Download Penicillin Allergy - Penn State Health

8/30/2012
Penicillin Allergy
Neeti Bhardwaj, MD, MS
Fellow, Allergy and Immunology
Penn State Milton S. Hershey
Medical Center
Financial Disclosures
• None
Case 1
• 67 year-old female with history of right
knee arthroplasty
• Post-operative course was complicated by
infection of prosthesis accompanied by
bacteremia
• Removal of prosthesis
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Case 1 (Contd…)
• Tissue and blood cultures cultures grew
penicillin sensitive MSSA
• Infectious disease specialists
recommended cefazolin based on culture
sensitivity results
• However,……….
Case 1 (Contd…)
• ….The patient had penicillin listed as a drug
allergy
• History: urticarial rash and passing out within
an hour after taking penicillin when she was
“very young”. Was treated in the emergency
room.
• Could not provide further specifics about the
“reaction”
• Had avoided penicillins and cephalosporins
all her life.
maxarmstrong.wikispaces.com
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• Is the reaction consistent with a drug
allergy?
• What are the options for diagnosis?
• What drugs are safe to use?
• How can we manage the patient?
Immediate Hypersensitivity
Reactions
• Caused by rapid IgE-mediated release of
vasoactive mediators from mast cells and
basophils
• Characterized by hives, pruritis, flushing,
respiratory compromise, hypotension
• Can be detected by skin testing
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
The Problem
• Approximately 10 % of patients report a
history of reacting to a penicillin class
antibiotic.
• When evaluated for penicillin allergy, up to
90 % of these individuals are able to
tolerate penicillins
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
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Why this discrepancy?
• Penicillin specific IgE antibodies rapidly
wane over time.
• Some reactions are the result of an
underlying bacterial or viral infection or an
interaction between the infectious agent
and the antibiotic.
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Why this discrepancy? (Cont…)
• Some patients may mislabel the antibiotic
they were treated with as penicillin
• Or may attribute predictable reactions
(such as diarrhea) as allergic
Why is this so important?
Treatment of patients assumed to be
penicillin allergic with alternate broadspectrum antibiotics may lead to:
• Multiple drug-resistant organisms
• Higher costs
• Increased toxic side-effects
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
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Why is this so important?
Evaluation of patients with reported
penicillin allergy by skin testing leads to:
• Reduction in the use of broad spectrum
antibiotics
• Decrease in treatment costs
Diagnostic Options
• Graded challenge: only when pre-test
probability is low.
• Skin testing
• In vitro tests: not reliable, limited to
experimental studies only
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Penicillin Skin Testing
• Detects the presence or absence of
penicillin specific IgE antibodies
• Major determinant: penicilloylpolylysine
(PLL)
• Native drug : Penicillin G (10,000 U/mL).
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
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Application of Penicillin G (1:10,000 U/mL)
and PPL by prick technique
Negative
Intradermal testing
Negative
Oral challenge with amoxicillin
with one hour observation
in the office
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Penicillin Skin Testing
• Negative predictive value: approaches
100%
• Positive predictive value: 40-100%
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Back to our patient…
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Case 1
Penicillin skin testing
followed by oral amoxicillin challenge
Testing negative
Patient treated with
cefazolin per ID recommendations
What if the skin test is
positive?
• Non-bactam antibiotic
• Induction of tolerance to the drug
• Graded challenge (recommended only if
the history of last reaction is remote and
benign)
• And what about cephalosporins?........
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
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Cephalosporin Administration to Patients with a History of Penicillin Allergy
Approximately, 2% of penicillin skin testpositive patients react with cephalosporins
(older literature suggests 10%)
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Skin test results for penicillin major
and minor determinants: negative
Safe to give cephalosporins,
regardless of severity of reaction
to penicillin
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Penicillin Skin Test Positive
non-β-lactam
antibiotic
Desensitization to
cephalosporin
Graded challenge
to cephalosporin
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
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Aztreonam
• Penicillin and cephalosporin allergic
patients may receive aztreonam , with the
exception of those allergic to ceftazidime
(theoretical risk of cross-reactivity due to similar side
chain)
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Carbapenems
• Penicillin allergic patients may receive
carbapenems (imipenem, meropenem) via
graded challenge
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
What if there is no alternative
to penicillin or cephalosporin?
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Drug Desensitization
• In patients with convincing history of IgEmediated reaction, particularly if recent.
• Informed consent must be obtained for
skin testing, graded challenge as well as
desensitization
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Drug Desensitization
• Temporary induction of drug tolerance
• Involves rapid administration of
incremental doses of the drug until the
target dose is reached
• Effector cells are rendered less reactive or
non-reactive
• Does not indicate a permanent state of
tolerance
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Graded Challenge
• May be indicated in patients with distant or
questionable reaction histories
• Administration of progressively increasing
doses of the medication until the full dose
is reached
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
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Graded Challenge
• Involves fewer doses than desensitization
and do not induce tolerance
• Intended to verify that the patient does not
have immediate hypersensitivity
Ann Allergy Asthma Immunol. 2010 Oct;105(4):259-273
Case 2
• A 5-year-old boy referred to Allergy and
Immunology clinic by his PCP for
evaluations of “antibiotic allergy”
• Had history of recurrent ear infections.
• Had a reaction to amoxicillin.
Case 2 (Contd…)
• Had previously tolerated amoxicillin
multiple times
• Developed a generalized “rash” with no
accompanying symptoms on the 7th day of
the last amoxicillin course.
• No other symptoms
• Parents were advised by the pediatrician
that the child should not receive penicillins
again
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bestpractice.bmj.com
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Is this a dangerous drug allergy?
What diagnostic tests are available?
Can this patient have penicillins again?
What about other beta lactams?
Benign T cell Mediated Reactions
• Delayed cutaneous eruptions, such as
maculopapular exanthems
• The exanthem may be a manifestation of
the underlying infection process
• Usually not reproducible upon
readministration
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Diagnostic options
• Give medication again
• Perform oral challenge (graded or full)
• Skin test to rule out IgE-mediated
mechanism if history is unclear
Case 2
History was not consistent
with true type 1 IgE mediated
reaction to the implicated drugs
Child was too young
to tolerate penicillin skin testing
Passed graded oral challenge in
to amoxicillin in the clinic
Cleared of penicillin and cephalosporin allergy
Take Home Messages…
• Ninety per cent of patients with reported
penicillin allergy are able to tolerate penicillin
• Treatment of patients assumed to be
penicillin allergic may compromise optimal
medical care
• Evaluation of patients with penicillin allergy
by skin testing leads to reduction in the use of
broad-spectrum antibiotics and may decrease
costs
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Take Home Messages…
• Patients with negative skin test results
may receive penicillin with minimal risk of
an IgE-mediated reaction
• Penicillin skin-test positive patients should
avoid penicillin. If there is an absolute
need, rapid induction of tolerance may be
performed
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