bluuebunny/crossref_metadata_2025 huggingface dataset:
699. Hepatobiliary Safety in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results
Authors: Lewis James H , Das Anita F , Stein Daniel , Gelone Steven P , Schranz Jennifer
Published: October 2019

Background

LEF efficacy and safety were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the hepatobiliary safety of LEF based on 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 600 mg q12h for 5 days or oral MOX 400mg q24h for 7 days. Exclusion criteria included infection with HBV/HCV, acute hepatitis, cirrhosis, AST or ALT >5xULN, total bilirubin >3xULN (unless Gilbert’s disease), AST or ALT >3xULN and total bilirubin >2xULN, and manifestation of end-stage liver disease. Hepatic safety was assessed from baseline (BL) and multiple post-BL blood samples using a central laboratory, TEAEs, and expert consultant adjudication. Pooled analyses included all randomized/treated patients (safety population).

Results

Of 1282 randomized/treated patients, 1251 had BL and post-BL hepatobiliary data (table). Post-BL distribution of ALT/AST was generally similar for both groups, although ALT >AST in the absence of muscle injury or alcohol use. Overall, rates of patients experiencing an increase in ALT/AST >3xULN, ALP >2xULN, or total bilirubin >1.5xULN were low (table). Patients with elevated vs. normal BL transaminases (TAs) were more likely to have post-BL elevations >3xULN, but the vast majority remained <5xULN. Among patients with ALT >5xULN, peak increases were generally seen in the first week after the first LEF dose and declined to within/near normal levels by late follow-up (day 28); for MOX, time to peak ALT was less consistent (figure). No LEF pt and 1 MOX pt met laboratory criteria for Hy’s Law. Elevations in TAs were reversible, with no evidence of chronic injury. The LEF injury pattern was predominantly hepatocellular (50.0%)/mixed (40.0%), with no apparent gender, age, or ethnic predominance. TEAEs in the hepatobiliary disorders system organ class were reported in 6 (0.9%) LEF patients and 6 (0.9%) MOX patients, with similar levels seen in patients with elevated BL TAs. There were no symptomatic patients, severe disease, or evidence of hypersensitivity.

Conclusion

Low incidences of hepatobiliary parameter elevations and TEAEs were observed, with no apparent differences between LEF and MOX.

Disclosures

All authors: No reported disclosures.
702. Hepatic Safety Among Patients Treated with Anti-Fungal Triazole Agent Posaconazole: Characterization of Adverse events in a Manufacturer’s Safety Database
Authors: Zhou Yun-Ping , O’Flynn Rose , Waskin Hetty , Leong Ronald W , Straus Walter
Published: October 2019

Background

Second-generation triazoles including posaconazole are highly efficacious for the prophylaxis and salvage treatment of life-threatening invasive fungal diseases. All triazoles have been associated with hepatic adverse events (AEs), which may affect their clinical use; however, risk factors for those AEs are poorly defined.

Methods

Reports of hepatobiliary AEs for posaconazole from clinical trials and post-market use in our company’s global safety database were reviewed to characterize concomitant medical conditions and drug exposure.

Results

As of 2018, 444 cases of hepatic AEs were reported; 139 (31%) led to discontinuation of posaconazole. Most hepatic AEs had a time to onset >20 days (55.5%). The most frequent AEs reported (per Medical Dictionary for Regulatory Activities) were: Hyperbilirubinaemia (17%); Hepatotoxicity (13.5%); Hepatic function abnormal (11.5%); and Hepatocellular injury (11.3%). Most patients were adults (18–64 years old) (65%). Hematological malignancy (128 cases, 29%) and hematopoietic stem cell transplant (91 cases, 20%) were leading concurrent medical conditions. Notably, 75% of the cases reported exposure to other drugs (often multiple ones) with known risks for drug-induced liver injury (DILI, e.g., acetaminophen, cytarabine, cyclosporine). Among 139 cases in which posaconazole treatment was discontinued due to hepatic AEs, 6 of the 20 most frequently used co-medications (used by >4.5% of the cases) were classified by the FDA in its DILIRank as “Most-DILI-Concern” (resulting in drug withdrawal, or prominent labeling for severe DILI risk in boxed warning or warnings and precautions), and 7 were “Less-DILI-concern” drugs (DILI risk language in warnings and precautions or adverse reactions). Similarly, of the top 35 concomitant medications for the entire group, 9 are classified as “Most-DILI-Concern” and 12 are “Less-DILI Concern” drugs.

Conclusion

The use of concomitant medications with known risks for hepatic injury appears to be an important contributor to the development of hepatotoxicity in patients treated with posaconazole. Co-administration of these drugs with anti-fungal triazole agents such as posaconazole, when needed, will continue to be carefully monitored.

Disclosures

All authors: No reported disclosures.
717. Lefamulin (LEF) vs. Moxifloxacin (MOX) in Patients With Community-Acquired Bacterial Pneumonia (CABP) at Risk for Poor Efficacy or Safety Outcomes: Pooled Subgroup Analyses From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Noninferiority Clinical Trials
Authors: Schranz Jennifer , Goldberg Lisa , Das Anita F , Alexander Elizabeth , Moran Gregory J , Sandrock Christian , Shorr Andrew F , Gelone Steven P
Published: October 2019

Background

In the United States, CABP is the second most common cause of hospitalization and a leading cause of infectious death. Patients with chronic obstructive pulmonary disease (COPD)/asthma or diabetes are at risk for CABP and associated mortality. Similarly, patients with underlying cardiac or liver disease are at risk for potential cardiac or liver toxicities, respectively, associated with CABP antimicrobials, and patients aged ≥65 years are at risk for both efficacy/safety concerns. We report pooled efficacy/safety outcomes in at-risk subgroups from the LEAP 1 and 2 phase 3 trials.

