IMD.

Results

We identified 2,179 IMD cases (46% male) with a median age of 44 years (interquartile range: 24–63 years). Increased risk of IMD was associated with HIV infection (OR 10.03 [95% confidence interval (CI), 2.91–34.66]), splenectomy/splenic resection (OR 6.88 [95% CI, 3.9–14.82]), solid organ transplantation (SOT) (OR 20.00 [95% CI, 5.00–79.96]), hemolytic anemia (OR 7.78 [95% CI, 2.90–20.90]), antibody deficiency (OR 6.67 [1.11–39.90]) and autoimmune diseases (OR 1.80 [95% CI, 1.44–2.14]). Primary immunodeficiency overall was not associated with an increased risk (OR 1.43 (95% CI, 0.61–3.36)).

Conclusion

This large study of Danish adults with IMD over four decades showed an increased risk of IMD associated with HIV infection, SOT, asplenia, hemolytic anemia, antibody deficiency, and autoimmune disease ranging from 2- to a 20-fold increased risk. Vaccination may be warranted in these populations.

Disclosures

Z. Barrella Harboe, Pfizer: independent physician, Travel grants.
Use of Adjunctive Steroids and Incidence of Delayed Cerebral Venous Thrombosis in Adults with Bacterial Meningitis
Authors: Gallegos Cinthia , Salazar Lucrecia , Tobolowsky Farrell , Nigo Masayuki , Hasbun Rodrigo
Published: October 2017

Background

Bacterial meningitis is associated with significant morbidity and mortality. Adjunctive steroids decrease mortality in adults with meningitis due to Streptococcus pneumoniaebut its use has been recently linked to the development of delayed cerebral thrombosis (DCT). The purpose of our study was to determine the utilization of adjunctive steroids and its incidence.

Methods

A retrospective multicenter study involving 10 Houston area hospitals from 2008 to 2016. Data was gathered from 120 adults with culture proven community-acquired bacterial meningitis. An adverse clinical outcome was defined as a Glasgow outcome score of 1–4.

Results

There was a total of 120 patients enrolled; of which, 55% were male. Adjunctive intravenous steroids were administered in 82 (68%) patients with bacterial meningitis. The steroid median duration was 3.8 days. The average age of patients was 55.3 years (range 20–92). There was no difference in Charlson comorbidity score, immunosuppression, presence of sinusitis or otitis, fever, meningeal signs or symptoms, abnormal neurological findings, Gram stain or severity of illness, based on Aronin score (P > 0.05), between patients who received steroids and those that did not. Older patients, age >65, were less likely to receive adjunctive steroids (P = 0.028). The most common organism isolated was Streptococcus pneumoniae, which occurred in 46 (38%) patients. An adverse clinical outcome was seen in 46 (38%) patients with no difference between groups (P = 0.819). Delayed cerebral thrombosis was seen in a total of 9 (7.5%) patients with bacterial meningitis. Of these, 1 patient (2.6%) did not receive steroids and the remaining 8 (10.9%) patients received steroids (P = 0.158). Five cases of meningitis that were complicated by DCT were caused by Streptococcus pneumoniae, 1 by Listeria monocytogenes, and 2 with Staphylococcus aureus.

Conclusion

Adjunctive steroids are being used in the majority of adults with bacterial meningitis but it is possibly associated with DCT, a devastating complication

Disclosures

All authors: No reported disclosures.
A Single-center, Quasi-experimental Study to Evaluate the Impact of a Multiplex Polymerase Chain Reaction System Combined with Antimicrobial Stewardship Intervention on Time to Targeted Therapy in Patients with Suspected Central Nervous System Infection
Authors: Powell Kelsey , Revolinski Sara , Gibble Allison , Daniels Anne , Wainaina J Njeri , Huang Angela
Published: October 2017

Background

Empiric treatment for central nervous system (CNS) infections consists of coverage with multiple antimicrobial agents that may be continued until a pathogen can be identified. Identification may take significant time to result, leading to extended durations of multiple antimicrobial agents, delays in targeted therapy and subsequent adverse effects, such as nephrotoxicity and Clostridium difficile infection. A multiplex polymerase chain reaction (PCR) system that can identify 14 pathogens responsible for community-acquired CNS infections in 1 hour was recently FDA-approved for cerebrospinal fluid (CSF) analysis. The objective of this study was to determine the effect of this PCR paired with antimicrobial stewardship (AMS) team intervention on the time to targeted therapy.

