Download Grand Round 21 May 2008 (1)

Antibiotic Allergy
Rahul Mukherjee
Consultant Physician, Milton Keynes Hospital NHS Foundation Trust
Honorary Lecturer in Medicine, University of Leeds
Visiting Professor, University of Delhi
Objectives
To understand the background why
antibiotic allergies are relevant today
The size of the problem
The nature of the problem
Some simple remedies
Why bother?
The development of antimicrobial guidelines is
one way in which institutions attempt to control
emerging resistance
The real challenge falls on promoting and
ensuring adherence to these guidelines
Investigating reasons for the prescribing of
alternative antimicrobial agents outside of these
guidelines is crucial for modifying practices that
may adversely impact institutional antimicrobial
goals
Why bother?
Clinicians frequently withhold antibiotics
(particularly the penicillins) based on
patients' self-reported clinical history of an
adverse reaction to penicillin and
 the clinicians' own misunderstandings about the
characteristics of a true penicillin allergy

(Alan R. Salkind, Paul G. Cuddy, John W. Foxworth JAMA. 2001;285:2498-2505.)
Why bother?
For example:
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The Centres for Disease Control and Prevention (CDC, Atlanta)
recommend vancomycin use in instances of penicillin allergy by
suggesting its appropriateness only when patients have a serious or
life-threatening allergy to beta-lactam antibiotics
Many studies have established prior vancomycin use as a risk
factor for colonization and infection with vancomycin-resistant
enterococci
BUT

Vancomycin remains the commonest drug for patients giving a
non-specific history of “penicillin allergy”
Hospital Infection Control Practices Advisory Committee. Recommendations for preventing the spread of
vancomycin resistance [review]. Infect Control Hosp Epidemiol. 1995;16:105-113. [published correction appears in
Infect Control Hosp Epidemiol. 1995;16:498].
Why bother?
This contributes to
 Withholding of
appropriate antibiotic
treatment in lifethreatening situations
 Emergence of resistant
strains
 Healthcare-associated
infections
 Rising drug costs
Why bother?
Withholding of appropriate antibiotic
treatment in life-threatening situations
 E.g.
GP withholding penicillin in a
patient with suspected bacterial
meningitis, pregnant woman requiring
treatment for syphilis
Why bother?
 Emergence
of resistant strains
 Healthcare-associated infections
 Rising drug costs


Hospital-acquired infections add an estimated $4.5 billion per
year to health care costs in the United States
While not all such infections can be eliminated, about one third
could be prevented by infection control measures and more
prudent use of antimicrobial agents (JAMA. 1998;279:1055-1056.)
Dr Ragunathan, Consultant Microbiologist
to speak
Why bother? The Precautionary Principle
“it is better to be roughly right in due time,
bearing in mind the consequences of being
very wrong, than to be precisely right too
late”
(Norwegian Research Council for Science and the Humanities
(NAVF), 1990)
The size of the problem: some ideas
Arch Intern Med, Oct 2000; 160: 2819 - 2822.
Arch Intern Med, Oct 2000; 160: 2819 - 2822.
The nature of the problem: some ideas
Is This Patient Allergic to
Penicillin?
An Evidence-Based Analysis of the Likelihood of
Penicillin Allergy. Alan R. Salkind, Paul G. Cuddy, John
W. Foxworth. JAMA. 2001;285:2498-2505.
Objectives To determine the likelihood of true penicillin
allergy with consideration of clinical history and to
evaluate the diagnostic value added by appropriate skin
testing.
Data Sources MEDLINE was searched for relevant
English-language articles dated 1966 to October 2000.
Is This Patient Allergic to
Penicillin?
Data Synthesis Patients' self-reported history has low
accuracy for diagnosis of true penicillin allergy.
Conclusions

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Only 10% to 20% of patients reporting a history of penicillin
allergy are truly allergic when assessed by skin testing
Taking a detailed history of a patient's reaction to penicillin may
allow clinicians to exclude true penicillin allergy, allowing these
patients to receive penicillin
Patients with a concerning history of type I penicillin allergy who
have a compelling need for a drug containing penicillin should
undergo skin testing. Virtually all patients with a negative skin test
result can take penicillin without serious sequelae.
Antibiotic hypersensitivities
Immediate (<1hour)
Anaphylaxis (hives, laryngeal oedema,
wheezing, hypotension)
 IgE-mediated
 much more likely with parenteral
administration, rare (1 in 50000 to 100000
penicillin treatment courses)
 more serious

Antibiotic hypersensitivities
Non-immediate (>1 hour)

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particularly maculopapular and urticarial eruptions
often in association with intercurrent infection
are common during beta-lactam treatment
mechanisms involved are heterogeneous
type-IV (cell-mediated) pathogenic mechanism may be
involved in some non-immediate reactions such as
maculopapular or bullous rashes and acute generalized
exanthematous pustulosis.
Antibiotic hypersensitivities:
Gell & Coombs Classification
Gell PGH, Coombs RRA, Hachmann PJ, eds. Clinical Aspects of Immunology. Oxford, England:
Blackwell Scientific Publications; 1975:761-781.
Antibiotic hypersensitivities: special situations
Immune hyper-responsiveness (e.g. Cystic
Fibrosis)
Decreased Glutathione levels (e.g. HIV
infection)
Altered Pharmacokinetics (e.g. HIV
infection)
Immune modulation (e.g. Infectious
mononucleosis)
Antibiotic hypersensitivities: Distinguishing
immune- and non-immune mediated reactions
Antibiotic hypersensitivities:
Temporal course
While we do not want to minimize the potential
importance of the presence of a medication
allergy, the data shows that immediate
hypersensitivity reactions to penicillin and betalactam antibiotics decrease with time

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Among a group of 825 patients allergic to penicillin, only 146
(18%) had current evidence for immediate cutaneous reactivity
to major and minor determinants.
Use of penicillin skin testing to detect antipenicillin IgE
antibodies, which cause anaphylaxis, urticaria, and other acute
reactions, would potentially reduce the overall number of
patients requiring alternative therapy to a very small %
Sogn DD, Evans III R, Shepherd G, et al. Results of the National Institute of Allergy and Infectious Diseases Collaborative
Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults.
Arch Intern Med. 1992;152:1025-1032
So, the history-taking for antibiotic
allergy must include
When & why the medication was taken (e.g. at what
age)
When symptoms began (interval between administration and
adverse reaction)
How long the symptoms lasted
A description of the symptoms
Any other medications taken during this time,
including over-the-counter drugs
Any concurrent infections/illnesses
Some remedies
Indications for referral to a physician with
interest in allergy/clinical immunologist
Anaphylaxis without an obvious or previously defined trigger
History of penicillin allergy and likely need for antibiotics in the
future
History of penicillin allergy and an infection with limited options
History of multiple drug allergies or intolerance
Allergy to protein based bio-therapeutics
History of an adverse reaction to an NSAID
Requirement of chemotherapy medication for cancer with h/o
prior hypersensitivity reaction to those medications
History of possible allergic reactions to local anaesthetics
HIV-infected patients with a history of adverse reactions to
trimethoprim-sulfamethoxazole (TM-S) and need this therapy