Methods

In LEAP 1, patients with CABP (PORT III–V) received IV LEF 150 mg q12h for 5–7 days or MOX 400mg q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, patients with CABP (PORT II–IV) received oral LEF 600 mg q12h for 5 days or MOX 400 mg q24h for 7 days. Both studies assessed early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Pooled analyses used a 10% noninferiority margin. Safety was assessed in all randomized and treated patients.

Results

1289 ITT patients were randomized to LEF (n = 646) or MOX (n = 643); of whom, 297 (23.0%) were aged 65–74 years and 220 (17.1%) were ≥75 years; 232 patients (18.0%) had COPD/asthma and 168 (13.0%) had diabetes mellitus (DM). At baseline, 501 patients (38.9%) had history of hypertension, 73 (5.7%) had history of arrhythmia, and 263 (20.4%) had transaminitis. The figure shows efficacy by age and in COPD/asthma and DM patients. Treatment-emergent adverse events, electrocardiogram assessments, and laboratory results in patients at risk for cardiac and hepatic safety concerns are shown in Tables 1 and 2.

Conclusion

In pooled analyses of LEAP 1 and 2, LEF efficacy was high and similar to MOX in patients at risk of efficacy concerns and LEF showed a safety profile similar to that of MOX in patients at risk of safety concerns. LEF is a promising new option for IV/oral monotherapy of CABP in patients at risk of poor outcomes due to CABP or to antimicrobial therapy for CABP.

Disclosures

All authors: No reported disclosures.
736. The Use of Bacteriophages to Inhibit Different Strains of Vancomycin-Resistant or Susceptible Enterococci
Authors: El Haddad Lynn , Harb Cynthia P , Stibich Mark , Chemaly Roy F , Chemaly Roy F
Published: October 2019

Background

Vancomycin-resistant Enterococci (VRE) is a well-known infectious complication among immunocompromised patients, especially hematopoietic cell transplant (HCT) recipients. VRE colonization of the gastrointestinal tract could be associated with VRE bacteremia and worse outcomes in HCT recipients. The use of systemic antibiotics to eradicate VRE colonization is highly discouraged because of the lack of efficacy, the rapid onset of antibiotic resistance, and the disruption of the normal microbiota. Bacteriophages (phages) may constitute a good alternative to antibiotics to eliminate specific pathogens without disrupting the patient’s normal microbiota.

Methods

Sewage samples were collected from the City of Houston for phages isolation. Samples were centrifuged, filtered and exposed to several targeted VRE host strains. After several amplification, the final filtrate was titrated and checked for the presence of VRE-specific phages. Isolated phages were observed under electron microscopy and were tested against multiple VRE strains isolated from different sources including patients’ stool samples, patients’ room environment, sewage samples, clinical isolates of daptomycin-resistant VRE strains or vancomycin-susceptible Enterococcus faecium (VSEF) and Enterococcus faecalis (VSEf) strains.

Results

Four VRE-specific phages were isolated from sewage samples (MDA1, MDA2, MDA3, and MDA4). All phages belong to the Caudovirales order. Phage MDA1 belongs to the Podoviridae family, phage MDA2 is a Siphoviridae, whereas MDA3 and MDA4 belong to the Myoviridae family (Figure 1A). All phages were lytic and were able to inhibit at least four VRE strains and only MDA1 had activity against VSEF and MDA4 against VSEf. The efficacy of these lytic phages complemented one another as the combination of these four phages inhibited all different VRE strains (Figure 1B).

Conclusion

Our results highlight the feasibility and the potential success of these phages in inhibiting VRE in vitro. These VRE-specific phage cocktails may be used in future studies to reduce VRE colonization and subsequent infections in HCT recipients.

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.
744. Antifungal De-escalation Strategy in ICU Patients: Clinical Success and Cost Savings
Authors: magira Eleni , Kalogianni Athanasia-Aikaterini , Zakynthinos Spyros
Published: October 2019

Background

The incidence of Candida spp infections in critically ill patients is increasing. Initial broad-spectrum empiric antifungal agents (e.g., echinocandins), followed by immediate switching to fluconazole if isolates are fluconazole sensitive could be a low-cost de-escalation strategy. The aim of this study was to evaluate the budget impact of the de-escalation strategy using fungostatin in ICU patients and clinical effectiveness.

Methods

This prospective study was conducted in a 30-bed mixed ICU, from January 2015 through January 2017. Critically ill patients with invasive candidiasis were placed on initial empiric broad-spectrum antifungal agents either on echinocandins or liposomal amphoteric B. De-escalation to fungostatin strategy at day 3 vs. patients without de-escalation were compared. Clinical characteristics and the presence of clinical success by the eighth-day of treatment and 28-day outcome were evaluated. Clinical success was defined as the complete eradication of Candida spp. in blood cultures. Economic outcomes included budget impact was also evaluated.

