Article Identification

Article Title: A pharmacist-driven deprescribing protocol for negative urine and sexually transmitted infection cultures in the emergency department increases antibiotic-free days

Authors: Yifan Wang, PharmD; Karlie Knobloch, PharmD; Shannon Lovett, MD; Neal Lyons, PharmD; Megan A. Rech, PharmD, MS, FCCM, FCCP, BCCCP

Journal: American Journal of Health-System Pharmacy (Am J Health-Syst Pharm), 2024;81:e83-e89

Type of Study: Single-center, prospective, observational, pre-post intervention study

DOI: 10.1093/ajhp/zxad255

Quick Reference Summary

Implementation of a pharmacist-driven deprescribing protocol in the emergency department (ED) increased antibiotic-free days from 35.1% in the preintervention group to 80.5% in the postintervention group (P=0.00).

This protocol effectively reduced unnecessary antibiotic use in patients discharged with negative urine cultures and sexually transmitted infection (STI) test results.

Core Clinical Question

Does a pharmacist-driven deprescribing protocol for patients with negative urine and STI cultures in the emergency department increase antibiotic-free days compared to standard culture callback protocols?

Background

Condition Overview

Overuse of antibiotics in the emergency department contributes to antimicrobial resistance and adverse reactions, including Clostridioides difficile infections.

Prior Data

• Approximately 30% of antimicrobials prescribed in outpatient and ED settings were inappropriate, leading to increased antibiotic resistance and adverse effects.^1,2
• Optimizing antimicrobial therapy and reducing unnecessary antibiotic usage are associated with improved long-term clinical outcomes.^1,2

Current Standard of Care

ED pharmacist-led culture callback protocols focus on positive cultures to recommend antimicrobial optimization but do not typically include de-escalation based on negative cultures.

Knowledge Gaps Addressed

Existing protocols do not utilize negative culture results for antibiotic deprescribing, leaving potential for overuse.

Study Rationale

Incorporating a de-escalation process into ED culture follow-up may enhance antimicrobial stewardship by increasing antibiotic-free days and reducing unnecessary antibiotic exposure.

Methods Summary

Study Design

Single-center, prospective, observational, pre-post intervention study.

Setting and Time Period

Loyola Medical University Center ED, November 1, 2020, to May 31, 2022.

Population Characteristics

Patients ≥18 years discharged from the ED with prescribed antibiotics and subsequent negative urine cultures or STI test results.

Inclusion/Exclusion Criteria

• Inclusion: Adults discharged with antibiotics and negative culture results.
• Exclusion: Hospital admission, ED mortality, transfers, pregnancy, diagnosis of pyelonephritis or pelvic inflammatory disease, unreachable after three call attempts.

Intervention Details

Pharmacist-led protocol where pharmacy residents reviewed daily culture reports, contacted patients to assess symptoms, and discontinued antibiotics if appropriate based on a standardized script and institutional antibiogram.

Control/Comparison Group

Preintervention group followed standard culture callback protocols without de-escalation based on negative results.

Primary and Secondary Outcomes

• Primary Outcome: Days free of antibiotics within 28 days post culture collection.
• Secondary Outcomes: Reduction in antibiotic use, potential decrease in antimicrobial resistance, and adverse drug events.

Statistical Analysis Approach

Descriptive statistics using Student’s t-test and Mann-Whitney U test for continuous data; chi-square or Fisher’s exact test for nominal data. Significance assessed at two-sided α=0.05.

Sample Size Calculations

Not specified.

Ethics and Funding Information

Institutional review board–approved. Funded in part by the ASHP Research and Education Foundation. No conflicts of interest declared.

Detailed Results

Participant Flow and Demographics

• Screened: 192 patients
• Included: 63 preintervention and 26 postintervention
• Excluded: 103 patients (23 pre – ED admissions; 16 post – urinary symptoms; 11 post – loss to follow-up)
• Baseline Characteristics: Predominantly female (69% pre vs. 56% post), majority African American (59% pre vs. 61% post), with hypertension as the most common comorbidity (13% pre vs. 23% post).

