bluuebunny/crossref_metadata_2025 huggingface dataset:
658. Cost-effectiveness of Molecular Diagnostic Assays for the Therapy of Severe Sepsis and Septic Shock in the Emergency Department
Authors: Zacharioudakis Ioannis , Zervou Fainareti , Shehadeh Fadi , Mylonakis Eleftherios , Mylonakis Eleftherios
Published: October 2019

Background

Sepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes.We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED.

Methods

We developed a decision analysis model with the primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients’ length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described.Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed.

Results

Under baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER −$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity ≥52%, panel efficiency ≥39%, and assay cost ≤$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained ≤$20,000/death averted for every studied sensitivity (i.e., 0.5–0.95), panel efficiency ≥34%, and assay cost ≤$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was ≤$135 and the panel efficiency was ≥77%.

Conclusion

The incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios.

Disclosures

Eleftherios Mylonakis, MD PhD, Sanofi-Pasteur: Grant/Research Support; T2 Biosystems: Grant/Research Support.
663. Efficacy and Safety of Lefamulin (LEF) vs. Moxifloxacin (MOX) for Legionella pneumophila (LP) in Patients with Community-Acquired Bacterial Pneumonia (CABP): Pooled Results From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Clinical Trials
Authors: Shorr Andrew F , Schranz Jennifer , Goldberg Lisa , Paukner Susanne , Das Anita F , Moran Gregory J , Sandrock Christian , File Thomas M , Alexander Elizabeth , Gelone Steven P
Published: October 2019

Background

LP is associated with severe CABP, rapid onset, and high morbidity/mortality. Poor outcomes in CABP have been linked to receiving inappropriate empiric therapy or delayed treatment (tx). LEF, a novel IV/oral pleuromutilin, demonstrated efficacy/safety in noninferiority studies (LEAP 1/2) vs. MOX in adults with CABP. We report efficacy/safety of LEF in patients with LP based on a pooled analyses of LEAP 1/2 data.

Methods

In LEAP 1, PORT III–V patients received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF for 5 days or oral MOX for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 hours after first dose in the intent-to-treat (ITT; all randomized patients) population and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (received ≥1 dose) and clinically evaluable (met predefined evaluability criteria) populations. LP was identified from baseline (BL) samples by culture, serology (IgG, Zeus L. pneumophila group 1–6 indirect fluorescent antibody assay), urine antigen testing (BinaxNOW), and real-time PCR (positive for ssrA). Efficacy analyses herein were done in the microbiological ITT (microITT, treated patients with BL CABP-causing pathogen), microITT-2 (no PCR), and microbiologically evaluable populations; safety analyses included all randomized/treated patients.

Results

Of 65 pooled microITT patients, median age was 60 y, 66% were male, 51% had a normal renal function, and 54%/25% were PORT III/IV. LP was identified in 9.3% (34/364) of LEF patients (7 [20.6%]/19 [55.9%]/8 [23.5%] PORT II/III/IV) and in 9.0% (31/345) of MOX patients (7 [22.6%]/16 [51.6%]/8 [25.8%] PORT II/III/IV), primarily by urine antigen or serology (table). Patients with LP in both tx groups achieved high and similar responses across all endpoints (Figures 1 and 2). In both tx groups, TEAE rates were low and comparable (~32%) and most were mild to moderate; 5 patients (3 LEF; 2 MOX) had treatment-emergent SAEs, all unrelated to tx. No patients died due to TEAEs; no LEF patients and 2 MOX patients discontinued tx due to TEAEs.

Conclusion

LEF appears to be as safe and effective as MOX in treating patients with LP, including when given as short-course (5 days) oral therapy.

Disclosures

All authors: No reported disclosures.
680. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa from ICU and Non-ICU Wards Collected in Latin America and Globally as Part of the ATLAS Surveillance Program 2016–2017
Authors: Lob Sibylle , Kazmierczak Krystyna , Stone Gregory , Sahm Daniel F
Published: October 2019

Background

Ceftazidime–avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases but not class B metallo-β-lactamases (MBLs). Antimicrobial resistance due to these β-lactamases and other mechanisms is increasing and is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Pseudomonas aeruginosa isolates from patients in ICU and non-ICU wards.

Methods

Nonduplicate clinical isolates were collected in 2016–2017 in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2019 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >2 µg/mL.

Results

The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global P. aeruginosa were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI (89% and 92% susceptible, respectively) and for amikacin and colistin. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 72% and 70% of isolates, respectively, of which 18.4% and 18.7% were MBL-positive. CAZ AVI inhibited >83% of MEM-NS MBL-negative isolates globally. In Latin America (LA), CAZ-AVI was active against 87% of isolates from both ward types. Susceptibility rates were generally lower than the global average, especially among MEM-NS isolates and isolates from non-ICU wards. The proportion of MBL-positive isolates in the MEM-NS subset was only slightly higher in LA than globally (19.2% and 19.5% in ICU and non-ICU wards, respectively), suggesting the presence of additional resistance mechanisms. Only colistin exceeded the activity of CAZ-AVI against isolates collected globally and in LA.

