1058. Decreases in Antibiotic Use Associated with the Implementation of Electronic Antibiotic Visualization Tools for Stewards at Eight Veterans Affairs (VA) Healthcare Facilities

Abstract 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.

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Decreases in Antimicrobial Use Associated With Multihospital Implementation of Electronic Antimicrobial Stewardship Tools

Clinical Infectious Diseases ◽

10.1093/cid/ciz941 ◽

2019 ◽

Vol 71 (5) ◽

pp. 1168-1176 ◽

Cited By ~ 2

Author(s):

Christopher J Graber ◽

Makoto M Jones ◽

Matthew Bidwell Goetz ◽

Karl Madaras-Kelly ◽

Yue Zhang ◽

...

Keyword(s):

Antimicrobial Agents ◽

Veterans Affairs ◽

Comparative Data ◽

Absolute Difference ◽

Antimicrobial Use ◽

Post Intervention ◽

Web Based ◽

Geographically Dispersed ◽

Learning Collaboratives ◽

Visualization Tools

Abstract Background Antimicrobial stewards may benefit from comparative data to inform interventions that promote optimal inpatient antimicrobial use. Methods Antimicrobial stewards from 8 geographically dispersed Veterans Affairs (VA) inpatient facilities participated in the development of antimicrobial use visualization tools that allowed for comparison to facilities of similar complexity. The visualization tools consisted of an interactive web-based antimicrobial dashboard and, later, a standardized antimicrobial usage report updated at user-selected intervals. Stewards participated in monthly learning collaboratives. The percent change in average monthly antimicrobial use (all antimicrobial agents, anti-methicillin-resistant Staphylococcus aureus [anti-MRSA] agents, and antipseudomonal agents) was analyzed using a pre–post (January 2014–January 2016 vs July 2016–January 2018) design with segmented regression and external comparison with uninvolved control facilities (n = 118). Results Intervention sites demonstrated a 2.1% decrease (95% confidence interval [CI], −5.7% to 1.6%) in total antimicrobial use pre–post intervention vs a 2.5% increase (95% CI, 0.8% to 4.1%) in nonintervention sites (absolute difference, 4.6%; P = .025). Anti-MRSA antimicrobial use decreased 11.3% (95% CI, −16.0% to −6.3%) at intervention sites vs a 6.6% decrease (95% CI, −9.1% to −3.9%) at nonintervention sites (absolute difference, 4.7%; P = .092). Antipseudomonal antimicrobial use decreased 3.4% (95% CI, −8.2% to 1.7%) at intervention sites vs a 3.6% increase (95% CI, 0.8% to 6.5%) at nonintervention sites (absolute difference, 7.0%; P = .018). Conclusions Comparative data visualization tool use by stewards at 8 VA facilities was associated with significant reductions in overall antimicrobial and antipseudomonal use relative to uninvolved facilities.

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Impact of Order-Set Modifications and Provider Education Following Guideline Updates on Broad-Spectrum Antibiotic Use in Patients Admitted With Community Acquired Pneumonia

Hospital Pharmacy ◽

10.1177/00185787211055797 ◽

2021 ◽

pp. 001857872110557

Author(s):

Jessica L. Colmerauer ◽

Kristin E. Linder ◽

Casey J. Dempsey ◽

Joseph L. Kuti ◽

David P. Nicolau ◽

...

Keyword(s):