Results

Forty-seven ICU patients with documented invasive candidemia enrolled and received empiric broad-spectrum antifungal agents with either echinocandins or liposomal amphotericin B. Of those, 22 (47%) were eligible for de-escalation at day 3 to fungostatin based on susceptibility test for fungi. Specific Candida species isolated in the de-escalation group were C. albicans (14, 64%), and non-C. albicans (8, 36%). Interestingly 6/22 (27%) invasive candidemia de-escalated cases relapsed by day 8 of initiation of the empiric therapy, vs. 2/25 (8%) of the control group (P = 0.12). Survival rates at day 28 were not statistically significant among the two groups [15/22 (68%) vs. 11/25 (44%), P = 0.12]. The budget impact of using de-escalation was greater, producing cost savings of €3,200 per patient but did not translate into significant clinical and mycological success.

Conclusion

Critically ill patients who had received empiric antifungal therapy for documented candidemia and underwent de-escalation from echinocandins or liposomal ambisome B to fungostatin had a potential economic cost–benefit but did not associate with significantly improved clinical success rates.

Disclosures

All authors: No reported disclosures.
749. Wide Variation in the Use of External Cooling Blankets Among Adult Intensive Care Unit Nurses for Fever
Authors: Sorge John , Levine Zachary , Szpunar Susan M , Johnson Leonard B
Published: October 2019

Background

There are limited data on whether external cooling blankets (ECBs) are beneficial in the treatment of fever that is not related to malignant hyperthermia (MH). There are no established national guidelines for the use of ECBs for fevers other than for MH. Thus, there may be a wide variation in nursing practice related to their use.

Methods

We performed a cross-sectional survey of adult intensive care unit (ICU) nurses at our hospital, using SurveyMonkeyTM, to evaluate nursing practices related to the use of ECBs in febrile patients other than MH. Data collected from the survey included years of experience as an ICU nurse, type of ICU, when ECBs are used and temperature of initiation and discontinuation. Continuous variables were compared using Student’s t-test and categorical variables were described as frequency distributions. Data were analyzed using SPSS v. 25.0 and a P-value of 0.05 or less was considered to indicate statistical significance.

Results

We invited 150 nurses to participate in the survey, 61 responded (40.7%). The mean number of years worked in an ICU was 8.6 ± 9.4 years (range: 1–34), 14 (23%) worked in a cardiovascular ICU (CVICU), 22 (36%) worked in a medical ICU (MICU), and 25 (41%) in a surgical ICU (SICU). A total of 58 (95.1%) of nurses reported using ECBs for fever, with 50 (82%) of nurses using ECBs only when other methods failed. MICU nurses (31.8%) were more likely to report using ECBs prior to failed attempt of other anti-pyrexia methods than SICU (16%) and CVICU (0.0%) nurses. There was no association between initiation and termination of ECB use by ICU type, years of nursing experience or a given range of temperature values.

Conclusion

There was a wide variation of practice among ICU nurses as it relates to the use of ECBs in patients with fevers. Medical ICU nurses tended to use ECBs before failure of other methods compared with other ICU nurses. Standardized protocols should be developed for their use based on existing medical literature. Further studies should be performed to confirm our findings.

Disclosures

All authors: No reported disclosures.
760. Assessment of DEXA Scan Ordering Among Infectious Disease Providers at a Large Tertiary-Care Urban Academic Center in the Midwest
Authors: Kumar Rebecca Nirmal , Masters Mary Clare , Krueger Karen
Published: October 2019

Background

Osteoporosis is compromised bone strength that predisposes to fracture. It can be diagnosed by Dual-energy x-ray absorptiometry (DEXA) measurement of bone mineral density (BMD). Persons with HIV (PWH) are at higher risk for the development of osteoporosis. As such, the HIV Medicine Association’s (HIVMA) primary care guidelines recommend DEXA screening for all HIV-infected postmenopausal women and men aged ≥50 years. The purpose of this study was to asses the frequency of DEXA utilization within a tertiary-care urban academic center in the Midwest and to identify prevalence of osteoporosis.

Methods

A representative sample PWH age ≥50 from our institution’s outpatient infectious disease (ID) clinic were included. All subjects had at least one clinic visit in the last year, were on antiretroviral therapy (ART), and virally suppressed. Unblinded chart review was performed to assess if DEXA was ordered, was DEXA ordered by an ID physician, was DEXA completed, results of DEXA, and whether patients were on a tenofovir disoproxil fumarate (TDF)-containing regimen.

Results

225 charts were reviewed. 186 (83%) patients were men, with a median age of 58 (range of 50–85). DEXA scans were ordered on 39 (17%) patients, 9 (23%) of which were ordered by their ID provider. Twenty-eight (72%) DEXA scans were performed. Of scans completed, 11 (39%) diagnosed osteoporosis, 15 (54%) osteopenia, and 2 (7%) showed normal BMD. Of all charts reviewed, 29 (13%) were on TDF-containing regimens. Of those individuals with diagnosed abnormal BMD (26), only 1 (4%) was on a TDF-containing regimen.

Conclusion

Despite HIVMA’s recommendation for osteoporosis screening in PWH, only 17% of eligible patients with well-controlled HIV in our clinic had been referred for DEXA. Of those who had undergone DEXA screening, nearly all (93%) had abnormal BMD. Further investigation is necessary to explore provider and patient barriers for osteoporosis screening in PWH.

