bluuebunny/crossref_metadata_2025 huggingface dataset:
785. Identifying Opportunities to Improve Adherence to Sepsis Care Guidelines Compliance
Authors: Balankura Tonnam , Odom Ashley
Published: October 2019

Background

Sepsis—a life-threatening organ dysfunction caused by a dysregulated host response to infection—is a major public health burden and is considered a leading cause of preventable death. Although sepsis care guidelines have been established by the Surviving Sepsis Campaign, improved compliance monitoring and analytics are required for sustainable improvement in clinical processes and patient outcomes. Using the Optum Pan-Therapeutic (PanTher) electronic medical record database, we developed granular process measures and a data analytics toolkit to measure compliance with sepsis care guidelines and provide insight into areas for improvement.

Methods

We identified 15,421 episodes of adult patients in January-June, 2017 with sufficient evidence of suspected sepsis. Episodes qualified if they: (1) met at least two of the quick Sequential Organ Failure Assessment (qSOFA) clinical criteria, (2) had a blood culture order initiated, and (3) had a serum lactate order. For these 15,421 episodes, we obtained the timestamps of antibiotics order and administration, blood culture order and collection, and when at least two of the qSOFA criteria were first met. Based on Surviving Sepsis Campaign care protocols for suspected Sepsis, we measured compliance for the timeliness of antibiotics administration and blood culture collection using a threshold of 3 hours after when the qSOFA criteria were first met.

Results

Compliance of the antibiotics administration and blood culture collection measures were found in 7,647/10,343 (74%) episodes and 1,219/1,530 (80%) episodes, respectively. The median times from when the qSOFA criteria were first met to antibiotics administration and blood culture collection were 77 minutes and 5 minutes, respectively.

Conclusion

We have developed new process measures and a data analytics toolkit to monitor compliance rates and identify episodes where sepsis protocols are not followed according to sepsis care guidelines. These noncompliant episodes are opportunities for care providers to identify root causes of noncompliance and proactively work toward improved adherence to sepsis care guidelines.

Disclosures

All authors: No reported disclosures.
1009. Measuring the quality of fluoroquinolone prescribing in hospitals: results from the Emerging Infections Program Hospital Prevalence Survey Antimicrobial Quality Assessment
Authors: Magill Shelley S , O’Leary Erin , Nadle Joelle , Johnston Helen , Janelle Sarah J , Maloney Meghan , Ray Susan , Wilson Lucy E , Lynfield Ruth , Rainbow Jean , Sievers Marla M , Dumyati Ghinwa , Ocampo Valerie , Samper Monika , Zhang Alexia Y , Evans Christopher D , Kainer Marion A , Edwards Jonathan R , Chea Nora , Neuhauser Melinda M
Published: October 2019

Background

Improving antimicrobial use is a key component of controlling antimicrobial resistance. Multiple factors influence inpatient provider antimicrobial prescribing decisions, making it challenging to develop standard methods to evaluate prescribing quality in hospitals. In 2015, CDC’s Emerging Infections Program (EIP) conducted a hospital antimicrobial use prevalence survey and collected data to assess prescribing quality in selected scenarios, including fluoroquinolone (FQ) treatment.

Methods

EIP sites (CA, CO, CT, GA, MD, MN, NM, NY, OR, TN) each recruited up to 25 hospitals for the survey. Each hospital selected a survey date during May–September 2015. Among randomly selected inpatients on the survey date, EIP staff identified those ≥18 years old who received FQ treatment on the survey date or the day prior and reviewed medical records to gather data on underlying conditions, infections, and diagnostic tests. We used these data to update a previously developed prescribing quality assessment pathway that categorized FQ treatment as supported or unsupported based on medical record documentation.

Results

Among 12,299 patients in 199 hospitals, 1084 (8.7%) received FQ treatment; 756 (70%) were treated for a single infection type during their hospitalization and were ≥18 years old. The pathway categorized FQ treatment as supported for 646 (85.4%) and unsupported for 110 patients (14.6%) (figure). Almost half of unsupported treatment was due to a lack of compatible signs or symptoms of infection in a patient from whom an organism susceptible or likely susceptible to an FQ was identified from a nonsterile site (49/110 patients, 44.5%), suggesting colonization.

Conclusion

Utilization of a pathway that incorporates detailed clinical data enabled us to apply a standard approach to assess FQ prescribing quality in hospitals. A high percentage of FQ treatment was supported, possibly reflecting efforts in recent years to reduce inappropriate use. Our assessment approach also identified opportunities for further improvements in inpatient FQ stewardship. Incorporation of additional elements in the pathway, such as the availability of other antibiotic choices in clinical scenarios where FQ use is currently supported (e.g., pneumonia) could further enhance the pathway’s performance.

Disclosures

All authors: No reported disclosures.
1011. Hospital Antibiogram Variation within a Veterans Affairs (VA) Regional Network
Authors: Ho Macy , Armstrong Elizabeth R , Graber Christopher J , Chau Tony T , Johns Scott T , Namdar Rocsanna , Varker Andrew S , Ma Ariel , Goetz Matthew B
Published: October 2019

Background

VISN 22 is comprised of eight VA hospitals serving Southern California, Arizona, and New Mexico. The VISN 22 Antimicrobial Stewardship Workgroup formed in November 2018 with the purpose of sharing strong practices and program strategies. We compared antibiogram compilation strategies and antimicrobial susceptibilities and correlated antimicrobial susceptibilities for Pseudomonas aeruginosa and Escherichia coli with inpatient and outpatient antibiotic use.