Broad Spectrum ◽

Antibiotic Use ◽

Community Acquired Pneumonia ◽

Intervention Period ◽

Provider Education ◽

Broad Spectrum Antibiotic ◽

Post Intervention ◽

Post Intervention Period ◽

Days Of Therapy ◽

Order Set

Purpose: Following updates to the Infectious Diseases Society of America (IDSA) practice guidelines for the Diagnosis and Treatment of Adults with Community-acquired Pneumonia in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for the prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education. Methods: This was a multi-center, quasi-experimental, retrospective study of patients with a diagnosis of CAP from September 1, 2019 to October 31, 2019 (pre-intervention) and September 1, 2020 to October 31, 2020 (post-intervention). Patients were identified using ICD-10 codes (A48.1, J10.00-J18.9) indicating lower respiratory tract infection. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal β-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS). Results: A total of 331 and 352 patients were included in the pre- and post-intervention cohorts, respectively. There were no differences in order-set usage (10% vs 11.3%, P = .642) between the pre- and post-intervention cohort, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period ( P < .001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs [190/312] 60.9%; P = .003). Hospital LOS was shorter in the post-intervention cohort (4.8 days [2.9-7.2 days] vs 5.3 days [IQR 3.5-8.5 days], P = .002). Conclusion: Implementation of an updated CAP order-set with accompanying provider education was associated with reduced use of broad-spectrum antibiotics. Opportunities to improve compliance and thus further increase guideline-concordant therapy require investigation.

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39. Impact of Antimicrobial Stewardship Interventions in a Community Hospital setting: An Interrupted Times Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.241 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S141-S142

Author(s):

Jason Li ◽

Ken Chan ◽

Hina Parvez ◽

Margaret Gorlin ◽

Miriam A Smith

Keyword(s):

Antimicrobial Stewardship ◽

Community Hospital ◽

Hospital Setting ◽

Interrupted Time Series ◽

Antibiotic Use ◽

Antimicrobial Use ◽

Intervention Period ◽

Prospective Audit ◽

Post Intervention ◽

The Impact

Abstract Background Community hospitals have fewer resources for antimicrobial stewardship programs (ASP) compared to larger tertiary hospitals. At our 312-bed community hospital, Long Island Jewish Forest Hills/Northwell, a combination of modified preauthorization, prospective audit feedback, and ASP education was implemented starting in August 2019 (Monday through Friday 9 am to 5 pm). Methods This retrospective study evaluated the impact of ASP interventions on the rate of targeted antimicrobial use over a 7 month pre- vs 7 month post- intervention period (Aug 2018 to Feb 2019 vs Aug 2019 to Feb 2020). Targeted antimicrobials included piperacillin-tazobactam, vancomycin, daptomycin, and carbapenems. The primary outcome was the monthly mean for overall targeted antimicrobial use measured by the rate of antimicrobial days per 1000 days present. Secondary outcomes were the individual rates of antimicrobial days per 1000 days present for each of the targeted antimicrobials, and the hospital’s overall standardized antimicrobial administration ratio (SAAR). Data were analyzed as a segmented regression of interrupted time series. Results Pre-intervention, there was an increasing trend (positive slope, p< 0.05) in the monthly mean, hospital SAAR, vancomycin and piperacillin-tazobactam use. Post-intervention, there was a significant change in slope for these same metrics, indicating a decrease in the mean use. Immediate impact of ASP interventions, measured by the difference in antibiotic use between the end of each intervention period, was visually evident in all cases except carbapenems (Fig. 1 through 4). The immediate impact on the overall monthly mean represented a significant reduction in the rate of antimicrobial days per 1000 days present, -12.72 (CI -21.02 to -4.42, P < 0.0066). The pre- vs post- ASP gap for all measures was negative and consistent with fewer days of antibiotic use immediately following intervention. Conclusion A targeted, multifaceted ASP intervention utilizing modified preauthorization, prospective audit feedback, and education significantly reduced antibiotic use in a community hospital. Disclosures All Authors: No reported disclosures

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How the COVID-19 Pandemic Affected Antimicrobial Prescribing Practices at a Tertiary-Care Healthcare System in Detroit, Michigan

Antimicrobial Stewardship & Healthcare Epidemiology ◽

10.1017/ash.2021.69 ◽

2021 ◽

Vol 1 (S1) ◽

pp. s37-s38

Author(s):

Angela Beatriz Cruz ◽

Jennifer LeRose ◽

Avnish Sandhu ◽

Teena Chopra

Keyword(s):

