Module 3 (of 3): Allergy Review *

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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
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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.

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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.

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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.

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Gell Coombs Classification

• Type I IgE mediation
• Type II Antibody mediation
• Type III Immune complex mediation
• Type IV Delayed hypersensitivity reaction

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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.

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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).

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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).

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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).

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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.

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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

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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.

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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.

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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

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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.

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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
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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.

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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.

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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.

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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).

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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

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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

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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