Primary Outcome Results

• Preintervention Group: 35.1% antibiotic-free days (163/465 days)
• Postintervention Group: 80.5% antibiotic-free days (150.5/187 days)
• Statistical Significance: P=0.00

Secondary Outcome Results

• Significant increase in the discontinuation of cephalexin (29 pre vs. 35 post, P=0.00).
• Trends towards reduced use of doxycycline and increased use of ceftriaxone in the postintervention group, though not all changes reached statistical significance.

Adverse Events/Safety Data

Not reported.

Results Tables

Table 1. Baseline Characteristics of Study Groups

Characteristic	Preintervention (n=63)	Postintervention (n=26)	P-value
Age, mean (SD), years	37.2 (16)	43.4 (21)	0.06
Female, No. (%)	44 (69)	15 (56)	0.23
Race, No. (%)
- Caucasian	18 (29)	4 (15)	0.19
- African American	37 (59)	16 (61)	0.81
- Hispanic/Latino	13 (21)	8 (31)	0.31
Comorbidities, No. (%)
- Hypertension	8 (13)	6 (23)	0.22
- History of malignancy	0	2 (8)	0.02
Documented Symptoms, No. (%)
- Dysuria	24 (38)	5 (19)	0.70
- Nausea/vomiting	14 (22)	0	0.14
- Unusual discharge	18 (29)	8 (31)	0.84
STI Test Performed, No. (%)
- Chlamydia	35 (56)	14 (54)	0.88
- Gonorrhea	35 (56)	14 (54)	0.50

Table 2. Urinalysis Characteristics of Study Groups

Characteristic	Preintervention (n=63)	Postintervention (n=26)	P-value
Presence of leukocyte esterase in urine, No. (%)	33 (52)	14 (54)	0.25
Presence of nitrite in urine, No. (%)	8 (13)	0	0.07
Patient received IV antibiotics (ceftriaxone), No. (%)	4 (6)	14 (54)	0.03

Table 3. Patient Receipt of Oral Antibiotics on Discharge, by Study Group

Antibiotic	Preintervention (n=63)	Postintervention (n=26)	P-value
Cephalexin	18 (29%)	9 (35%)	0.00
Doxycycline	12 (19%)	12 (46%)	0.06
Others	Various	Various	Varied

Table 4. Results for Primary Endpoint by Study Group

Endpoint	Preintervention (n=63)	Postintervention (n=26)
Days of antibiotic courses completed, No./Total (%)	465/465 (100%)	36.5/187 (19.5%)
Days free of antibiotics, No./Total (%)	0/465 (0%)	150.5/187 (80.5%)

Authors' Conclusions

• Primary Conclusions: A pharmacist-driven deprescribing protocol significantly increased antibiotic-free days in patients discharged from the ED with negative urine cultures and STI test results.
• Interpretation of Results: Implementing an expanded culture callback program that includes negative cultures can enhance antimicrobial stewardship by reducing unnecessary antibiotic use.
• Clinical Implications: Adoption of pharmacist-led deprescribing protocols in ED settings may lead to decreased antimicrobial resistance and fewer adverse drug reactions.
• Future Research Recommendations: Further investigation is needed to assess the statistical significance of extended protocols and their impact on long-term clinical outcomes and antimicrobial resistance patterns.

Literature Review

A. Previous Studies and Meta-Analyses

1. Shealy SC, et al. Pharmacist-driven culture and sexually transmitted infection testing follow-up program in the emergency department. Pharmaceutics. 2020;8(2):E72.
   Findings: Demonstrated that pharmacist-led follow-up programs reduce time to antimicrobial optimization.
2. Stoll K, et al. Pharmacist-driven implementation of outpatient antibiotic prescribing algorithms in the emergency department. J Pharm Pract. 2021;34(6):875-881.
   Findings: Showed improved guideline adherence and reduced inappropriate antibiotic prescribing.