Disclosures

All authors: No reported disclosures.
763. 30 Day Readmission Outcomes in Patients Over 80 Years of Age Enrolled in an Outpatient Parenteral Antibiotic Therapy (OPAT) Program
Authors: Sheridan Kathleen R , Wingfield Joshua , McKibben Lauren , Clouse Natalie
Published: October 2019

Background

OPAT is a well-established model of care for the monitoring of patients requiring long-term IV antibiotics1. We have previously reported a reduction in the 30-day readmission rate to our facility for patients managed in our OPAT program. However, little has been published to date regarding outcomes in OPAT patients over 80 years of age 2–3. Our OPAT program was established in 2013. Patients can be discharged to a facility or home to complete their course of antibiotics.

Methods

We conducted a retrospective chart review of all OPAT patients discharged from our facility from 2015 to 2018. Patients were divided into two groups based on age, <80 (n = 4618) and >80 (n = 562).

Results

Patient demographics are listed in Table 1. The overall 30-day readmission rate for patients older than 80 was 27.8%. For patients over 80 that had a follow-up ID clinic appointment, the 30-day readmission rate decreased to 15.7%. For patients younger than 80, the 30-day readmission rate was 36.0% with a decrease to 16.2% if patients were evaluated in the outpatient clinic. Figure 1. Staphylococcus Aureus was the predominant organism in both age categories. Vancomycin was the most common antibiotic used in both age groups followed by β lactams.

Conclusion

In general, patients aged over 80 years were more likely to be discharged to a facility to complete their antibiotic course than younger patients. These patients also were more likely to have other comorbidities. The 30-day readmission rate in each age group was relatively similar. OPAT in patients over age 80 can have similar 30-day readmission rates as for patients less than 80 years of age

Disclosures

All authors: No reported disclosures.
764. Patients with Substance Use Disorder Discharged from Safety Net Hospital to Skilled Nursing Facility for OPAT: Baseline Characteristics and Clinical Outcomes
Authors: Bird Cylaina , Collins Ryan , Mang Norman , Nijhawan Ank E , Nijhawan Ank E , Bhavan Kavita
Published: October 2019

Background

Self-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) is offered at Parkland Memorial Hospital for uninsured patients requiring an extended course of intravenous (IV) antibiotics to complete treatment at home.1 At Parkland, S-OPAT has been demonstrated to be safe and effective with >70,000 inpatient bed days avoided to date, lower 30-day readmission rates, and significant cost savings.1 Patients with a history of substance use are not eligible for S-OPAT and are discharged to skilled nursing facilities (SNF) to complete IV antibiotic therapy. This study aims to describe clinical outcomes of a patient population with history of substance use discharged to SNF for OPAT.

Methods

The electronic medical record was used to identify patients with substance use discharged to an SNF for OPAT between January 1, 2017 and April 30, 2018. Data were retrospectively reviewed for demographics, substance use history, treatment plan and clinical outcomes.

Results

76 patients with history of substance use were discharged to SNFs for OPAT in the study period. 62% of patients reported non-IV drug use and 38% reported IV drug use (IVDU). The mean age for patients with non-IV drug use was 47 (83% male) vs. 43 years for patients with IVDU (86% male). Of patients with non-IV drug use, 30% reported cocaine use, 11% methamphetamine use and 59% polysubstance use or other. Of patients with IVDU, 38% reported heroin use, 10% methamphetamine use and 52% polysubstance use or other. When comparing outcomes of IVDU vs. non-IV drug use patients, 34% vs. 21% did not complete the prescribed treatment course, 28% vs. 11% left against medical advice (AMA), and 20% vs. 15% were readmitted to the hospital within 30 days.

Conclusion

The majority of patients with substance use, 74%, completed their prescribed IV antibiotic course when sent to an SNF. However, a subset of these patients is at risk for poor clinical outcomes. A greater proportion of patients with prior IVDU compared with patients with prior non-IV drug use left treatment AMA and were readmitted to our hospital within 30 days of discharge. Future efforts to identify patients with substance use disorder who may be appropriate for S-OPAT with integration of addiction medicine services may improve clinical outcomes.

Disclosures

Ank E. Nijhawan, MD, MPH, Gilead Sciences, Inc.: Research Grant.
771. A Quality Improvement Initiative to Reduce 30-days Sepsis-Related Readmissions by Internal Medicine Residents
Authors: Ahmed Mahmoud , Khalid Nida , Ahmad Faran
Published: October 2019

Background

Early readmissions after sepsis treatment are associated with an increased cost of care and poor outcome. Based on nationwide Medicare data, one-third of sepsis survivors get readmitted and wide variation exists between hospitals. Internal medicine residents aimed to determine the most common factors associated with readmission after hospitalization for sepsis at Rochester General Hospital and Unity Hospital in Rochester, New York.

Methods

This quality improvement (QI) project involved a retrospective chart review of 30 days sepsis-related readmissions from January to July 2017. We used Rochester General Hospital and Unity Hospital electronic database of the admitted patients with ICD 9/ICD 10 diagnoses for sepsis at admission or during the hospital course. This data were used for interpreting predominant risk factors for readmission. Based on the specific determinants, a “readmission alert” is being implemented in the electronic medical record to address the specific area of concern with relevant interventions. In the next phase of the performance improvement, six-monthly follow-up retrospective chart review will be carried out to look for the outcome.