Broad Spectrum ◽

Treatment Guidelines ◽

Tertiary Care ◽

Antibiotic Use ◽

Modern Medicine ◽

Antimicrobial Use ◽

Prescribing Practices ◽

Primary Object ◽

Antibiotics Use ◽

Over Time

Background: Inappropriate antimicrobial use continues to threaten modern medicine. The ongoing pandemic likely exacerbated this problem because COVID-19 presents similarly to bacterial pneumonia, confusion exists regarding treatment guidelines, and testing turnaround times (TATs) are slow. Our primary object was to quantify antimicrobial use changes during the pandemic to rates before the crisis. A subanalysis within the COVID-19 cohort was completed based on SARS-CoV-2 status. Methods: The pre–COVID-19 period was January–May 2019 and the COVID-19 period was January–May 2020. Subanalyses were used to explore differences in antibiotics use between persons not under investigation (non-PUIs), SARS-CoV-2–negative PUIs, and SARS-CoV-2–positive PUIs. Non-PUI patients were those without respiratory symptoms and/or fever. The χ2 and Wilcoxon signed rank-sum tests were used for analysis. Results: During the 2019 and 2020 study periods, 7,909 and 7,283 patients received >1 antimicrobial, respectively (Figure 1). Overall, antibiotic therapy per 1,000 patient days increased from 633.1 before COVID-19 to 678.5 during COVID-19, a 7.2% increase (Table 1). Notably, broad-spectrum respiratory antibiotics demonstrated a significant increase between pre–COVID-19 and COVID-19 cohorts (p < 0.001). Of the 7,283 patients within the COVID-19 cohort, 34.7% (n = 2,532) were PUI and 13.8% (n = 1,002) of these patients tested SARS-CoV-2 positive. Again, broad-spectrum respiratory antibiotics use was significantly increased for COVID-19 patients (p < 0.001). Of note, the proportion of patients receiving respiratory antibiotics steadily decreased over time (R2 = 0.99). Conclusions: There was a significant increase in antibiotic use during the COVID-19 pandemic. Encouragingly, antimicrobial use decreased over time, likely due to (1) faster TATs, (2) real-time education to clinicians and subsequent de-escalation of unnecessary antimicrobials, and (3) development of treatment guidelines as new research emerged.Funding: NoDisclosures: None

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894. Universal Decolonization in Nursing Homes: Effect of Chlorhexidine and Nasal Povidone–Iodine on Prevalence of Multi-Drug-Resistant Organisms (MDROs) in the PROTECT Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.053 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S24-S24 ◽

Cited By ~ 1

Author(s):

Loren G Miller ◽

James A McKinnell ◽

Raveena Singh ◽

Gabrielle Gussin ◽

Ken Kleinman ◽

...

Keyword(s):

Nursing Homes ◽

Cluster Randomized Trial ◽

Antibiotic Use ◽

Routine Care ◽

Post Intervention ◽

Healthcare Facilities ◽

Carbapenem Resistant ◽

Nasal Swabs ◽

The Difference ◽

Cluster Randomized

Abstract Background The prevalence of MDROs in nursing homes (NH) is much higher than that of hospitals. Decolonization to reduce the reservoir of MDRO carriage in NH residents may be a strategy to address MDRO spread within and among healthcare facilities. Methods PROTECT is an 18-month cluster randomized trial of 1:1 universal decolonization vs. routine care in 28 NHs in California. Decolonization consists of chlorhexidine (CHG) bathing plus twice daily nasal iodophor on admission and Monday–Friday biweekly. We assessed pre- vs. post-intervention MDRO prevalence by sampling 50 randomly selected residents at each NH as an outcome unrelated to the trial’s primary intent (infection, hospitalization reduction). NH residents had nasal swabs cultured for methicillin-resistant S. aureus (MRSA), and skin (axilla/groin) swabs taken for MRSA, vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase producers (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE). Generalized linear mixed models (GLM) assessed the difference in differences of MDRO prevalence using an arm by period interaction term, clustering by NH. Results Four NHs dropped from the trial. Among the 24 NHs that remained, MDRO colonization at baseline was 49.4% and 47.5% of residents in control (N = 650) vs. decolonization (N = 550) NHs, with no difference in MRSA, VRE, ESBL, and CRE (Table 1). Among remaining NHs, decolonization was associated with 28.8% raw decrease in MDRO prevalence in decolonization sites (GLM OR = 0.51, P < 0.001), 24.3% raw decrease in MRSA (OR = 0.66, P = 0.03), 61.0% raw decrease in VRE (OR = 0.17, P < 0.001), and 51.9% raw decrease in ESBL (OR = 0.40, P < 0.001). CRE increased, but numbers were small (Control arm: 10 in baseline, 4 in intervention; intervention arm: 1 in baseline, 2 in intervention, P = NS). Conclusion Universal NH decolonization with CHG bathing and nasal iodophor resulted in a marked decrease in Gram-positive and Gram-negative MDRO prevalence. This decrease may lower MDRO acquisition, infection, and antibiotic use within NHs, as well as regional MDRO spread to other healthcare facilities. Disclosures All Authors: No reported Disclosures.

