Reducing Empiric VAncomycin Use in Pediatric Suspected Sepsis (REVAMP)

Children's Healthcare of Atlanta, St. Louis Children's Hospital, Johns Hopkins University, University of Pennsylvania, Centers for Disease Control and Prevention

The goal of this quasi-experimental interventional study is to determine the effectiveness of a multifaceted stewardship intervention in reducing overall vancomycin use in five tertiary care Pediatric Intensive Care Units (PICU). There are two groups of subjects in this study: PICU clinicians/sepsis stakeholders and patients admitted to one of the participating PICUs during the study period. The intervention will at a minimum include: Implementation of a clinical guideline indicating when vancomycin should and should not be used Unit-level feedback on overall vancomycin use within and across centers Clinician education.

Vancomycin is among the most commonly prescribed antibiotics in United States children's hospitals, and inappropriate use of vancomycin is common. Given the high prevalence of acute kidney injury associated with vancomycin of up to 25%, reducing vancomycin overuse is a key opportunity to reduce preventable patient harm. The primary objective of this study is to determine the effectiveness of a multifaceted stewardship intervention in reducing overall vancomycin use in five tertiary care PICUs. This intervention will be informed by baseline data surrounding vancomycin use and infections due to organisms requiring vancomycin therapy which will allow selective use of vancomycin, as well as a concurrent mixed methods process and formative evaluation to inform implementation of the intervention. During the baseline period, Electronic Health Record (EHR) data will be used to retrospectively quantify unit-level vancomycin use over 24 months (measured as vancomycin days of therapy [DOT]/1000 patient days), as well as the frequency of vancomycin use and prevalence of infections due to organisms requiring vancomycin therapy among patients with suspected and confirmed sepsis. During the post-intervention period, which will last approximately 24 months, a multifaceted stewardship intervention to reduce vancomycin use informed by these baseline data, including: The creation of a consensus guideline for vancomycin use; Ad hoc education related to vancomycin overuse, and; Unit-level feedback on vancomycin prescribing. The feedback on vancomycin use will be provided to clinicians at each site, both within their site (to compare to past performance) and across sites (to compare local performance to the performance of other sites). This intervention will be locally adapted by the investigative team and sepsis stakeholders at each site. Data from the EHR will be used to assess vancomycin use (DOT/1000 patient days), as well as the secondary outcomes. Investigators will perform semi-structured interviews and repeat surveys 9 months after the implementation of the intervention. This mixed-methods process and formative evaluation will help investigators understand which elements of implementation were successful and which were not.

Sepsis, Sepsis Mrsa, Sepsis Bacteremia, Antimicrobial - Induced Nephropathy, Sepsis, Severe, Septic Shock, Septic Syndrome

Sepsis, Vancomycin use, methicillin-resistant Staphylococcus aureus (MRSA), Antibiotic Stewardship, Implementation science

Clinicians and sepsis stakeholders in the participating sites will be primarily recruited via email. During the course of this multifaceted intervention: All the PICU (Pediatric Intensive Care Unit) prescribing clinicians and sepsis stakeholders in the participating sites will receive clinical guidelines, unit-level feedback reports, and education on Vancomycin use during the intervention. Investigators will perform semi-structured interviews with 90 PICU clinicians and sepsis stakeholders. Surveys will be sent to all eligible clinicians, estimated to be up to 2500 individuals across the 4 sites. These structured surveys will be done at baseline and at 9 months post-implementation.

Research procedures involving patients will be limited to medical record review. This medical record review will help inform the intervention directed at PICU clinicians/stakeholders and the assessment of study outcomes. Approximately 50,000 patients will participate in the study. Data elements will be collected at each site and stored as password-protected Comma-separated values (CSV) files. These files will not contain any direct Protected Health Information (PHI) but will contain elements of date (e.g., date of admission, date of suspected sepsis episode). The study Identification (ID) number will be used to identify each unique patient. Each site will collect and store data in compliance with the Children's Hospital of Philadelphia (CHOP) and local Institutional Review Board (IRB) policies.