Conclusion

CAZ-AVI showed potent antimicrobial activity, second only to that of colistin, against P. aeruginosa isolates from both ICU and non-ICU wards, with >88% of isolates collected globally testing as susceptible. Activity was in part compromised by MBLs, although additional resistance mechanisms may also be responsible.

Disclosures

All authors: No reported disclosures.
693. In Vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Enterobacteriaceae and Pseudomonas aeruginosa Collected From Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2014–2017
Authors: Kazmierczak Krystyna , Stone Gregory , Sahm Daniel F
Published: October 2019

Background

Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacteriaceae (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2014–2017.

Methods

A total of 53416 Eba and 15050 Pae nonduplicate clinically significant isolates, including 5155 Eba and 845 Pae isolated from bloodstream infections, were collected by 167 hospital laboratories in 36 countries in Europe, Latin America, Asia/Pacific (excluding China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes.

Results

Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.2–2.8% lower among Eba and Pae from bloodstream infections compared with isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and subsets of CAZ-NS and colistin-resistant (CST-R) isolates (MIC90, 0.5–2 µg/mL, 96.0–100% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because all MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/mL, 89.5% S). Activity was reduced against CAZ-NS, MEM-NS and CST-R subsets (53.7–85.0% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 15–65%. CST and amikacin were the only tested comparators that demonstrated comparable or greater activity against Pae bloodstream isolates.

Conclusion

CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates.

Disclosures

All authors: No reported disclosures.
696. Cefiderocol Susceptibility Against Molecularly Characterized Carbapenemase-Producing Gram-Negative Bacteria in North America and Europe Between 2014 and 2017: SIDERO-WT-2014 to -2016 Studies
Authors: Sato Takafumi , Tsuji Masakatsu , Kazmierczak Krystyna M , Hackel Meredith M , Echols Roger , Yamano Yoshinori , Sahm Daniel F
Published: October 2019

Background

Antibiotic susceptibility surveillance is the foundation for selecting treatment options as well as immediate and long-term strategies for combating antimicrobial resistance. We have conducted three surveillance studies SIDERO-WT-2014/-2015/-2016 with approximately 30,000 Gram-negative strains isolated in North America and Europe between 2014 and 2017. Here, we present the latest data of molecular analysis on acquired carbapenemase genes and antibiotic susceptibility of 3691 meropenem-nonsusceptible strains in the surveillance studies.

Methods

Meropenem-nonsusceptible strains isolated in North America (n = 1009) and Europe (n = 2,682), consisting of 1,897 Acinetobacter baumannii, 1,154 Pseudomonas aeruginosa, 447 Klebsiella pneumoniae, and 193 other Enterobacteriaceae were tested. Conventional PCR was used to detect known carbapenemases. Cefiderocol MICs were determined by broth microdilution method using iron-depleted cation-adjusted Mueller–Hinton broth.

Results

The percentages of known carbapenemases detected in 3 main pathogens are shown in the Table. In A. baumannii complex, OXA-23 was predominant followed by OXA-24 in most countries. The detection rates of VIM in P. aeruginosa were ≥40% in Greece and Russia, but none of the strains in the United States carried VIM. In K. pneumoniae, the predominant carbapenemase varied among the countries, with KPC predominating in the USA, Greece and Italy, while OXA-48-like was dominant in Russia, Spain and Turkey. Cefiderocol MIC90 were ≤4 μg/mL against these 3 pathogens in all 6 countries, except for A. baumannii strains in Russia.

Conclusion

Carbapenemase detection rates, especially in P. aeruginosa and K. pneumoniae, were quite different among the countries. Cefiderocol demonstrated potent in vitro activity against meropenem-nonsusceptible strains irrespective of the presence of specific carbapenemases.

Disclosures

All authors: No reported disclosures.
716. In vitro and In vivo Nonclinical Efficacy of AR-501 (Gallium Citrate)
Authors: Woo Jennifer , Hearne Ken , Kelson Andy , Yee Luisa , Espadas Cecilia , Truong Vu L
Published: October 2019

Background

Gallium nitrate citrate exhibits strong antibacterial activity and was recently shown to be safe and efficacious when intravenously administered to cystic fibrosis patients in a Phase 2 clinical study conducted by the University of Washington. We are developing an inhaled formulation of gallium citrate (AR-501), which is being tested in a Phase 1/2a clinical study. The in vitro antimicrobial activities, drug resistance profile, activities in combination with selected antibiotics, and in vivo animal efficacy if the inhaled vs. IV formulation is being presented.

Methods

MIC tests were performed on strains using the CLSI susceptibility test standards. Resistance testing exposed bacteria to 20 cycles at ranges above and below the MIC level of the drug used.SPF mice (C57BL/6J, 7–9 weeks) were inoculated intranasally with P. aeruginosa under ketamine/xylazine anesthesia. Inhalation of AR-501 used an Aeroneb Solo nebulizer. Gallium levels were determined by elemental analysis using atomic absorption spectroscopy. CFU levels were measured by enumeration of bacterial colonies following serial dilution of tissue homogenates.