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Road to Increasing AMR: A Study on Antibiotics Prescribing Pattern

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.1174 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s496-s497

Author(s):

Bobson Derrick Fofanah ◽

Christiana Conteh ◽

Jamine Weiss

Keyword(s):

Broad Spectrum ◽

Inappropriate Prescribing ◽

Antibiotic Use ◽

Prescribing Patterns ◽

Antibiotic Prescribing ◽

Antimicrobial Use ◽

Strict Adherence ◽

Targeted Interventions ◽

Broad Spectrum Antibiotics ◽

Trade Names

Background: Infectious diseases and the rapid emergence of multidrug-resistant pathogens continue to pose a threat to global health. The development of antimicrobial-resistant organisms is an alarming issue caused by inappropriate use of antibiotic agents. It is estimated that death from antimicrobial resistant pathogens could increase >10-fold to ~10 million deaths annually by 2050 if action is not taken. “It is essential to have reliable data on how medicines are used in order to identify areas to develop targeted interventions” (WHO 2011). Investigating antimicrobial use in hospitals is the first step in evaluating the underlying causes of AMR. In Sierra Leone, no other study related to antibiotic prescribing patterns in hospital setting has been undertaken. Objective: To investigate antibiotic prescription patterns using the WHO hospital antimicrobial use indicator tool at the Kingharman Hospital for 1 month. Methods: Data were collected from patient charts for 1 month, January 1–31, 2019. A data extraction tool was used to capture information on patient demographics, diagnosis, and antibiotics prescription details regarding dosage, duration, and frequency of administration. The tool adopted 6 selected indicators from the WHO antimicrobial use manual to measure the extent of antibiotic use in hospital and performance among prescribers. Results: Of the 189 charts reviewed, 175 included antibiotic prescriptions. The percentage of prescriptions involving antibiotics was 92.5%. The average number of drugs prescribed was 2, with an average duration of 5.2 days. Moreover, 50.5% of antibiotics prescribed were generic, and 96.6% were from the Ministry of Health and Sanitation Essential Medicine List (EML). The most commonly used antibiotics were ciprofloxacin (38.8%), followed by ceftriaxone (23.0%), amoxicillin (16.8%), metronidazole (8.5%), and others(12.7%). Typhoid accounted for 34.8% of broad-spectrum antibiotics, UTI accounted for 17.7%, malaria accounted for 12.5%, 25.5% were unspecified, and 9.5% were for unclear diagnoses. Typically, combinations of fluroquinolones and cephalosporins were used to treat typhoid and UTIs. Conclusions: This cross-sectional study represents a broad picture of antibiotic prescribing patterns at the King Harman Hospital. There was no strict adherence to the WHO recommended prescribing guidelines. These findings also indicate the degree of irrational and inappropriate prescribing of broad-spectrum antibiotics. This study highlights the need for a comprehensive assessment of antimicrobial use to gain a better understanding of national antibiotic use and to guide interventions to reducing AMR.Funding: NoneDisclosures: NoneIf I am discussing specific healthcare products or services, I will use generic names to extent possible. If I need to use trade names, I will use trade names from several companies when available, and not just trade names from any single company.DisagreeChristiana Kallon

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1149. Reducing Piperacillin/Tazobactam Use in Children with Acute Perforated Appendicitis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1013 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S410-S410

Author(s):

Talal B Seddik ◽

Laura Bio ◽

Hannah Bassett ◽

Despina Contopoulos-Ioannidis ◽

Lubna Qureshi ◽

...

