135. Association Between Implementation of the Centers for Medicare & Medicaid Services Sepsis Performance Measure (SEP-1) and Outcomes in U.S. Hospitals

Abstract Background In October 2015, CMS began requiring U.S. hospitals to report compliance with the Severe Sepsis/Septic Shock Early Management Bundle (SEP-1). We evaluated the impact of SEP-1 implementation on sepsis treatment patterns and outcomes using detailed clinical data from diverse hospitals. Methods We conducted a quasi-experimental interrupted time-series analysis of adults admitted to 114 hospitals in the Cerner HealthFacts dataset from October 2013-December 2017 with suspected sepsis (defined by blood culture orders, SIRS criteria, and acute organ dysfunction) within 24 hours of hospital arrival. The primary outcome was quarterly short-term mortality rates (in-hospital death or discharge to hospice). Secondary outcomes included lactate testing and administration of anti-MRSA or anti-Pseudomonal beta-lactam antibiotics within 24 hours of hospital arrival. Generalized estimating equations with robust sandwich variances were used to fit logistic regression models to assess for immediate SEP-1 impact and changes in quarterly trends after October 2015, adjusting for baseline characteristics and severity-of-illness. Results The cohort included 117,510 patients with suspected sepsis on admission. Lactate testing rates increased over the study period (61.9% pre-SEP-1 vs 77.9% post-SEP-1) with a significant immediate increase in risk-adjusted testing rates after SEP-1 (OR 1.34, 95% CI 1.04-1.74) (Figure 1). There was also an increase in utilization of anti-MRSA (20.6% pre vs 23.2% post-SEP-1) and anti-Pseudomonal antibiotics (30.1% vs 39.8%), %), but these trends began before SEP-1 implementation. Unadjusted short-term mortality was similar in the pre vs post-SEP-1 periods (20.3% vs 20.4%). SEP-1 was not associated with either an immediate change (OR 0.94, 95% CI 0.68-1.29] or quarterly trend change (OR 1.00, 95% CI 0.97-1.04] in risk-adjusted short-term mortality (Figure 2). Figure 1. Quarterly risk-adjusted rates of A) lactate testing, B) anti-MRSA antibiotic administration, and C) anti-Pseudomonal beta-lactam antibiotic administration within 24 hours of hospital presentation for patients with suspected sepsis before and after SEP-1 implementation in Q4 2015. All models included time (in quarters), an indicator of the post-SEP-1 implementation period (starting Q12016, to allow for evaluation of an immediate policy effect), and a two-way interaction term to assess whether SEP-1 implementation resulted in a change in trend. When data suggested no change in trend, models were also fit without this interaction term; this yielded a significant association for an immediate level change in lactate testing (OR 1.34 [95% CI 1.04-1.74]) but not antibiotic utilization. All analyses were adjusted for patient severity of illness and baseline characteristics including age, sex, race, initial vital signs (systolic blood pressure, temperature, respiratory rate, heart rate), and initial laboratory results (creatinine, platelet count, bilirubin, white blood cell count) if done within 24 hours. Figure 2. Quarterly risk-adjusted outcomes of patients with suspected sepsis before and after SEP-1 implementation in Q4 2015: A) In-hospital death or discharge to hospice, and B) In-hospital death alone. Models included time (in quarters), an indicator of the post-SEP-1 implementation period (starting Q12016, to allow for evaluation of an immediate policy effect), and a two-way interaction term to assess whether SEP-1 implementation resulted in a change in trend. Analyses were adjusted for patient severity of illness and baseline characteristics including age, sex, race, initial vital signs (systolic blood pressure, temperature, respiratory rate, heart rate), and initial laboratory results (creatinine, platelet count, bilirubin, white blood cell count) if done within 24 hours. Conclusion SEP-1 implementation was associated with an immediate increase in lactate testing rates, no significant change in already-rising rates of broad-spectrum antibiotic use, and no change in short-term mortality rates for patients with suspected sepsis in a large cohort of hospitals. Other approaches to decrease sepsis mortality may be warranted. Disclosures Chanu Rhee, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author) Sameer S. Kadri, MD, MS, FIDSA, Nothing to disclose Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