Results

In vitro efficacy: MIC testing demonstrates the efficacy of AR-501 against gram (−), gram (+) and several species of mycobacteria of clinical isolates and the comparative antibacterial response with antibiotics. Resistance testing showed that AR-501 exhibited lower propensity to develop resistance than the antibiotics tested. In vivo efficacy: AR-501 Inhalation also increased the median survival time compared with IV dosing in the murine model. Bacterial clearance was increased when Tobramycin and AR-501 are co-administered. Comparative analysis of AR-501 after IH route demonstrate increased gallium levels in BAL and reduced levels in the kidney in contrast to IV route.

Conclusion

In vitro studies demonstrate the susceptibility of gram (−), gram (+) and mycobacteria pathogens and the dose range of AR-501 compared with SOC antibiotics. In vivo studies confirm the therapeutic efficacy of AR-501 in bacterial pneumonia by IH delivery and demonstrate that bacterial clearance is enhanced when SOC antibiotics are used in combination with AR-501.

Disclosures

All authors: No reported disclosures.
735. Bacteriophage Therapy Improves Survival of Galleria mellonella Larvae Injected with Vancomycin-Resistant Enterococcus faecium
Authors: El Haddad Lynn , Harb Cynthia P , Stibich Mark , Chemaly Roy F , Chemaly Roy F
Published: October 2019

Background

Vancomycin-resistant Enterococcus faecium (VRE) is a major multidrug-resistant organism which may cause infection or colonization in hematopoietic cell transplant (HCT) patients. The use of VRE-specific bacteriophages (phages) may potentially help eradicate VRE colonization and subsequent infections. To test the efficacy and safety of phages against VRE in vivo, a cocktail combining four phages was used in a VRE-infected larva model.

Methods

The pre-screening model Greater Wax Galleria mellonella larva was used in this study. Larvae were infected with VRE by injecting a VRE strain isolated from stools of a VRE-colonized HCT patient at a concentration of 107 colony-forming units/10 μL. A single phage (MDA1) or a phage cocktail (MDA1, MDA2, MDA3, and MDA4) were also injected at a concentration of 106 colony-forming units/10 μL. Two model groups were tested; a prevention group (PG) and a treatment group (TG). For the PG, phages were administered 1 hour before bacterial injection whereas the TG were injected with phages 1 hour post bacterial injection. Control groups included larvae injected with bacteria alone, phages alone (to measure toxicity due to phage administration), sterile media (to measure any lethal effects due to physical trauma from the injection), or without any manipulation. Every group was composed of 5 larvae. The insect’s health state was observed and scored after 8 hours of incubation at 37ºC using a published health index scoring system.

Results

Phages improved survival of VRE-infected larvae (table). Only 32% of the VRE-infected larvae survived after 8 hours of infection whereas more than 80% survived when adding phages, whether phages were administered before or after VRE infection. The phage cocktail was shown to be more effective than the single phage MDA1 in improving survival (66% vs. 82% survival). Injecting larvae with phages alone was safe as the same survival rate was observed when compared with those injected with sterile media or those without manipulation.

Conclusion

The use of larva model G. mellonella allows for rapid and efficient screening of the bacterial virulence and phage efficacy and safety. Such results highlight the feasibility and the potential impact of phage therapy on VRE colonization and infections.

Disclosures

Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.
741. TravMil Surveillance of Travel-Related Illness in a Prospective Cohort of US Military Beneficiaries, 2010–2018
Authors: Manley Morgan , Lalani Tahaniyat , Telu Kalyani , Tribble David , Tilley Drake H , Ganesan Anuradha , Kunz Anjali , Geist Charla , Fraser Jamie , Mitra Indrani , Yun Heather , Lindholm David
Published: October 2019

Background

Increasing international travel places larger populations at risk for infections outside of their usual exposure. Deployed military personnel have unique risks for such infections. Our cohort’s rates of travelers’ diarrhea and influenza-like illness have been defined, but the rate of travelers with symptoms apart from a clinical syndrome has not. We present a survey of intra-travel symptoms of all travelers and confirmed diagnoses of ill-returned travelers in a cohort of military and civilian travelers.

Methods

TravMil is a prospective, multicenter observational study enrolling US military beneficiaries traveling outside the continental United States from 2010–2018; beneficiaries could also enroll after travel if they presented for a possible travel-related illness. Demographic information, intra-travel symptoms, and confirmed diagnoses were recorded.

Results

2671 travelers embarked on 3050 trips: 63.1% male; median age 38 years (IQR 27, 57); median trip duration 20 days (IQR 13, 46). Common purposes of travel: military deployment (45.9%), vacation (23.7%), and visiting friends/relatives (10.9%). Ninety-seven travelers (3.2%) enrolled post-travel. Top regions of travel: Africa (31.5%), South and Central America/Caribbean (25.5%), and Southeast and North Asia/Oceania (19.4%). During travel, 56.6% experienced gastrointestinal (GI) symptoms, 11.9% respiratory symptoms, and 3.0% fever; of those, 10.3% sought medical care. Eighty returned travelers sought medical care (21 prospective enrollees vs. 59 post-travel enrollees): 5 vs. 17 malaria cases, 3 vs. 16 arbovirus infections, and 6 vs. 14 GI syndromes. All malaria cases in prospective enrollees were in military subjects. Post-travel enrollees accounted for 1 acute human immunodeficiency virus and 3 rickettsial infections.

