UMEM Educational Pearls

Background:

Approximately 10% of patients presenting to the emergency department (ED) report penicillin allergies, which may lead to use of second- or third-line agents. Alternative therapies (such as aztreonam, clindamycin and fluroquinolones) carry an increased risk of mortality and complications such as Clostridioides difficile infection. Considering that less than 10% of penicillin allergies may be confirmed by formal testing results, the PEN-FAST clinical decision tool was created to identify patients with low risk of true penicillin allergy who do not require formal skin testing for rechallenging with a beta-lactam:

Though PEN-FAST has only been validated in the clinic and inpatient settings, a study from Tran et al. published this January sought to determine the safety and efficacy of utilizing this tool to assess penicillin allergies and re-challenge patients in the ED.

Study design:

This was a single-center, prospective, observational cohort study. Emergency medicine (EM) pharmacists screened patients in the ED with:

• A documented penicillin, amoxicillin or ampicillin allergy who also had an order for IV or oral clindamycin, levofloxacin or aztreonam OR
• A documented penicillin, amoxicillin or ampicillin allergy and an EM physician placed a general consult order to pharmacy requesting evaluation of antibiotic selection.

Screened patients were excluded from the study if orders were placed by a non-EM physician, if they previously tolerated a penicillin/cephalosporin within the healthcare system of the study site, if they were unable to participate in bedside interview, if the antibiotics selected were appropriate despite the penicillin allergy or if there were time constraints that would delay care if the PEN-FAST assessment needed to be completed. 

Study Intervention:

EM pharmacists completed the PEN-FAST assessment for all included patients. They recommended rechallenging with an appropriate beta-lactam for patients with a score of 0-2, recommended to consider rechallenging for patients scoring 3, and did not recommend rechallenging for scores of 4-5 or if it was confirmed patients previously experienced anaphylaxis, angioedema or severe cutaneous reactions with a beta-lactam. Orders for any change in therapy were only placed with discussion and agreement from EM physicians. Rechallenged patients were assessed at bedside for any immune-mediated reactions 45 to 75 minutes after initiation of antibiotics. The primary outcome was the percent of patients with a PEN-FAST score of 0-2 who tolerated a beta-lactam after being rechallenged.

Patient Characteristics:

After screening, one hundred patients were included in this study.

• Median age: 72 [IQR 59-81]
• Penicillin Allergy Label:
  • Penicillin VK, G or unspecified = 88%
  • Amoxicillin or ampicillin = 11%
  • Combined amoxicillin/clavulanate = 1%
• Calculated PEN-FAST scores:
  • 0 = 31%
  • 1 = 26%
  • 2 = 4%
  • 3 = 30%
  • 4 = 3%
  • 5 = 6%

Results:

Primary Outcome: 

• Out of 61 patients with a PEN-FAST score of 0-2, 52 patients were rechallenged. All 52 patients (100%) tolerated rechallenge with a beta-lactam.

Secondary Outcomes:

• Out of 30 patients with a PEN-FAST score of 3, six patients were rechallenged. All six patients (100%) tolerated rechallenge with a beta-lactam.
• The number of immune mediated reactions among all patients rechallenged was 0.
• Median time from initial order entry to entry of new antibiotic order for patients who were re-challenged was 17 minutes (IQR 10-23)
• Median time from initial order to antibiotic administration for patients who were re-challenged was 41 minutes (IQR 29-65)

Key Takeaways:

• The PEN-FAST decision tool was able to safely identify and risk-stratify eligible patients for beta-lactam rechallenge in the ED in this exploratory study.
• Prudent antibiotic selection is of particular significance in the ED, given that antibiotic therapy initiated in the ED influences inpatient ordering.

References

1. Tran K, Lund J, Sealy C, Langley D, Kisgen J. PEN-FAST-ED: Utilizing the PEN-FAST decision tool to guide antibiotic prescribing in the emergency department. Am J Emerg Med. Published online January 19, 2025. doi:10.1016/j.ajem.2025.01.039
2. Blumenthal, Kimberly G et al. “Antibiotic allergy.” Lancet (London, England) vol. 393,10167 (2019): 183-198. doi:10.1016/S0140-6736(18)32218-9?
3. Trubiano JA, Vogrin S, Chua KYL, et al. Development and Validation of a Penicillin Allergy Clinical Decision Rule. JAMA Intern Med. 2020;180(5):745–752. doi:10.1001/jamainternmed.2020.0403