Keyword(s):

Clinical Outcomes ◽

Broad Spectrum ◽

Perforated Appendicitis ◽

Antibiotic Use ◽

Broad Spectrum Antibiotic ◽

Post Intervention ◽

Stewardship Program ◽

Days Of Therapy ◽

Significant Difference ◽

The Impact

Abstract Background Children with perforated appendicitis have more frequent complications compared with nonperforated appendicitis. Existing data suggest broad-spectrum antibiotics are not superior to narrow-spectrum antibiotics for this condition. In an effort to safely decrease broad-spectrum antibiotic use at our hospital, we evaluated the impact of an antimicrobial stewardship program (ASP) intervention on the use of piperacillin/tazobactam (PT) and clinical outcomes in children with perforated appendicitis. Methods Single-center, retrospective cohort study of children ≤ 18 years with perforated appendicitis who underwent primary appendectomy. Children with primary nonoperative management or interval appendectomy were excluded. Prior to the intervention, children at our hospital routinely received PT for perforated appendicitis. An electronic health record (EHR)-integrated guideline that recommended ceftriaxone and metronidazole for perforated appendicitis was released on July 1, 2017 (Figure 1). We compared PT utilization, measured in days of therapy (DOT) per 1,000 patient-days, and clinical outcomes before and after the intervention. Results A total of 74 children with perforated appendicitis were identified: 23 during the pre-intervention period (June 1, 2016 to June 30, 2017) and 51 post-intervention (July 1, 2017 to September 30, 2018). Thirty-three patients (45%) were female and the median age was 8 years (IQR: 5–11.75 years). Post-intervention rate of guideline compliance was 84%. PT use decreased from 556 DOT per 1000 patient-days to 131 DOT per 1000 patient-days; incidence rate ratio of 0.24 (95% CI: 0.16–0.35), post-intervention vs. pre-intervention. There was no statistically significant difference in duration of intravenous antibiotics, total antibiotic duration, postoperative length of stay (LOS), total LOS, ED visits/readmission, or surgical site infection (SSI) between pre- and post-intervention periods (Table 1). Conclusion An EHR-integrated ASP intervention targeting children with perforated appendicitis resulted in decreased broad-spectrum antibiotic use with no statistically significant difference in clinical outcomes. Larger, multicenter trials are needed to confirm our findings. Disclosures All authors: No reported disclosures.

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Application of Standardized Antimicrobial Administration Ratio as a Motivational Tool within a Multi-Hospital Healthcare System

Pharmacy ◽

10.3390/pharmacy9010032 ◽

2021 ◽

Vol 9 (1) ◽

pp. 32

Author(s):

Stephanie Shealy ◽

Joseph Kohn ◽

Emily Yongue ◽

Casey Troficanto ◽

P. Brandon Bookstaver ◽

...

Keyword(s):

Healthcare System ◽

Antimicrobial Stewardship ◽

Broad Spectrum ◽

Antimicrobial Use ◽

Post Intervention ◽

Sustained Reduction ◽

The Mean ◽

Student’S T ◽

Student’S T Test ◽

Antimicrobial Administration

The standardized antimicrobial administration ratio (SAAR) is a novel antimicrobial stewardship metric that compares actual to expected antimicrobial use (AU). This prospective cohort study examines the utility of SAAR reporting and inter-facility comparisons as a motivational tool to improve overall and broad-spectrum AU within a three-hospital healthcare system. Transparent inter-facility comparisons were deployed during system-wide antimicrobial stewardship meetings beginning in October 2017. Stakeholders were advised to interpret the results to foster competition and incorporate SAAR data into focused antimicrobial stewardship interventions. Student’s t-test was used to compare mean SAARs in the pre- (July 2017 through October 2017) and post-intervention periods (November 2017 through June 2019). The mean pre-intervention SAARs for hospitals A, B, and C were 0.69, 1.09, and 0.60, respectively. Hospital B experienced significant reductions in SAAR for overall AU (from 1.09 to 0.83; p < 0.001), broad-spectrum antimicrobials used for hospital-onset infections (from 1.36 to 0.81; p < 0.001), and agents used for resistant gram-positive infections in the intensive care units (from 1.27 to 0.72; p < 0.001) after the interventions. The alignment of the SAAR across the health-system and sustained reduction in overall and broad-spectrum AU through implementation of inter-facility comparisons demonstrate the utility in the motivational application of this antimicrobial use metric.

