Full-dose challenge of moderate, severe, and unknown beta-lactam allergies in the emergency department

Authors: Adam M. Anderson MD, Stephanie Coallier MD, Reid E. Mitchell DO, Lisa E. Dumkow PharmD, Lauren M. Wolf PharmD

Journal Name: Academic Emergency Medicine, Year: 2024, Volume: 00, Issue: 1–5

Type of Study: Single-center, retrospective, descriptive study

DOI: 10.1111/acem.14893

Quick Reference Summary

A full-dose challenge of documented moderate, severe, or unknown beta-lactam allergies in the emergency department (ED) was performed on 184 patients, with only 2.7% experiencing mild allergic reactions and no anaphylactic events, demonstrating the safety of this approach.

86.4% of challenged patients continued beta-lactam therapy upon admission, and 73.4% had their allergy profiles updated, reducing the reliance on suboptimal alternative antibiotics.

Core Clinical Question

In adults presenting to the emergency department with moderate, severe, or unknown beta-lactam allergies, does a full-dose beta-lactam antibiotic challenge safely allow continuation of optimal antibiotic therapy compared to avoiding beta-lactams due to reported allergies?

Background

Penicillin Allergy Prevalence: Approximately 10% in the United States, leading to widespread avoidance of beta-lactam antibiotics.

Cross-reactivity Misconceptions: Previously believed all beta-lactams cross-react; recent research indicates cross-reactivity is primarily driven by side chain similarities rather than the beta-lactam ring itself.

Current Standard of Care: Often involves penicillin skin testing and avoidance of beta-lactams, which can be time-consuming and resource-intensive, especially in the ED setting.

Knowledge Gaps Addressed by Study: This study addresses safety and outcomes of performing full-dose beta-lactam challenges in the ED for patients with moderate, severe, or unknown allergies and offers practical alternatives to skin testing.

Study Rationale: To determine if full-dose beta-lactam challenges in the ED can safely allow for optimal antibiotic therapy without resorting to less effective alternatives, thereby improving antimicrobial stewardship and patient outcomes.

Methods Summary

Study Design: Single-center, retrospective, descriptive study.

Setting and Time Period: Conducted at a 350-bed community teaching hospital in the United States with a 44-bed ED, from January 1, 2021, to December 31, 2022.

Population Characteristics: Adults ≥18 years old admitted to the hospital through the ED with documented moderate, severe, or unknown beta-lactam allergy in the EMR.

Inclusion Criteria: Adults (≥18 years) with moderate, severe, or unknown beta-lactam allergy who received a full-dose beta-lactam antibiotic challenge in the ED.

Exclusion Criteria: Documented mild beta-lactam allergy or intolerance; missing/deleted encounter data; documented prior tolerance to beta-lactams.

Intervention Details: Full-dose administration of a beta-lactam antibiotic without a test dose. Patients and nursing staff were informed of potential symptoms and monitored accordingly.

Control/Comparison Group: Not applicable; descriptive study focusing on outcomes post-challenge.

Primary Outcome: Incidence of allergic reactions post beta-lactam challenge.

Secondary Outcomes: Continuation of beta-lactam therapy upon admission, updates to allergy profiles, adverse drug reactions.

Statistical Analysis Approach: Descriptive statistics using SPSS Version 22. Summary of demographic and clinical characteristics, reaction rates.

Sample Size Calculations: Not specified in the provided text.

Ethics and Funding Information: Study approved by the regional institutional review board and conducted in accordance with ethical standards required in scientific research.

Results

Participant Flow and Demographics

Total Screened: 850 patients.

Included: 184 patients.

Excluded: 474 due to prior tolerance to beta-lactams; 153 due to mild allergies/intolerances.

Median Age: 68 years (IQR 59–80).

Gender: 65.2% female.

Primary Diagnoses:

• Pneumonia (PNA) 36.4%
• Urinary Tract Infection (UTI) 31.5%
• Intra-abdominal infection 15.2%
• Skin/Soft tissue infection 10.9%
• Sepsis 3.3%
• Febrile neutropenia 1.6%
• Meningitis 1.1%

Primary Outcome Results

Allergic Reactions: 5 out of 184 patients (2.7%) experienced allergic reactions post-challenge.

ED Reactions: 1 patient (0.5%) developed mild itching.

Inpatient Reactions: 4 patients (2.2%) developed rash or itching within 72 hours of admission. All reactions were mild (rash or itching); no anaphylaxis occurred.

Secondary Outcome Results

Beta-lactam Continuation: 86.4% continued beta-lactam therapy upon admission.