Conclusion

A majority of our travelers experienced symptoms during travel. Post-travel diagnoses, although uncommon, emphasize needed improvements in the application of known risk mitigation strategies. Our findings can help clinicians optimize their pretravel counseling by focusing education on self-treatment of common travel-related symptoms, prevention of GI, arthropod-borne, and respiratory illness, and emphasizing symptoms that should prompt medical care.

Disclosures

All authors: No reported disclosures.
755. Outpatient Parenteral Antimicrobial Therapy Program Evaluation within a Large Veterans Affairs Healthcare System
Authors: Kent Michael , Kouma Marcus , Tomasz Jodlowski , Cutrell James B , Cutrell James B
Published: October 2019

Background

Outpatient parenteral antimicrobial therapy (OPAT) allows safe delivery of IV antibiotics in ambulatory settings to facilitate hospital discharge. Within the Veterans Affairs (VA) system, OPAT programs face the unique challenges of large geographic coverage areas and referrals for veterans from non-VA hospitals.

Methods

Patients enrolled in the VA North Texas Health Care System OPAT program during fiscal years 2016 to 2018 had data collected on demographics, comorbidities, OPAT indications, antimicrobials used, pharmacist interventions, and complications during therapy. Data were collected from retrospective chart review as a quality improvement project. All enrolled OPAT patients required either an inpatient infectious disease (ID) consult or, for patients from non-VA facilities, required medical records review and telephone consultation with approval by a VA ID clinician. A third-party infusion company provided all medications and line care. Weekly laboratory monitoring and follow-up telephone visits were conducted by ID-trained pharmacists.

Results

During the evaluation period, 485 unique OPAT encounters (425 patients) were completed, with 164 patients (33%) directly admitted to OPAT upon referral from non-VA hospitals. Most common OPAT indications were osteomyelitis/diabetic foot infections (40.4%), bacteremia (17.3%), prosthetic joint infections/septic arthritis (12.4%), and urinary/intrabdominal infections (11.7%). Following standardization of pharmacist documentation, the volume and consistency of documented notes and interventions increased. Readmission rates while on therapy were similar, ranging from 13.4% to 13.7% each year. Patient demographics and OPAT outcomes demonstrated steady growth in the program (Table 1) with low rates of complications on therapy (Table 2). The program served patients in 35 counties and 158 zip codes across a broad geographic region in North Texas and southern Oklahoma (Figure 1). The most commonly used antibiotics are shown in Figure 2.

Conclusion

Our program has demonstrated the ability to safely and effectively provide OPAT across a large geographic region from a central location. ID-trained clinical pharmacists are critical to the care coordination and safety monitoring of OPAT in this unique setting.

Disclosures

All authors: No reported disclosures.
781. Nurse-Driven Time-of-Triage Sepsis Screening Tool Improves Timely Intervention in Ambulatory Emergency Department (ED) Patients with Suspected Sepsis
Authors: Howland Catalina , Chang Arthur , Selvanayagam Stephen , Kim Stacy , Bounthavong Mark , Catipon Nora , Rambaran Kerry , Yoon Christine , Sinha Rakesh , Ha David
Published: October 2019

Background

Sepsis is a potentially life-threatening, systemic complication of infection. Rapid intervention is critical to reduce morbidity and mortality; however, early recognition of sepsis is challenging due to a highly variable and nonspecific presentation. Recognition is particularly problematic in ambulatory (walk-in) patients who receive minimal to no medical attention prior to ED presentation. There is limited literature addressing sepsis intervention among the ambulatory population in the ED. Our organization has employed an electronic, nurse-driven sepsis screening tool into the triage process for all ambulatory patients who present to the ED.

Methods

This was a retrospective, quasi-experimental study conducted from November 2015 to May 2018 in three consecutive timeframes: pre-implementation (12 months), implementation (7 months), and post-implementation (12 months). Adult ambulatory ED patients were included if they had a coded diagnosis of sepsis, septic shock, or an infectious syndrome, had fever or hypothermia and systemic inflammatory response syndrome signs on presentation. The primary outcome measure was hourly time interval to antibiotic administration from time of ED registration.

Results

A total of 902 patients were included with 286, 208, and 408 patients in the pre-implementation, implementation and post-implementation cohorts, respectively. Baseline characteristics including comorbid conditions and infection source were similar between cohorts. The primary outcome of hourly time interval to antibiotic administration was significantly different (P = 0.044) between the three cohorts with the most substantial increase in administration specifically in the less than 1-hour interval. Between the pre-implementation, implementation, and post-implementation cohorts, significant decreases were observed in mean time to fluids (3.6, 3.0, and 2.5 hours, respectively, P = 0.003) and average length of stay (5.5, 5.8, and 4.2 days, respectively, P < 0.001) and a significant increase was observed in ED sepsis alert activations (26%, 48%, 51%, respectively, P < 0.001).

Conclusion

A nurse-driven electronic time-of-triage sepsis screening tool improved timely recognition and intervention in ambulatory ED patients with suspected sepsis.

