bluuebunny/crossref_metadata_2025 huggingface dataset:
20. Cost-Effectiveness of Recombinant Zoster Vaccine for Vaccinating Immunocompromised Adults Against Herpes Zoster in the United States
Authors: Curran Desmond , Salem Ahmed , Lorenc Stéphane , Patterson Brandon , Carrico Justin , Hicks Katherine A , La Elizabeth M , Poston Sara , Carpenter Christopher F
Published: December 2021

Background

Individuals who are immunocompromised (IC) due to disease or therapy are at increased risk of herpes zoster (HZ), with HZ cases in IC populations also resulting in increased health care resource use and costs as compared with the immunocompetent population. This study assesses the cost-effectiveness of recombinant zoster vaccine (RZV) versus no vaccine for the prevention of HZ in IC adults aged ≥ 18 years in the United States (US).

Methods

A Markov model with a one-year cycle length was developed to follow a hypothetical cohort of one million IC individuals for a 30-year time horizon. The model estimates health and cost outcomes associated with RZV versus no vaccine. The base-case analysis considered hematopoietic stem cell transplant (HSCT) recipients who were assumed to remain IC for five years post-transplant. Second-dose compliance was assumed to be 100%, with efficacy and waning inputs based on clinical trial data. Epidemiological, cost, and utility inputs were obtained from standard US sources and published literature. Costs and quality-adjusted life-years (QALYs) were discounted at 3% per year. Sensitivity, threshold, and scenario analyses were conducted, including scenarios of four other IC conditions.

Results

In the modeled hypothetical cohort of one million HSCT recipients, RZV resulted in 116,790 fewer HZ cases and 21,446 fewer postherpetic neuralgia cases versus no vaccine, 5,545 fewer QALYs lost and a societal cost-savings of &5.4 million. The number needed to vaccinate to prevent one HZ case was estimated to be 9. HSCT population results were shown to be robust in sensitivity and threshold analyses. In scenario analyses, RZV was cost saving for renal transplant recipients. Incremental cost-effectiveness ratios for other IC populations were &33,268 per QALY gained for human immunodeficiency virus, &67,682 for breast cancer, and &95,972 for Hodgkin lymphoma.

Conclusion

Results suggest that RZV is a cost-effective option for vaccinating US IC adults for the prevention of HZ and associated complications.

Disclosures

Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder) Ahmed Salem, MSc, The GSK group of companies (Employee) Stéphane Lorenc, NA, GSK group of companies (Consultant) Brandon Patterson, PharmD, PhD, GSK group of companies (Shareholder) Justin Carrico, BS, GSK group of companies (Consultant)RTI Health Solutions (Employee) Katherine A. Hicks, MS, BSPH, GSK group of companies (Consultant)RTI Health Solutions (Employee) Elizabeth M. La, PhD, The GSK group of companies (Employee, Shareholder) Sara Poston, PharmD, The GSK group of companies (Employee, Shareholder) Christopher F. Carpenter, MD, MHSA, GSK group of companies (Consultant)
22. An Innovative Approach to Examining the Waning of Vaccine Effectiveness Using Automated Healthcare Data
Authors: Aukes Laurie , Bartlett Joan , Fireman Bruce , Hansen John , Lewis Ned , Marks Morgan , Saddier Patricia , Klein Nicola P
Published: December 2021

Background

We conducted a large real-world study of the long-term vaccine effectiveness (VE) of the live attenuated zoster vaccine (Zostavax; ZVL). Using an innovative approach with automated observational data we measured VE for incident herpes zoster (HZ) and severe HZ outcomes including post-herpetic neuralgia (PHN), herpes zoster ophthalmicus (HZO), and hospitalized HZ. This approach could be useful in long-term effectiveness studies of other vaccines.

Methods

We assessed VE against HZ, PHN, HZO and hospitalized HZ for up to 10+ years after vaccination at Kaiser Permanente Northern California. We identified incident cases using diagnoses, laboratory tests and prescriptions, and validated a sample by chart review. For each outcome, we used a Cox regression model with a calendar timeline to estimate VE in relation to year since vaccination. The model for HZ included 11 time-varying vaccination status indicators to denote -- at each timepoint during follow-up -- either the number of years since ZVL vaccination (30 days to < 1 year, 1 to < 2 years, . . ., and 10+ years) or that the individual is unvaccinated (reference group). Analyses were adjusted for demographics and time-varying measures of immune compromise status, healthcare use and comorbidities.

Results

From 2007-2018, 1.5 million people contributed to analyses; 507,000 (34%) were vaccinated. During 9 million person-years of follow-up, we observed 75,135 HZ cases, including 4,982 (7%) with PHN, 4,418 (6%) with HZO, and 555 (< 1%) who were hospitalized. VE for HZ was 67% (95% Confidence Interval [CI]: 65-69%) in the first year after vaccination, waned to 50% (CI: 47-52%) in the second year after vaccination, and then waned more gradually to 15% (CI: 5-24%) by 10+ years after vaccination. Initial VE was higher against PHN (83%; CI: 78-87%) and hospitalized HZ (89%; CI: 67-97%) with less waning observed over time (42% by Year 8 for PHN and 53% in Years 5 to < 8 for hospitalized HZ). VE against HZO was 71% in Year 1 and waned to 29% in Years 5 to < 8.