Methods

2018 antibiograms were collected from each hospital. Antibiotic utilization rates (antibiotic days per 1000 patient-days present) were extracted from VA Corporate Data Warehouse data. Pearson correlation coefficients were calculated between 2018 utilization of specific agents and P. aeruginosa and E. coli susceptibilities to those agents at each facility.

Results

Antibiograms varied according to authorship (microbiology and/or infectious diseases), reporting frequency, rules regarding isolate reporting, and location and specimen specificity (Table 1). Facilities reported at least 90% susceptibility to a median of 3 antibiotics (range 1 to 5) for P. aeruginosa and 5 antibiotics (range 1 to 7) for E. coli.

The strongest negative correlations between antimicrobial use and susceptibility were observed for meropenem/imipenem (-0.43) and piperacillin–tazobactam (-0.41) with P. aeruginosa and piperacillin–tazobactam (-0.23) and fluoroquinolones (-0.21) with E. coli. A moderate negative correlation was observed between outpatient fluoroquinolone prescriptions per 1000 patients and E. coli susceptibility (-0.24).

Conclusion

Antibiogram composition is variable across VISN 22; not all reporting is consistent with CLSI recommendations. There was a modest correlation between some categories of antimicrobial use and resistance in P. aeruginosa and E. coli. Sharing antibiogram and antibiotic utilization data are helpful in developing antimicrobial stewardship strategies especially as we examine those hospitals with lower rates of resistance and antibiotic use.

Disclosures

All authors: No reported disclosures.
1032. Impact of an Antimicrobial Stewardship Team-Led Initiative – Assessment of Therapy Appropriateness at Patient Discharge
Authors: Epie Loveta Eningan , Timothy Caroline , Douglas-Louis Rachid , Onwumbiko Chi , Shah Gita K
Published: October 2019

Background

Current focus and emphasis on managed care have encouraged the practice of discharging patients admitted for infections as soon as possible which in-turn has increased the likelihood of patients being discharged on antimicrobials once the acute infection is under control. Many programs have demonstrated success of antimicrobial stewardship (AMS) initiatives but there is little in the published literature surrounding transitional care AMS.

Methods

Patients admitted to University of Maryland Prince George’s Hospital who were to be discharged on antimicrobials within 24 hours were identified during multidisciplinary patient rounds over a 2-phase period (each 3 weeks long). Rounds were attended by the AMS team composed of Post-Graduate Year 1 pharmacy residents and/or the AMS pharmacist and/or the AMS physician. Both the choice of antimicrobial and total treatment days including post-discharge days were evaluated and interventions were made based on adherence to current published guidelines. If antimicrobial selection or treatment duration appeared to be inconsistent with guidelines, the case was discussed with the prescriber and agreed-upon changes made prior to the patient’s discharge. Accepted and denied recommendations were documented. Patients were also educated on indications, directions and side effects of their antimicrobials.

Results

The AMS team evaluated patients for selected antimicrobial drug and duration of outpatient treatment over the 2-phase period with 20 patients in phase 1 and 26 patients in phase 2. Interventions needed to be made for 100% of patients in phase 1 but only for 50% of patients in phase 2. Duration of treatment was the only intervention which needed to be made with 85% of the interventions in phase 1 accepted and 85% in phase 2. The most common indications for treatment are represented in Figure 1.

The average decrease in treatment duration for phase 1 and 2 was 3.6 days and 2.8 days respectively.

Conclusion

These findings suggest that discharge AMS initiatives can decrease patients’ overall antimicrobial exposure and potential adverse events, educate providers on treatment guidelines especially of common disease states, increase overall provider compliance with evidence-based literature, and ascertain the appropriateness of therapy choices.

Disclosures

All authors: No reported disclosures.
1038. Impact of an Electronic Antibiotic Timeout on the Utilization of Frequently Prescribed Antibiotics in Hospitalized Patients
Authors: Drake Ty C , Janak Chase E , Garey Kevin W , Carlson Travis J , Musick William L , Gentry Clare N , Perez Katherine K
Published: October 2019

Background

Methods to operationalize antibiotic timeouts (ATO) among hospitalized patients are often constrained by the high volume of antibiotic orders that surpass the capabilities of the antimicrobial stewardship program (ASP) to intervene. Houston Methodist Hospital implemented a streamlined electronic ATO process that alerted providers to evaluate the need for continued antibiotics on day 4 of predefined anti-infective therapy. Unresolved alerts were reviewed by clinical pharmacists the following day. The objective of this study was to determine the impact of this electronic ATO on frequently prescribed antibiotics.

Methods

This was a quasi-experimental study in a 924-bed quaternary care hospital comparing days of therapy (DOT) in patients admitted prior to (February 2017 – January 2018) and after implementing an ATO process (March 2018 – February 2019). Antibiotics evaluated included vancomycin, cefepime, piperacillin/tazobactam, and meropenem. ATO alert logic was simulated retrospectively to capture the pre-ATO cohort. The primary outcome was mean composite DOT per patient admission. Secondary outcomes included total hospitalization cost, Clostridioides difficile infection (CDI) and multidrug-resistant organism (MDRO) rates.

