Impact of Emergency Medicine Clinical Pharmacist Practitioner-Driven Sepsis Antibiotic Interventions

Authors (Top 5):

1. Aubrie Hammond, PharmD
2. Regan Porter, PharmD
3. Kevin E. Lynch, PharmD
4. Taylor H. Cason, PharmD
5. Patrick Passaretti, PharmD

Journal Name: American Journal of Emergency Medicine

Year: 2024

Volume: 76

Issue: 24–28

Type of Study: Retrospective Comparison Study

DOI: 10.1016/j.ajem.2023.11.012

Quick Reference Summary

• Implementation of an Emergency Medicine Clinical Pharmacist Practitioner (EM CPP)-driven protocol significantly increased appropriate empiric antibiotic selection from 57.5% to 86% (p < 0.01) in septic patients.
• The protocol also reduced time-to-first antibiotic administration by 64 minutes (p < 0.01), enhancing the timeliness of sepsis management in the emergency department.

Core Clinical Question

Does an Emergency Medicine Clinical Pharmacist Practitioner-driven protocol for antimicrobial selection, compared to physician-ordered antibiotics without pharmacist intervention, improve the appropriateness of empiric antibiotic utilization and reduce time-to-antibiotic administration in adult patients with sepsis in the emergency department?

Background

• Disease Overview: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, affecting over 1.7 million American adults annually and resulting in approximately 270,000 deaths.
• Prior Data:
  • Improved Outcomes with Pharmacists: Studies have demonstrated that pharmacist involvement in sepsis care enhances time-to-antibiotic administration and antibiotic appropriateness ([Liu VX et al., 2017]; [Messina AP et al., 2015]).
  • Challenges with SEP-1 Guidelines: The 2021 Surviving Sepsis Campaign (SSC) Guidelines recommend antimicrobial administration within the first hour. However, the SEP-1 requirements for broad-spectrum antibiotics often conflicted with antimicrobial stewardship, leading to misuse and overuse ([Pulia MS et al., 2017]; [Trinh TD & Klinker KP, 2015]).
• Current Standard of Care: Immediate administration of antimicrobials upon sepsis recognition as per SSC Guidelines.
• Knowledge Gaps:
  • Lack of studies evaluating antibiotic use in sepsis driven entirely by EM Clinical Pharmacist Practitioners.
  • Limited understanding of the impact of pharmacist-driven protocols post-removal of SEP-1 prespecified antibiotic lists.
• Study Rationale: EM Clinical Pharmacists are strategically positioned to optimize antimicrobial selection and administration timing, potentially bridging gaps in sepsis management and enhancing patient outcomes.

Methods Summary

• Study Design: Single-center, retrospective comparison study.
• Setting and Time Period: CaroMont Regional Medical Center's Emergency Department (ED) from October 1, 2021 – February 28, 2022 (no pharmacist intervention) compared to October 1, 2022 – February 28, 2023 (with EM CPP intervention).
• Population Characteristics: Adults (≥18 years) admitted from the ED with a diagnosis of sepsis, identified through two SIRS criteria and a suspected source of infection.
• Inclusion/Exclusion Criteria:
  • Inclusion: Patients ≥18 years with sepsis based on two SIRS criteria and a confirmed source of infection.
  • Exclusion: Unconfirmed infection sources, multiple infection sources, vulnerable populations (pregnant, incarcerated), transferred patients, advanced directives, comfort measures only, or those who expired prior to admission.
• Intervention Details: EM CPPs reviewed patient profiles, historical admissions, culture data, and allergy profiles to guide antimicrobial selection. They entered orders under their scope of practice with formal documentation in the electronic medical record (EMR).
• Control/Comparison Group: Antibiotic orders placed by EM physicians without EM CPP consultation.
• Primary and Secondary Outcomes:
  • Primary Outcome: Rate of appropriate empiric antibiotic utilization in the ED.
  • Secondary Outcomes: Time-to-antibiotic administration, antibiotic administration within 60 minutes, broadening of empiric antibiotics on admission, hospital length of stay (LOS), in-hospital mortality, and association between Rapid Emergency Medicine Score (REMS) and mortality.
• Statistical Analysis Approach: Utilized Chi-square tests, Student's t-tests, and descriptive statistics. Statistical significance was defined as p < 0.05.
• Sample Size Calculations: Required 77 patients per group to achieve 90% power with α = 0.05, targeting a post-intervention appropriate antibiotic selection rate of 75%.
• Ethics and Funding Information: Approved by the institutional review board. No specific grants or funding sources; no conflicts of interest disclosed.