Conclusion

Our large population, long follow-up and innovative methods let us estimate VE against HZ, PHN, HZO and hospitalized HZ for 10+ years after vaccination. Our approach could help assess waning and need for boosters for vaccines against other agents including COVID-19.

Disclosures

Morgan Marks, PhD, ScM, Merck & Co Inc. (Employee) Patricia Saddier, MD, PhD, Merck & Co Inc (Employee) Nicola P. Klein, MD, PhD, GlaxoSmithKline (Grant/Research Support)MedImmune (Grant/Research Support)Merck & Co Inc (Grant/Research Support)Pfizer (Grant/Research Support)Protein Sciences (now Sanofi Pasteur) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)
24. An analysis of the National Institutes of Health All of Us Research Database: Sociodemographic Disparities Among Patients Who Received Vaccinations
Authors: Ng Ding Quan , Jia Stanley , Cadiz Christine , Wisseh Cheryl , Nguyen Megan H , Lee Joyce , McBane Sarah , Nguyen Lee , Chan Alexandre , Hurley-Kim Keri
Published: December 2021

Background

The National Institutes of Health All of Us (AoU) research program is building a diversified database of 1 million+ adult subjects. With this database, we seek to describe the sociodemographic characteristics of those with documented vaccinations.

Methods

The AoU recruited subjects ≥ 18 years beginning in 2018. Eligible subjects were subsequently divided into five vaccine cohorts based on their vaccine history [influenza, hepatitis B (HepB), pneumococcal (Pneu) < 65, Pneu ≥ 65, human papillomavirus (HPV)]. The vaccine cohorts were compared to the general AoU cohort. Subjects in the influenza cohort had documented influenza vaccinations from 09/2017-05/2018. Other vaccine cohorts comprised subjects with ≥ 1 lifetime record(s) of vaccination by 12/2018. The Pneu < 65 and ≥ 65 cohorts comprised those who received pneumococcal vaccination before or after (inclusive) 65 years old, respectively. Descriptive statistics for all cohorts were generated using survey and electronic health record (EHR) data.

Results

We analyzed 315297 subjects in the AoU dataset R2020Q4R2. The cohort sizes were: influenza (n=15346), HepB (n=6323), HPV (n=2125), and Pneu (< 65 n=15217; ≥65 n=15100). For all vaccine cohorts, comparing the 95% confidence intervals (CIs), the proportions of whites and non-Hispanics/Latinos were statistically higher than the general AoU cohort, the largest being from the Pneu ≥ 65 cohort (Table 1). For educational attainment, the Pneu < 65 (36.5%) had the smallest proportion of college or advanced degree graduates while the largest was observed in the Pneu ≥ 65 cohort (59.0%). The proportions of subjects with < &10k in annual household income (AHI) were largest among Pneu < 65 (17.1%) and smallest among Pneu ≥ 65 (3.8%). In contrast, the largest proportion of subjects with ≥ &100k AHI was among Pneu ≥ 65 (25.3%) and the smallest among Pneu < 65 (15.8%).

Table 1. Sociodemographic characteristics of subjects in the All of Us research program based on vaccine receipt

Conclusion

Racial and ethnic disparities in vaccinations were apparent. Pneumococcal vaccination at age 65 years and above was more prevalent among white, non-Hispanic/Latino subjects who were also more educated and affluent. Conversely, those receiving pneumococcal vaccination before age 65 years were less educated and had lower AHI.

Disclosures

All Authors: No reported disclosures
27. Immunologic Hyporesponsiveness with Subsequent Dosing of Meningococcal Vaccines: Re-Evaluating the Current Paradigm
Authors: Findlow Jamie , Balmer Paul
Published: December 2021

Background

Immunologic hyporesponsiveness (HyR) is considered as an inability to mount immune responses to vaccination of at least the same degree as earlier doses. For meningococcal vaccines, HyR has classically been associated with unconjugated but not conjugated polysaccharide (PS) vaccine dosing, but the clinical relevance is unclear.

Methods

To characterize meningococcal vaccine HyR, a PubMed search was conducted without date limits as follows: (hyporespons*) AND (meningococcal) AND (vaccine OR mechanism OR MOA OR causes). Papers from the authors’ files, including HyR insights with other vaccines, were included.

Results

Classic HyR with repeat unconjugated PS vaccine (MPV) dosing is thought to be associated with memory B-cell (BC) depletion, causing reduced responses on redosing with the same PS. This lack of immunologic memory and interference is seen years after MPV dosing across age groups. As data is added, other examples seem to fit the HyR definition but differ from the classical mechanism and its implications. First, passively transferred maternal antibodies (Abs) may interfere with neonatal adaptive immune response and ultimately those of childhood vaccination by binding to vaccine antigen (Ag) and inhibiting Ab production. Second, multiple dose schedules of meningococcal conjugate vaccines can show reduced responses to later doses in the series but memory is still established and amnestic booster response later achieved. Finally, carrier-induced epitopic suppression, occurring when PS Ag epitopes presented on a protein carrier are inhibited by prior/concurrent dosing with the same carrier, has also been reported. These 3 examples of alternative HyR mechanisms are not associated with memory BC depletion but are likely due to high circulatory Ab levels reducing responses, which is transient, reduces with Ab waning, immunologic memory remains intact, and is not clinically significant.

Conclusion

This literature review identified HyR mechanisms other than the classic mechanism associated with memory BC depletion that may account for decreased immune response to subsequent vaccination. Understanding the type of HyR observed with meningococcal vaccines is crucial, as these mechanisms vary in terms of potential clinical significance and the duration of their impact.

