About 10-15% of all adults report that they are allergic to penicillin or other antibiotics, although the accuracy and significance of these reports remain unclear. In the outpatient setting, clinicians often face a dilemma in prescribing for patients with a history of an allergic reaction to antibiotics. Which drugs should these patients avoid? Are these patients at increased risk for an allergic reaction to related drugs? This Issue Brief summarizes several large studies that can help guide and improve the management of patients with antibiotic allergies

Apter, Andrea J

Strom, Brian L

English

ScholarlyCommons@Penn

University of PennsylvaniaScholarlyCommonsIssue Briefs Leonard Davis Institute of Health Economics7-20-2006Reacting to Antibiotic AllergiesAndrea J. ApterUniversity of PennsylvaniaBrian L. StromUniversity of PennsylvaniaFollow this and additional works at: http://repository.upenn.edu/ldi_issuebriefsThis paper is posted at ScholarlyCommons. http://repository.upenn.edu/ldi_issuebriefs/60For more information, please contact repository@pobox.upenn.edu.Apter, Andrea J. and Strom, Brian L.. Reacting to Antibiotic Allergies. LDI Issue Briefs. 2006; 11 (7). http://ldi.upenn.edu/brief/reacting-antibiotic-allergiesReacting to Antibiotic AllergiesAbstractAbout 10-15% of all adults report that they are allergic to penicillin or other antibiotics, although the accuracyand significance of these reports remain unclear. In the outpatient setting, clinicians often face a dilemma inprescribing for patients with a history of an allergic reaction to antibiotics. Which drugs should these patientsavoid? Are these patients at increased risk for an allergic reaction to related drugs? This Issue Brief summarizesseveral large studies that can help guide and improve the management of patients with antibiotic allergies.LicenseThis work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.This brief is available at ScholarlyCommons: http://repository.upenn.edu/ldi_issuebriefs/60Leonard Davis Institute of Health EconomicsLDI Issue BriefVolume 11, Number 7Summer 2006Andrea J. Apter, MD, MScLDI Senior Fellow,Associate Professor of MedicineBrian L. Strom, MD, MPHLDI Senior Fellow,George S. Pepper Professor of PublicHealth and Preventive MedicineCenter for Clinical Epidemiology andBiostatisticsCenter for Education and Researchon TherapeuticsUniversity of PennsylvaniaAntibiotic allergies arecommon, but the risk forsubsequent allergicreactions is not knownContinued on next page.Reacting to Antibiotic AllergiesEditor’s note: About 10-15% of all adults report that they are allergic topenicillin or other antibiotics, although the accuracy and significance ofthese reports remain unclear.  In the outpatient setting, clinicians oftenface a dilemma in prescribing for patients with a history of an allergicreaction to antibiotics. Which drugs should these patients avoid?  Arethese patients at increased risk for an allergic reaction to related drugs?This Issue Brief summarizes several large studies that can help guide andimprove the management of patients with antibiotic allergies.The discovery of antibiotics was one of the greatest medical advances of the modernera.  Since the 1940s, successive classes of antibiotics have been introduced to fightbacterial infections and treat new or resistant organisms.  These classes includesulfonamides (“sulfa” drugs), followed by penicillins, aminoglycosides, tetracyclines,cephalosporins, flouroquinolones, and macrolides.• Antibiotics are the most commonly prescribed drugs today, and the mostcommon cause of drug-related allergies. While most allergic reactions involvemild skin irritations, some reactions can be life-threatening.• Prescribing for a patient with an antibiotic allergy is complicated by concern overwhether the patient has a related sensitivity to a different drug, a process known as“cross-reactivity.”  For example, patients allergic to penicillin may be allergic tocephalosporins, which have structural similarities to penicillins.• Both overestimating and underestimating the risk of allergic reactions can harmpatients.  Overestimating the risk can lead to unnecessary use of more costlyantibiotics or selection of less effective drugs, and may contribute to thedevelopment of drug-resistant microorganisms.To better understand the risk of antibiotic allergies in the outpatient setting, Stromand colleagues used the General Practice Research Database (GPRD), a largeelectronic database of primary care medical records and prescriptions in the UnitedKingdom.  The GPRD contains records from nearly 700 general practitionerpractices in England and Wales.Large-scale studies shedlight on antibiotic allergiesin outpatient settingsAllergy to sulfa antibioticsmay indicate apredisposition to allergicreactions to other drugs,not just to those that aresulfa-based• Using the GPRD, the researchers sought to document the nature and prevalenceof allergic reactions and cross-reactivity among antibiotics.  