Allergy Resources

OVERVIEW

Approximately 25 % of patients report being allergic to at least one antibiotic, most commonly penicillin (PCN).1,8 

Studies indicate true allergy to penicillin (see Data below) and risk of cross-reactivity to related antibiotic classes are significantly lower than previously estimated.   Overestimation of allergy has negatively impacted care, leading to poor outcomes, increased adverse drug events (ADE), antibiotic resistance, antibiotic-associated infections, hospital length of stay, healthcare cost and mortality.2-8

More effective tools and guidelines for evaluating and testing for allergy and cross-reactivity are available.   3,11,13,14  This allows patients to receive first line antibiotics for prophylaxis and treatment avoiding ADEs and antimicrobial resistance.

 

Approximately 7-16% of people report a PCN allergy and 1-2% a cephalosporin allergy. 1,8,15  In patients with reported PCN allergy: reassessment demonstrates 95% of patients tolerate penicillins15  and cross-reactivity with cephalosporins is low in those with confirmed PCN allergy (~1% and 2.6%). Hypersensitivity to PCN often diminish over time16: 50% of patients with a PCN allergy will not show signs of an allergy after 5 years and 80% of patients with a PCN allergy will not show signs of an allergy after 10 years.

 

 

Hospitalized patients with stated PCN allergy are more likely to: receive fluoroquinolones, clindamycin, vancomycin; experience 0.59 days increased length of stay; and be infected with C.difficile, MRSA, VRE.5

 

 

Patients undergoing surgery with and without reported PCN allergy were studied to determine antibiotics received and risk for subsequent surgical site infection.  Antibiotic changes are depicted in graph, reported PCN allergy was associated with surgical prophylaxis alterations and increased risk of surgical site infection.6

 

 

 

Selection of second line therapy can lead to suboptimal outcomes (e.g. MSSA treatment with cefazolin vs vancomycin).9, 10

SYSTEMATIC APPROACH TO THE PATIENT WITH REPORTED ANTIBIOTIC ALLERGY

Consider listed antibiotic allergy, reaction and if conflicts with optimal antibiotic for therapy/prophylaxis then consider the following approaches. A detailed allergy history allows for more effective prophylaxis and treatment while ensuring patient safety. 

 

  • Causative antibiotic: name and formulation (be as specific as possible to actual drug and not just PCN or cephalosporin).
  • Reaction description/severity: determine the nature of the allergic reaction (e.g., rash, anaphylaxis, gastrointestinal upset, localized/generalized).  Avoid “unknown” reaction, family history, etc.
  • Timing: Reaction relative to antibiotic administration (e.g., immediate reaction <1 hour).
  • Date of reaction:  Specific date or time estimate (e.g. 3 years ago vs 30 years).
  • Treatment: Outpatient, inpatient, observation. Antihistamine, steroids, epinephrine.
  • Subsequent exposure history: Listed antibiotic or related antibiotic since reaction.
  • Verified:  Allergy validated by skin testing or challenge. 

ANTIBIOTIC HYPERSENSITIVITY AND INTOLERANCE TYPES

Urticaria fulfilling ‘‘1-1-1-1’’ criterion (appearance within 1 hour after the first dose and regression within 1 day and occurred within 1 year) suggests a high likelihood of having a positive skin test.

CROSS REACTIVITY USE OF ANTIBIOTICS

Guidelines have been updated based on several recent studies indicating that the risk of cross-reactivity among beta-lactams is lower than previously reported.  The following charts give guidance for patients with either penicillin or cephalosporin allergies.11

 

 

* Can be given without additional precautions or testing.

Takeaways:

  • Patients with non-anaphylaxis PCN allergy can receive cephalosporins.
  • Patients with non-anaphylaxis cephalosporin allergy can receive PCNs.
  • Both classes of drug remain treatment options for patients with “Dated” (>10 years old) non-anaphylactic allergy.