Disclosures

Jamie Findlow, PhD, Pfizer (Employee, Shareholder) Paul Balmer, PhD, Pfizer (Employee, Shareholder)
28. The Paradox of an Integrated MAT OPAT Program
Authors: Eckardt Paula , Reed Jessica , Vicencio Claudia P , Augsten Alberto
Published: December 2021

Background

Patients with substance use disorders (SUD), specifically opioid use disorder (OUD) and injection drug use (IDU) utilize healthcare resources for prolonged inpatient treatment of serious infections stemming from their addictions. For a variety of reasons, physicians treating these patients refuse to send these patients home to receive outpatient parenteral antimicrobial therapy (OPAT), and instead keep the patient in the hospital for several weeks or longer to complete treatment for the injection-related infections. Patients who do not have history of IDU are sent home with a PICC line to receive OPAT once they are no longer acutely ill and therefore no longer meet criteria to remain inpatient, which is the established standard of care. Patients with OUD and IDU are not allowed the same standard of care, and furthermore do not receive adequate, if any, therapy for their primary problem and reason for their serious infection – the addiction.

Flow chart of the MAT-OPAT process

Methods

Medication-assisted treatment (MAT) with buprenorphine-naloxone has been approved for treating adults with opioid use disorder as part of a comprehensive treatment program that also includes counseling and behavioral therapy. Until now in our healthcare system there has been no comprehensive and integrated program to safely discharge patients with OUD and IDU to receive OPAT via a PICC line, while simultaneously treating their addiction. We describe the implementation of a MAT-OPAT program. Please refer to the chart included.

Results

We present a successful case of a 36-year-old male with a history of endocarditis associated with IV drug use and the intervention of the Healthcare System to link the patient to appropriate Infectious disease, behavioral health and medication adherence treatment for opioid abuse. The patient completed the IV antibiotic therapy and remained enrolled in the behavioral health program with a successful outcome.

Conclusion

MAT-OPAT implementation in large healthcare system with continuous outpatient support that includes Infectious Disease services, behavioral health and drug abuse rehabilitation therapy can be a successful strategy to minimize readmisión, cost and complications in patients with history of IV drug use and infections that require prolonged intravenous antibiotic therapy.

Disclosures

All Authors: No reported disclosures
30. Implementation of the PEN-FAST Penicillin Allergy Screening Tool in the Emergency Department During Medication Reconciliation
Authors: Kaur Satwinder Sony , Adams David T , Parker Brittany
Published: December 2021

Background

The purpose of this study is to implement the PEN-FAST Penicillin Allergy Screening Tool in the emergency department to identify low risk patients with inappropriate penicillin-related allergies to transition them to a beta-lactam. Newly published, validated, penicillin allergy clinician decision tool (PEN-FAST) allows healthcare providers to identify low risk penicillin allergies with a negative predictive value of 96%. This quick, five question clinical decision tool allows healthcare providers and antimicrobial stewardship programs to identify patients who would also test negative if a formal penicillin allergy test was performed, making the process to confidently identify inappropriately labeled penicillin-related allergies more efficient.

Methods

During routine medication reconciliations, pharmacists will identify patients who have a documented penicillin-related allergy in the EMR and use the PEN-FAST screening tool. Patients meeting inclusion criteria will have their penicillin-related allergy updated in the EMR based upon their assessed risk of very low, low, moderate, or high. The primary outcomes for this study are the percentage of patients screened that were classified as “very low and low risk” and percentage penicillin-related allergies updated. The secondary outcomes are the percentage of patients that required antibiotic therapy (post-allergy update) that were transitioned to a beta-lactam, inpatient broad-spectrum antibiotic usage before and after allergy update, and time spent interviewing each patient.

Results

A total of 59 patients were interviewed using the PEN-FAST Tool. The results for the primary outcomes indicate 92% (n=54) of patient allergies updated in the EMR, 24% (n=13) of patients classified as “very low risk” and 34% (n=18) of patients classified as “low risk”. Results for the secondary outcome showed out of the 36 patients that were on non-beta lactams during allergy update, 72% (n=26) of those patients were transitioned to a beta-lactam. The average time to complete the PEN-FAST Tool was 4.2 minutes.

Conclusion

The results of this study support the use of the PEN-FAST Tool in efficiently updating patient’s allergies in the EMR and identifying low risk patients who may be eligible for beta-lactam therapy.

Disclosures

All Authors: No reported disclosures
34. Stemming the Rise in Antibiotic Prescription for Community Acquired Respiratory Infections (ARI) During COVID-19 Pandemic in Singapore General Hospital (SGH)
Authors: Lim Shena Yun Chun , Zhou Peijun Yvonne , Yii Daphne Yah Chieh , Hung Kai Chee , Lee Lai Wei , Liew Yi Xin , Lim Jia Le , Loo Li Wen , Koomanan Narendran , Chua Nathalie Grace Sy , Cherng Benjamin Pei Zhi , Thien Siew Yee , Lee Winnie , Kwa Lay Hoon Andrea , Chung Shimin Jasmine
Published: December 2021

Background

In early months of COVID-19 pandemic, SGH recorded a year-on-year increase in antibiotic (ABx) use for community acquired acute respiratory infection (CA ARI) from Feb-Apr 2019 (48.7 defined daily doses (DDD)/100 bed-days) to 2020 (50.8 DDD/100 bed-days). To address concerns of misuse, the antibiotic stewardship unit (ASU) expanded prospective audit feedback (PAF) to CA ARI patients admitted to ARI wards, with low procalcitonin (PCT). PAF was conducted on day 2-3 of ABx, on weekdays. Doctors received feedback to stop/modify when ABx was deemed inappropriate. Here, we describe the impact of ASU’s adaptive approach to curb rising ABx use in patients admitted for ARI during COVID-19 pandemic.