Disclosures

All authors: No reported disclosures.
787. Improving ED Sepsis Care
Authors: Sloan William A , Kemmerly Sandra , Jain Surma , Shreves Ashley , Dauterive Kirsten
Published: October 2019

Background

Sepsis is a severe, life-threatening illness in response to an infection from the body’s immune system. Sepsis can progress rapidly, causing hypotension, organ failure, and death. Mortality from severe forms of sepsis and septic shock range between 20% to 50%, but with appropriate and timely treatment, mortality decreases to 5%-10%.

Before completing the Improving ED Sepsis Care project, there was only 18% and 12% compliance with the CMS 3 and 6-hour core measure bundles, respectively, within the Ochsner Main Campus Emergency Department.

Methods

A multi-disciplinary team followed Lean methodology for process improvement. The failure to identify sepsis patients as high acuity in triage was a key root causes identified. There was also a need to simplify the process and workflow to facilitate antibiotic administration and resuscitation.

A triage tool called “Code Sepsis” was created to allow for early identification of severe forms of sepsis, to ensure an appropriate ESI score, and to dedicate immediate attention from staff. A provider order set was created that included the necessary lab work standardized antibiotics.

Results

3-hour bundle compliance increased from 18% to 90% following the intervention. Improvements were noted in time to antibiotic administration, volume resuscitation, and appropriate initiation of vasopressors. The addition of the “Code Sepsis” triage tool decreased the median time to antibiotic administration from 1 hour 53 minutes to 33 minutes. Improvements were also noted in the elements of the 6-hour “perfect care” bundle; however, compliance rates were lower than goal.

Conclusion

Early identification and appropriate treatment of sepsis is key to improving survival. Despite widespread knowledge early treatment, many EDs struggle to meet the CMS sepsis care bundles. Utilizing the Lean framework allowed the improvement team to breakdown a multi-siloed, interdependent care process.

Disclosures

All authors: No reported disclosures.
993. Pharmacist-driven Penicillin Allergy Assessment in the Emergency Department – Antimicrobial Stewardship at the Point of Prescription
Authors: Campbell Samantha , Srinivas Pavithra , Hauler Gregory , Immler Ellen , Seiti Susan , Dandache Patricia
Published: October 2019

Background

Β-lactam allergy assessment is endorsed by the IDSA as an antimicrobial stewardship tool to enhance the use of first-line agents. We evaluated the impact of pharmacist-driven penicillin (PCN) allergy assessment at the point of prescription on antibiotic use in our emergency department (ED).

Methods

Retrospective, quasi-experimental study of adult patients with a PCN allergy receiving antibiotics at a community hospital ED. The intervention comprised an ED pharmacist performing allergy assessment and discussing therapy options with providers at the point of prescription. The primary outcome was to evaluate impact on guideline-preferred antibiotic prescription in the ED pre-intervention (March 1, 2017–August 31, 2017) vs. post-intervention (March 1, 2018–August 31, 2018). Secondary outcomes included types of reported allergic reactions, safety of allergy assessment process, and impact on downstream antibiotic use.

Results

Overall, 381 patients were evaluated (256 pre-intervention, 125 post-intervention). The median age was similar between groups and 85% of patients presented to the ED from the community. Most common infectious syndromes encountered in the ED were UTIs (35%), respiratory tract infections (25%), and skin/soft-tissue infections (18%). The proportion of guideline-preferred antibiotic prescriptions in the ED increased from 37% pre to 44% post (P = 0.171). Proportion of fluoroquinolone (FQ) prescriptions in the ED was reduced from 37.5% pre to 26% post (P = 0.021). Proportion of cephalosporin prescriptions increased from 26% pre to 42% post (P = 0.002). Types of reported allergic reactions were similar between groups and 55% of patients had tolerated a β-lactam agent since the listed allergy. Overall, 70% of patients were hospitalized from the ED. Similar trends in antibiotic use were observed at admission – decreased FQs (38% pre vs. 27% post, P = 0.059), increased cephalosporins (24% pre vs. 38.4% post, P = 0.021). Two patients (1.6%) experienced a nonsevere reaction within 24 hours of β-lactam administration post-allergy assessment.

Conclusion

Pharmacist-driven PCN allergy assessment at the point of prescription in the ED was safe and effective at improving the use of guideline-preferred antibiotics and reducing FQ use.

Disclosures

All authors: No reported disclosures.
998. Challenging Penicillin Allergies: Pharmacist led program in a community hospital
Authors: Patel Radha , Saccone Nicole , Stock Kent , Utley Sara , Bouknight Dawn
Published: October 2019

Background

Penicillin (PCN) allergy has been approximated to be reported in 10% of the United States population. Studies utilizing PCN skin testing have demonstrated that less than 1% of the population have a true PCN allergy. With increasing data on the negative consequences associated with a PCN allergy diagnosis, correctly identifying these patients is imperative. PCN skin testing has resulted in high rates of penicillin de-labeling; however, there are limited data evaluating the impact of a pharmacist-led PCN allergy evaluation with removal through utilization of oral challenges. The aim of this study was to utilize pharmacists to correctly identify those who are not penicillin-allergic to help decrease unnecessary use of broad-spectrum antibiotics and to optimize therapy.

