Important Information to Collect for Allergy Assessment
- Source of reported allergy history (patient, family member, healthcare provider)
- Indication of inciting drug
- Dose/route of medication
- Signs/symptoms experienced
- Timing of onset of reaction in relation to initiation of medication
- Any concurrent medications (prescription or non-prescription), change in detergent used or changes in diet?
- Reaction required hospitalization?
- Treatment given for the reaction and response
- Did the patient take the medication again since prior reaction
- If yes, did any recurrent signs or symptoms occur with subsequent exposure?
Idiopathic Reactions
- Not clearly immune mediated
- Maculopapular rash
- If occurs, not a contraindication to taking the antibiotic again
Cross-Reactivity
If anaphylaxis to one beta lactam, avoid antibiotic class if clinically possible and contact Infectious Disease Service for alternate therapeutic options
- Between Penicillins and Cephalosporins: estimated cross-reactivity ~5%
- Between Penicillins and Carbapenems: estimated cross-reactivity is ~ 1%
- Between Cephalosporins: cross-reactivity low due to the significant heterogeneity of side chains (C-3 and C-7)
- Mechanism for cross-reactivity: occurs between various penicillins and cephalosporins as a result of similar side chains at C-3 or C-7 (see Table 1). For example, cefazolin has a unique side chain and therefore would not cross react with cephalexin
Table 1. Groups of cephalosporins and beta-lactams with similar C3 and C7 side chains ^2
C-7 Side Chain
| Similar side chain cross-reactivity possible WITHIN these 3 groups * | Completely dissimilar side chains make cross-reactivity unlikely ** |
|---|---|
| Group 1 Cefoxitin Cephalothin Penicillin Group 2 Amoxicillin Ampicillin Cefaclor Cephalexin Group 3 Cefepime Cefotaxime Ceftriaxone | Cefotetan Cefazolin Cefuroxime Cefixime Cefprozil Ceftazidime |
How to use this table: Check the antibiotic your patient is allergic to for possible cross-reactivity with other antibiotics based on both the 7-position (C-7) and 3-position (C-3) side chains. Avoid drugs that share structural similarity of either side chain position. Antibiotics that do not share similarity of either side chain are unlikely to exhibit cross-reactivity and can be recommended.
* For example, based on the 7-position side chain structure similarity, allergy cross-reactivity might occur among cefoxitin, cephalothin and penicillin.
** Based on the 7-position side chain structure uniqueness, allergic cross-reactivity would be highly unlikely for all of these cephalosporins with each other and with other cephalosporins and/or penicillins
C-3 Side Chain
Similar side chain cross-reactivity possible between cefuroxime and cefoxitin
Testing for Penicillin / Beta-Lactam Allergy
Skin testing is available at HHS and SJH through Immunology department. It is primarily used for determination of IgE-mediated reactions. Penicillin is the only drug class with a valid skin test. Penicillin skin testing has a high negative predictive value since 97-99% of patients with a negative skin test to both the major and minor determinants will not have an immediate type 1 reaction (e.g. anaphylaxis). For patients who are deemed to be skin-test positive, all penicillin compounds should be avoided. For those individuals for whom an alternative class of antibiotics cannot be substituted, desensitization may be required.
| Type of Reaction | Coombs and Gell Classification | Onset | Mediator |
|---|---|---|---|
| Idiopathic reactions including maculopapular rash | n/a | Delayed usually 7 days | unclear |
| Anaphylaxis, urticarial (hives), angioedema, hypotension, bronchospasm, laryngeal edema, pruritus | Type I Immediate and accelerated hypersensitivity | < 1 hour (rarely 1- 72 hours) | IgE antibodies |
| Hemolytic anemia, thrombocytopenia, neutropenia | Type II Delayed cytotoxic antibodymediated hypersensitivity | > 72 hours | IgG and IgM antibodies |
| Serum sickness (fever, cutaneous eruptions, lymphadenopathy, arthralgias, myalgias), glomerulonephritis, small vessel vasculitis, drug fever | Type III Antibody complex- mediated hypersensitivity | > 72 hours (7- 14 days) | IgG and/or IgM complexes |
| Contact dermatitis, exfoliative dermatitis, maculopapular or morbilliform drug eruptions, pustulosis | Type IV Delayed type hypersensitivity | > 72 hours | T-cells |
| Stevens-Johnson Syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and erythema multiforme are rare with beta-lactams but because of the severity, antibiotic should be avoided | n/a | > 72 hours | unclear |
Reference
- Pichichero ME. J Family Practice; 2006;55:106-112.
- Lagace-Wiens P, Rubinstein E. Expert Opin Drug Saf 2012;11:381-399.
- Li, James T., M.D., PH.D., Mayo Clinic and Foundation, Rochester, Minnesota Am Fam Physician. 2002 Aug 15;66(4):621-625.
- Lasley MV, Shapiro GG. Pediatr Rev. 2000;21:39–43.