Results

A total of 8,458 patients met ATO alert criteria for inclusion in the pre-ATO timeframe and 6,901 patients with an ATO alert in the post-ATO group; 2,642 (38%) prompted a pharmacists’ review. The average composite DOT was 11.5 per admission in the pre-ATO cohort compared with 11.1 in the post-ATO cohort (P = 0.02). After multivariate linear regression, the ATO was significantly associated with a decrease of 0.5 DOT per patient admission (P < 0.001). Other factors associated with a reduction in DOT included age (P < 0.001), service line (P = 0.003), and admission source (P = 0.031). Mean hospital costs per admission were significantly reduced in the post-ATO group: $67,613 vs. $66,615 (P = 0.01). There was no difference in rates of CDI and MDRO.

Conclusion

Implementation of our electronic ATO process demonstrated significant reductions in overall DOT for frequently prescribed antibiotics and decreased total hospital costs across a diverse patient population. This process provides a real-world strategy to operationalize a large-scale ATO as an adjunct to an ASP.

Disclosures

All authors: No reported disclosures.
1054. Impact of Prospective Review and Feedback with Peer Comparison on Carbapenem Utilization by Physicians Practicing at a Community Teaching Hospital
Authors: Rosa Rossana M , Bushman Amanda
Published: October 2019

Background

Behavioral interventions such as peer comparison have shown to reduce inappropriate antibiotic utilization in outpatient settings. We aimed to estimate the impact of prospective review and feedback with periodic peer comparison on carbapenem use by physicians in an inpatient setting.

Methods

Interrupted time series study conducted at a 400-bed community teaching hospital with an Antimicrobial Stewardship Program (ASP) in place since 2012. Prospective review and feedback is the ASPs main strategy. Carbapenem use is not restricted. The intervention was limited to internal medicine residents, system-employed hospitalists, critical care specialists, surgery residents and surgery attendings directly supervising residents. Each carbapenem day of therapy (DOT) was reviewed by an infectious diseases (ID) physician or ID pharmacist and classified as adequate, suboptimal unnecessary or inappropriate. For the purposes of peer comparison, each DOT was attributed to the physician directly responsible for patient care on the day a carbapenem was administered. Among patients admitted to teaching services, both the resident and their supervising attending were deemed responsible. Individual physicians’ proportions of adequate use were calculated and compared with the aggregate proportion of adequate use by service, i.e., hospitalists were compared with other hospitalists. An email summarizing utilization metrics and comparing to their peers was sent on a monthly basis. The main outcome of interest was hospital-wide carbapenem use measured in DOT per thousand patient-days. Carbapenem DOT use by service was a secondary outcome. Changes in post-intervention trends were calculated as incidence rate ratios (IRR).

Results

Following the onset of the intervention there were no changes in hospital-wide trends of carbapenem use (IRR 1.04; 95% CI 0.98–1.10; P = 0.21) (Figure 1). Analysis of carbapenem use by service showed prescribing trends remained stable within services, with IRR in medical service of 0.98 (95% CI 0.92–1.05; P = 0.61) and IRR in the surgical service of 1.05 (95% CI 0.99–1.13; P = 0.11) (Figures 2 and 3). No changes were seen in proportions of adequate use.

Conclusion

Addition of peer comparison to an ASP utilizing prospective review and feedback did not decrease carbapenem use.

Disclosures

All authors: No reported disclosures.
1079. Impact of Antimicrobial Stewardship Program (ASP) on Patients with Neurological Conditions
Authors: Hoon Andrea Kwa Lay , Wen Loo Li , Liew Yixin , Piotr Chlebicki Maciej
Published: October 2019

Background

Rising rates of antimicrobial resistance worldwide has dire consequences on patient care, as infections with resistant organisms impair patients’ recovery, resulting in protracted illness and hence prolonged hospital stay. Antimicrobial Stewardship Programs (ASPs) have shown to effectively reduce antibiotic resistance. Locally, we observed that patients with neurological conditions were often initiated on antibiotics for change in mental state or isolated fevers. Little is known whether these patients truly require antibiotics and hence, we aim to study the impact of ASP in these patients.

Methods

Retrospective review of ASP database between January 2014 and December 2017 was conducted, among all patients admitted to the neurology department in SGH and in whom the ASP team recommended discontinuation of empiric use of antibiotics. Demographics were collected. Clinical outcomes, duration of antibiotics therapy, length of hospital stay (LOS), infection-related readmissions and mortality, were compared between interventions accepted and rejected groups.

Results

The ASP team recommended 184 interventions [overall acceptance rate of 82.6% (152/184)]. There was no significant difference in underlying demographics, and Charlson Co-morbidity score between the 2 groups. However, the interventions-acceptance group had shorter duration of therapy by 1.67 days (4.99 ± 2.50 days vs. 6.66 ± 2.34 days; P < 0.01) and LOS by 2 days (22.5 ± 51.4 days vs. 24.5 ± 3.04 days; P = 0.83). There were no significant differences in 14-day mortality and readmission rates between the 2 groups.

Conclusion

In patients with neurological conditions, ASP interventions were safe, and associated with a significant reduction in the duration of therapy and LOS.