Background. Rhinovirus (RV) is a major respiratory virus that poses a threat to immunocompromised people and those with underlying disease. However, there are no approved therapies. Moreover, RV infection cannot be prevented by a vaccine because there are over 100 serotypes. Here we report the pharmacological profile of a novel small-molecule host-targeted antiviral (HTA), KRP-A218 (A218). A highly potent and selective inhibitor of phosphatidylinositol 4 kinase beta (PI4KB), a key host factor of RV replication, A218 is undergoing clinical study.
Methods. in vitro antiviral activities of A218 and Vapendavir (Vap), a virus-targeted antiviral, were examined by inhibition of CPE, viral load, or replication. in vivo antiviral activity and pathological analysis of A218 were examined in coxsackievirus B3 (CVB3; belong to the genus enterovirus as with RV)-infected mice as a surrogate model of RV infection as CVB3, unlike RV, replicates very well in both mouse and human tissue. Daily oral dosing of A218 (1-10 mg/kg) was started 2 days post intraperitoneal infection with CVB3. Tissue viral load, pancreas pathological change at 4 days post infection, and survival rate up to 14 days were evaluated. PI4KB heterozygous kinase-dead mice (PI4KB KD) were established by a CRISPR-Cas9 system. Viral load and survival rate following viral infection were evaluated in these mice.
Results. A218 showed broad antiviral activity for RV and enteroviruses (Table) and has a higher barrier to drug resistance than Vap. These results are consistent with expectations for HTAs. Repeated dosing of A218 starting 2 days post infection decreased viral load and improved acute pancreatitis, accompanied by decrease of inflammatory and pancreatitis markers in plasma. Moreover, therapeutic dosing of A218 improved survival rate in a CVB3-infected lethal mouse model ( Figure). These results show the first evidence that a PI4KB inhibitor has potent therapeutic efficacy in a severe viral infection model. Similar effects were observed in PI4KB KD, supporting the on-target effect of A218.  Background. In October 2015, CMS began requiring U.S. hospitals to report compliance with the Severe Sepsis/Septic Shock Early Management Bundle (SEP-1). We evaluated the impact of SEP-1 implementation on sepsis treatment patterns and outcomes using detailed clinical data from diverse hospitals.
Methods. We conducted a quasi-experimental interrupted time-series analysis of adults admitted to 114 hospitals in the Cerner HealthFacts dataset from October 2013-December 2017 with suspected sepsis (defined by blood culture orders, SIRS criteria, and acute organ dysfunction) within 24 hours of hospital arrival. The primary outcome was quarterly short-term mortality rates (in-hospital death or discharge to hospice). Secondary outcomes included lactate testing and administration of anti-MRSA or anti-Pseudomonal beta-lactam antibiotics within 24 hours of hospital arrival. Generalized estimating equations with robust sandwich variances were used to fit logistic regression models to assess for immediate SEP-1 impact and changes in quarterly trends after October 2015, adjusting for baseline characteristics and severity-of-illness.
All models included time (in quarters), an indicator of the post-SEP-1 implementation period (starting Q12016, to allow for evaluation of an immediate policy effect), and a two-way interaction term to assess whether SEP-1 implementation resulted in a change in trend. When data suggested no change in trend, models were also fit without this interaction term; this yielded a significant association for an immediate level change in lactate testing (OR 1.34 [95% CI 1.04-1.74]) but not antibiotic utilization. All analyses were adjusted for patient severity of illness and baseline characteristics including age, sex, race, initial vital signs (systolic blood pressure, temperature, respiratory rate, heart rate), and initial laboratory results (creatinine, platelet count, bilirubin, white blood cell count) if done within 24 hours. Models included time (in quarters), an indicator of the post-SEP-1 implementation period (starting Q12016, to allow for evaluation of an immediate policy effect), and a two-way interaction term to assess whether SEP-1 implementation resulted in a change in trend. Analyses were adjusted for patient severity of illness and baseline characteristics including age, sex, race, initial vital signs (systolic blood pressure, temperature, respiratory rate, heart rate), and initial laboratory results (creatinine, platelet count, bilirubin, white blood cell count) if done within 24 hours.
Conclusion. SEP-1 implementation was associated with an immediate increase in lactate testing rates, no significant change in already-rising rates of broad-spectrum antibiotic use, and no change in short-term mortality rates for patients with suspected sepsis in a large cohort of hospitals. Other approaches to decrease sepsis mortality may be warranted.
Disclosures. Chanu Rhee, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author) Sameer S. Kadri, MD, MS, FIDSA, Nothing to disclose Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author) Background. Outpatient parenteral antibiotic therapy (OPAT) provides select patients a cost-effective alternative to completing intravenous (IV) antibiotic therapy outside the hospital. The Infectious Diseases Society of America (IDSA) OPAT practice guidelines and handbook recommend weekly laboratory monitoring and timely follow-up for OPAT patients. An analysis at VA Palo Alto Healthcare System (VAPAHCS) conducted prior to pharmacist involvement demonstrated that IDSA recommendations were not routinely followed, leading to a clinical cure rate of 62.7%. This led to the implementation of an OPAT pharmacist in 2019. This analysis aims to determine the impact of a pharmacist-managed OPAT program at VAPAHCS.

Impact of an OPAT Pharmacist on Guideline Adherence and Clinical Outcomes
Methods. This comparative, retrospective analysis included patients who received OPAT at VAPAHCS between October 1, 2019 and September 30, 2020 and those who received OPAT in a prior analysis. Primary outcomes included rates of adherence to IDSA recommendations on follow-up visits and weekly lab monitoring during OPAT. Secondary outcomes included rates of clinical cure, 90-day readmission, and adverse events or complications. Data was analyzed using Fisher's exact test and independent t-test.