Methods

A Pre- & Post-intervention study was conducted. All patients started on ABx (ceftriaxone/co-amoxiclav/piptazo/carbapenems/levofloxacin) for CA ARI & PCT < 0.5µg/L were analysed. Those who died ≤48h of admission; admitted to intensive care; required ABx escalation; >1 infective sites; complex lung infection were excluded. Primary objective was to compare the proportion of ABx stopped ≤4 days (time to final infection diagnosis) Pre (22/3-18/4/20) & Post (21/4-13/7/20).

Results

184 (Pre) & 528 (Post) ABx courses were analysed. ASU audited 51 (Pre) & 380 (Post) courses with the rest discontinued/discharged before review. Patients were largely similar in both periods; a third had low likelihood of bacterial infection (C reactive protein < 30mg/L). In Post, 73 feedback was given to stop ABx (often because symptoms suggested viral/fluid overload) & 18 to switch to oral ABx. 82 (90%) feedback was accepted. No ABx was restarted ≤48h or deaths ≤30 days due to ARI. 1 patient had C. difficile diarrhoea a day after ABx cessation as per ASU feedback.

Proportion of all ABx stopped ≤4 days was higher in Post than Pre [27/184 (15%) vs 152/528 (29%), p< 0.01]. Median duration of therapy of IV ABx was reduced (6.5 vs 3 days, p< 0.01), with corresponding shorter median length of stay (10.5 vs 6 days, p< 0.01).

Conclusion

PAF directly and indirectly reduced ABx duration in patients treated for CA ARI as prescribers become more conscious about stopping ABx when investigations show low likelihood of bacterial infection. ASU must remain agile during pandemics to detect emerging problems and adapt processes to counter early.

Disclosures

All Authors: No reported disclosures
36. Evaluation of a Best Practice Alert (BPA) to Improve Pneumocystis jirovecii Prophylaxis Prescribing in Cancer Patients Receiving High-dose Corticosteroids in an Outpatient Setting
Authors: Ross Justine Abella , Tegtmeier Bernard , Johnson Deron , Nanayakkara Deepa , Puing Alfredo , Ho Stephanie , Taplitz Randy , Dadwal Sanjeet , Dickter Jana
Published: December 2021

Background

In patients (pts) with cancer, the risk of Pneumocystis jirovecii pneumonia (PJP) is a function of dose and duration of corticosteroids (CS), underlying immunodeficiency, and immunosuppressive drugs. Trimethoprim/sulfamethoxazole (TMP/SMX) and atovaquone (ATO) are effective prophylaxis (ppx) agents against PJP. Guidelines recommend PJP ppx for pts on > 20 mg /day of prednisone or its equivalent for ≥ 1 month. A best practice alert (BPA) to identify pts receiving CS may assist with improving PJP ppx prescribing in cancer pts.

Methods

PJP BPA was created to identify pts on CS (excluding hydrocortisone) with no active prescription for TMP/SMX or ATO ppx in EMR. Dapsone and pentamidine excluded since not preferred agents at our institution. PJP case: positive PJP polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) > 84 copies or positive PJP direct fluorescent antibody (DFA) or cytology with clinical and radiographic suspicion. PJP PCR from BAL < 84 copies/ml with negative DFA and cytology excluded. Preventable PJP (P-PJP): pts after CS > = 30 days without PJP ppx. Non-preventable PJP (NP-PJP) : pts after CS < 30 consecutive days, or on PJP ppx (non-compliance, failure), or day +1 to +30 post hematopoietic cell transplant (HCT). Pre-intervention (pre-i) PJP pts 3/1/2018 to 7/31/19 (17 months), post-intervention (post-i) PJP pts 8/1/19 to 2/1/20 (18 months) evaluated to assess BPA impact on PJP inpatient (inpt) admissions.

Results

In the post-i, the BPA fired 3,588 times in 1,302 pts. Pre-i: 20 P-PJP, 13 NP-PJP out of 33 pts. Post-i: 6 P-PJP, 25 NP-PJP out of 31 pts. The BPA fired in 4/31 PJP pts in the post-i period: 2/6 of P-PJP, 2/25 NP-PJP. The number of P-PJP decreased from 20 to 6 in the post-i period (p=0.0097).

Conclusion

Implementation of a decision support tool significantly decreased the number of P-PJP. The BPA was limited by identifying pts after CS were prescribed after the initial visit leading to periods of CS use without ppx and inability to calculate CS dosing and length of prescription. BPA provided passive education in the outpatient setting and future opportunities include refining the EMR to better identify pts at risk for developing PJP.

Disclosures

All Authors: No reported disclosures
37. Impact of a Vancomycin/Piperacillin-tazobactam Audit and Feedback Program
Authors: Atluri Vidya , Tverdek Frank , Elsayed Sarah , Chan Beverly , Liu Catherine , Pottinger Paul , Jain Rupali
Published: December 2021

Background

Vancomycin and piperacillin-tazobactam (VPT) combination therapy is associated with nephrotoxicity and provides broad-spectrum coverage that may be unnecessary. We conducted a pre-post implementation study to assess the impact of an audit and feedback program for VPT at our academic medical center.