Disclosures

All authors: No reported disclosures.
1084. A Pre- and Post-Intervention Study to Implement a Successful Antimicrobial Stewardship Program at an Urban Chronic Hemodialysis Center
Authors: Park Jenny , Nakeshbandi Mohamed , Saggi Subodh , Sharma Roopali
Published: October 2019

Background

Patients receiving chronic outpatient hemodialysis (CHD) are at high risk for bloodstream and vascular access infections due to the immune-compromised status of patients and repeated vascular access. CHD patients are especially vulnerable to multidrug-resistant organisms due to extensive exposure to antibiotics (ABX). It is estimated that more than 40% of CHD patients receive ≥1 ABX course each year. As data characterizing ABX use and reasons for inappropriate prescribing is still scarce in CHD patients, our objective was to assess ABX use pre- and post-implementation of antimicrobial stewardship program (ASP).

Methods

A retrospective cohort study to analyze appropriate ABX use from 2015–2018 in CHD patients was conducted. Starting January 15, 2019, ASP was established at the hemodialysis center and tracked all ABX doses including appropriate indication, dosage, frequency, route, therapeutic drug monitoring (TDM) and duration of therapy. All results are presented as descriptive statistics.

Results

Of the 250 accounts of antibiotics that were assessed retrospectively in all patients from ages 12 to 95 years old, 50% of antibiotics ordered were inappropriately prescribed. The following were the reasons for inappropriateness: indication (59%), duration (14%), culture susceptibility (7%), dose (12%), narrow-spectrum warranted (2%), TDM (6%). Twenty-three accounts were assessed post-implementation phase. ASP implementation led to 100% compliance with regards to the appropriateness of ABX usage (indication, dose, and duration). Additional, ASP interventions included recommendations to obtain blood cultures and conduct TDM in 47% of patients.

Conclusion

This study identified inappropriateness of antibiotic usage without an established ASP in CHD patients. Implementation of ASP was associated with a positive impact on all ABX doses prescribed and this can have a significant outcome on optimizing ABX use in CHD patients.

Disclosures

All authors: No reported disclosures.
1094. Safety of Administering Cefazolin vs. Other Antibiotics in Penicillin Allergic Patients with Anaphylaxis for Surgical Prophylaxis
Authors: Song Wendy , Lau Tim , Grant Jennifer , Shajari Salomeh , Aulakh Amneet , Forrester Leslie , Partovi Nilu
Published: October 2019

Background

Approximately 10% of patients report a history of penicillin allergy. Recent literature suggests cross-reactivity between cephalosporins and penicillins are due to side-chain similarities. Since cefazolin has a unique side-chain from other β lactams, it can be safely administered in penicillin-allergic patients for surgical prophylaxis. Since October 2018, our hospital updated all surgical prophylaxis preprinted orders to use cefazolin in penicillin-allergic patients, except in those with histories of cefazolin-specific allergy or delayed skin reactions (e.g., Stevens–Johnson syndrome). This study aims to retrospectively determine outcomes and safety of cefazolin as compared with other antibiotics for surgical prophylaxis in penicillin-allergic patients with histories of anaphylaxis prior to implementation of cefazolin preprinted orders.

Methods

All patients with reported anaphylactic reactions to penicillins prescribed surgical prophylaxis from October 9, 2017 to October 9, 2018 were included. Patients were stratified based on antibiotic received (i.e., cefazolin, clindamycin, vancomycin, other antibiotic) and a retrospective chart review was performed to assess for outcomes and safety.

Results

One-thousand-seventy-three prescriptions for prophylactic antibiotics were identified. Of these, 223 cases met inclusion with histories of anaphylaxis to pencillins: 72 (32%) cefazolin, 70 (31%) clindamycin, 34 (15%) vancomycin, and 47 (21%) other antibiotics. General and orthotrauma surgeries used the most cefazolin in penicillin-allergic patients, while gynecology clindamycin and thoracics vancomycin. Amongst those receiving cefazolin, no critical incidents of allergic reactions were reported and the rates of adverse events, such as pruritus, hives and rash, did not differ between any antibiotic group.

Conclusion

Cefazolin appears to be a safe option for surgical prophylaxis in patients with history of penicillin anaphylaxis. No differences in incidences of allergic reactions, complications or surgical delays were reported, as compared with alternate antibiotics. Further larger studies are needed to confirm our findings and determine rates of adverse events associated with the various antibiotic regimens.

Disclosures

All authors: No reported disclosures.
1098. Perioperative Antibiotic Stewardship for Interventional Radiology Cases Improves Antibiotic Decision-Making
Authors: Sterling Stephanie , Decano Arnold , Fabian Evelyn
Published: October 2019

Background

Appropriate periprocedural antibiotic prophylaxis is critical to optimize in order to reduce excessive antibiotics exposure for patients and to minimize the risk for procedure-related infection. Wrong antibiotic or excess antibiotics increase the risk for development of antimicrobial resistance, Clostridium difficile infection, adverse side effects. Incorrect or missed antibiotic can put the patient at risk for an infection.

Methods

Interventions included education of vascular and interventional radiology (IR) consult RN and physicians regarding updated institutional antimicrobial prophylaxis guidelines for vascular and IR procedures, creation of a consulting template that incorporated ongoing antibiotics. Review of recent cultures was incorporated into workflow and consult evaluation. Handoff between the IR RN and IR attendings was expanded to include a review of antimicrobials.