Previously, most ofthe evidence about antibiotic allergies had come from small studies of hospitalpatients, even though most antibiotics are prescribed in office settings.• In each study, the researchers identified “allergic-like events” in the database thatoccurred within 30 days after receipt of an antibiotic prescription. They used botha narrow and broad definition of these events.  The narrow definition includeddiagnostic codes for rashes and hives, wheezing, unspecified allergic drugreactions, and more serious reactions such as anaphylaxis.  The broad definitionexpanded the set of codes to include asthma, eczema, or an unspecified adversedrug effect.• One advantage of the study design is that it used diagnoses in the medical recordsto identify an allergic reaction, rather than relying on patient reports.  It is likelythat the true incidence of allergic reactions is higher than the rate ascertained bythe narrow definition, and lower than the rate ascertained by the broad definition.However, the results in each study were similar using either definition, lendingcredibility to the findings.Sulfa antibiotics are no longer the first-line treatment for most infections, althoughthey are still used to treat urinary tract infections.  However, non-antibiotic sulfadrugs are widely used today to treat common conditions such as hypertension,osteoarthritis, and diabetes.  Clinicians have been concerned about cross-reactivitybetween sulfa-based drugs, and whether non-antibiotic sulfa drugs are safe forindividuals with prior allergic reactions to sulfa antibiotics.  To answer this question,Strom and colleagues compared allergic reactions to other sulfa drugs in those whodid and did not have an allergic reaction to a sulfa antibiotic. They also examinedreactions to subsequent penicillins, a biochemically distinct class of antibiotic.• The researchers identified 20,225 patients in the database who had received asulfa antibiotic and a subsequent non-antibiotic sulfa drug from 1987-1999.Overall, 4.8% of patients (969) had an apparent allergic reaction (using the broaddefinition) after receiving the initial sulfa antibiotic. Of these, 9.9% (96) had anallergic reaction after subsequently receiving a sulfa non-antibiotic. Of thepatients who had no allergic reaction after a sulfa antibiotic, 315 (1.6%) had anallergic reaction after a sulfa non-antibiotic. Adjusting for other factors, patientswith a history of allergies to sulfa antibiotics had nearly three times the risk of areaction to a non-antibiotic sulfa drug as those with no such history.• However, when looking at patients who received a sulfa antibiotic and asubsequent a penicillin, those with a prior reaction to a sulfa antibiotic had aneven greater risk of a reaction after receiving a penicillin. These patients hadnearly four times the risk of a reaction to penicillin than those without a historyof a reaction to a sulfa antibiotic.• The researchers conclude that a history of allergy to sulfa antibiotics is a marker ofincreased risk for allergies to subsequent drugs. This risk appears to be due to apredisposition to allergic reactions rather than to cross-reactivity with sulfa-baseddrugs.Allergic reaction topenicillin is less frequentthan previously thought;second prescription afteran allergic-like event iscommon, and rarely causesproblemsBased on case studies of inpatients, the overall frequency of penicillin allergy hasbeen reported to be about 2% per course, with the rate of recurrence upon re-exposure to penicillin as high as 60%.  The rate of anaphylaxis is estimated to be 1for every 5,000-10,000 courses of penicillin.  Apter and colleagues sought toconfirm these estimates in the GPRD, using the narrow definition of allergic-likeevents.• The researchers identified more than three million patients who had received atleast one penicillin prescription from 1987-2001. Of these, 6,212 (0.18%)experienced an allergic-like event after the initial prescription.• Sixty per cent of all patients received a second penicillin prescription at least 60days later.  Almost half—3,014 (48.5%)—of the patients who had had an allergicreaction received a second prescription. Fifty-seven (1.9%) of these patientsexperienced a second reaction to the antibiotic. Few of the reactions were serious;none resulted in death.  Hives accounted for about 75% of the events. Only onepatient had anaphylaxis after both prescriptions.• More than two million patients who did not have a reaction to the initialpenicillin were given a second penicillin prescription.  Of these, 3,452 (0.17%)patients had a reaction to the second prescription.  Adjusting for other factors,patients with an initial reaction to penicillin were 9 times more likely toexperience a second reaction to penicillin, although the absolute risk is small—lessthan 2%.