1. Antibiotic Allergy Protocol
Thomas M File Jr. MD, MSc, MACP, FIDSA, FCCP
Chair, Infectious Disease Division
Summa Health System, Akron, Ohio;
Professor of Internal Medicine, Chair ID Section
Northeast Ohio Medical University
Rootstown, Ohio

2. DISCLOSURES
Research Support: Nabriva, Pfizer Consultant/Scientific Advisory Board Allergan, Medicine’s Co., Meiji, Merck, MotifBio, Paratek, Shionogi, BioMerieux, Curetis,

3. LEARNING OBJECTIVES
At the end of this lecture, the learner will be able to: 1) Classify drug reactions 2) List implications of penicillin allergy labeling by patients 3) List approaches to evaluation and management of patients who have a history of penicillin

4. Allergic Reaction Classification
Modified from Weiss ME, Adkinson NF. Clin Allergy 1988; 18: 515

5. Drug Allergy Reported in 20-40% of patients Impact often negative
Frequently leads to less optimal or more toxic agents.
Most common drug allergy: Best-lactams
While a reaction related to drug allergy is an adverse event, avoidance of a more appropriate antimicrobial because of ‘fear’ of allergy can be associated with even worse effects
Blumenthal KG, Shenoy ES. Clin Infect Dis. 2016; 63: y E,

6. Impact of Antibiotic Allergy History
Increased Broad spectrum ABX
Increased Cost
Increased LOS
Increased Adverse effects
Delay in administration of AB
Reported in 20-40% of patients (2X longer)
Increased Mortality
lee et al Ann Intern Med 2000;; Unger et al Pharmacotherapy 2013; Howlett et al. Eastern States Conf Pharmacy, 2011;
Huagn K et al. AAAAI ,

7. Implications of Antibiotic Allergy
Retrospective, controlled cohort study; 51,582 patients with ‘penicillin allergy’ label
MORE ‘suboptimal’ antibiotics (p< )
Fluoroquinolones, Clindamycin, Vamcomycin
MORE CDI by 23%
MORE VRE
INCREASED LOS (0.6 days)
Macy E, Contreraa R. J Allergy Clin Immunol 2013

8. Impact of Reported Beta-Lactam Allergy on Inpatient Outcomes
MacFadden DR et al. Clin Infect Dis. 2016

9. Penicillin Allergy
Penicillin allergy is reported by 8-25% of patients across inpatient and outpatient settings
Only 10% of patients with reported penicillin allergy are skin test positive
Most common reaction to penicillin is rash
Prevalence of life-threatening anaphylactic reaction to penicillin is estimated between 0.02% and 0.04%
Key Point – Among all patients with a reported allergy to penicillin, up to 90% are able to tolerate penicillins after complete evaluation either because they were never allergic or an earlier allergy has resolved
Gonzalez-estrada A et al. Penicillin allergy: a practical guide for clinicians. Cleveland Clinic Journal of Medicine. 2015; 82(5):
Drug Allergy: an updated practice parameter. Ann Allergy, Asthma Immunol 2010;105:

10. Penicillin Allergy Protocol (SUMMA)
Protocol developed by Antimicrobial Stewardship Team, Pharmacy, and Anesthesiology Department
Approved by P&T Committee in November 2016
Implementation system-wide

12. Continue ciprofloxacin + metronidazole
Case #1
45 y/o female admitted with diverticulitis confirmed on CT. History of PCN allergy. Started empirically on ciprofloxacin + metronidazole. When questioned about her PCN allergy, she had diarrhea. Course of action?
Continue ciprofloxacin + metronidazole
Change therapy to piperacillin/tazobactam
Change ciprofloxacin to ceftriaxone

13. Vancomycin and aztreonam Vancomycin and ciprofloxacin
Case #2
70 y/o male presents from SNF for Pneumonia; recently treated with cipro for UTI. PCN allergy listed with reaction of rash which occurred 5 days after initiation of the antimicrobial. This occurred ~20 years ago. Course of action?
Vancomycin and aztreonam
Vancomycin and ciprofloxacin
Vancomycin and cefepime

14. Questions to ask patient/family
What were the characteristics of the reaction?
IgE-mediated versus Non-IgE-mediated
IgE-mediated (Type I):
Urticaria (most common), angioedema, laryngeal edema, bronchospasm, shortness of breath, presyncope or syncope, hypotension, and cardiopulmonary collapse
Non-IgE-mediated:
Maculopapular eruptions, hemolytic anemia, serum sickness, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, acute interstitial nephritis and toxic epidermal necrolysis

15. Questions to ask patient/family
If a rash is described, determine the characteristics of the rash.
Types of rash include:
Urticaria (IgE-mediated) - pruritic, raised and erythematous eruption with central pallor.
Maculopapular or morbilliform (non-IgE-mediated) - begin in dependent areas and then generalize. Often pruritic and associated with mucous membrane erythema.
When did rash occur in relation to start of antibiotic:
Within minutes/hours
More than a day (delayed)

16. Questions to ask patient/family
How was the reaction managed? What was the outcome?
Use of and response to epinephrine and antihistamines with resolution or significant improvement within a few hours may indicate an IgE-mediated
How long after taking penicillin did the reaction occur?
Immediate (IgE-mediated) versus delayed (Non-IgE-mediated)
IgE-mediated (Type I):
Immediate, usually occur within 1 hour of the first dose (occasionally take 2 hours if taken orally with food)
Non-IgE-mediated:
Delayed in onset, often occurring days after start of treatment
Have you tolerated other forms of penicillin since the reaction?

17. Questions to ask patient/family
How many years ago did the reaction occur?
Most patients lose their sensitivity to penicillin over
time. (50% within 5 years, ≥ 80% within 10 year 
What was the indication for penicillin?
Many cutaneous reactions are a result of an underlying viral or bacterial infection or an interaction between the antimicrobial and the disease state (e.g. rash developing with ampicillin and infectious mononucleosis)

18. Questions to ask patient/family ARTERY

20. Allergy Protocol Evaluation (pilot)
Evaluated the safety and validity of the protocol
Compared patients with listed B-lactam allergy who tolerated B-lactams after pharmacist evaluation
Patients were admitted from 12 December 2016 through 15 February 2017 with listed B-lactam allergy and already received the first dose of a non-B-lactam antibiotic were included in the study
Pharmacy resident performed patient interviews, and subsequently made antibiotic recommendations to the prescribers based on the developed antibiotic allergy protocol, clinical treatment guidelines and culture/susceptibility results
Summa Health Sample Preso

21. Allergy Protocol Evaluation (pilot)
84 patients were included in the study (Intervention: 29; Control: 55).
% of patients with a listed B-lactam allergy who tolerated B-lactam in the intervention and control group was 75.9% and 55.4% respectively (P=0.078).
The incidence of adverse reactions and length of hospital stay were similar between the groups.
Total cost of antibiotics/day was $21.20 in the intervention arm, and $61.00 in the control group (P<0.001).
Post-intervention change in cost of antibiotics per day per patient was -$13.07 (P=0.022).
Conclusion: The utilization of a standardized antibiotic allergy assessment tool along with pharmacist intervention promoted the appropriate use of antibiotics in the health system, and significantly reduced the cost of antimicrobial expenditures.

22. Antibiotic Allergy-Key points
A patient history of allergy is associated with worse clinical ourtcomes
Leads to less optimal antimicrobial usage
Increase AEs, cost, LOS, in some cases mortality
Most patients with history of allergy are NOT allergic
Asking appropriate questions (what reaction, how long ago) can provide clarification in majority of cases and allow better use of antimicrobials