Results

All IR cases were reviewed for antibiotic administration for 3 months pre- and post-intervention. In the pre-intervention timeframe, 23 of 290 procedures (7.9%) were associated with inappropriate antibiotic administration, further delineated as 6 cases where no antibiotics were given, 7 cases of inappropriate antibiotics administered, and 10 cases where extraneous antibiotics were administered. Of the 39 total procedures where antibiotics were indicated, 17 (43.6%) were associated with antibiotic errors. In the post-intervention period, only 9 of 309 total procedures (10.3%) were associated with inappropriate antibiotic administration: missed antibiotics in 3 cases, inappropriate antibiotics in 4 cases, and unnecessary antibiotics in 2 cases. Of the 32 cases where antibiotics were indicated, only 7 (21.9%) were associated with antibiotic errors.

Conclusion

Incorporating current antibiotics and review of culture data in a preoperative review and template for patients who need a surgical procedure helps guide appropriate antibiotic decision-making and greatly decreases administration of unnecessary antibiotics.

Disclosures

All authors: No reported disclosures.
1110. Outcomes Following Implementation of a Urine Culture
Authors: Simpson Timothy , Wu Janet , Choudhary Chirag , Shah Sneha
Published: October 2019

Background

Antimicrobials are often inappropriately initiated for asymptomatic bacteriuria (ASB). At our institution, urinalysis (U/A) and urine culture (UCx) are ordered simultaneously, leading to an increased rate of catheter-associated UTI (CAUTI) diagnosis and antimicrobial initiation. A UCx algorithm was implemented in the medical intensive care unit (MICU) to guide the appropriate ordering of UCx in patients with foley catheters. The purpose of this study was to assess the impact of this UCx algorithm paired with nursing and prescriber education on overall patient outcomes.

Methods

This was a single-center, pre- and post-analysis of patients admitted to the MICU with an order for a U/A and/or UCx for suspected UTI. Patients were excluded if they had a suspected co-infection from another source, absence of foley catheter or UCx drawn prior to MICU admission. The pre-implementation phase was November 1, 2017 to April 31, 2018, and the post-phase was May 1, 2018 to October 31, 2018. The primary objective was to compare the incidence of CAUTI between pre- and post-implementation phases. Secondary objectives included rate of adherence to the algorithm, number of UCx ordered, rate and days of antimicrobial therapy for ASB, duration of catheterization and 30-day mortality between pre- and post-implementation phase.

Results

There were 94 patients in the pre-phase and 77 patients in the post-phase. Baseline characteristics were similar between groups, except a greater proportion of patients in the pre-phase had a catheter prior to admission (12.8% vs. 2.6%; P = 0.02). Incidence of CAUTI decreased following algorithm implementation (16% vs. 6.5%; P = 0.05). Complete algorithm adherence was 2.6%, whereas partial adherence was 49.4%. Number of UCx ordered were 126 (comprising 100% of patients) and 76 (comprising 86% of patients) in the pre- and post-phase, respectively. Antimicrobial therapy for ASB was initiated in 55.3% of patients in the pre-phase vs. 37.7% in the post-phase; P = 0.02. There were no differences in duration of ASB treatment, catheterization or 30-day mortality.

Conclusion

Implementation of UCx algorithm paired with educational intervention resulted in a significant decrease in CAUTI and ASB treatment. Additional interventions may be necessary to optimize adherence to the algorithm.

Disclosures

All authors: No reported disclosures.
1117. A Retrospective Analysis of Paediatric Prescribing in British Columbia from 2013 to 2016
Authors: Saatchi Ariana , Patrick David M , McCormack James , Morris Andrew , Marra Fawziah
Published: October 2019

Background

Antibiotic prescribing in pediatric care is highly prevalent. Often children are prescribed antibiotics for conditions that are commonly self-limiting and viral in etiology such as upper respiratory tract infections. The purpose of this study was to examine the scope of pediatric antibiotic prescribing in British Columbia from 2013 to 2016 and identify potential new provincial antimicrobial stewardship targets.

Methods

Antibiotic prescription data for children were extracted from a provincial prescription database, and linked to demographic files in order to obtain patient age, sex and geographic location. Prescription rates were then calculated, and trends were examined by major anatomical therapeutic chemical (ATC) classification.

Results

Our cohort included an average of 271,134 children per year and 1,767,652 antibiotic prescriptions. Over the 4 years, rates of antibiotic prescribing increased 4.5% (from 453 to 474 prescriptions per 1,000 population per year). The greatest increase, across all classes of antibiotics, was seen in children aged 0–2 years of age. By 2016, the greatest increase in prescribing, by class, was observed in J01X (e.g., nitrofurantoin, fosfomycin) with a 1360% increase for children aged 3–9. Across all ages, quinolones (J01M) increased 98%. Remaining classes, including β lactams (J01C), and macrolides (J01F), experienced modest reductions in the older age groups.

Conclusion

Past studies have illustrated decreasing or static rates of antibiotic prescribing in British Columbia. However, we have identified a paradoxical (4.5%) increase in pediatric antibiotic prescribing since 2013. Although it appears that provincial efforts have been successful in reducing the use of broad-spectrum penicillins (J01C), marked surges in the use of classes like tetracylines (J01A), quinolones (J01M), and other antibacterials (J01X) identify a new potential target for provincial stewardship.