Methods

This is a single-center, prospective review looking at a 10-month period of a pharmacist-led de-labeling project of patients with a PCN allergy. The electronic medical record system and decision support software were used to identify eligible patients. Adults ≥18 years of age with a PCN allergy were included. During the evaluation, pharmacists utilized a series of standardized questions which was reviewed with the infectious disease physician to classify the patient’s allergy. Based on classification a protocol was followed that either led to the patient retaining their allergy, or removal. The primary objective is to evaluate the rate of removal of penicillin allergies. Secondary objectives reviewed removal rate of patients on active antibiotics, and evaluate how many were switched to β-lactam.

Results

A total of 492 patients with PCN allergies were interviewed by a pharmacist. Pharmacist de-labeled 99/492 (20%) PCN allergies. Of those patients, 23% were removed through oral challenge and 76% through patient history. There were 175 patients on active antibiotics and 52/175 (30%) had their allergies removed. Finally, 36/52 (69%) were switched to a β-lactam.

Conclusion

A pharmacist-led penicillin allergy de-labeling project is beneficial in reducing PCN allergies when skin testing is unavailable in community hospitals. As seen about 1 in 5 patients were able to remove their allergy through allergy evaluation or oral challenge. Furthermore, pharmacist evaluation of the allergy not only helped remove the allergy but also resulted in the most appropriate antibiotic.

Disclosures

All authors: No reported disclosures.
1000. The Impact of Pharmacy Students Performing Penicillin Allergy Reconciliation in a Community Health System
Authors: Jones Bruce M , Gamble Kelly , Sizemore Summer , Bland Christopher M
Published: October 2019

Background

Antimicrobial stewardship programs (ASP) play an important role in the assessment of patients with a reported history of penicillin allergy. Full-time pharmacists performing antimicrobial stewardship face many time barriers and limited resources to interviewing and investigating self-reported allergies. Pharmacy students on Advanced Pharmacy Practice Experience (APPE) rotations during their fourth year can potentially play an important role in this evaluation if properly trained, but data are limited. This study evaluated APPE student interventions on hospital inpatients self-reporting a penicillin allergy.

Methods

This quasi-experimental study assessed patients with a self-reported penicillin allergy who were interviewed by APPE students from October 2018 through March 2019. Students on a 5-week infectious diseases rotation were trained in allergy assessment and interview skills by their preceptor and given a daily list of all inpatients with a self-reported penicillin allergy. After reviewing patients with the preceptor, the electronic health record was updated with specifics of the allergy, including the range, reaction, and any β-lactams tolerated since. Interventions included penicillin re-challenge, graded challenge, penicillin skin testing, desensitization, or removal or the allergy. The primary outcome was interventions attributed to APPE student patient interviews.

Results

A total of 12 APPE students participated in the study. Reported reactions ranged from mild allergies (itching, rash) or adverse reactions (nausea, vomiting) to intermediate or severe allergies (hives, anaphylaxis). For the primary outcome there were 162 interventions performed, with 154 verbal, 2 re-challenges, and 6 skin tests. For the verbal interventions, 95 had their allergy updated, 34 removed, and 33 confirmed. None of the 8 patients who were skin tested or re-challenged had a subsequent reaction.

Conclusion

Pharmacy students can expand ASP allergy reconciliation services for patients with penicillin allergies in settings with limited resources. After proper training, students were effective in multiple aspects of allergy reconciliation with a significant number able to have their penicillin allergy removed.

Disclosures

All authors: No reported disclosures.
1001. Feasibility and Outcomes of a Pre-Transplant Antibiotic Allergy Evaluation Program for Allogeneic Hematopoietic Cell Transplant (HCT) Candidates
Authors: Liu Catherine , Krantz Elizabeth M , Stohs Erica J , Imlay Hannah , Rampur Lahari , Sweet Ania , Zier Jacqlynn C , Pergam Steven A , Mielcarek Marco , Henderson William , Altman Matthew
Published: October 2019

Background

Antibiotic allergies impact the management of hematopoietic cell transplant (HCT) patients who are often prescribed antibiotics for infection prophylaxis and treatment. We evaluated the feasibility and outcomes of an antibiotic allergy evaluation program prior to allogeneic HCT.

Methods

In August 2017, we implemented a program to expedite allergy clinic referrals for adult allogeneic HCT candidates who reported an antibiotic allergy at their initial pre-transplant evaluation visit (PTEV). Allergy labels and clinical data including outcomes of allergy evaluation were prospectively collected for patients with PTEVs between 8/10/17 and November 15/18. The use of selected antibiotics was collected in the 100 days following HCT among patients with a reported β-lactam allergy (BLA). Choice of prophylactic agent for Pneumocystis jiroveci among patients with reported sulfa allergies was assessed among HCT recipients after engraftment.