Methods

During the intervention (Int) phase (January 25, 2017–April 30, 2017), all PCR results were called to the AMS team, who reviewed clinical data and provided antimicrobial recommendations per pre-determined protocol. Recommendations consisted of de-escalation or addition of therapy. The pre-intervention (PI) group consisted of patients with CSF culture obtained between January 25, 20116 and April 30, 2016.

Results

A total of 138 patients were evaluated; 46 in the Int group and 92 in the PI. Of the 46 patients in the Int group, 25 had a negative PCR result and were never initiated on antimicrobials. One patient required antimicrobial escalation. Twenty patients were started on empiric therapy and were candidates for de-escalation. In the PI group, there were no patients with CSF cultures that required therapy escalation, while 33 patients were initiated on empiric antimicrobials. Results from the subgroup of patients in whom empiric therapy was started as shown in Table 1.

Conclusion

Implementation of a multiplex PCR with AMS intervention resulted in decreased time to targeted therapy.

This project was funded through a competitive stewardship grant provided by Merck & Co.

Disclosures

S. Revolinski, Merck: Grant Investigator, Research grant; J. N. Wainaina, Merck: Grant Investigator, Research grant; A. Huang, Merck: Grant Investigator, Research grant
Strongyloides stercoralis Infection Incidence, Risk Factors and Outcomes Among Solid Organ Transplant Candidates and Recipients; a Florida Center Experience
Authors: Castro Robert , Aslam Sadaf , Albers Christopher , Gutierrez Louise , Gonzalez Marijesmar , Alrabaa Sally
Published: October 2017

Background

Most infections of Strongyloides stercoralis are asymptomatic but can be fulminant in the immunosuppressed. Fatal infections in transplant patients have been reported in United States but incidence estimates are lacking. Our protocol for Strongyloides until 2009 screened immigrants and those with travel history to endemic areas. In 2010, we began universal screening of SOT candidates due to a case of disseminated Strongyloidiasis in an unscreened lung transplant recipient with unknown risk factors. We calculated the incidence of Strongyloides stercoralis in our SOT candidates and associated risk factors, treatment, and outcomes since protocol change.

Methods

A retrospective review was performed of patients who underwent transplant evaluation from January 2014 to July 2016. Patients positive for Strongyloides stercoralis were reviewed for age, sex, ethnicity, place of birth, travel history, occupation, eosinophilia, treatment, and outcome. We report descriptive statistics.

Results

Of a total of 2,351 SOT patients, 116 tested positive (heart 33, lung 24, kidney 26, liver 31, pancreas 2) with an incidence of 4.9%. A total of 113 charts were available for review. The characteristics of the patients are summarized in Table 1. Fifty patients had traditional risk factors (44%) and 63 lacked them (56%). Eosinophilia was present in 15% of cases. Of those transplanted, 87% received prophylaxis and none developed active Strongyloidiasis.

Conclusion

Our results show that S. stercoralis infection has a relatively high incidence in SOT patients and universal screening identified a substantial number that otherwise would go undetected, placing the transplant patient at risk of a fatal, yet preventable complication.

Disclosures

All authors: No reported disclosures.
Outcomes of Kidney Transplantation with a CMV Matching Allocation Schema
Authors: Strasfeld Lynne , Basuli Debargha , Norman Douglas , Langewisch Eric , Olyaei Ali , Lockridge Joseph
Published: October 2017

Background

Cytomegalovirus (CMV) infection continues to be a major cause of morbidity in kidney transplant recipients. The CMV donor-positive (D+)/recipient-negative (R−) serostatus pairing poses highest risk for CMV disease.