Disclosures

All authors: No reported disclosures.
LB8. Microarray Patch Delivery of Long-Acting HIV PrEP and Contraception
Authors: Rein-Weston Annie , Tekko Ismaiel , Vora Lalit , Jarrahian Courtney , Spreen Bill , Scott Trevor , Donnelly Ryan , Zehrung Darin
Published: October 2019

Background

The purpose of this research was to develop a microarray patch (MAP; also known as a microneedle patch) for delivery of long-acting cabotegravir (CAB LA) for HIV pre-exposure prophylaxis (PrEP) and co-delivery of long-acting CAB LA and a hormonal contraceptive to enable a future multi-purpose prevention technology. This abstract presents preclinical pharmacokinetic results of MAP delivery of CAB LA.

Methods

MAPs are an alternative delivery technology in clinical development for intradermal delivery of vaccines and pharmaceuticals. A MAP consists of an array of micron-scale projections (<1 mm in height) amassed on a baseplate and applied to the skin like a bandage. MAPs could provide a discreet delivery system that enables self-administration, which could be particularly important for HIV prevention and contraception for young women and girls in low-resource settings. The purpose of this 3-year, USAID-funded project is to develop a MAP for delivery of long-acting HIV PrEP through to the point of Phase I clinical readiness. Key attributes of the MAP for long-acting HIV PrEP, as defined by our target product profile, include patch size similar to commercially available transdermal patches (20 to 140 cm2), wear-time of less than 24 hours (ideally 20 minutes), weekly or monthly administration to achieve therapeutic efficacy, and ideally successful self-administration after reading simple product instructions.

Results

We successfully formulated and optimized MAP projection geometry to accommodate high drug-loading requirements of CAB LA (5.86 mg CAB LA per 1 cm2 MAP), a hydrophobic drug. The MAPs are stable for 6 months under accelerated aging conditions in foil packaging, readily pierce the skin, and rapidly dissolve. In rats, plasma concentration levels of CAB LA were maintained above therapeutic targets of 4xPA-IC90 for 28 days; however, bioavailability was lower than IM or ID injection controls. Photos: QUB. MAPs dissolving over time in phosphate-buffered solution; MAP projections fully dissolved within 25 minutes.

Conclusion

Additional development work is warranted, including optimizing bioavailability, evaluating MAPs as a maintenance dose in vivo, conducting cost of manufacturing and cost of delivery analyses, and assessing potential end-user acceptability.

Disclosures

Bill Spreen, PharmD, ViiV Healthcare (Employee), Trevor Scott, RPh, PhD, ViiV Healthcare (Employee). Others Authors: No reported disclosures.
LB16. The Role of Adults in the Measles Outbreak in New York State Outside of New York City, 2018–2019
Authors: Dufort Elizabeth , Johns Dylan , Patel Manisha , Patel Manisha , Ahmad Nina , Ruppert Patricia S , Rausch-Phung Elizabeth , Gastanaduy Paul , Gastanaduy Paul , McDonald Robert , Souto Maria , Bryant Patrick , McKay Kevin T , McNulty Lissette , McGraw Nancy , Huang Ada J , Wester Rachel E , St. George Kirsten , Sommer Jamie N , Southwick Karen L , Hoefer Dina , Landis Vanessa , Adams Eleanor , Adams Eleanor , Ostrowski Stephanie , Levin Toby R , Gelman Irina , Hutton Brad , Zucker Howard , Blog Debra
Published: October 2019

Background

The United States is experiencing the largest measles outbreak since elimination was declared in 2000, with the majority of cases in NYS reported in undervaccinated communities. The objective of this evaluation was to describe adult measles cases in the NYS measles outbreak outside of New York City (NYC).

Methods

We included all confirmed cases aged ≥18 years in NYS residents (excluding NYC) during October 1, 2018–July 25, 2019 that met the CSTE measles case definition. We defined measles cases attributable to adults as the sum of measles cases among adults and children who contracted disease directly from adults.

Results

Among 371 confirmed measles cases, the median age was 5.5 years (range: 1 day to 64 years); 79 (21%) were in adults, 4 (5%) of whom were born before 1957 (3 unvaccinated and 1 with unknown vaccine status). Among the 75 cases born during or after 1957, 65 (87%) were unvaccinated or had unknown vaccine status, while 3 had one dose and 7 had 2 doses of measles vaccine. Notably, 5 of 11 internationally imported measles cases were adults, and all were unvaccinated or had unknown vaccine status. During the first month of the outbreak, 26 of the 51 (51%) cases were attributable to adults; of the 26, 15 (58%) were in adults and 11 (42%) were in children who acquired infection from adults (Figure 3).

Conclusion

The majority of measles cases occurred in unvaccinated children emphasizing the importance of ongoing and focused efforts on pediatric vaccination. However, measles cases in unvaccinated adults played an important role in both importations and disease transmission early in the outbreak. These data strongly support current recommendations of 1 dose of measles, mumps, rubella vaccine (MMR) for most adults and 2 doses of MMR for adults traveling internationally and at high-risk such as those in outbreak areas, as determined by local/state public health.