Note: Patients with history of penicillin or cephalosporin allergy, a carbapenem or aztreonam (except allergy to ceftazidime due to same R1 side chain) may be administered without testing or additional precautions regardless of whether the reaction was anaphylactic.11

RISK ASSESSMENT

The following tools may be used to identify patients that may be at low risk of allergic reaction or antibiotics that are lowest risk for cross reactivity.

PEN-FAST13  Validated clinical decision tool for point-of-care risk assessment of patient reported penicillin allergies to identify low-risk PCN allergies that do not require formal allergy testing.  The tool uses 3 clinical criteria of time from allergy episode, phenotype, and treatment required to calculate a score that relates to validated risk of positive PCN allergy

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Enhanced Allergy Assessment and Side Chain Cross Reactivity Table14  Due to the R-group side chain of beta-lactams primarily being responsible for allergic cross reactivity, a side chain cross-reactivity table combined with enhanced allergy assessment (specific antibiotic, reaction/timing, and tolerance similar antibiotics) was developed to improve utilization of primary surgery prophylaxis (e.g. cefazolin) in those with stated beta-lactam allergies.  The table indicates antibiotics that can be used safely due to dissimilar side chains compared to those causing the allergic reaction. 

General Antibiotic Cross Reactivity Table  Antibiotic allergy cross-reactivity tables to summarize potential reaction potential depending on the antibiotic, relative structures, side chains, and reactions.  Utilizing these tables along with the antibiotic allergy and reaction can increase the available antibiotics that can be given safely.  ­­­

ACTIVE INTERVENTIONS11

Challenge

  • Procedure where the antibiotic is administered to determine tolerance.  Typically performed in patients reporting unverified non-anaphylactic hypersensitivity reactions or where the clinical probability of reaction is low.  One-step Challenge: one treatment dose of the antibiotic is given and then observed for allergic reaction.

Graded (2-step) Challenge

  • A smaller dose, such as 10% of the treatment dose of the antibiotic is administered and observed for reaction, followed 20-30 minutes later by the remainder (90%) of the treatment dose if no symptoms occur.

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Desensitization12

  • Process to temporarily induce antibiotic tolerance, typically for IgE-mediated reactions.  This is accomplished by giving multiple (typically 5-10) gradually increasing doses of the antibiotic within a short period of time to induce tolerance allowing for the antibiotic to be used for treatment.  This antibiotic tolerance is only temporary and antibiotic exposure must be maintained to continue tolerance or the process will need to be repeated. 
  • There are contraindications to desensitization including: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Steven Johnson Syndrome (SJS), cytopenia, among others which are summarized in the article cited below. 

Skin Testing

  • Process to test for allergic reaction by pricking the skin and placing a small amount of the allergen (antibiotic causing allergy) on the skin and observe for reaction.  If no reaction, an intradermal injection of the allergen is placed and observed.  If negative, an oral challenge with the antibiotic may be done.  If no reaction during testing, then the antibiotic may be given for treatment.  Based on tolerance, documented allergies need to be updated or removed.
  • Primarily for patients with a history of anaphylaxis or a recent reaction suspected to be IgE-mediated (e.g. immediate onset urticaria).  This testing should only be performed by personnel trained and skilled in the application and interpretation of this type of skin testing. 

DOCUMENTATION

Effective documentation of antimicrobial allergies is crucial but often overlooked in managing patient allergies. Detailed documentation including the specific antibiotic, reaction types, timing, and dates is essential for informed decision-making. Additionally, documenting antibiotic tolerance, results of antibiotic challenges and skin tests, and delabeling/removal of allergies provides critical information for future treatment options.

Differences in how antimicrobial allergies and tolerances are documented in various medical records can affect treatment outcomes. Inconsistent documentation may trigger allergy alerts unnecessarily, limiting effective antibiotic choices. However, recent guidelines indicate that antibiotic cross-reactivity is less common than previously thought, emphasizing the importance of accurate documentation to broaden treatment options.

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Electronic Medical Record (EMR) allergy algorithms are evolving to consider intricate details like cross-reactivity patterns, but functionality varies across systems. Healthcare providers must understand their specific EMR’s allergy protocols to ensure accurate documentation and most effective patient care.