Methods

Automated alerts were used to identify patients on VPT at the University of Washington Medical Center (UWMC)-Montlake (ML) and UWMC-Seattle Cancer Care Alliance (SCCA) hospitals. Baseline data was collected on patients from 1/20/20-6/2/20: electronic medical records were reviewed for antibiotic indication, duration, renal function, and presence of Infectious Disease (ID) consult. From 6/25/20-10/31/20, all patients on combination therapy without an ID consult were reviewed by the antimicrobial stewardship programs at ML and SCCA, respectively. If intervention was warranted, the ML steward discussed the case with the provider then documented the conversation. The SCCA steward, instead, discussed the case with the team pharmacist. The primary outcome was change in VPT duration post intervention. Secondary outcomes included nephrotoxicity rates and carbapenem escalation.

Results

Prior to the intervention, 66 ML and 33 SCCA patients were started on the combination compared to 110 ML and 50 SCCA patients post-intervention. Overall, 50% of ML and 14% of SCCA patients were on surgical primary services. Amongst ML patients, there was a decrease in patients on VPT for > 4 days (22 % to 8%), incidence of renal injury (30.3% to 10%), and percentage of ID consults (53.0% to 43.6%). Escalation to a carbapenem was stable (4.5% to 4.5%). In SCCA patients the percentage of patients on VPT for > 4 days decreased slightly (18.2% to 15.2%), incidence of renal injury was stable (18.2% to 18%), percentage of ID consults increased (45.5% to 50.0%), and escalation to a carbapenem was stable (12.1% vs 13.5%).

Conclusion

Prospective audit and feedback of VPT was associated with a decrease in duration and nephrotoxicity in ML but not SCCA patients. The difference in outcomes could be due to the patient populations, primary services, or intervention process. This study highlights the importance of tailoring interventions even within the same medical system.

Disclosures

All Authors: No reported disclosures
38. Impact of Antimicrobial Stewardship Interventions on Adherence to Clostridioides difficile Treatment Guidelines
Authors: Neuner Elizabeth , Krekel Tamara , Durkin Michael , Dubberke Erik R , Hseuh Kevin
Published: December 2021

Background

Facility-specific treatment guidelines are a priority intervention recommended in the CDC Core Elements of Hospital Antimicrobial Stewardship Programs (ASPs). Our ASP sought to improve adherence to the facility C. difficile infection (CDI) treatment guideline by implementing prospective audit and feedback of CDI cases, changing fidaxomicin from being restricted to Infectious Diseases consult use, to only requiring prospective audit and feedback, and allowing fidaxomicin and oral vancomycin orders only through the order set. This study reviews the impact of these interventions.

Methods

This single-center retrospective quasi-experimental study evaluated inpatient CDI lab events 3 months pre-intervention (10/1/2019-12/31/2019) and post-intervention (10/14/2020-1/14/2021). Patient and treatment data was evaluated via chart review. The primary outcome was adherence to CDI treatment guideline. ASP intervention types were categorized. Statistical analyses were performed using Chi-squared or Fischer’s exact, where appropriate.

Results

Baseline characteristics were well matched between the 58 and 70 patients pre and post intervention respectively (Table 1). ASP interventions resulting from the prospective audit and feedback are described in Table 2 and overall acceptance rates were high (88%). Guideline adherence improved significantly from 71% pre to 90% post-intervention (p=0.005). Reasons for non-adherence included vancomycin dose incorrect for the severity of illness (9 pre vs 2 post), inappropriate duration (4 pre vs 0 post), use of combination therapy in non-fulminant disease (5 pre vs 3 post), and not using fidaxomicin for recurrent disease (3 pre vs 2 post). Clinical outcomes pre and post intervention were not different in this small sample size: colectomy 1 (2%) vs 1 (1%) p=1, 60 day all- cause mortality 15 (26%) vs 14 (20%) p=0.43, and CDI recurrence at day 60 9/43 (21%) vs 5/56 (9%) p=0.131.

Conclusion

A bundle of ASP interventions including prospective audit and feedback of CDI cases improved adherence to facility-specific CDI treatment guidelines.

Disclosures

Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) Erik R. Dubberke, MD, MSPH, Ferring (Grant/Research Support)Merck (Consultant)Pfizer (Consultant, Grant/Research Support)Seres (Consultant)Summit (Consultant)
40. Impact of an Antimicrobial Intake Process within a Post-acute Medical System
Authors: Shea Katherine M , Wayne Segars , Stocker Jamie , Velez Meredith , Davis Elizabeth , Snider Darrell
Published: December 2021

Background

Implementation of antimicrobial stewardship programs (ASPs) within long-term acute care facilities (LTACs) is challenging due to limited resources and missing patient data from transferring facilities. In October 2018, an ASP was established within a 43-hopital system consisting of LTACs and rehabilitation hospitals. Despite the presence of a restricted antimicrobial policy, increased utilization was observed for five restricted antimicrobials. The system ASP committee implemented a multipronged approach to optimize utilization of these five agents. Investigators sought to assess the impact of an antimicrobial intake process on antimicrobial consumption.