Methods

In September 2012, we adopted a CMV matching allocation policy at the centers served by our organ procurement organization, the Pacific Northwest Transplant Bank. CMV serostatus was used as a criterion in determining deceased donor kidney allocation, whereby R− kidney transplant recipients were preferentially paired with a D− organ, and R+ recipients with an R+ organ. We performed a retrospective analysis of CMV-related outcomes for 400 consecutive kidney recipients, 196 prior to (January 1, 2010– August 31, 2012) and 204 following (September 1, 2012–December 3, 2014) implementation of the CMV matching allocation schema at our center. We also looked at waitlist time for patients transplanted during the same period.

Results

The percentage of D+/R− transplants performed decreased from 17.3% to 2.5% (P < 0.001) after implementation of the CMV matching allocation strategy (Figure 1). CMV viremia decreased from 13.3% to 5.9% (P = 0.0118), and CMV syndrome or disease decreased from 9.2% to 2.9% (P = 0.00859) (Table 1). The percentage of patients treated for CMV infection overall decreased from 10.7% to 5.4% (P = 0.0498). Median days on the waitlist prior to transplantation increased from 793 (PRE) to 944 (POST) due to growing wait list size, but neither R− nor R+ patients appeared to be disadvantaged: wait times increased from 808.5 to 958 for the R− subset and from 777.5 to 933 for the R+ subset (Figure 2).

Conclusion

CMV disease occurred infrequently in our cohort, in the context of 6 months of valganciclovir prophylaxis post-transplant and post-prophylaxis pre-emptive monitoring strategy for our D+/R− recipients. Following implementation of an allocation schema that took CMV serostatus into account, the rate of CMV infection and antiviral treatment decreased significantly.

Disclosures

L. Strasfeld, Merck: Independent Contractor, Salary
Collaborative Use Repurposing Engine (CURE): FDA-NCATS/NIH Effort to Capture the Global Clinical Experience of Drug Repurposing to Facilitate Development of New Treatments for Neglected and Emerging Infectious Diseases
Authors: Stone Heather , Sacks Leonard , Tiernan Rosemary , Duggal Mili , Sheils Timothy , Southall Noel
Published: October 2017

Background

Repurposing approved products has proven a critical strategy to serve unmet medical needs. Historically, 40% of drugs approved for treatment of tropical diseases were repurposed, including albendazole for echinococcosis and neurocysticercosis, and azithromycin for trachoma. Advantages of repurposing include that approved drugs are well characterized, do not require expensive development programs needed for new drugs, and are frequently active against multiple diseases. Owing to the limited number of drugs approved to treat neglected tropical diseases (NTDs) and emerging or drug-resistant infections, healthcare practitioners use existing drugs in novel ways to treat patients with these conditions. This clinical experience, regardless of whether the outcomes are positive or negative, often is not reported or shared, and the knowledge is therefore lost.

Methods

FDA and NCATS/NIH have built a pilot program called Collaborative Use Repurposing Engine (CURE) to capture and centralize the global experience of new uses of approved medical products to treat emerging threats, NTDs, and multidrug-resistant organisms. CURE includes a website (https://cure.ncats.io/) and a mobile app (download “PROJECT CURE” at Google Play Store). CURE provides a simple case report form for health care providers to report their experiences, and a collection of cases that have already been reported (including successful and unsuccessful treatments) which they can browse. Healthcare providers who register can also participate in a Treatment Discussion Forum, allowing for engagement with fellow clinicians. CURE could be a global network connecting major treatment centers, academics, private practitioners, government facilities, and other clinicians serving as a means of rapid communication of treatment outcomes between providers treating patients with these conditions.

Results

See attached screen shots.