Detailed Results

Participant Flow and Demographics

• Total Patients Included: 144 (80 no pharmacist intervention, 64 EM CPP consulted).
• Age: No pharmacist group mean age 59.7 ± 15.2 years vs. EM CPP group 65.4 ± 13.6 years (p = 0.02).
• Gender: No significant difference (49% vs. 59%, p = 0.20).
• BMI: No significant difference (30.3 ± 8.4 vs. 28.0 ± 7.9, p = 0.10).
• REMS: No significant difference between groups (6.0 ± 3.4 vs. 6.9 ± 3.1, p = 0.09).
• Suspected Sources of Infection: Pneumonia (40% vs. 57.8%), Genitourinary (21.3% vs. 18.7%), Intra-abdominal (16.2% vs. 9.4%), among others.

Primary Outcome Results

• Appropriate Empiric Antibiotic Selection: Increased from 57.5% (46/80) in the no intervention group to 86.0% (55/64) in the EM CPP consulted group (difference 28.5%; p < 0.01).
• Confidence Intervals: Not reported.

Secondary Outcome Results

• Time-to-First Antibiotic Administration: Reduced by 64 minutes in the EM CPP group (p < 0.01).
• Antibiotic Administration Within 60 Minutes: No significant difference (p = 0.12).
• Broadening of Antibiotics on Admission: No significant difference overall (p = 0.25), but subgroup analysis for pneumonia showed a non-significant trend towards reduced inappropriate broadening (43.7% vs. 24.3%; p = 0.09).
• Hospital Length of Stay: No significant difference (p = 0.82).
• In-Hospital Mortality: No significant difference (7.5% vs. 7.8%; p = 0.94).

Subgroup Analyses

• Pneumonia:
  • Appropriate empiric antibiotics: 57.5% vs. 83.3% (p = 0.65)
  • Broadening on admission: 43.7% vs. 24.3% (p = 0.09)
• Genitourinary:
  • Appropriate empiric antibiotics: 41.2% vs. 41.7% (p = 0.98)
  • Broadening on admission: 41.2% vs. 41.7% (p = 0.98)
• Intra-abdominal:
  • Appropriate empiric antibiotics: 46.1% vs. 83.3% (p = 0.13)
  • Broadening on admission: 53.8% vs. 66.7% (p = 0.60)

Adverse Events/Safety Data

• In-Hospital Mortality: 11 patients expired; no significant difference in REMS between expired and survived patients.
• REMS Analysis: Mean REMS for expired patients was 8.36 ± 3.44 vs. 6.21 ± 3.23 for survivors, translating to a 3% risk of mortality across both groups.

Results Tables

Authors' Conclusions

• Primary Conclusions: An EM Clinical Pharmacist Practitioner-driven protocol significantly improved the rate of appropriate empiric antimicrobial selection and reduced time-to-antibiotic administration in septic patients within the emergency department.
• Interpretation of Results: The involvement of EM CPPs enhances antimicrobial stewardship by ensuring guideline-concordant antibiotic selection and expedited administration.
• Clinical Implications: Integrating EM CPPs into sepsis management protocols can lead to more appropriate antibiotic use and faster treatment initiation, potentially improving patient outcomes.
• Future Research Recommendations: Expand CPP services, investigate long-term patient-centered outcomes, and evaluate the generalizability of these findings across multiple centers and diverse clinical settings.