Results

Of 2,221 patients admitted with a sepsis diagnosis from January to July 2017, 462 (20.8%) were readmitted within 30 days of discharge of which the majority were older than 65 years (66.4%). 66 (16.6%) patients had a septic shock on readmission and 19.3% died within 30-days of discharge after readmission. In 39.7% of cases, there was no primary care provider(PCP) communication at discharge. In 137 (65.5%) cases, Infectious disease(ID) consults service was not involved in care on initial admission. 242 (60.8%) readmitted patients had a follow-up clinic appointment more than a week after discharge. 12.5% of patients were discharged with IV antibiotics on initial admission, whereas 32.9% of the readmitted patients were not provided visiting nursing services after initial discharge.

Conclusion

Reducing sepsis-related readmission requires a multidisciplinary collaboration of primary care providers, visiting nursing services and infectious disease consult team. This pilot QI project results indicate that early follow-ups are important for reducing readmission.

Disclosures

All authors: No reported disclosures.
783. Infectious complications in IV abusers: a detailed review of hospitalized IV abusers
Authors: Gonzalez Jaime , Diago-Navarro Elizabeth , Ameen Eve , Azab Nancy , Milla Lucia , Fries Bettina C
Published: October 2019

Background

With 337 heroin-related deaths between 2009 and 2013, Suffolk County reported more such deaths than any other county in New York State. Suffolk County’s population of 1.5 million is larger than that of some states. Compared with the rest of New York State, median annual household income is the third highest of New York’s 62 counties and the income gap between socioeconomic classes is smaller.

Methods

Detailed retrospective chart review was performed on admitted patients to Stony Brook University Hospital (SBUH) from November 2015 to October 2018 with active IV drug abuse and infection. Demographics, drug use characteristics, microbiology, co-morbidities, and outcome were assessed.

Results

198 active IV heroin users were admitted with a complicated infection during this time frame. Most patients were Caucasian (94%) and more were male (64%). The median age was 33 (range 17 to 58). Most patients (90%) had health insurance, many lived with others at home and were unemployed. Thirty-three were on methadone and 28 on suboxone. The median length of stay was 4.7 days (ranging from 1 to 140 days) and 29% of admitted patients left against medical advice. 60% of the patients had been admitted to a hospital in the prior 12 months. The majority (58%) presented with cellulitis, 12% were diagnosed with endocarditis, 10% with osteomyelitis, 6.5% with bacteremia/sepsis. Ten were also pregnant. Infectious disease was consulted in 55%, and Psychiatry and social worker in 46% of cases. HIV, HepC and HBV testing were not performed in less than 50% of patients. There was a total of 5 deaths during the hospitalization, 2 patients with endocarditis, 2 with sepsis and one overdose. 45% of patients with endocarditis and 43% of patients with osteomyelitis required surgical intervention. S. aureus was a common pathogen and identified in 61% of the cases, where a pathogen was isolated.

Conclusion

Our data show that even in an affluent community opioid addiction is not properly addressed during hospital admissions. As a consequence, users sign out against medical advice, have frequent hospital admissions, remain out of addiction treatment, and outcome is poor. A systematic multidisciplinary approach will be required to improve the care for this vulnerable patient population

Disclosures

All authors: No reported disclosures.
996. Impact of Penicillin Allergy Labels on Carbapenem Use in a Multi-Center Study
Authors: Ling Dorothy , Seidelman Jessica , Dodds Ashley Elizabeth , Davis Angelina , Dyer April , Jones Travis M , Johnson Melissa D , Yarrington Michael E , Anderson Deverick J , Sexton Daniel J , Moehring Rebekah W
Published: October 2019

Background

Antibiotic allergy labels lead to excess exposure to broad-spectrum antibiotics and can result in patient harm. We aimed to describe the prevalence of penicillin allergy labels (PAL) across a variety of hospital settings and its association with carbapenem exposure.

Methods

We performed a retrospective cohort analysis of inpatient admissions from 14 hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) and Duke Health System from 2016 to 2018. Data were collected from the DASON central database which is derived from electronic health record extracts. PAL was defined from drug allergy documentation indicating any reaction to penicillin or its related agents, but did not include labels for other β-lactam agents (e.g., cephalosporin). Carbapenem exposure was defined as a binary variable indicating receipt of at least one dose of meropenem, ertapenem, doripenem or imipenem on an inpatient unit. The association between PAL and carbapenem exposure was assessed using multivariable logistical regression with candidate covariates including age, gender, comorbidity score, and exposure to intensive care or hematology/oncology unit. Hospital-level PAL prevalence was defined as the percentage of inpatient admissions. Hospital-level carbapenem use rates were assessed as days of therapy (DOT) per 1000 patient-days and stratified by PAL to understand the portion of use associated with PAL.

Results

Of the 727,168 admissions included in this study, 84,033 (11.6%) patients had a PAL. The majority of admissions with documented PAL were in patients >65 years old (47.9%, n = 40,240) and female (57.8%, n = 418,472). PAL was associated with a 2-fold higher risk of receipt of carbapenem (adjusted odds ratio 2.13, 95% CI 0.89–2.40, P < 0.0001). PAL prevalence varied among hospitals (median 14%, range 5–20%). Hospitals with antibiotic allergy-focused stewardship programs (ASP) had a similar PAL prevalence (median 13.8 vs. 15.9%, P = 0.08), but the percent of carbapenem DOT used in patients with PAL was similar (median 23% vs. 24%, P = 0.6).