• The rate of anaphylaxis was much smaller than previously reported, and wasestimated to be between 8-16 per million penicillin prescriptions.Penicillins and cephalosporins have structural similarities, giving rise to concernabout cross-reactivity.  Small studies have reported that up to 10% of patients whoare allergic to penicillin may experience a reaction to cephalosporins.  Apter andcolleagues investigated the relationship between penicillin and cephalosporin allergyin the GPRD, using the narrow definition. To distinguish cross-reactivity from ageneral predisposition to allergic reactions, they also investigated reactions tosubsequent sulfa antibiotics.• Of the more than three million patients receiving a penicillin prescription from1987-2001, 534,810 received a subsequent cephalosporin at least 60 days later.• About 1% of the 3,920 patients who had an allergic reaction after penicillin alsohad reaction after the cephalosporin.  This is 10 times greater than the risk of acephalosporin reaction in patients who did not have a reaction to penicillin.However, in a separate analysis of patients receiving penicillin followed by a sulfaantibiotic, patients who had a reaction following penicillin had 7 times the risk ofa reaction to a sulfa antibiotic. These results suggest that cross-reactivity does notadequately explain the increased risk.• Although the relative risk of a subsequent reaction is high, the absolute risk is verysmall.  For example, in patients with a previous penicillin reaction, the absoluterisk of anaphylaxis after a cephalosporin was less than 0.001%.Cephalosporins are notmuch more likely to causeallergic reactions inpenicillin allergic patientsthan any other antibioticContinued on back.This Issue Brief is based on the following articles:  A.J. Apter, J.L. Kinman, W.B. Bilker, M. Herlim, D.J. Margolis, E. Lautenbach, S. Hennessy, B.L. Strom. Is therecross-reactivity between penicillins and cephalosporins? American Journal of Medicine, April 2006, vol. 119, pp. 354.e11-354.e20;  A.J. Apter, J.L. Kinman, W.B.Bilker, M. Herlim, D.J. Margolis, E. Lautenbach, S. Hennessy, B.L. Strom.  Represcription of penicillin after allergic-like events.  Journal of Allergy and ClinicalImmunology, April 2004, vol. 113, pp. 764-70; B.L. Strom, R. Schinnar, A.J. Apter, D.J. Margolis, E. Lautenbach, S. Hennnessy, W.B. Bilker, D. Pettitt. Absence ofcross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics.  New England Journal of Medicine, October 2003, vol. 349, pp. 1628-35.This Issue Brief was supported by the Agency for Healthcare Research and Quality, Center for Education and Research on Therapeutics, University of PennsylvaniaSchool of Medicine (U18 HS10399).  The opinions expressed are those of the authors and not the funding agency.Published by the Leonard Davis Institute of Health Economics, University of Pennsylvania, 3641 Locust Walk, Philadelphia, PA 19104-6218.Janet Weiner, MPH, Associate Director for Health Policy, Editor (215-573-9374)David A. Asch, MD, MBA, Executive DirectorNonprofit OrganizationU.S. PostageP  A  I  DPermit No. 2563Philadelphia, PA 19104Issue Brief Published by theLeonard Davis Instituteof Health EconomicsUniversity of Pennsylvania3641 Locust WalkPhiladelphia, PA 19104-6218215.898.5611fax 215.898.0229ADDRESS CORRECTION REQUESTED© 2006 Leonard Davis InstituteVisit us on the web at www.upenn.edu/ldiPOLICY IMPLICATIONS These studies provide large-scale epidemiologic evidence about antibiotic allergies asthey are encountered in an outpatient setting.  It sheds light on the relative andabsolute risks of allergic-like events, and clarifies the risk of cross-reactivity.• Clinicians should recognize the importance of taking a careful history aboutantibiotic allergies, given that prior events may be a marker for a generalpredisposition to allergic reactions.  However, concerns about cross-reactivitybetween antibiotic drugs seem unwarranted.  These data indicate thatcephalosporins can be considered for patients with penicillin allergy, and thatpatients with an allergy to sulfa antibiotics do not need to be steered away fromsulfa-based drugs.• In outpatient settings, the incidence of serious reactions to penicillin (such asanaphylaxis) is much lower than previously reported, and represcription ofpenicillin is much more frequent than anticipated.• However, these results must be interpreted with caution in light of theretrospective nature of the studies. Patients at risk for severe reactions may havebeen underrepresented, and not all of the reactions patients experienced may havebeen reported to their physician. Furthermore, the results apply only tooutpatients given oral antibiotics; the risks associated with intravenousadministration to inpatients may be much higher.• Further research is needed to understand the mechanisms by which patients witha history of allergic reactions to antibiotics are at increased risk for subsequentreactions to unrelated compounds.