Conclusion

Although this evidence may be insufficient to establish the safety or effectiveness of a new use for an existing product, this clinical experience may provide signals and generate hypotheses for future clinical study. It may allow for rapid identification of promising treatment approaches in urgent situations such as during outbreaks of emerging infectious threats.

Disclosures

All authors: No reported disclosures.
Evolution of Antibiotic Tolerance During Oxacillin, Daptomycin and Dalbavancin Therapy Results in Breakthrough Staphylococcus aureus Bacteremias
Authors: Berti Andrew , Schroeder Jeremy , Rottier Aaron , McCrone Sue , Wang Jade , Rose Warren
Published: October 2017

Background

Clinicians can employ suppressive antimicrobial therapy in patients with persistent or relapsing bacteremia. However, bacteria with favorable susceptibility profiles may exhibit antimicrobial tolerance wherein bacteria cannot proliferate yet can survive in high concentrations of antibiotics. The antimicrobial tolerance phenotype can thwart efforts to prevent bacteremia recurrence with prolonged exposure to antimicrobials and may contribute to breakthrough bacteremias while the patient is receiving active therapy. Here we present a patient case consisting of multiple episodes of breakthrough Staphylococcus aureus bacteremia over several years in the setting of appropriately dosed antimicrobial suppressive therapy and describe organism mutations that developed during therapy.

Methods

Six clinical bloodstream isolates were recovered from the patient during distinct episodes of MSSA bacteremia over a 5-year period. The identified source for each bacteremia was a central line infection (CLABSI). Isolates recovered were susceptible to the individual therapies received, which included oxacillin, daptomycin, and dalbavancin. Bacterial whole genome sequence data were collected using Illumina technology.

Results

The first two isolates (USA600) and the last four isolates (USA800) represent distinct populations and suggest that a distinct MSSA strain displaced the previous population between bacteremia episodes 2 and 3. Of note, all of these strains were able to survive and establish breakthrough bacteremias despite favorable susceptibility profiles to the agents used as suppressive therapy. Although the MICs remain low and in the susceptible range to oxacillin, daptomycin, and dalbavancin, these isolates progressively developed significant antimicrobial tolerance phenotypes, which coincided with mutations in walK (yycG), htrA2, ftsW, ebh and iarS that may be advantageous to survival under antibiotic pressure.

Conclusion

These genetic, phenotypic and patient case data identify important changes that can occur in bacterial populations over time that are distinct from antibiotic susceptibility. These findings point to factors that may result in breakthrough bacteremia, limiting the clinical utility of antimicrobial suppressive therapy.

Disclosures

W. Rose, Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Merck: Grant Investigator, Research grant; The Medicines Company: Speaker’s Bureau, Speaker honorarium; Visante, Inc: Consultant, Consulting fee.
Carbapenem-resistant Enterobacteriaceae (CRE) or Delayed Appropriate Therapy (DAT)—Does One Affect Outcomes More Than the Other Among Patients With Serious Infections Due to Enterobacteriaceae?
Authors: Lodise Thomas , Berger Ariel , Altincatal Arman , Wang Rosa , Bhagnani Tarun , Gillard Patrick , Bonine Nicole G
Published: October 2017

Background

While CRE and DAT are both associated with worse outcomes, their relative impact to the clinical and economic burden among patients with infections due to Enterobacteriaceae is not well understood. This study assessed the independent and combined effect of these two items on selected outcomes among patients with these infections.

Methods

Hospitalized adults between July 2011 and September 2014 were identified from Premier Hospital Database. Patients were diagnosed with complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, and had a positive culture for Enterobacteriaceae from a site consistent with infection type (date of culture draw was index date). Patients were required to receive antibiotics on this date or ≤2 days after. Delayed therapy was defined as no receipt of an antibiotic with microbiologic activity during this period. CRE was defined as resistant to ≥1 carbapenems. Inverse probability weighting and multivariate regression analyses were used to estimate the associations between CRE status, DAT and outcomes. Logistic models were used for composite mortality (in-hospital death or discharge to hospice), in-hospital mortality, and discharge to home (reference group was timely therapy plus non-CRE); generalized linear models, for post-index duration of antibiotic therapy, hospital length of stay (LOS), and costs.