Conclusion

PAL was associated with increased carbapenem exposure on the patient level. Allergy-focused ASP activities may affect PAL but it is unclear whether it reduces carbapenem use based on these observational data.

Disclosures

All authors: No reported disclosures.
1006. Do Antibiotic Choices Made in the ED Influence Inpatient Therapy?
Authors: Jones Travis M , Dodds Ashley Elizabeth , Johnson Melissa D , Moehring Rebekah W , Sarubbi Christina , Wrenn Rebekah
Published: October 2019

Background

Inappropriate antibiotic use (AU) is common among inpatients and may begin in the emergency department (ED). ED clinicians often make the first antibiotic decisions in patient care, but it is unknown whether or not these decisions influence inpatient AU. Understanding prescribing practices at transitions of care is critical for implementing effective stewardship initiatives.

Methods

We performed a retrospective cohort study of AU in patients admitted to Duke University Hospital through the ED between July and December 2018. Included encounters had a minimum 2-day length of stay and received an antibiotic in both the ED and inpatient setting. Individual encounter IDs were used to link ED and inpatient AU reports generated from the DASON Antimicrobial Stewardship Assessment Portal. We compared the last ED administration date/time to the first inpatient unit administration for each agent. An antibiotic started in the ED was considered continued upon admission if the first inpatient administration occurred within 30 hours following the last ED administration. Demographic, clinical indication on order entry, length of therapy, and prescriber data were also collected.

Results

We included 3,336 encounters and 2,940 unique patients in the analysis. The median (IQR) patient age was 60 (42–72) years, and the most common indications for AU in the ED were sepsis (23.1%), pneumonia (17.8%), ABSSSI (15.5%), and intra-abdominal infection (12.8%). At least one antibiotic initiated in the ED was continued upon admission within 30 hours in 2,495 (74.8%) encounters. The most common antibiotics continued upon admission were piperacillin/tazobactam (32.8%), vancomycin (24.9%), and ceftriaxone (13.7%). The most common indications for agents continued upon admission were pneumonia (18%), intra-abdominal infection (15%), and ABSSSI (15%). Two or more antibiotics were continued upon admission in 916 (27.4%) encounters.

Conclusion

In our retrospective review of ED antibiotic encounters resulting in admission for at least 2 days, three out of four encounters had at least one antibiotic continued upon admission. This finding highlights the importance of initial appropriate antibiotic selection and suggests stewardship interventions should target EDs as well as inpatient prescribing.

Disclosures

All authors: No reported disclosures.
1012. Characterization of Antibiotic Superutilizers in the Inpatient Setting
Authors: Burns Jonathan , Mersinger Katherine , Saw Stephen , Morgan Steven C , Athans Vasilios , Pegues David , Degnan Kathleen , Dutcher Lauren S , Binkley Shawn , Hamilton Keith W
Published: October 2019

Background

Inappropriate use of antibiotics is a major public health concern that contributes to increased antibiotic resistance, adverse effects, and healthcare costs. Little is known about the highest utilizers, or superutilizers, who may be appropriate targets for antibiotic stewardship efforts. The purpose of this study was to characterize superutilizers at an academic hospital.

Methods

All adult patients who were admitted to the Hospital of the University of Pennsylvania and received at least one day of antibiotics between July 1, 2017 and June 30, 2018 were identified. All inpatient administrations for systemic antibacterial agents were identified. Antibiotics given in procedural areas and the emergency department were excluded, as were any antifungals and antivirals. Usage was reported as days of therapy (DOT). We compared the demographics and DOT among the superutilizers (defined as the top 1% of patients) to different groupings of the rest of the population.

Results

Overall, 13,559 patients (and 183,082 DOT) were included in the analysis, including 136 superutilizers. The superutilizers received 15% of the total antibacterial DOT and a median of 56 DOT during the 12-month period. (table)

Conclusion

Inpatient antibiotic use is unevenly distributed across the population. Higher meropenem and sulfamethoxazole/trimethoprim DOT suggest that treatment of multidrug-resistant organisms and opportunistic infection prophylaxis are more common in the superutilizer group. Additional study is needed to determine whether antimicrobial stewardship efforts could impact antibiotic use in the superutilizer population.

Disclosures

All authors: No reported disclosures.
1022. Is it Time to Re-Evaluate Oral Β-Lactam Antibiotics for Step-Down Therapy of Uncomplicated Gram-Negative Bacteremia?
Authors: McAlister Michael , Rose Dusten T , Jaso Theresa , Olivares Brian , Parker Hudson F
Published: October 2019

Background

Bloodstream infections (BSI) due to Enterobacteriaceae often require empiric intravenous (IV) antibiotics. Oral antibiotics for the definitive treatment of these infections have been reserved to antibiotics with “high” oral bioavailability, mainly fluoroquinolones (FQ). Safety concerns and increasing resistance associated with FQ has modified clinical practice to identify alternative oral therapies. Select β-lactam (BL) antibiotics are well-tolerated, have moderately high bioavailability, and possess in-vitro activity against Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Proteus mirabilis (P. mirabilis). Limited evidence exists for oral BL step-down therapy for definitive treatment of BSI due to these organisms.

