Title: Module 3 (of 3): Allergy Review *
1Module 3 (of 3) Allergy Review
Allergy to ß-lactam Antibiotics By Keith
Teelucksingh, PharmD Infectious Disease
Pharmacist, Kaiser Permanente Vallejo With
contributions from Linh Van, PharmD Infectious
Disease Pharmacist, Kaiser Permanente Oakland
? See Notes
2Goal
- The goal of this presentation is to provide
pharmacists with up-to-date information regarding
penicillin allergy and the cross reactivity with
related antibiotics.
3Objectives
- After completing this module, the participant
will be able to - Describe the different types of allergy (per Gell
Coombs classification) as they relate to
penicillin and the ß-lactam-related antibiotics. - Be able to identify clinical situations where it
is safe or unsafe to use ß-lactam-related
antibiotics given a patients allergy history.
4Allergy to the ß-lactam antibiotics
- There are several classification schemes. They
can be applied to other drug classes but are best
characterized for the ß-lactam antibiotics - Gell and Coombs
- Based on immunopathologic reactions (all of which
have been seen w/ß-lactam antibiotics). - Levine
- Reactions specific to penicillin (PCN) according
to time of onset.
5Gell Coombs Classification
- Type I IgE mediation
- Type II Antibody mediation
- Type III Immune complex mediation
- Type IV Delayed hypersensitivity reaction
6Type I IgE mediation
- Serious and life threatening
- Can include erythema, pruritis, urticaria
(hives), angioedema, bronchospasm, hypotension,
arrhythmias. - Mechanism
- Interaction of ß-lactam antigens with preformed
ß-lactam specific IgE bound to mast cells ?
causes release of histamine, proteases,
prostaglandins, leukotrienes.
7Type I (contd)
- Time course
- Usually starts lt15 min after drug administration,
can also occur gt1 hour after but less common. - Pearl
- If patient has type I hypersensitivity to PCN,
unless patient has tolerated before, probably
judicious to avoid cephalosporins. If unable to
get specific history as to what type of rash
occurred and in what timeframe, err on the side
of caution. - If PCN use is absolutely indicated, consult
allergy for skin testing (e.g., PCN for
neurosyphilis).
8Type II Antibody Mediation
- Reactions
- Hemolysis, thrombocytopenia, neutropenia,
interstitial nephritis - Mechanism
- Result when ß-lactam specific cytotoxic
antibodies (usually IgG or IgM) become attached
to circulating blood cells or renal interstitial
cells that have ß-lactam antigens bound to their
cell surface. The antibody-antigen complex can
activate complement system (resulting in cell
lysis), neutrophil or macrophage attachment
(leading to cell injury).
9Type II (contd)
- Time course
- Usually longer term, gt 7 days
- Pearl
- Long term, high-dose ß-lactam treatment
predisposes to this reaction (nafcillin for
endocarditis, high-dose Zosyn for Pseudomonal
infection).
10Type III Immune Complex Mediation
- Serum-sickness like reaction
- Mechanism
- ß-lactam specific IgG or IgM antibodies may form
circulating complexes with ß-lactam antigens.
These complexes can fix complement and lodge in
tissue sites, possibly causing serum
sickness/drug fever.
11Type III (contd)
- Time course 621 days after exposure
- Pearl
- Best example is classic serum-sickness like
reaction seen with cefaclor. - Signs/symptoms fever, arthralgia,
lymphadenopathy, skin eruption
12Type IV Delayed Hypersensitivity
- Delayed hypersensitivity reaction
- Contact dermatitis, delayed non-urticarial
rashes. - Mechanism
- T-cell mediated release of cytokines causing
tissue inflammation and injury.
13Type IV (contd)
- Time course not well defined
- Pearl/example
- Penicillin was available topically in the past,
but high rate of dermatitis led to its
discontinuation as a marketed product.
14Idiopathic Reactions
- Not included in Gell Coombs classification since
pathogenesis is not well defined. - Examples
- Maculopapular reactions (rash, etc.)