Results

Of 276 allogeneic HCT candidates, 109 (39.5%) reported >= 1 antibiotic allergy (Table 1). Of the 109, 69 (63%) were referred for allergy evaluation; 83% (57/69) of those referred were evaluated at a median of 14 days after PTEV, and a median of 18 days before transplant. Among evaluated patients, 45 (79%) had >= 1 antibiotic allergy de-labeled including 74% (28/38) of those with BLA (Figure 1). Of the 10 patients whose BLAs could not be delabeled, 1 had a possible immediate IgE-mediated reaction, 5 had a delayed type IV hypersensitivity, and 4 had other reactions or required additional testing. Post-transplant antibiotic use among evaluated vs. nonevaluated patients reporting BLA is shown in Figure 2. Among 31 patients with reported sulfa allergies who underwent HCT, those who were evaluated received TMP-SMX rather than alternative prophylaxis more often (48%; 11/23) than those who were not evaluated (25%; 2/8). 10 (43%) of 23 evaluated patients were delabeled; 7 of 10 delabeled patients received TMP-SMX.

Conclusion

Antibiotic allergies are frequently reported among HCT candidates. Pre-transplant antibiotic allergy evaluation was feasible, led to de-labeling of the majority of reported allergies, and may alter antibiotic prescribing and increase the use of preferred agents following transplant.

Disclosures

All authors: No reported disclosures.
1015. Antibiotic use and indications in a community sample of adults in Wisconsin
Authors: Schletzbaum Maria , Safdar Nasia , Shirley Daniel , LeCaire Tamara , Malecki Kristen , Peppard Paul , Sethi Ajay
Published: October 2019

Background

There is significant inappropriate and overuse of antibiotics in the United States. We describe patterns of self-reported actual use of antibiotics and indications in Wisconsin adults.

Methods

The Survey of the Health of Wisconsin (SHOW) is an annual health study of a wide range of health determinants and outcomes among a population-based sample of residents with targeted recruitment of underrepresented minorities. In 2016, SHOW initiated WARRIOR (Winning the War on Antibiotic Resistance), an ancillary study that assessed actual antibiotic use and indications among adults. Antibiotics were grouped by pharmacologic class, and indications were grouped into clinical categories. Descriptive statistics and logistic regression were used to examine factors associated with antibiotic use.

Results

Overall, 756 adults [435 female and 321 male; mean (SD) age=54.2 (16.5)] were recruited, and 256 (33.5%) reported antibiotic use in the past year. Females (OR=1.87, 95% CI: 1.29, 2.70), people with current comorbidities or history of certain health conditions (OR=2.04, 95% CI: 1.23, 3.39), and people with a mental health or developmental condition (OR=1.93, 95% CI: 1.33, 281) were statistically significantly more likely to report antibiotic use. BMI (kg/m2) was slightly higher among antibiotic users (31.2) than nonusers (29.8; P = 0.064). Diabetes, heavy drinking, and smoking history were not correlated with antibiotic use.

Top antibiotic classes used were penicillins (31%), macrolides (12%), first-generation cephalosporins (9%), tetracyclines (8%), quinolones (7%), and nitroimidazoles (3%). Top indications reported were upper respiratory infection (URI; 32.3%), dental condition or procedure (21.0%), surgery (12.6%), lower respiratory infection (11%), urinary tract, bladder, or kidney infection (7%), skin or soft-tissue infection (6%), and insect bite or insect-borne infection (6%).

Conclusion

Antibiotic use varies among Wisconsin adults, and certain groups are more likely to have used antibiotics in the last year. The top two reported indications for antibiotics were categories with known high rates of inappropriate (e.g., URI) and prophylactic (i.e., dental) prescribing. Further studies are needed to determine specific opportunities to reduce antibiotic use in Wisconsin.

Disclosures

All authors: No reported disclosures.
1025. Inappropriate Aztreonam Usage – Antimicrobial Stewardship Strikes Back
Authors: Smith Brandon J , Batykefer Bridget , Andrzejewski Christina , Yassin Mohamed , Arbulu Ricardo
Published: October 2019

Background

Several studies have demonstrated that patients with reportedly β-lactam allergies (BLA) receive less efficacious and more toxic alternative antibiotics. A previous study at our institution utilizing aztreonam as a surrogate marker for BLA demonstrated nearly 50% of patients receiving aztreonam had previously tolerated an alternative β-lactam (BL). In response to those results, our Antimicrobial Stewardship Program (ASP) provided dedicated hospitalist, medical resident and pharmacist education on appropriate utilization of aztreonam and BLA. Additionally, members of the ASP team began receiving real-time clinical surveillance alerts for all aztreonam orders.

Methods

A retrospective chart review of inpatients >18 years old who received at least one dose of aztreonam between July 1, 2018 – December 31, 2018. Patients were excluded if they did not have a documented BLA or if they received aztreonam as de-escalation therapy. Cost of aztreonam therapy was compared with the cost of alternative BL agents based on prior and subsequently tolerated classes of BLs. Comparator agents included: piperacillin/tazobactam (penicillin), cefepime (cephalosporin) and meropenem (carbapenem). Comparisons of total number of aztreonam patients and doses, cost of aztreonam, and cost of alternative therapy were compared with the index population from 2017

Results

Similar to our prior study, 43.7% (48.5% in 2017) had prior BL tolerance with an additional 31.3% (19.4% in 2017) demonstrated subsequent BL tolerance following aztreonam administration. Following the ASP interventions, orders, doses and cost of aztreonam was reduced. Forty-eight patients during the 6-month period received aztreonam, a 26.7% reduction. There was a 38.5% reduction in the number of aztreonam doses (P = 0.001), which yielded a cost savings of $14,067.67 (extrapolated to 1 year). Median aztreonam cost in 2017 $382.40 vs. $191.20 in 2018 (P = 0.004). In 2018, 41.7% of patient’s allergy profiles were appropriately updated compared with 3.3% in 2017.