Methods

This retrospective cohort study compares clinical outcomes of patients treated with oral BL antibiotics to those who received oral FQ or trimethoprim/sulfamethoxazole (TS) for the treatment of BSI due to E. coli, K. pneumoniae, and P. mirabilis. The primary outcome is a composite of 30-day all-cause mortality, 30-day readmission due to recurrence, and/or change in oral antibiotic therapy. Secondary endpoints include 90-day development of Clostridium difficile infection, 90-day all-cause readmission, hospital length of stay (LOS), and 90-day recovery of a multi-drug-resistant organism.

Results

Nine hundred eighty-one patients were screened and 397 adult patients were included. Excluded patients: IV only (n = 291), polymicrobial blood culture (n = 112), immunocompromised (n = 61), other (n = 120). Two-hundred patients received oral step-down therapy with a BL, and 197 with either an FQ or TS. E. coli was the causative organism for most patients in both groups, and urinary tract was the most common source of BSI. The median total duration of therapy was 14 days in both groups. There was no significant difference in the primary composite endpoint (7% vs. 5.6%, P = 0.561). There was no mortality or differences in secondary outcomes, except LOS (6 vs. 5 days, P = 0.043).

Conclusion

Utilization of oral BL for the step-down therapy of uncomplicated BSI due to E. coli, K. pneumoniae, and P. mirabilis did not result in worse outcomes compared with those receiving oral FQ or TS.

Disclosures

All authors: No reported disclosures.
1034. Automating Assessments of Vancomycin Appropriateness
Authors: Holmer Haley K , McCracken Caitlin M , Tallman Gregory B , Gore Sara J , Shan Timothy , Yu Diana , Bearden David T , McGregor Jessina C
Published: October 2019

Background

Assessing appropriateness of hospital antibiotic use is typically a labor-intensive task for antimicrobial stewardship teams and relies heavily on clinician judgement rather than a systematic process. Vancomycin is a frequently used agent that is a common stewardship target. We developed an algorithm to automatically classify the appropriateness of vancomycin days of therapy (DOTs) based upon electronic health record data.

Methods

We constructed a retrospective cohort of Oregon Health and Science University (OHSU) Hospital and Doernbecher Children’s Hospital patients admitted August 1, 2017 to July 31, 2018 receiving vancomycin. Data were collected on demographic, encounter, pharmacy, microbiology, and surgery data. An electronic algorithm was applied to classify vancomycin DOTs as appropriate, inappropriate, or indeterminate. Inappropriate use was defined as any case in which there was an opportunity for de-escalation as identified using microbiology data, ICD-10 codes, and procedure codes.

Results

We included 4,231 encounters; 493 (12%) were pediatric patients. Our algorithm automatically classified 59%, 3%, and 38% of encounters as having either appropriate, inappropriate, or indeterminate DOTs, respectively. Forty-four percent of all encounters received no more than a 24-hour course of vancomycin and were considered appropriate empiric therapy; half of these were attributed to surgical prophylaxis. Nine percent of all encounters had vancomycin administered within 3 days of a blood, sputum or tissue culture in which either a methicillin-resistant Staphylococcus species or an ampicillin-resistant, vancomycin-susceptible Enterococcus species was isolated and were classified as appropriate. Six percent of all encounters had cultures in which only Gram-negatives, fungi, or yeast were isolated and were therefore considered appropriate in the empiric period (≤48 hours) but inappropriate thereafter.

Conclusion

Automated assessments of antibiotic appropriateness could facilitate more informed antimicrobial stewardship initiatives and serve as a valuable stewardship metric. Characterization of indeterminate vancomycin use may inform increased automated classification. Further effort is needed to validate these assessments.

Disclosures

All authors: No reported disclosures.
1057. The Impact of Temporary Suspensions of an Antimicrobial Stewardship Audit and Feedback Program on Antimicrobial Utilization of General Internal Medicine Inpatients
Authors: Wong Cynthia , Taggart Linda R , Leung Elizabeth
Published: October 2019

Background

A goal of Antimicrobial Stewardship Programs (ASP) is to optimize antimicrobial use; many using audit and feedback (AAF). Although AAF decreases unnecessary target antimicrobial use, it is resource-intensive. As a result, temporary suspensions in AAF activity may occur from human resource limitations or other factors. We describe the impact of these temporary suspensions and intensity of care on antimicrobial utilization trends.

Methods

This retrospective study describes the initiation and temporary suspensions of AAF in the General Internal Medicine (GIM) unit at an urban teaching hospital. Data were collected over 65 months. During active-AAF, a dedicated ID trained clinical pharmacist and ID physician-reviewed antimicrobial use for all GIM patients and provided patient-specific advice to physicians. Antimicrobial use was measured by Defined Daily Doses (DDD) normalized per 1,000 patient-days. To assess the impact of temporary suspensions, data were compared in two ways: 1. All nonactive-AAF time-frames were compared with active AAF 2. Pre-ASP was compared with Post-ASP Initiation which includes suspension periods. To determine whether differences in trends were seen based on acuity level of the patients (identified at admission as benefiting from frequent monitoring), analyses were repeated after stratification of patients admitted to the Step-Up unit (GIM-SU) and the regular ward (GIM-W).

Results

Comparing nonactive AAF vs. active-AAF, significant changes (P < 0.05) in mean normalized DDD were observed for total antimicrobials (-19%), antipseudomonals (-21%) fluoroquinolones (−41%) and first-generation β lactams (−30%). Pre ASP vs. Post ASP comparisons showed similar but less pronounced trends. Following stratification to GIM-SU and GIM-W, greater variation in significant changes to targeted antimicrobials between comparisons was observed. Different significant antimicrobial changes were seen in SU vs. W.