Results

A total of 50,069 patients were included in the analyses; 514 had CRE and 16,414 received DAT. A gradient effect was observed across strata as the burden of serious infections was least among the reference group, and greatest among patients with CRE infection who received DAT (Figure). For example, as compared with the reference group, the risk of composite mortality increased nearly fourfold in patients with CRE infection who received DAT; total in-hospital costs more than doubled.

Conclusion

DAT has a stronger association than CRE on outcomes, and their effects are synergistic. Given these findings, better methods of early pathogen identification (especially organisms such as CRE) should reduce time to appropriate therapy, thereby improving outcomes in this patient population.

Disclosures

T. Lodise, Allergan plc: Consultant, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; A. Berger, Allergan plc: Consultant, Consulting fee; A. Altincatal, Evidera: Consultant, Salary; R. Wang, Evidera: Employee, Salary; T. Bhagnani, Allergan plc: Consultant, Consulting fee; P. Gillard, Allergan plc: Employee, Salary; N. G. Bonine, Allergan plc: Employee, Salary
HIV Transmission Rates and Factors Associated with Recent HIV Infection: Results from the Ndhiwa HIV Impact Assessment, South Nyanza, Kenya, 2012
Authors: Agyemang Elfriede , Zeh Clement , Mukui Irene , Maman David , Kim Andrea
Published: October 2017

Background

Identifying populations with high HIV transmission rates is important for prevention and treatment strategies. Persons with recently acquired HIV infection are drivers of HIV transmission due to high levels of HIV viral load (VL). We assessed annual HIV transmission rates and factors associated with recent infection to inform targeted interventions in a hyperendemic region in Kenya.

Methods

The Ndhiwa HIV impact assessment was a population-based survey among persons aged 15–59 years living in South Nyanza, Kenya in 2012. Respondents were tested for HIV using rapid tests per national guidelines and provided blood for centralized testing. Specimens from HIV+ persons were tested for VL and recent infection. Recent infection was defined as normalized optical density value <1.5 on the Limiting Antigen Enzyme Immunoassay, VL >1,000 copies/mL, and no report of HIV treatment. The annual HIV transmission rate per 100 persons living with HIV (PLHIV) was calculated as HIV incidence divided by HIV prevalence, multiplied by 100. Annualized HIV incidence was estimated, assuming a mean duration of recent infection of 141 days (confidence interval [CI] 123–160). Multivariate analysis identified independent factors associated with recent infection. Estimates were adjusted for survey design.

Results

Of 6,076 persons tested, 1,457 were HIV+, and 28 were recently infected. HIV incidence and prevalence were 1.7% (CI 1.5–2.0) and 24.1% (CI 22.6–25.5), respectively. Per 100 PLHIV, the annual HIV transmission rate was 7.0 and varied by sex (4.6 male vs. 8.3 female), age (5.2 aged 30+ vs. 10.4 aged <30), and residence (1.4 Kobama vs. 12.0 Riana vs. 12.1 Pala divisions). After controlling for age, sex, and residence, recently infected persons were significantly more likely to reside in Pala division (AOR 8.3, CI 1.1–62.9) than HIV-uninfected persons.

Conclusion

Approximately 7 in 100 PLHIV transmitted to HIV-uninfected persons in South Nyanza in 2012, similar to national rates observed in the 2012 Kenya AIDS Indicator Survey. HIV transmission rates were higher in females than males, younger than older, and Riana and Pala than other divisions. Residence in Pala was a risk factor for recent infection. These findings could guide prioritization of interventions to interrupt HIV transmission in this hyperendemic setting.

Disclosures

All authors: No reported disclosures.
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

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 < 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

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.