Methods

This was a retrospective analysis within a 43-hospital system of LTACs and rehabilitation hospitals, comparing use of five restricted antibiotics before (Jul19-Jun20) and after (Jul20-Apr21) implementation of a data-collection and system review process. An antibiotic intake form and process for review for five restricted antibiotics (ceftaroline, ceftazidime/avibactam, ceftolozane/tazobactam, fidaxomicin, meropenem/vaborbactam) was approved at the system ASP committee. The intake form consisted of a restricted antibiotic form, cultures and susceptibilities, physician notes, and other pertinent data. Any orders for the five antibiotics required completion of an intake form and submission to system ASP members for review and recommendations. Antibiotic consumption was measured in cost per acute patient day (cost/pd) using a 2-sided t-test.

Results

Post-implementation, the five restricted antibiotics comprised 29.1% of the total antibiotic expenditure for the healthcare system compared to 35.6% pre-implementation. Ten months after program implementation, the total antibiotic cost/PD decreased 29.45% [(&12.02 ± 2.29) vs. (&8.48 ± 1.45); p=0.0003]. The cost/PD of the five restricted antibiotics decreased 42.52% [(&4.28 ± 1.09) vs. (&2.46 ± 0.99) ; p=0.0005].

Conclusion

Implementation of an antimicrobial intake process within a post-acute medical system resulted in a significant reduction in antibiotic consumption for five targeted antibiotics as well as overall antibiotic expenditure.

Disclosures

All Authors: No reported disclosures
41. Impact of Discharge Antimicrobial Stewardship at an Academic Medical Center
Authors: Parsels Katie A , Kufel Wesley D , Burgess Jeni , Seabury Robert , Mahapatra Rahul , Miller Christopher , Steele Jeffrey M
Published: December 2021

Background

The Centers for Disease Control and Prevention estimates approximately 30% of antimicrobials prescribed in the outpatient setting are unnecessary and up to 50% are inappropriate. Despite this, antimicrobial stewardship (AS) efforts mostly focus on the inpatient setting and limited data describe AS interventions at hospital discharge. Acknowledging the potential for discharge AS, we used our existing resources to review discharge antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy to potentially optimize antimicrobial therapy.

Methods

Discharge antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy, reviewed by an infectious disease (ID) pharmacist, and recorded into the REDCap® data collection tool from September 1, 2020 to February 28, 2021 were evaluated retrospectively. Both adult and pediatric patients were included. The primary outcome was to identify the frequency a DRP was identified by an ID pharmacist while reviewing discharge antimicrobial prescriptions. Secondary outcomes included DRP characterization, percentage of prescriptions with interventions, intervention acceptance rate, and the reduction in antimicrobial days dispensed at discharge when interventions to limit treatment duration were accepted.

Results

Of the 803 discharge antimicrobial prescriptions reviewed, at least one DRP was identified in 43.1% (346/803). The most frequently identified DRPs pertained to treatment duration, drug selection, and dose selection. The most common intervention categories included different antimicrobial duration, antimicrobial discontinuation, and different dose or frequency. At least one intervention was recommended in 42.8% (344/803) of prescriptions. In total, 438 interventions were made and the acceptance rate was 75.6% (331/438). When interventions to reduce the treatment duration were accepted, the median (interquartile range) number of antimicrobial days decreased from 8 (5 – 10) to 4 (0 – 5.5) days (P < 0.001).

Conclusion

ID pharmacist review of discharge antimicrobial prescriptions sent to our hospital-operated outpatient pharmacy resulted in identification of DRPs and subsequent interventions in a substantial number of prescriptions.

Disclosures

Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member)
44. Cost Effectiveness and Clinical Outcomes of Long Acting Lipoglycopeptides Used in Transitions of Care for Deep-Seated Infections
Authors: Antosz Kayla S , Justo Julie Ann , Al-hasan Majdi N , Tabor Benjamin , Kohn Joseph , Milgrom Alexander , Lu Kevin , Brandon Bookstaver P
Published: December 2021

Background

Dalbavancin and oritavancin are long-acting lipoglycopeptides (LaLGPs) FDA-approved for one-time only dosing for skin and skin structure infections. The use of these agents in serious, deep-seated infections requiring protracted antibiotic courses is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT).

Methods

This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients who received a LaLGP were matched 1:1 to those who received standard of care (SOC) therapy by age (+/- 10 years), infection type, microorganism, and socioeconomic factor (e.g. persons who inject drugs, homelessness). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. Secondary outcomes included hospital length of stay and proportion of patients who left against medical advice (AMA).

Results

A total of 46 patients were included (23 per group). The most frequent indication was endovascular infection and the most common organism methicillin-resistant Staphylococcus aureus. The average length of stay was 22.9 days vs. 31.9 days in the LaLGP and SOC cohorts, respectively (p=0.153). The average total healthcare-related cost of care was USD &295,589 in the LaLGP cohort compared to &326,089 in the SOC cohort (p=0.282). LaLGPs were associated with a mean savings of &30,500 - &55,831 per patient (cumulative cost savings of &701,510). There was no difference in clinical failure between the two cohorts (22% vs. 30%; p=0.491). Nearly 26% of patients in the SOC cohort left AMA compared to 0% in the LaLGP cohort (p=0.022).

Conclusion

Receipt of LaLGPs may be a beneficial treatment option for patients with socioeconomic factors and deep-seated infections who are not candidates for oral transition or OPAT.