Reacting to Antibiotic Allergies

Kosmopolis

University of Pennsylvania
ScholarlyCommons
Issue Briefs Leonard Davis Institute of Health Economics
7-20-2006
Reacting to Antibiotic Allergies
Andrea J. Apter
University of Pennsylvania
Brian L. Strom
University of Pennsylvania
Follow this and additional works at: http://repository.upenn.edu/ldi_issuebriefs
This paper is posted at ScholarlyCommons. http://repository.upenn.edu/ldi_issuebriefs/60
For more information, please contact repository@pobox.upenn.edu.
Apter, Andrea J. and Strom, Brian L.. Reacting to Antibiotic Allergies. LDI Issue Briefs. 2006; 11 (7). http://ldi.upenn.edu/brief/
reacting-antibiotic-allergies
Reacting to Antibiotic Allergies
Abstract
About 10-15% of all adults report that they are allergic to penicillin or other antibiotics, although the accuracy
and significance of these reports remain unclear. In the outpatient setting, clinicians often face a dilemma in
prescribing for patients with a history of an allergic reaction to antibiotics. Which drugs should these patients
avoid? Are these patients at increased risk for an allergic reaction to related drugs? This Issue Brief summarizes
several large studies that can help guide and improve the management of patients with antibiotic allergies.
License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.
This brief is available at ScholarlyCommons: http://repository.upenn.edu/ldi_issuebriefs/60
Leonard Davis Institute of Health Economics
LDI Issue Brief
Volume 11, Number 7
Summer 2006
Andrea J. Apter, MD, MSc
LDI Senior Fellow,
Associate Professor of Medicine
Brian L. Strom, MD, MPH
LDI Senior Fellow,
George S. Pepper Professor of Public
Health and Preventive Medicine
Center for Clinical Epidemiology and
Biostatistics
Center for Education and Research
on Therapeutics
University of Pennsylvania
Antibiotic allergies are
common, but the risk for
subsequent allergic
reactions is not known
Continued on next page.
Reacting to Antibiotic Allergies
Editor’s note: About 10-15% of all adults report that they are allergic to
penicillin or other antibiotics, although the accuracy and significance of
these reports remain unclear.  In the outpatient setting, clinicians often
face a dilemma in prescribing for patients with a history of an allergic
reaction to antibiotics. Which drugs should these patients avoid?  Are
these patients at increased risk for an allergic reaction to related drugs?
This Issue Brief summarizes several large studies that can help guide and
improve the management of patients with antibiotic allergies.
The discovery of antibiotics was one of the greatest medical advances of the modern
era.  Since the 1940s, successive classes of antibiotics have been introduced to fight
bacterial infections and treat new or resistant organisms.  These classes include
sulfonamides (“sulfa” drugs), followed by penicillins, aminoglycosides, tetracyclines,
cephalosporins, flouroquinolones, and macrolides.
• Antibiotics are the most commonly prescribed drugs today, and the most
common cause of drug-related allergies. While most allergic reactions involve
mild skin irritations, some reactions can be life-threatening.
• Prescribing for a patient with an antibiotic allergy is complicated by concern over
whether the patient has a related sensitivity to a different drug, a process known as
“cross-reactivity.”  For example, patients allergic to penicillin may be allergic to
cephalosporins, which have structural similarities to penicillins.
• Both overestimating and underestimating the risk of allergic reactions can harm
patients.  Overestimating the risk can lead to unnecessary use of more costly
antibiotics or selection of less effective drugs, and may contribute to the
development of drug-resistant microorganisms.
To better understand the risk of antibiotic allergies in the outpatient setting, Strom
and colleagues used the General Practice Research Database (GPRD), a large
electronic database of primary care medical records and prescriptions in the United
Kingdom.  The GPRD contains records from nearly 700 general practitioner
practices in England and Wales.
Large-scale studies shed
light on antibiotic allergies
in outpatient settings
Allergy to sulfa antibiotics
may indicate a
predisposition to allergic
reactions to other drugs,
not just to those that are
sulfa-based
• Using the GPRD, the researchers sought to document the nature and prevalence
of allergic reactions and cross-reactivity among antibiotics.  Previously, most of
the evidence about antibiotic allergies had come from small studies of hospital
patients, even though most antibiotics are prescribed in office settings.