Patient engagement is key in allergy management. Discussing allergies, changes, and their implications with patients reduces anxiety and ensures consistent allergy information across different healthcare settings that are not connected. Patient-carried allergy cards, health information apps, and patient education can aid in maintaining up-to-date allergy records across a patient’s providers.

Standardizing allergy approach and documentation protocols, ongoing provider training, and patient education are essential steps to address these challenges. Enhancing EMR capabilities in allergy documentation promotes patient safety, supports informed decision-making, and enhances overall quality of care across healthcare settings.

SELECTED REFERENCES

  1. Bertram CM, Postelnick M, Mancini CM, Fu X, Zhang Y, Schulz LT, et al. Association of beta-lactam allergy documentation and prophylactic antibiotic use in surgery: a national cross-sectional study of hospitalized patients. Clin Infect Dis 2021;72:e872-5.
  2. Blumenthal KG, Kuper K, Schulz LT, Bhowmick T, Postelnick M, Lee F, et al. Association between penicillin allergy documentation and antibiotic use. JAMA Intern Med 2020;180:1120-2.
  3. Blumenthal KG, Shenoy ES, Huang M, Kuhlen JL, Ware WA, Parker RA, et al. The impact of reporting a prior penicillin allergy on the treatment of methicillin sensitive Staphylococcus aureus bacteremia. PLoS One 2016;11:e0159406.
  4. Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of methicillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ 2018; 361:k2400.
  5. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol 2014;133:790-6.
  6. Blumenthal KG, Ryan EE, Li Y, Lee H, Kuhlen JL, Shenoy ES.  The impact of a reported penicillin allergy on surgical site infection risk. Clin Infect Dis.2018;66(3):329-336.
  7. Blumenthal KG, Lu N, Zhang Y, Walensky RP, Choi HK. Recorded penicillin allergy and risk of mortality: a population-based matched cohort study. J Gen Intern Med 2019;34:1685-1687.
  8. Lee CE, Zembower TR, Fotis MA, Postelnick MJ, Greenberger PA, Peterson LR, Noskin GA.  The incidence of antimicrobial allergies in hospitalized patients. JAMA 2000;160:2819-22.
  9. Stryjewski ME, Szczech LA, Benjamin DK, Inrig JK, Kanafani ZA, et al. Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis.2007;44(2):190-6.
  10. Kim SH, Kim KH, Kim HB, Kim NJ, Kim EC, Oh Md, Choe KW. Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia. Antimicrob Agents Chemother.2008;52(1):192-197.
  11. Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, et al. Drug allergy: a 2022 practice parameter update. J Allergy Clin Immunol. 2022;150(6):1333-1393.
  12. Chastain DB, Hutzley VJ, Parekh J, Alegro JV.  Antimicrobial desensitization: A review of published protocols. Pharmacy(Basil). 2019;7(3):112.
  13. 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.
  14. Collins CD, Scheidel C, Anam K, et al. Impact of an antibiotic side-chain-based cross-reactivity chart combined with enhanced allergy assessment processes for surgical prophylaxis antimicrobials in patients with b-lactam allergies. Clin Infect Dis.2021;72(8):1404-12.
  15. Sacco KA, Bates A, Brigham TJ, et al. Clinical outcomes following inpatient penicillin allergy testing: a systematic review and meta-analysis. Allergy.2017;72:1288-1296.
  16. Blanca M, Torres MJ, Garcia JJ, et al. Natural evolutioin of skin test sensitivity in patients allergic to beta-lactam antibiotics. J Allergy Clin Immunol.1999;103(5 Pt 1):918-24.

IMPORTANT DISCLAIMER—THIS WEBPAGE DOES NOT PROVIDE MEDICAL ADVICE

The information provided on this webpage is intended as general overview and background information. It is not intended to be, and should not be considered to be, medical advice or used in any way for the diagnosis or treatment of any specific medical condition. As to any specific medical condition, you should always seek the advice of a physician or other qualified health care provider. You also should not disregard professional medical advice given directly to you based on information contained on this webpage.

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