Penicillin Allergy De-labeling: Evaluating a Health

System’s Implementation of the PEN-FAST Tool

within an Infectious Disease Clinic
Jennifer N. McCarthy, PharmD, MS
PGY-1 Pharmacy Resident

Mentors:
Trent G. Towne, PharmD, BCPS, BCIDP; Parkview Health
Aaron C. Daseler, PharmD, BCCCP; Parkview Health
Jamie L. Gaul, PharmD, BCPS; Parkview Health

The speaker and mentors have no actual or potential conflict of interest in relation to this presentation
 Why the Term Penicillin Allergy is Misleading
• Estimated that ~10% of all US patients report an allergic reaction to a beta-lactam antibiotic
• Approximately over 80% of these patients lose their sensitivity after 10 years
• <1% of the whole population have a true IgE mediated allergy

• Excessively broad term as most agents may not have cross reactivity
• Leading to an inappropriate antibiotic class allergy

"Penicillins" refers to four When patients report

general groups of "penicillin allergy" they
antibiotics: commonly refer to:
• Natural penicillins • Aminopenicillin
• Anti-staph penicillins • Penicillin G
• Aminopenicillins • Penicillin VK
• Anti-pseudomonal penicillins

Caruso C. et al. J Asthma Allergy. 2021;14:31-46.; Centers for Disease Control and Prevention.
 Side Chain Role in Drug Allergies
• Previously thought to be related to the core beta-lactam ring structure
• Would confer reaction to all beta-lactam antibiotics
• Beta-lactams are too small to bind to IgE
▪ IgE mediated allergies occur via R-1 side chains

• Development of IgE antibodies to the R-1 specific side chain structure

▪ Via protein binding

De Rosa M. et al. International Journal of Molecular Sciences. 2021; 22(2):617; www.mdpi.com

Penicillin & Cephalosporin Cross
Reactivity
• Cross reactivity stems from similar R-1 side chains
• Not antimicrobial class

• Reported rates range ~16% to 40% in agents with

similar side chains

• Antibiotics that have unique side chains are

not cross allergic with other drugs
• i.e. cefazolin & ceftaroline

University of Nebraska. unmc.edu/intmed/_documents/id/asp/clinicpath-beta-lactam-cross-reaction-tip-sheet.

The Cost of Inappropriate Penicillin Allergies
Emergence of Suboptimal
Delays in
antibiotic Antibiotic
patient care
resistance Therapy

Increased Healthcare Costs

• Skin test ordering

• Hospital readmissions & Increased
length of stay
• Increased use of alternative agents
Liu MY. et al. Int Forum Allergy Rhinol. 2023;13(6):973-978
The Organization’s Current Approach to Allergy De-Labeling
• Antibiotic Allergy Skin Testing
• Specialized 2-Step Process
1. Intradermal Skin testing, if negative,
Followed by
2. Oral challenge with a penicillin
• i.e. amoxicillin ± clavulanic acid

• Historical practice at institution

• Use is limited by cost & lack of a penicillin challenge

• Goal
• Phase out completely with more clinically effective
& cost saving methods
Caruso C. et al. J Asthma Allergy. 2021;14:31-46
 What is the PEN-FAST Tool?
• Standardized clinical decision tool
• Predicts patients who are likely to test
negative on a formal penicillin allergy skin
test
• Scores <3 share a negative predictive
value of 96% in positive skin tests
• Widely studied & validated within clinical
trials evaluating its translation to skin
tests
• A point of care tool to identify
inappropriately labeled penicillin allergies

• Available in online calculators

Trubiano JA. Et al. JAMA Intern Med. 2020;180(5):745-752.

 Support From Primary Literature
Evaluating the PEN-FAST Clinical Decision-making Tool to Enhance Penicillin Allergy
De-labeling. JAMA Intern Med. (2023)
PEN-FAST scores were compared with positive skin test results and direct oral penicillin
Outcomes
challenges to stratify risk of a positive result:
Evaluated
• Sensitivity, specificity, NPV, and positive likelihood ratio (PPV)
Majority of US patients have a low-risk NPV: ~96% & PPV: 4% (PEN-FAST Scores <2)
penicillin allergy
Immune mediated reaction rates were Future studies should focus on direct challenges
Key Points similar between both groups in low-risk patients

Validated PEN-FAST score correlation with Confirms that low risk patients would be ideal
anticipated skin test results candidates to undergo a DOPC