Disclosures

Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)
45. Significantly Decreased Broad Spectrum Antimicrobial Use (Carbapenems And Fluoroquinolones) with Implementation of Antibiotic Stewardship Program (ASP) and Pharmacist Interventions
Authors: Kaushik Ashlesha , Gupta Sandeep , Thieman Corey , Padomek Michael
Published: December 2021

Background

According to the WHO, carbapenems and fluoroquinolones (FQ) should be key targets for stewardship programs.

Methods

A multifaceted antimicrobial stewardship program (ASP) was implemented in July 2018 at a 160-bed tertiary care center serving the tristate area of Iowa, South Dakota and Nebraska. Carbapenem and FQ use during pre-ASP intervention period (P1: 12/01/2016-6/30/2018) was compared with ASP-intervention period (P2: 07/01/2018-1/31/2020). ASP interventions included: stewardship educational pearls in monthly physician newsletters; educational posters in provider areas; suppression of carbapenem results on microbiology susceptibility reports; provider counseling for appropriate ordering; creating carbapenem alternative alert in order-entry software; removing FQ and carbapenems from order-sets where appropriate; default antibiotic stop dates changed to 7 days in EMR (Epic); adverse effects warning fired as an alert when ordering FQ. Pharmacist interventions: procalcitonin protocol allowing pharmacists to reorder follow-up procalcitonin and make recommendations to discontinue therapy where appropriate.

Results

FQ use declined significantly from a mean of 133 days of therapy (DOT) per 1000 days to 46 DOT per 1000 patient days during P2 (p< 0.0001). Carbapenem use declined significantly from a mean of 65 DOT per 1000 patient days during P1 to 9 DOT per 1000 patient days in P2 (p< 0.001). All hospital units showed a significant decrease in use, with intensive care units (ICUs) noting 56% reduction (p< 0.00001) during P2 compared to P1. During P2, 55% of orders for carbapenems and FQ during P2 were found to be appropriate compared to 39% in P1 (p< 0.0001). Sensitivity profile for Pseudomonas aeruginosa improved from 86% carbapenem sensitivity during P1 to 89% in P2 and no Carbapenem-Resistant Enterobacteriaceae isolates were identified during the study period; FQ sensitivity remained stable at 81%. Cost savings of &757 per 1000 patient days were recognized in P2 as a result of reduced use.

Conclusion

With ASP and pharmacist interventions, a significant decline in total utilization of carbapenem and FQ, considerable cost savings and an increase in proportion of appropriate use were observed.

Disclosures

All Authors: No reported disclosures
46. Templated Microbiology Comments with Candiduria to Enhance Antimicrobial Stewardship
Authors: Schartz Weston , Bennett Nick , Aragon Laura , Kennedy Kevin , Boyd Sarah E , Humphrey Matthew , Essmyer Cindy
Published: December 2021

Background

Behavioral interventions have been shown to improve antimicrobial selection. Such practices are low cost and effective means of stewardship promotion. One area of overtreatment that contributes to unnecessary antifungal use is in hospitalized patients with candiduria. We implemented a templated microbiology comment to guide prescribing of antifungals for hospitalized patients with candiduria.

Methods

This was a quasi-experimental, multi-center, single health system study. When Candida is isolated, the following comment appears in the microbiology result section along with the urine culture result: “In the absence of symptoms, Candida is generally considered normal flora. No therapy indicated unless high risk (pregnant, neonate or neutropenic) or undergoing urologic procedure. If Foley catheter present, remove or replace when able.” We compared a pre-implementation cohort (June 2018-Janurary 2019) to a post-implementation cohort (June 2019-Janurary 2020). Patients were included in the study if they were inpatients, 18 years and older, with candiduria. The primary outcome was the rate of antifungal administration within 72 hours after culture results became available. Secondary outcomes include duration of therapy and rate of antifungal given within 73-240 hours after culture result.

Results

The study included a total of 297 patients between the two groups (156 pre-implementation, 141 post-implementation). The primary outcome was found to be significantly lower in the post-implementation group (48.1% vs 34.0%, p=0.014). A multivariate adjustment for baseline characteristics that were significantly different between groups revealed that post-implementation group maintained its effect (OR 0.49 (0.29, 0.82), p=0.0067). For secondary outcomes, no difference was found in patients requiring antifungal administration within 73-240 hours after microbiology results were available (1.3% vs 3.5%, p=0.199). There was no difference in mean antifungal duration (4 vs 3 days, p=0.449).

Conclusion

Adding a templated comment to urine cultures was associated with a significant reduction in the number of antifungals prescribed in patients with candiduria. This strategy is an effective low-cost, passive education technique to improve antimicrobial stewardship.

Disclosures

All Authors: No reported disclosures
47. Transitioning to Batch Dosing of High-Cost Antimicrobials in the Inpatient Setting
Authors: Lokant Matthew , Lee Shu Xian , Nevin Connor , Lindsay John D , Acri Colby , Graves Miles , Bergman Katherine L , Guilfoose John , Howard Catessa
Published: December 2021

Background

Antimicrobial stewardship (AMS) committees ensure appropriate antimicrobial utilization. One stewardship intervention is to evaluate the delivery model of high-cost antimicrobials to better utilize resources and mitigate expenses. We analyzed the total medication waste and costs of high-cost antimicrobials, specifically daptomycin, ertapenem, amphotericin, and micafungin, at our institution and propose innovative cost-savings changes at a systems level.