- Occurs in 2 percent to 3 percent of penicillin
courses, usually late in treatment. - Eosinophilia
- Stevens-Johnson syndrome
- Exfoliative dermatitis
15Choosing an Antibiotic
- Always note the REACTION to a given drug
- Nausea, vomiting, GI upset are NOT allergic
reactions. - Rash reactions
- Need to either clarify type of rash and onset or
err on side of caution and use alternative agents
with low chance of cross reactivity.
16Cross-Reactivity
If patient is allergic to Can this be used?
1. Penicillin Penicillin-class drug (amoxicillin, ampicillin, etc.)
2. Penicillin Cephalosporin
3. Cephalosporin Penicillin
4. Penicillin Carbapenem
17Penicillin Penicillin Class
- If patient has IgE mediated reaction to
penicillin, likely to have similar reaction to
ampicillin, amoxicillin, dicloxacillin and
piperacillin. - Patients with allergy to penicillin may be prone
to allergic reactions to drugs in general. - Aztreonam seems to be safe to use even in
patients with Type I reactions. Use caution in
patients with ceftazidime allergy, since these
drugs have the same side chain. Reactions still
can occur but tend to be very rare.
18Penicillin Cephalosporin
- Incidence may have been higher with earlier
preparations of cephalosporins . - In general, patients with documented Type I
reactions to penicillin should not be challenged
with a cephalosporin unless there is
documentation that patient has tolerated
cephalosporins in the past. - No good answer at this time.
19Cephalosporin - Penicillin
- Allergic reactions to cephalosporins in the
general population tend to be rare. - Chance of cross-reactivity between patients with
cephalosporin allergy being exposed to penicillin
may be higher (50 percent) with first-generation
cephalosporins than that with second or third
generation (10 percent).
- For example, if a patient is allergic to
cefazolin and exposed to a penicillin-class drug,
s/he may be more likely to have an allergic
reaction. If the patient is allergic to either
cefuroxime or ceftriaxone, s/he may be less
likely to have an allergic reaction to a
penicillin-class drug.
20Penicillin Carbapenem
- Incidence was thought to be close to 50 percent.
- Emerging data suggests that carbapenems may be
safe to use in patients with Type I penicillin
allergy. - Some data to suggest that patients with type IV
reactions to penicillins will have a 5 percent
chance of cross-reaction with carbapenems
(imipenem).
21References
- Chen, S. Serum sickness. http//emedicine.com
- Weiss, M., Adkinson, N. Chapter 24 ß-lactam
Allergy. Mandell, Bennett Dolin. Principles
and Practice of Infectious Disease. 7th ed. 2009. - Robinson, et al. Practical aspects of choosing an
antibiotic for patients with a reported allergy
to an antibiotic. Clin Infect Dis. 2002 Jul
135(1)26-31. - Patriarca, et al. Tolerability of aztreonam in
patients with IgE-mediated hypersensitivity to
beta-lactams. Int J Immunopathol Pharmacol. 2008
Apr-Jun21(2)375-9. - Schiavino, et al.Cross-reactivity and
tolerability of imipenem in patients with
delayed-type, cell-mediated hypersensitivity to
beta-lactams. Allergy 2009 Apr 14. - Romano, et al. Brief communication tolerability
of meropenem in patients with IgE-mediated
hypersensitivity to penicillin. Ann Intern Med.
2007 Feb 20146(4)266-9 - Prescott, et al. Incidence of carbapenem-associate
d allergic-type reactions among patients with
versus patients without a reported penicillin
allergy. Clin Infect Dis. 2004 Apr 1538(8)1102-7
22Acknowledgments
- Thank you to the following individuals for their
support of and/or assistance with this program - Dan Dong, Pharm D, Area Pharmacy Director
Kaiser Permanente East Bay
Service Area - Kathleen Hiroshima, Pharm D, Drug Information
Services Kaiser Permanente California
Regions - Matangi Venkateswaran, Pharm D, Inpatient
Quality-Clinical Supervisor, Kaiser Permanente
Central Valley Service Area - Sam S Lee, Pharm D, Inpatient Pharmacy Supervisor
Kaiser Permanente Santa Rosa
23Conclusion
- This concludes Module 3 of the Review of
Basic Principles and
Selected Antimicrobials. - Upon completion of Modules 1, 2 and 3, you may
proceed to the post-test and evaluation. - Thank you for participating in this continuing
education program.
? See Notes