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139. association of Physician Orders for Life-sustaining Treatment (POLST) with Antimicrobial Use at End of Life in Cancer Patients: An Antimicrobial Stewardship Opportunity

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.449 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S199-S200

Author(s):

Olivia Kates ◽

Elizabeth M Krantz ◽

Juhye Lee ◽

John Klaassen ◽

Jessica Morris ◽

...

Keyword(s):

End Of Life ◽

Cancer Patients ◽

Symptom Management ◽

Research Study ◽

Antibiotic Use ◽

Antimicrobial Use ◽

Study Investigator ◽

Days Of Therapy ◽

Life Sustaining Treatment ◽

Rate Ratios

Abstract Background IDSA/SHEA guidelines recommend that antimicrobial stewardship programs support providers in antibiotic decisions for end of life care. Washington State Physician Orders for Life-Sustaining Treatment (POLST) forms allow patients to indicate antimicrobial use preferences. We sought to characterize antimicrobial use in the last 30 days of life for cancer patients by presence of a POLST and antimicrobial use preferences. Methods We performed a single-center, retrospective cohort study of cancer patient deaths from January 1, 2016 - June 30, 3018. Patient demographics, clinical characteristics, POLST, and antimicrobial use within 30 days before death were extracted from electronic records. To test for an association between POLST completed at least 30 days before death and inpatient antimicrobial days of therapy (DOT) in the 30 days before death, we used negative binomial models adjusted for age, sex, race, and service line (hematologic versus solid malignancy); model estimates are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI) Results Of 1796 patients, 406 (23%) had a POLST. 177/406 (44%) were completed less than 30 days before death, and 58/177 (32.8%) specified limited antibiotic use; 40/177 (23%) did not specify any antimicrobial use preference (Fig 1). Of 1295 patients with at least 1 inpatient day in the 30 days before death, 1070 (83%) received at least 1 inpatient antimicrobial with median DOT of 1077 per 1000 inpatient days (Tab 1). There was no difference in DOT among patients with and without a POLST > /= 30 days before death (IRR 0.92, CI 0.77, 1.10). Patients with a POLST specifying limited antibiotic use had significantly lower inpatient IV antimicrobial DOT compared to those without a POLST (IRR 0.64, CI 0.42–0.97) (Fig 2). Figure 1. Classification of Patients by Presence of POLST, Timing, and Antimicrobial Preference Content of POLST. Numbers shown represent the number of patients (percentage). Full antibiotic use refers to the selection “Use antibiotics for prolongation of life.” Limited antibiotic use refers to the selection “Do not use antibiotics except when needed for symptom management.” Table 1: Antimicrobial use for all patients and by advance directive group Figure 2. Forest plot of model estimates, represented as incidence rate ratios (IRR) with 95% confidence intervals (CI), for associations between POLST antimicrobial specifications completed at least 30 days before death and inpatient antibiotic days of therapy (DOT) in the 30 days before death. Estimates represent comparisons between each POLST category and no POLST completed at least 30 days before death. Dots represent the IRR and brackets extend to the lower and upper limit of the 95% CI. Blue estimates are for the inpatient antibiotic DOT outcome and red estimates are for the inpatient IV antibiotic DOT outcome. Conclusion POLST completion is rare > /= 30 days before death, with few POLSTs specifying antimicrobial use. Compared to those with no POLST in this time frame, patients who indicated that antibiotics should be used only for symptom management received significantly fewer inpatient IV antimicrobials. Early discussion of advance directives including POLST with specification of antimicrobial use preferences may promote more thoughtful use of antimicrobials near the end of life in a compassionate, patient-centered way. Disclosures Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

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Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation

Antibiotics ◽

10.3390/antibiotics10040439 ◽

2021 ◽

Vol 10 (4) ◽

pp. 439

Author(s):

Christopher G. Bunick ◽

Jonette Keri ◽

S. Ken Tanaka ◽

Nika Furey ◽

Giovanni Damiani ◽

...

Keyword(s):

Broad Spectrum ◽

Bacterial Resistance ◽

Antibiotic Use ◽

In Vivo Studies ◽

Infection Model ◽

Severe Acne ◽

Rat Paw Edema ◽

Infection And Inflammation

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.

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