Conclusion

Our results show that the temporary suspension of ASP AAF impacts antimicrobial utilization trends. Greater sustained decreases in targeted antimicrobials utilization were associated with active AAF. Stratification by patient acuity lead to increased variation in the impact on target antimicrobials and increased the impact of suspension.

Disclosures

All authors: No reported disclosures.
1058. Decreases in Antibiotic Use Associated with the Implementation of Electronic Antibiotic Visualization Tools for Stewards at Eight Veterans Affairs (VA) Healthcare Facilities
Authors: Graber Christopher J , Jones Makoto M , Goetz Matthew B , Madaras-Kelly Karl , Zhang Yue , Butler Jorie M , Weir Charlene , Chou Ann F , Youn Sarah Y , Samore Matthew H , Glassman Peter A
Published: October 2019

Background

To identify areas for improved antibiotic use, we developed and pilot-tested visualization tools to quantify antibiotic use at 8 VA facilities. These tools allow a facility to review its patterns of total use, and use by antibiotic class, compared with patterns of use at VA facilities with similar (or user-selected) complexity levels.

Methods

Antibiotic stewards from 8 VA facilities participated in iterative report development and implementation, with the final product consisting of two components: an interactive web-based antibiotic dashboard and a standardized antibiotic usage report updated at user-selected intervals. Stewards also participated in monthly learning collaboratives. The percent change in average monthly antimicrobial use (all antibiotics; anti-methicillin-resistant S. aureus agents (anti-MRSA); and broad-spectrum agents predominantly used for hospital-onset/multi-drug-resistant organisms (anti-MDRO)) was analyzed using a pre-post (January 2014–January 2016 vs. July 2016–January 2018) with un-involved controls (all other inpatient VA facilities, n = 132) design modeled using Generalized Estimation Equations segmented regression.

Results

Intervention sites had a 2.1% decrease (95% CI = [−5.7%,1.6%]) in all antibiotic use pre-post-intervention, vs. a 2.5% increase (95% CI = [0.8%, 4.1%]) in nonintervention sites (P = 0.025 for difference). Anti-MRSA antibiotic use decreased 11.3% (95% CI = [−16.0%,−6.3%]) at intervention sites vs. a 6.6% decrease (95% CI=[−9.1%, −3.9%]) at nonintervention sites (P = 0.092 for difference). Anti-MDRO antibiotic use decreased 3.4% (95% CI = [−8.2%,1.7%]) at intervention sites vs. a 3.6% increase (95% CI = [0.8%,6.5%]) at nonintervention sites (P = 0.018 for difference) (Figure 1). Examples of graphs include overall antibacterial use (Figure 2), and usage of broad-spectrum Gram-negative therapy (Figure 3) in intensive care units.

Conclusion

The use of data visualization tools use and participation in monthly learning collaboratives by antimicrobial stewards in a pilot implementation project at eight VA facilities was associated with decreases in antimicrobial use relative to uninvolved sites.

Disclosures

All authors: No reported disclosures.
1068. Implementation of an Antimicrobial Stewardship Program (ASP) Managed by an Infectious Disease Physician and Pharmacists in a Community Hospital
Authors: Brady PharmD Jeanne , Poudel Mahendra
Published: October 2019

Background

The implementation of antimicrobial stewardship program (ASP) is one of the basis for the control of multidrug-resistant bacteria (MDR), optimization of antibiotic use, minimization of adverse events, and reduction of unnecessary costs. We demonstrate the design, development, and participation in ASP program following CDC and Prevention Core Elements strategies.1,3,4 The objective is to evaluate the impact of clinical pharmacists working in conjunction with infectious disease (ID) physician on tracking and documenting antibacterial utilization in per patient-days, pharmacist clinical interventions, prescriber practices, and antibiotic purchases.

Methods

We conducted a multidisciplinary-team project of pharmacist-led prospective-audit-with-feedback ASP from 2015 to 2018. The ID physician and clinical pharmacist conducted patient care rounds twice weekly to make recommendations that include de-escalation, intensification of treatment, alternative therapy, dose optimization, order clarification, stop date/duration, additional monitoring, education, restriction enforcement, consult, IV to PO conversion, rejection of recommendation, and total monitored interventions requiring no changes.

Results

Pharmacist tracked between 150 and 200 interventions monthly through the EMR system, reflecting both self-stewardship and during rounds with ID physician. Figures 2–8: Charts display the number of patient-days of therapy per 1,000 days at risk and yearly SVMH Antibacterial Utilization Rates compared nationally to other Teaching and Nonteaching hospitals.5 Below each graph exhibits yearly Drug Spend per patient-days of Therapy.6

Conclusion

Overall, the antibiotic utilization rates decreased over 4 years, particularly with aztreonam, meropenem, and levofloxacin.The formalization of an antimicrobial stewardship partnership between ID physician and pharmacy team led to increases in pharmacist-recommended interventions, streamlining of antimicrobial therapy, as well as decreases in antimicrobial purchasing costs. Proactively working in conjunction with hospitalists allows the pharmacists to play a critical role in sustaining a robust ASP service at our community hospital. The ASP at SVMH can serve as a model for other community hospitals with similar resources.

Disclosures

All authors: No reported disclosures.