Clinical guidelines and group-level feedback on vancomycin use will be provided to clinicians/sepsis stakeholders at each site. The semi-structured interviews will be performed by a trained member of the research team, under the supervision of a medical sociologist who is one of the co-investigators. A semi-structured interview guide will be used during the interviews. Interviews will be recorded and transcribed, then uploaded to a qualitative analysis software for management and coding. Names will not be recorded, and pseudonyms will be used in notes, communications about the study, and any presentations. Verbal consent will be obtained before conducting and recording the interviews. The surveys will be performed using REDCap survey software, and participation will be voluntary. No identifiers will be collected.

Vancomycin use will be measured as DOT per 1000 PICU patient days, measured monthly. Every day in which one or more doses of parenteral vancomycin is administered is classified as one vancomycin DOT. Every day or portion of a day a patient is admitted to the PICU is classified as one PICU patient day.

Change in the rate of suspected and confirmed sepsis episodes in which new or persistent respiratory, renal, cardiovascular, or hematologic organ dysfunction occur at day 3 and at day 7.

All-cause mortality will be measured at 30 days following sepsis onset as a proportion of suspected and confirmed sepsis episodes. Only one episode of suspected or confirmed sepsis will be counted in this measure.

Readmission to the PICU is defined as an admission to the PICU occurring within 30 days following discharge from an admission in which there was one or more episodes of suspected or confirmed sepsis. Only one episode of suspected or confirmed sepsis will be counted in this measure. Patients without a readmission to the index hospital or health system will be counted as no readmission, due to the inability to assess readmissions to outside institutions.

The percentage of patients that are readmitted to the hospital within 30 days following discharge from an admission in which there was one or more episodes of suspected or confirmed sepsis. Only one episode of suspected or confirmed sepsis will be counted in this measure.

Cefepime, ceftriaxone, and piperacillin-tazobactam DOT/1000 PICU days, measured monthly (as a non-equivalent dependent variable).

Linezolid, Ceftaroline, clindamycin, and trimethoprim-sulfamethoxazole in DOT/1000 patient days, measured monthly (as a balancing measure to evaluate any increase in other anti-MRSA antibiotics that may occur as an unintended consequence of reducing vancomycin use).

Microbiologic outcome measures will focus on the prevalence of vancomycin-requiring organisms in the suspected and confirmed sepsis cohorts, and will also be measured relative to the frequency of empiric vancomycin administration and compliance with the guideline.

Adoption, the decision to adhere to the guideline for vancomycin use, will be measured as the proportion of sepsis episodes in which the clinician adhered to the guideline based on medical record review. Adoption will be evaluated in a 10% random sample of sepsis episodes each month by chart review.

Appropriateness, the perceived compatibility of the intervention to the PICU practice setting, will be measured during surveys and semi-structured interviews using the Likert Scale; where 1 = completely disagree and 5 = completely agree.

Acceptability, how well the intervention was received by the PICU clinicians will be measured during surveys and semi-structured interviews using the Likert Scale; where 1 = completely disagree and 5 = completely agree.

Feasibility, the extent to which the intervention can be carried out in the setting, will be determined in collaboration with our local stakeholders but may include the proportion of PICU clinicians who attend educational sessions and/or unit-based meetings during which vancomycin use data is reviewed.

Patient Inclusion Criteria: Admitted to one of the participating PICUs during the study period Patient Exclusion Criteria: None Clinician Inclusion Criteria: PICU prescribing clinician (including attending physicians, fellows, residents, nurse practitioners, and physician assistants) OR sepsis stakeholder (leader of sepsis quality improvement work, medical director) at one of the participating sites at the time the survey is deployed Age ≥ 18 years old Employed by one of the participating sites Clinician Exclusion Criteria: Volunteers or other non-employee hospital staff Limited English proficiency

This study was initiated prior to the NIH Data Management and Sharing Policy update that was released on January 25, 2023.

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