Methods

This retrospective study consisted of 263 patients. All patients were at least 18 years old who was admitted to our academic institution from January 2020 to April 2021 and received daptomycin, ertapenem, amphotericin, or micafungin. Demographics, daily medication dosage, total doses received, the date and time of the start of the medication, last administered dose, and discontinued order were recorded.

Results

The daptomycin cohort consisted of 143 patients with 46.2% females and average age of 56.3 years. In this group, 145.3 vials were wasted which equated to a loss of &22,630. The ertapenem group had 53 patients with 62.3% females and a mean age of 62.3 years. There were 24 vials wasted with a calculated loss of &1080. The amphotericin cohort had 32 patients with an average age of 52.2 years and 43.8% females. There were 189 vials wasted with a loss of &46,116. The micafungin group had 35 patients with 42.9% females and average age of 60.4 years. This group had 12 vials wasted with a loss of &2052.

Conclusion

Each antimicrobial has a specific formulation protocol. Daptomycin and ertapenem formulation occurs in the early morning. Amphotericin formulation occurs 2 hours prior to medication use. Micafungin formulation occurs at the time the order label prints. These medications were more often administered in the late morning to early afternoon timeframe. The order to discontinue the medications also occurred at the same interval. One reason could be due to decisions made on morning rounds from primary teams and specialty input. These orders would then be placed after rounds. A cost-saving method would be to batch and change the formulation time for all antimicrobials to later in the afternoon, which would not only prevent waste, but also allow the AMS team to effectively audit appropriate antimicrobial use.

Disclosures

All Authors: No reported disclosures
49. Impact of a Rapid Genotypic Platform for Gram-negative Bloodstream Infections, Paired with an Antimicrobial Stewardship Intervention, on Time to Optimal Antimicrobial Therapy
Authors: Donnelly Madison , Walls Jennifer , Wood Katlyn , Bandali Aiman
Published: December 2021

Background

Gram-negative bacteremia is associated with significant morbidity and mortality. Development of an algorithm for antimicrobial selection, using institution-specific antibiogram data and rapid diagnostics (RDT), achieves timely and appropriate antimicrobial therapy. The objective of this study is to assess the impact of a pharmacy-driven antimicrobial stewardship initiative in conjunction with ePlex® BCID on time to optimal antimicrobial therapy for patients with gram-negative bloodstream infections.

Methods

This retrospective, observational, single-center study included adult patients with a documented gram-negative bloodstream infection in whom the ePlex® BCID was employed. A pharmacist-driven antimicrobial stewardship intervention was initiated on December 1, 2020; pre-intervention (December 2019 – March 2020) was compared to the post-intervention (December 2020 – February 2020) period. The following organisms were included: Citrobacter spp., Escherichia coli, Klebsiella aerogenes/pneumoniae/oxytoca, Proteus spp, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Polymicrobial bloodstream infections or those who had an ePlex® panel performed prior to admission were excluded. The following clinical outcomes were assessed: time to optimal antimicrobial therapy, length of stay (LOS), and inpatient-30-day mortality.

Results

One hundred and sixty-three met criteria for inclusion; 98 patients in the pre-intervention group and 65 patients in the post-intervention group. The mean Pitt Bacteremia Score was 1 in both groups (p=0.741). The most common organism identified by ePlex® BCID was E. coli (65.3% vs 70.8%; p=0.676). Eight E. Coli isolates were CTX-M positive; no other gene targets were detected. The most common suspected source of bacteremia was genitourinary (72.5% vs 72.3%; p=1.0). Time to optimal therapy was reduced by 29 hours [37 (31 – 55) vs. 8 (4 – 28); p=0.048). Length of stay and mortality was similar between groups.

Conclusion

Implementation of a rapid blood culture identification panel along with an antimicrobial stewardship intervention significantly reduced time to optimal therapy. Further studies are warranted to confirm these results.

Disclosures

All Authors: No reported disclosures
50. Impact of Antibiotic Stewardship Interventions on Colistin Use and Acinetobacter Resistance
Authors: Eljaaly Khalid
Published: December 2021

Background

Our hospital had a widespread use of colistin and tigecycline, and very high resistance of Acinetobacter Spp. to colistin. The hospital did not have any infectious disease (ID) pharmacist and had only one ID consultant physician. The objective of this study was to evaluate the impact of our intervention on the utilization of colistin and tigecycline and resistance of Acinetobacter Spp.

Methods

This was a before an observational before-and-after study at a tertiary medical center. An ID pharmacist trained in antibiotic stewardship program (ASP) was invited by a tertiary hospital to help create an ASP. The hospital also hired four ID assistant consultants to help the primary ID consultant and pharmacists. The ASP started by restriction of colistin and tigecycline. The study outcomes were antibiotic consumption and resistance of Acinetobacter spp.

Results

Colistin utilization decreased by 60%, and the resistance of Acinetobacter spp. to colistin significantly decreased from 31% to 3% in a year. In addition, tigecycline utilization decreased by 46%. On the other hand, there were no significant changes in carbapenem utilization and resistance, which could be explained by switching from colistin and tigecycline to carbapenems.

Conclusion

Adding an ID pharmacist and ID assistant consultants to the ASP team, and the strict restriction of colistin use was associated with significant reduction in colistin use and Acinetobacter resistance.

Disclosures

All Authors: No reported disclosures