Conclusion

Our study demonstrates that ASP interventions including increased education, allergy documentation and clinical surveillance alerts targeted at reducing aztreonam utilization can reduce pharmaceutical expenditures.

Disclosures

All authors: No reported disclosures.
1027. Vancomycin Use in Community-Acquired Pneumonia: Assessing Inappropriate Therapy
Authors: Shan Timothy , Gore Sara J , McCracken Caitlin M , Tallman Gregory B , Holmer Haley K , Bearden David T , McGregor Jessina C
Published: October 2019

Background

Current Infectious Disease Society of America guidelines recommend anti-methicillin-resistant Staphylococcus aureus(MRSA) agents for treatment of community-acquired pneumonia (CAP) only in specific high-risk patients. There are limited data on duration of vancomycin use that is appropriate in hospitalized patients with CAP. The objective of this study was to evaluate the use of vancomycin for CAP among inpatients.

Methods

We conducted a retrospective cohort study of inpatients at Oregon Health and Science University Hospital from August 1st, 2017 to July 31st, 2018 who received IV vancomycin and had a pneumonia encounter ICD-9 diagnosis code. Patients with hospital or ventilator-associated pneumonia were excluded. Appropriate therapy was defined as empiric therapy with known risk-factors, concordant therapy with no de-escalation option, or concurrent sepsis or febrile neutropenia. Vancomycin appropriateness was assessed based on medical history and microbiology for both empiric and definitive therapy. We characterized patients receiving inappropriate therapy and calculated the proportion of inappropriate days of therapy (DOT).

Results

We identified 52 patients with CAP who were treated with vancomycin for a median of 2 DOT (Interquartile Range (IQR): 1–3). Approximately 21% (11/52) of patients had risk factors warranting vancomycin empiric therapy and 42% (22/52) had concurrent sepsis. Nine CAP patients received inappropriate courses of vancomycin, median of 1 day (IQR: 1–2.25) of inappropriate therapy. The most common reason for classifying use as inappropriate was a positive culture for organisms other than MRSA. Patients receiving inappropriate therapy were more frequently transferred from another hospital (44% vs. 30%, P = 0.22). Overall, 16% (20/125) of vancomycin DOT were inappropriate.

Conclusion

In our study,CAP patients accounted for a small number of pneumonia patients who received vancomycin. The median inappropriate DOT was relatively short, possibly indicating that identification and de-escalation was performed quickly. Further work is required to determine the impact of these findings on patients.

Disclosures

All authors: No reported disclosures.
1030. Analysis of a Novel Mortality Prediction Rule for Organizing and Guiding Antimicrobial Stewardship Team Activities
Authors: Collins Curtis D , Scheidel Caleb , Dietzel Christopher J , Leeman Lauren R , Morrin Cheryl A , Malani Anurag N
Published: October 2019

Background

Antimicrobial stewardship team (AST) surveillance at our hospital is facilitated by an internally-developed database. In 2013, the database was expanded to incorporate a validated internally-developed prediction rule for patient mortality within 30 days of hospital admission. AST prospective audit and feedback expanded to include all antimicrobials prescribed in patients with the highest risk for mortality determined by risk score. This study describes the impact of an expanded AST review in patients at the highest risk for mortality.

Methods

This retrospective, observational study analyzed all adult patients with the highest mortality risk score who received antimicrobials not historically captured via AST review. Patients were identified through administrative and AST databases. Study periods were defined as 2011 – Q3 2013 (historical group) and Q4 2013 – 2018 (intervention group). Primary and secondary outcomes were assessed for confounders including demographic data and infection-related diagnoses. Outcomes were assessed using both unweighted and propensity score weighted versions of the t-test or Wilcoxon rank-sum test for continuous variables and the chi-squared test or Fisher’s Exact test for discrete variables.

Results

A total of 2,852 and 5,460 patients were included in the historical and intervention groups, respectively. After adjusting for demographic and clinical characteristics, there were significant reductions in median antimicrobial duration (5 vs. 4, P = 0.002), antimicrobial days of therapy (7 vs. 7, P = 0.001), length of stay (LOS) (6 vs. 5 days, P = 0.001), intensive care unit (ICU) LOS (3 vs. 2 days, P < 0.001), and total hospital cost ($11,017 vs. $9,134, P < 0.001) in the intervention cohort. There were no significant differences observed in 30-day mortality or 30-day readmissions. Secondary analyses showed significant decreases in fluroquinolone and intravenous vancomycin utilization between cohorts.

Conclusion

Reductions in antimicrobial use, inpatient and ICU length of stay, and total hospital costs were observed in a cohort of patients following incorporation of a novel mortality prediction rule to guide AST surveillance.

Disclosures

All authors: No reported disclosures.