• In each study, the researchers identified “allergic-like events” in the database that
occurred within 30 days after receipt of an antibiotic prescription. They used both
a narrow and broad definition of these events.  The narrow definition included
diagnostic codes for rashes and hives, wheezing, unspecified allergic drug
reactions, and more serious reactions such as anaphylaxis.  The broad definition
expanded the set of codes to include asthma, eczema, or an unspecified adverse
drug effect.
• One advantage of the study design is that it used diagnoses in the medical records
to identify an allergic reaction, rather than relying on patient reports.  It is likely
that the true incidence of allergic reactions is higher than the rate ascertained by
the narrow definition, and lower than the rate ascertained by the broad definition.
However, the results in each study were similar using either definition, lending
credibility to the findings.
Sulfa antibiotics are no longer the first-line treatment for most infections, although
they are still used to treat urinary tract infections.  However, non-antibiotic sulfa
drugs are widely used today to treat common conditions such as hypertension,
osteoarthritis, and diabetes.  Clinicians have been concerned about cross-reactivity
between sulfa-based drugs, and whether non-antibiotic sulfa drugs are safe for
individuals with prior allergic reactions to sulfa antibiotics.  To answer this question,
Strom and colleagues compared allergic reactions to other sulfa drugs in those who
did and did not have an allergic reaction to a sulfa antibiotic. They also examined
reactions to subsequent penicillins, a biochemically distinct class of antibiotic.
• The researchers identified 20,225 patients in the database who had received a
sulfa antibiotic and a subsequent non-antibiotic sulfa drug from 1987-1999.
Overall, 4.8% of patients (969) had an apparent allergic reaction (using the broad
definition) after receiving the initial sulfa antibiotic. Of these, 9.9% (96) had an
allergic reaction after subsequently receiving a sulfa non-antibiotic. Of the
patients who had no allergic reaction after a sulfa antibiotic, 315 (1.6%) had an
allergic reaction after a sulfa non-antibiotic. Adjusting for other factors, patients
with a history of allergies to sulfa antibiotics had nearly three times the risk of a
reaction to a non-antibiotic sulfa drug as those with no such history.
• However, when looking at patients who received a sulfa antibiotic and a
subsequent a penicillin, those with a prior reaction to a sulfa antibiotic had an
even greater risk of a reaction after receiving a penicillin. These patients had
nearly four times the risk of a reaction to penicillin than those without a history
of a reaction to a sulfa antibiotic.
• The researchers conclude that a history of allergy to sulfa antibiotics is a marker of
increased risk for allergies to subsequent drugs. This risk appears to be due to a
predisposition to allergic reactions rather than to cross-reactivity with sulfa-based
drugs.
Allergic reaction to
penicillin is less frequent
than previously thought;
second prescription after
an allergic-like event is
common, and rarely causes
problems
Based on case studies of inpatients, the overall frequency of penicillin allergy has
been reported to be about 2% per course, with the rate of recurrence upon re-
exposure to penicillin as high as 60%.  The rate of anaphylaxis is estimated to be 1
for every 5,000-10,000 courses of penicillin.  Apter and colleagues sought to
confirm these estimates in the GPRD, using the narrow definition of allergic-like
events.
• The researchers identified more than three million patients who had received at
least one penicillin prescription from 1987-2001. Of these, 6,212 (0.18%)
experienced an allergic-like event after the initial prescription.
• Sixty per cent of all patients received a second penicillin prescription at least 60
days later.  Almost half—3,014 (48.5%)—of the patients who had had an allergic
reaction received a second prescription. Fifty-seven (1.9%) of these patients
experienced a second reaction to the antibiotic. Few of the reactions were serious;
none resulted in death.  Hives accounted for about 75% of the events. Only one
patient had anaphylaxis after both prescriptions.
• More than two million patients who did not have a reaction to the initial
penicillin were given a second penicillin prescription.  Of these, 3,452 (0.17%)
patients had a reaction to the second prescription.  Adjusting for other factors,
patients with an initial reaction to penicillin were 9 times more likely to
experience a second reaction to penicillin, although the absolute risk is small—less
than 2%.
• The rate of anaphylaxis was much smaller than previously reported, and was
estimated to be between 8-16 per million penicillin prescriptions.