Trubiano JA. Et al. JAMA Intern Med. 2020;180(5):745-752; Su C Et al. JAMA Intern Med. 2023;183(8):883-885.
Assessment Question #1
According to clinical
trials, a negative a) ≤1
predictive value of b) ≤2
96% was associated c) ≤3
with what PEN-FAST
score? d) ≤4
 Assessment Question #1
According to clinical
trials, a negative a) ≤1
predictive value of b) ≤2
96% was associated c) ≤ 3**
with what PEN-FAST
score? d) ≤4

**Typo in “≤” question answers, correct symbol is “<“

Assessment Question #2
A 58-year-old patient reports an allergy to
amoxicillin in childhood with a reaction of
hives where he was then switched to a
different antibiotic. If a skin test was
performed today, what risk category of a
positive skin test result would this patient fall
based on the PEN-FAST?

a) Very low risk

b) Low risk
c) Moderate risk
d) High risk

Trubiano JA. Et al. JAMA Intern Med. 2020;180(5):745-752.

Assessment Question #2
A 58-year-old patient reports an allergy to
amoxicillin in childhood with a reaction of
hives where he was then switched to a
different antibiotic. If a skin test was
performed today, what risk category of a
positive skin test result would this patient fall
based on the PEN-FAST?

a) Very low risk

b) Low risk
c) Moderate risk
d) High risk

Trubiano JA. Et al. JAMA Intern Med. 2020;180(5):745-752.

Purpose
Evaluate the number of patients with a penicillin allergy
within the organizations patient population who can
become de-labeled to optimize efforts related to:

• Antimicrobial stewardship
• Costs related to skin testing
Parkview Health Infectious Disease
• Not-for-profit, community
teaching health system
• Provides services to Northeast
Indiana & Northwest Ohio
• Two clinics located in
Northeast Indiana

• Both clinics see ~700

patients/month on average

• Onsite ID clinical pharmacist at

each clinic
 Design
• Single center, retrospective cohort
• Adopted based on previous clinical trials

Inclusion Criteria Exclusion Criteria

• ≥18 years of age • Documented
• Documented penicillin incomplete PEN-FAST
class or drug allergy score due to no
penicillin allergy

**Approved by Parkview Health Institutional Review Board

Outcomes
Primary Secondary
• Number of patients • Number of:
classified as “Very low • Oral penicillin challenge
post-documentation
& low risk” • Skin test use pre-
• PEN-FAST score <3 documentation
• Documented allergies with:
• Severity
• Specified reaction
• As a non-penicillin allergy
Intervention Early Phases – Aug 2023
Obtaining Initial Denial & Next Steps to
Approval Obstacles Identify
• Request to launch • Concerns for
PEN-FAST workflow additional • Key
in the ED workflow for stakeholder(s)
clinical staff
• Emphasized • Opportunities for
streamlined process • Uncertainty of the crossover and
for entering benefit the tool updating allergy
antibiotic allergies would provide information in
within the current real time
• Acknowledged population
additional workload
Clinic Workflow Education
• Timeframe: November 2023 – February 2024
Patient presents for
Clinic staff will undergo the
first visit post
screening assessment
implementation

How long ago was the

Allergy has not reaction? (5 years or less)
been updated OR
reports a penicillin
allergy Was the reaction
anaphylaxis or
angioedema?

Requires one Was the reaction

documentation per categorized by SJS/TENs?
patient only unless
update to allergies
Did the reaction require
treatment?
Clinic Workflow Education cont.
• Timeframe: November 2023 – February 2024
Clinic staff documents Provider could access
answers reported by documented score
patient in addition to

Score is easily
Progress note
obtainable within EMR

Flowsheet total Requires minimal

score further investigation in
the chart

PEN-FAST score
within comment Provider can decide to
section of challenge with a
penicillin allergy penicillin
Baseline Characteristics
Table 1. Baseline Characteristics
(n = 148 patients)
• Majority of patients had a primary
Infectious Disease Problem # of Patients (%)
problem of:
Osteomyelitis 26 (18%)
• Osteomyelitis
HIV 23 (16%)
• HIV Hepatitis C 10 (7%)
Cellulitis/Diabetic Foot Infection 8 (5%)
• Most patients had a concurrent Bacteremia 8 (5%)
antibiotic allergy Recurrent UTI’s 7 (5%)
Endocarditis 7 (5%)
Additional Antibiotic Allergies # of Patients (%)
• 50% of performed skin tests were
Cephalosporin 32 (22%)
unread
Miscellaneous Antibiotics 63 (43%)
 Primary Outcome
Table 2. Proportion of Patients
• A large majority of the organization's Stratified by PEN-FAST Score
patient population would qualify to (n = 148)
become “de-labeled” PEN-FAST Score # of Patients (%)
• 81% of patients had a PEN-FAST Unknown 5 (3%)
score <3 0 77 (52%)
1 16 (11%)
2 27 (18%)
• Majority of patients could theoretically
3 17 (11%)
tolerate a penicillin challenge
4 2 (1%)
5 5 (3%)
 Secondary Outcomes
Penicillin Challenges By
PEN-FAST Score
(n = 148) Current Severity Documentation
No Oral Penicillin Challenge Oral Penicillin Challenge of Penicillin Allergies
76 (n = 148)