Allergy Profile Updates: 73.4% had their allergy profiles updated post-challenge.

Subgroup Analyses

Severe Allergies: 24 patients with severe documented allergies were challenged; none had allergic reactions post-challenge.

Adverse Events/Safety Data

Five mild allergic reactions occurred (rash or itching). No severe reactions or anaphylaxis reported.

Results Tables

Table 1: Baseline Characteristics

Table 2: Reported Beta-lactam Allergy History

Table 3: Beta-lactam Challenge Characteristics and Outcomes

Table 4: Characteristics of Patients with Post-Challenge Allergic Reactions

Authors’ Conclusions

Primary Conclusions: Full-dose challenges of moderate, severe, or unknown beta-lactam allergies can be safely performed in the emergency department, with a low incidence of mild allergic reactions and no instances of anaphylaxis.

Interpretation of Results: Implementing full-dose beta-lactam challenges within a robust antimicrobial stewardship program in the ED effectively reduces unnecessary avoidance of beta-lactams without compromising patient safety.

Clinical Implications: This approach allows for the continued use of first-line beta-lactam antibiotics, enhancing treatment efficacy and reducing the use of suboptimal alternative regimens.

Future Research Recommendations: Investigate long-term outcomes post-discharge to monitor for delayed allergic reactions and explore strategies to improve allergy profile documentation prior to patient discharge.

Critical Analysis

A. Strengths

• Robust Sample Size: Included 184 patients, providing sufficient data for descriptive analysis.
• Clinical Relevance: Addresses a common issue in ED settings, optimizing antibiotic stewardship.
• Detailed Adverse Event Reporting: All allergic reactions were monitored and reported, ensuring transparency in safety outcomes.
• Implementation of ASP: Supported by an established antimicrobial stewardship program, enhancing the study’s practical application.

B. Limitations

• Single-Center Study: Results may not be generalizable to other settings with different patient populations or resources.
• Retrospective Design: Potential for selection bias and reliance on accurate EMR documentation.
• Lack of Control Group: Descriptive study limits ability to establish causality between intervention and outcomes.
• Short Follow-up Duration: Patients were not tracked post-discharge for delayed allergic reactions.
• Incomplete Allergy Profile Updates: Only 73.4% had updated allergy profiles, indicating potential for misclassification.

Literature Context

A. Previous Studies and Meta-Analyses

Research indicates that cross-reactivity between penicillin and cephalosporins is primarily based on side chain similarities rather than the beta-lactam ring, suggesting that direct challenges may be safer than previously thought (Khan DA et al., J Allergy Clin Immunol Pract. 2019;7(7):2105-2114).

B. Contrasting Methodological Quality

Previous studies conducted outside of the ED and in low-risk populations have shown benefits of challenging allergies with less stringent protocols, whereas this study extends findings to a broader and potentially higher-risk ED population (Trubiano JA et al., Infect Dis. Open Forum. 2018;5(12):1-5).

C. Comparisons with Guidelines

Current antimicrobial stewardship guidelines often recommend beta-lactam challenges with adjusted protocols, and this study provides evidence supporting direct challenges in the ED setting, aligning with evolving guidelines that advocate for stewardship and appropriate antibiotic use (Copaescu AM et al., JAMA Intern Med. 2023;183(9):944-952).

D. This Trial’s Contribution

Adds real-world evidence supporting the safety and efficacy of full-dose beta-lactam challenges in the ED, potentially influencing guideline updates and clinical practice by demonstrating low reaction rates and high continuation of optimal antibiotics.

Clinical Application

Changing Current Practice: Implementing full-dose beta-lactam antibiotic challenges in the emergency department can safely increase the use of first-line antibiotics for patients with documented moderate, severe, or unknown beta-lactam allergies, reducing reliance on alternative, less effective treatments.

Applicable Patient Populations: Particularly beneficial for adult patients presenting with acute bacterial infections such as pneumonia or urinary tract infections who have reported non-anaphylactic beta-lactam allergies, and in settings with established antimicrobial stewardship programs to support safe challenge protocols.

Additional Notes for Clarity

Conflicts of Interest: The authors declare no conflicts of interest.

Areas of Uncertainty: Potential for delayed allergic reactions post-discharge was not assessed, and the lower update rate of allergy profiles pre-discharge suggests room for improvement in documentation practices.

Funding Sources: Not explicitly stated in the provided text.

Integration with Existing Evidence: Supports recent trends in antimicrobial stewardship advocating for the reassessment of reported beta-lactam allergies to optimize antibiotic use.