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Module 3 (of 3): Allergy Review *

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Module 3 (of 3): Allergy Review * Allergy to -lactam Antibiotics By Keith Teelucksingh, PharmD Infectious Disease Pharmacist, Kaiser Permanente Vallejo – PowerPoint PPT presentation

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Title: Module 3 (of 3): Allergy Review *


1
Module 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
2
Goal
  • The goal of this presentation is to provide
    pharmacists with up-to-date information regarding
    penicillin allergy and the cross reactivity with
    related antibiotics.

3
Objectives
  • 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.

4
Allergy 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.

5
Gell Coombs Classification
  • Type I IgE mediation
  • Type II Antibody mediation
  • Type III Immune complex mediation
  • Type IV Delayed hypersensitivity reaction

6
Type 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.

7
Type 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).

8
Type 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).

9
Type 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).

10
Type 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.

11
Type 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

12
Type IV Delayed Hypersensitivity
  • Delayed hypersensitivity reaction
  • Contact dermatitis, delayed non-urticarial
    rashes.
  • Mechanism
  • T-cell mediated release of cytokines causing
    tissue inflammation and injury.

13
Type 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.

14
Idiopathic 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

15
Choosing 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.

16
Cross-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
17
Penicillin 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.

18
Penicillin 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.

19
Cephalosporin - 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.

20
Penicillin 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).

21
References
  • 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

22
Acknowledgments
  • 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

23
Conclusion
  • 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
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