Penicillins and cephalosporins have structural similarities, giving rise to concern
about cross-reactivity.  Small studies have reported that up to 10% of patients who
are allergic to penicillin may experience a reaction to cephalosporins.  Apter and
colleagues investigated the relationship between penicillin and cephalosporin allergy
in the GPRD, using the narrow definition. To distinguish cross-reactivity from a
general predisposition to allergic reactions, they also investigated reactions to
subsequent sulfa antibiotics.
• Of the more than three million patients receiving a penicillin prescription from
1987-2001, 534,810 received a subsequent cephalosporin at least 60 days later.
• About 1% of the 3,920 patients who had an allergic reaction after penicillin also
had reaction after the cephalosporin.  This is 10 times greater than the risk of a
cephalosporin reaction in patients who did not have a reaction to penicillin.
However, in a separate analysis of patients receiving penicillin followed by a sulfa
antibiotic, patients who had a reaction following penicillin had 7 times the risk of
a reaction to a sulfa antibiotic. These results suggest that cross-reactivity does not
adequately explain the increased risk.
• Although the relative risk of a subsequent reaction is high, the absolute risk is very
small.  For example, in patients with a previous penicillin reaction, the absolute
risk of anaphylaxis after a cephalosporin was less than 0.001%.
Cephalosporins are not
much more likely to cause
allergic reactions in
penicillin allergic patients
than any other antibiotic
Continued on back.
This Issue Brief is based on the following articles:  A.J. Apter, J.L. Kinman, W.B. Bilker, M. Herlim, D.J. Margolis, E. Lautenbach, S. Hennessy, B.L. Strom. Is there
cross-reactivity between penicillins and cephalosporins? American Journal of Medicine, April 2006, vol. 119, pp. 354.e11-354.e20;  A.J. Apter, J.L. Kinman, W.B.
Bilker, M. Herlim, D.J. Margolis, E. Lautenbach, S. Hennessy, B.L. Strom.  Represcription of penicillin after allergic-like events.  Journal of Allergy and Clinical
Immunology, April 2004, vol. 113, pp. 764-70; B.L. Strom, R. Schinnar, A.J. Apter, D.J. Margolis, E. Lautenbach, S. Hennnessy, W.B. Bilker, D. Pettitt. Absence of
cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics.  New England Journal of Medicine, October 2003, vol. 349, pp. 1628-35.
This Issue Brief was supported by the Agency for Healthcare Research and Quality, Center for Education and Research on Therapeutics, University of Pennsylvania
School of Medicine (U18 HS10399).  The opinions expressed are those of the authors and not the funding agency.
Published by the Leonard Davis Institute of Health Economics, University of Pennsylvania, 3641 Locust Walk, Philadelphia, PA 19104-6218.
Janet Weiner, MPH, Associate Director for Health Policy, Editor (215-573-9374)
David A. Asch, MD, MBA, Executive Director
Nonprofit Organization
U.S. Postage
P  A  I  D
Permit No. 2563
Philadelphia, PA 19104
Issue Brief
Published by the
Leonard Davis Institute
of Health Economics
University of Pennsylvania
3641 Locust Walk
Philadelphia, PA 19104-6218
215.898.5611
fax 215.898.0229
ADDRESS CORRECTION REQUESTED
© 2006 Leonard Davis Institute
Visit us on the web at www.upenn.edu/ldi
POLICY IMPLICATIONS These studies provide large-scale epidemiologic evidence about antibiotic allergies as
they are encountered in an outpatient setting.  It sheds light on the relative and
absolute risks of allergic-like events, and clarifies the risk of cross-reactivity.
• Clinicians should recognize the importance of taking a careful history about
antibiotic allergies, given that prior events may be a marker for a general
predisposition to allergic reactions.  However, concerns about cross-reactivity
between antibiotic drugs seem unwarranted.  These data indicate that
cephalosporins can be considered for patients with penicillin allergy, and that
patients with an allergy to sulfa antibiotics do not need to be steered away from
sulfa-based drugs.
• In outpatient settings, the incidence of serious reactions to penicillin (such as
anaphylaxis) is much lower than previously reported, and represcription of
penicillin is much more frequent than anticipated.
• However, these results must be interpreted with caution in light of the
retrospective nature of the studies. Patients at risk for severe reactions may have
been underrepresented, and not all of the reactions patients experienced may have
been reported to their physician. Furthermore, the results apply only to
outpatients given oral antibiotics; the risks associated with intravenous
administration to inpatients may be much higher.
• Further research is needed to understand the mechanisms by which patients with
a history of allergic reactions to antibiotics are at increased risk for subsequent
reactions to unrelated compounds.


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