Disclosures

Kirsten St. George, MAppSc, PhD, Akonni Biosystems (Other Financial or Material Support), ThermoFisher (Grant/Research Support), Zeptometrix (Other Financial or Material Support, royalty generating collaborative agreement). .
Retrieval of an Intracranially Migrated Dental Injection Needle Through the Foramen Ovale: 2-Dimensional Operative Video
Authors: Aoun Salah G , El Ahmadieh Tarek Y , Ban Vin Shen , Patel Vishal J , Vance Awais , Patel Ankur R , Tandon Rahul , Zuniga John R , Batjer H Hunt , Barnett Sam
Published: October 2019

Dental injection needle migration is a rare complication of orthodontal procedures. When these needles fracture, they typically dislodge into the cervical space or the facial musculature. Migration into the cranial vault is difficult because of the obstacle created by the skull base. We report a rare case of intracranial migration of an anesthetic injection needle through the foramen ovale. A 59-yr-old man underwent the extraction of a right maxillary molar. The distal end of a 25-gauge injection needle broke into his pterygoid musculature, causing him pain while chewing. Vascular imaging obtained after a computed tomography scan of his face showed that the needle had migrated, potentially because of his efforts of mastication, and had traversed the foramen ovale into the middle cranial fossa. The patient started experiencing intermittent right facial numbness, likely due to compression or injury to the right trigeminal nerve. Our oral and maxillofacial colleagues did not believe that the needle could be retrieved from its facial end. The patient elected to undergo the recovery of the needle through a craniotomy given the fact that the object was contaminated and because he was becoming increasingly symptomatic. A right pterional craniotomy was planned. Extradural dissection was performed until the dura going into the foramen ovale was revealed. We could feel the metallic needle under the dural sheath of the trigeminal nerve. The dura was opened sharply directly over the needle. We then proceeded to mobilize the needle into the face, and then pulled it out completely through the craniotomy to avoid injury to the temporal lobe. The patient recovered well and was asymptomatic at the time of discharge.

This case report was written in compliance with our institutional ethical review board. Institutional review board (IRB) approval and patient consent were waived in light of the retrospective and deidentified nature of the data presented in accordance with the University of Texas Southwestern (UTSW) IRB.
Sensible Over-Determination
Authors: Sethi Umrao
Published: October 2019

I develop a view of perception that does justice to Price's intuition that all sensory experience acquaints us with sensible qualities like colour and shape. Contrary to the received opinion, I argue that we can respect this intuition while insisting that ordinary perception puts us in direct contact with the mind-independent world. In other words, Price's intuition is compatible with naïve realism. Both hallucinations and ordinary perceptions acquaint us with instances of the same kinds of sensible qualities. While the instances in hallucination are mind-dependent, those in veridical perception are not. The latter are ontologically over-determined—they have their existence guaranteed both in virtue of having a material bearer and in virtue of being perceived by a mind. Such over-determined instances are mind-independent—they can continue to exist unperceived, because, in addition to the minds that perceive them, their existence is guaranteed by the material objects that are their bearers.
Association between depression and rheumatoid arthritis: two longitudinal follow-up studies using a national sample cohort
Authors: Kim So Young , Chanyang Min , Oh Dong Jun , Choi Hyo Geun
Published: October 2019

Objective

To investigate the bidirectional relation between RA and depression.

Methods

Data from the Korean Health Insurance Review and Assessment Service – National Sample Cohort from 2002 to 2013 were analysed. Patients ≥20 years of age were included. Study I was conducted with 38 087 depression patients and 152 348 matched control participants. Study II was conducted with 7385 RA patients and 29 540 matched control participants. Stratified Cox proportional hazards models were used to analyse the hazard ratios (HRs) for depression and RA (study I) and for RA and depression (study II). The data were adjusted by the Charlson comorbidity index; rheumatic disease was excluded. Subgroups were also analysed according to age and sex.

Results

A total of 0.7% (1260/38 087) of the depression group and 0.6% (883/152 348) of the control I group had RA (P = 0.02). The HR for RA in the depression group was not significantly higher than that in control I group. In study II, 5.5% (408/7385) of the RA group and 4.3% (1246/29 540) of the control II group presented with depression (P < 0.001). The RA patients showed an adjusted depression HR that was 1.20 times higher (95% CI 1.07, 1.34; P = 0.002) than that of the control group. The >30-years-old and women subgroups of RA patients showed higher depression HRs than the control subgroups.

Conclusion

RA increased the risk of depression; however, depression did not increase the risk of RA in the Korean adult population.
Involuntary Detention and Treatment: Are We Edging Toward a “Paradigm Shift”?
Authors: Szmukler George
Published: October 2019

Recent challenges to conventional mental health laws concerning involuntary detention and treatment of persons with a mental disorder have led to proposals, or indeed an insistence, that fundamental reform is necessary. A key theme has been the need to eliminate unfair discrimination against people with a mental disorder because their human rights are not respected on an equal basis with other people. Some proposals depart radically from conventional assumptions concerning the justification of involuntary detention and treatment. One is a “fusion law,” a generic law applying to all persons lacking the ability to make a treatment decision, whether resulting from a “mental” or “physical” illness. An authoritative interpretation of the UN Convention on the Rights of Persons with Disabilities (2006) goes so far as to maintain that involuntary interventions are a violation of the Convention.
Dietary preferences and diet effects on life-history traits of tardigrades
Authors: Bryndová Michala , Stec Daniel , Schill Ralph O , Michalczyk Łukasz , Devetter Miloslav
Published: October 2019