Critical Analysis

A. Strengths

• Methodological Strengths:
  • Implementation of a pharmacist-driven protocol based on Infectious Diseases Society of America (IDSA) guidelines and antimicrobial stewardship principles.
  • Use of standardized antibiotic decision trees for each suspected source of infection, enhancing consistency in antibiotic selection.
  • Subgroup analyses provided insights into specific infection sources and antibiotic appropriateness.
  • Data reliability was ensured through a 10% medical record review, achieving a kappa coefficient of 0.74, indicating substantial agreement among reviewers.
• Internal Validity:
  • Appropriate comparison between intervention and control groups, with statistically significant primary outcomes.
  • Controlled for potential confounders by excluding patients with multiple infection sources and vulnerable populations.
• External Validity:
  • Findings are applicable to similar single-center EDs with access to credentialed Clinical Pharmacist Practitioners.

B. Limitations

• Study Design: Retrospective design introduces potential for selection bias and information bias.
• Sample Size: Small, single-center study with a total of 144 patients, potentially limiting generalizability and statistical power for secondary outcomes.
• Selection Bias: Inclusion criteria based on specific SIRS criteria and confirmed infection sources may exclude a broader patient population presenting with sepsis.
• Confounding Factors: CMS-required broad-spectrum antibiotics in the no intervention group may have confounded appropriateness grading, as these antibiotics were often broader than guideline-recommended empirics.
• Variability in Time-to-Antibiotic Administration: Large standard deviation in time-to-antibiotic administration could be influenced by factors such as patient acuity and nurse-to-patient ratios, potentially masking the uniformity of the intervention's impact.
• Lack of Confidence Intervals: Absence of confidence intervals for primary and secondary outcomes limits the understanding of precision and variability in effect estimates.

C. Literature Context

• Previous Studies and Meta-Analyses:
  • Liu VX, et al. (2017): Demonstrated a 9% increased risk of mortality per hour delay in antibiotic administration for sepsis patients ([JAMA, 2017](#references)).
  • Messina AP, et al. (2015): Showed that pharmacist participation in antimicrobial stewardship improved timeliness across multiple hospitals ([Infect Dis Ther, 2015](#references)).
  • Kalich BA, et al. (2016): Reported that an antibiotic-specific sepsis bundle enhanced appropriate antibiotic administration in the ED ([J Emerg Med, 2016](#references)).
• Contrasting Methodological Quality:
  • Prior studies often utilized prospective designs and multi-center settings, enhancing generalizability, whereas this study was retrospective and single-center, which may affect the robustness of comparisons.
• Comparisons with Guidelines:
  • The study aligns with the 2021 Surviving Sepsis Campaign Guidelines advocating for prompt antimicrobial administration but addresses the need for targeted antibiotic selection beyond the broad-spectrum requirements of CMS SEP-1.
• This Trial's Contribution:
  • First study to evaluate the impact of EM CPP-driven antibiotic protocols on sepsis management post SEP-1 antibiotic removal, highlighting the role of pharmacists in enhancing antibiotic appropriateness and administration timing within the ED setting.

Clinical Application

• Practice Change: The findings support integrating EM Clinical Pharmacist Practitioners into sepsis management protocols to enhance appropriate antibiotic selection and expedite administration.
• Applicable Populations/Scenarios: Particularly beneficial in emergency departments handling adult sepsis patients, especially where antimicrobial stewardship is a priority.
• Implementation Considerations: Requires a team-based approach, standardized protocols, and training for both pharmacists and physicians to optimize collaboration and ensure consistent application of guidelines.
• Integration with Existing Evidence: Consistent with previous research demonstrating the positive impact of pharmacist involvement in antimicrobial stewardship and sepsis management.

How to Use This Info In Practice

Emergency departments should consider integrating Clinical Pharmacist Practitioners into sepsis protocols to enhance the appropriateness of empiric antibiotic selection and reduce the time-to-antibiotic administration, thereby improving patient care outcomes.

References

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Appendix A. Supplementary Data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.ajem.2023.11.012.