B. Contrasting Methodological Quality

The current study's prospective observational design contrasts with previous randomized controlled trials (RCTs) that may offer higher internal validity. However, the real-world applicability of this study provides valuable external validity.

C. Comparisons with Guidelines

Centers for Disease Control and Prevention (CDC), 2020. Antibiotic stewardship guidelines emphasize the importance of reducing unnecessary antibiotic use to combat resistance.¹⁹

D. This Trial's Contribution

This study adds to existing evidence by demonstrating that including negative culture results in pharmacist-led deprescribing protocols can significantly increase antibiotic-free days, supporting broader antimicrobial stewardship efforts in ED settings. It confirms and extends findings from prior studies that highlight the critical role of pharmacists in optimizing antibiotic use.¹⁹

Critical Analysis

A. Strengths

• Methodological Strengths:
  • Prospective design enhances data reliability.
  • Clear inclusion and exclusion criteria reduce selection bias.
• Internal Validity:
  • Consistent implementation of the deprescribing protocol by trained pharmacists.
• External Validity:
  • High patient volume setting increases generalizability to similar ED environments.

B. Limitations

• Study Design Limitations:
  • Observational pre-post design may be subject to confounding factors.
• Potential Biases:
  • Selection bias due to exclusion of unreachable patients.
• Generalizability Issues:
  • Single-center study limits applicability to other settings with different patient populations or resources.
• Statistical Limitations:
  • Small sample size, particularly in the postintervention group, may affect the robustness of findings.
• Missing Data Handling:
  • Assumed 100% antibiotic adherence in the preintervention group without actual compliance data.

C. Literature Context

The study aligns with previous research demonstrating the effectiveness of pharmacist-led interventions in reducing antibiotic misuse and optimizing antimicrobial therapy in emergency settings. It extends these findings by incorporating negative culture results into the deprescribing protocol, thus addressing a previously unmet aspect of antimicrobial stewardship.

Clinical Application

• The findings suggest that integrating pharmacist-driven deprescribing protocols into ED workflows can substantially reduce unnecessary antibiotic use, promoting better antimicrobial stewardship.
• This approach is particularly applicable to patients discharged from ED with negative urine cultures and STI results, potentially leading to decreased antimicrobial resistance and fewer adverse drug events.
• Implementation requires collaboration between pharmacists and ED physicians, with adequate training and resources to ensure timely patient outreach and accurate assessment for antibiotic discontinuation.

How to Use This Info In Practice

Practitioners should consider implementing pharmacist-led deprescribing protocols for patients with negative urine and STI cultures in the emergency department to reduce unnecessary antibiotic use and enhance antimicrobial stewardship.

References

1. Centers for Disease Control and Prevention. Antibiotic use in the United States, 2018 update: progress and opportunities. Published November 12, 2020. Accessed July 27, 2022. https://www.cdc.gov/antibiotic-use/stewardship-report/2018.html
2. Centers for Disease Control and Prevention. Antibiotic use in the United States, 2020 update: progress and opportunities. Published July 12, 2022. Accessed July 27, 2022. https://www.cdc.gov/antibiotic-use/stewardship-report/2020.html
3. Shealy SC, Alexander C, Hardison TG, et al. Pharmacist-driven culture and sexually transmitted infection testing follow-up program in the emergency department. Pharm Technol (Basel). 2020;8(2):E72. doi:10.3390/pharmacy8020072
4. Stoll K, Feltz E, Ebert S. Pharmacist-driven implementation of outpatient antibiotic prescribing algorithms in the emergency department. J Pharm Pract. 2021;34(6):875-881. doi:10.1177/0897190020930979
5. Davis LC, Covey RB, Weston JS, Hu BBY, Laine GA. Pharmacist-driven antimicrobial optimization in the emergency department. Am J Health-Syst Pharm. 2016;73(5)(suppl 1):S49-56. doi:10.2146/sp150036