Tardigrades may be divided into the following feeding groups: herbivores, carnivores and omnivores. However, little is known about their specific feeding preferences. Here, we used a number of laboratory experiments with 18 potential food sources, representing a wide variety of organisms, to test feeding preferences, survival and fecundity of three tardigrade species, representing different feeding modes. We also tested for differences in preferences between juveniles and adults, and differences in survival between two age groups: one that started the experiment as juveniles and the other as adults. In our experiments, Milnesium inceptum is confirmed to be a carnivore, being able to reproduce only on animal prey. We also show that Hypsibius exemplaris is a herbivore, feeding on cyanobacteria, algae and fungi. Paramacrobiotus fairbanksi, on the other hand, is demonstrated to be an omnivore, feeding on cyanobacteria, algae, fungi and animals. In some cases, juveniles preferred different types of food than adults. Reproduction was strongly affected by food type. Finally, we demonstrate that tardigrades may ingest food types that they are not able to digest. Thus, gut content analysis may be misleading as a method of studying tardigrade feeding habits.
Effect of Fungicide Mobility and Application Timing on the Management of Grape Powdery Mildew
Authors: Warneke Brent , Thiessen Lindsey D. , Mahaffee Walter F.
Published: October 2019

Grape powdery mildew (GPM) fungicide programs consist of 5 to 15 applications, depending on region or market, in an attempt to achieve the high fruit quality standards demanded by the market. Understanding how fungicides redistribute and targeting redistributing fungicide to critical crop phenological stages could improve fungicide protection of grape clusters. This study evaluated fungicide redistribution in grapevines from major fungicide groups labeled for GPM control. Translaminar and xylem redistribution was examined by placing fungicide-impregnated filter disks on the adaxial or abaxial leaf surface of detached leaves for 10 min and then incubating for 48 h before inoculating the abaxial surface with conidia. Vapor redistribution used Teflon disks sprayed with fungicides and placed on the abaxial leaf surface of detached leaves 48 h before inoculation. Disease development was rated 10 days later. Translaminar movement through calyptra was tested using flowering potted vines. All fungicides tested redistributed through at least one mechanism. Fungicide timing at critical phenological stages (early, mid, and late bloom) was assessed in small plots of cultivar Pinot noir vines. The application of trifloxystrobin, quinoxyfen, or fluopyram at different bloom stages showed that applications initiated at end of bloom resulted in the lowest berry infection probabilities of 0.073, 0.097, and 0.020, respectively. The results of this study suggest that integrating two carefully timed applications of redistributing fungicides initiated at end of bloom into a fungicide program may be an effective strategy for wine grape growers in western Oregon to produce fruit with low GPM infection.
Differential estrogen‐receptor activation regulates extracellular matrix deposition in human airway smooth muscle remodeling via NF‐κB pathway
Authors: Ambhore Nilesh Sudhakar , Kalidhindi Rama Satyanarayana Raju , Pabelick Christina M. , Hawse John R. , Prakash Y. S. , Sathish Venkatachalem
Published: October 2019

Altered airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition in airways are characteristic features of remodeling in asthma. Increased ECM production modulates ASM cell proliferation and leads to airway remodeling. Our previous studies showed that ASM from patients with asthma exhibited increased expression of estrogen receptor (ER)‐β, which upon activation down‐regulated ASM proliferation, implicating an important role for estrogen signaling in airway physiology. There is no current information on the effect of differential ER activation on ECM production. In this study, we evaluated the effect of ER‐α vs. ER‐β activation on ECM production, deposition, and underlying pathways. Primary human ASM cells isolated from asthmatics and nonasthmatics were treated with E2, an ER‐α agonist [propylpyrazoletriol (PPT)], and an ER‐β agonist [WAY‐200070 (WAY)] with TNF‐α or platelet‐derived growth factor (PDGF) followed by evaluation of ECM production and deposition. Expression of proteins and genes corresponding to ECM were measured using Western blotting and quantitative RT‐PCR with subsequent matrix metalloproteinase (MMP) activity. Molecular mechanisms of ER activation in regulating ECM were evaluated by luciferase reporter assays for activator protein 1 (AP‐1) and NF‐κB. TNF‐α or PDGF significantly (P < 0.001) increased ECM deposition and MMP activity in human ASM cells, which was significantly reduced with WAY treatment but not with PPT. Furthermore, TNF‐α‐ or PDGF‐induced ECM gene expression in ASM cells was significantly reduced with WAY (P < 0.001). Moreover, WAY significantly down‐regulated the activation of NF‐κB(P < 0.001) and AP‐1 (P < 0.01, P < 0.05) in ASM cells from asthmatics and nonasthmatics. Overall, we demonstrate differential ER signaling in controlling ECM production and deposition. Activation of ER‐β diminishes ECM deposition via suppressing the NF‐κB pathway activity and might serve as a novel target to blunt airway remodeling.—Ambhore, N. S., Kalidhindi, R. S. R., Pabelick, C. M., Hawse, J. R., Prakash, Y. S., Sathish, V. Differential estrogen‐receptor activation regulates extracellular matrix deposition in human airway smooth muscle remodeling via NF‐κB pathway. FASEB J. 33, 13935‐13950 (2019). www.fasebj.org