6%

14% Low
# of Patients

Medium

High
25 17%
63% Unspecified
17
14
2 2 5 5
1 2
0 1 2 3 4 5 Unknown
PEN-FAST Score
Secondary Outcomes
Cefazolin Skin Test Results By
PEN-FAST Scores Table 3. Skin Test Usage and Results
(n = 148)
By PEN-FAST Score
Positive Negative Not Read
PEN-FAST Skin Test Result
12 Score Negative Not Read
0 1 1
# of Skin Tests

8
7 1 1 0
5 3 1 0
4
Unread
Documented
1 1 1 Skin Test Results
Tests (n)
(n; %)
0 1 2 3 Unknown Cefazolin 40 10 (25%)
PEN-FAST Score
Ceftriaxone 4 1 (25%)
 Secondary Outcomes
Allergy Severity Documentation by
Antibiotic Class
(n = 148)
Table 4. Proportion of Patients with
Penicillin Cephalosporin Other Antibiotics Concurrent Antibiotic Allergies and
93 Documented Reactions
(n = 148)
# of Patients

# of Patients
47
(n, %)
Concurrent Non-Penicillin
105 (71%)
21
25 Antibiotic Allergies
14 14 14
9 6 9
2 3 Documented Reaction 121 (81%)

Unspecified Low Medium High

Allergy Severity
Discussion
• Lack of oral penicillin challenges likely secondary to:
• No indication for antibiotic treatment with a penicillin

• Indication for broader application outside ID clinic setting as majority of penicillin

allergies are low risk and not documented correctly with current process
• Streamlined process could improve compliance
• Application in these settings would allow for more opportunities for oral penicillin challenges
• (i.e. family practice offices, inpatient)

• Large amount of unread skin tests indicate current practice is not being utilized
properly
• Further indication for implementing a more cost-effective alternative
Conclusion
• Limitations
• Partner relationships in trialing a new quality improvement initiative
• Timeline of collection conflicted with holiday clinic schedule
• Potential subjectivity in PEN-FAST question answers
• Important to provide definitions

• Next Steps
• Implementation of the PEN-FAST in place of skin testing outside ID
clinics ± inpatient setting over a longer timeframe (>3 months)
• Focus on penicillin challenge to confirm specificity of assessment
Penicillin Allergy De-labeling: Evaluating a Health
System’s Implementation of the PEN-FAST Tool
within an Infectious Disease Clinic
Jennifer N. McCarthy, PharmD, MS
PGY-1 Pharmacy Resident
jennifer.mccarthy@parkview.com

The speaker and mentors have no actual or potential conflict of interest in relation to this presentation
References
1. Is it really a penicillin allergy? - centers for Disease Control and ... Is It Really a Penicillin Allergy? Accessed
March 5th, 2024. https://www.cdc.gov/antibiotic-use/community/pdfs/penicillin-factsheet.pdf.
2. Caruso C, Valluzzi RL, Colantuono S, Gaeta F, Romano A. β-Lactam Allergy and Cross-Reactivity: A Clinician's
Guide to Selecting an Alternative Antibiotic. J Asthma Allergy. 2021;14:31-46. Published 2021 Jan 18.
doi:10.2147/JAA.S242061
3. https://www.mdpi.com/2226-4787/7/3/103
4. De Rosa M, Verdino A, Soriente A, Marabotti A. The Odd Couple(s): An Overview of Beta-Lactam Antibiotics Bearing More
Than One Pharmacophoric Group. International Journal of Molecular Sciences. 2021; 22(2):617.
https://doi.org/10.3390/ijms22020617. Accessed March 5th, 2024.
5. Beta-Lactam Allergy Tip Sheet Hypersensitivity Type, Mechanism, and Clinical Manifestations.
https://www.unmc.edu/intmed/_documents/id/asp/clinicpath-beta-lactam-cross-reaction-tip-sheet.pdf
6. Liu MY, McCoul ED, Brooks EG, Lao VF, Chen PG. Inaccurate penicillin allergy labels: Consequences, solutions, and
opportunities for rhinologists. Int Forum Allergy Rhinol. 2023;13(6):973-978. doi:10.1002/alr.23173
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