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Clinicians commonly encounter patients with a history of allergy to penicillin and other
beta-lactam antibiotics, since about 10% of the population reports such an allergy. At the same
time, it is known that about 90% of these patients are not truly allergic and could safely receive
beta-lactam antibiotics. Instead, these patients are treated unnecessarily with alternate broad-
spectrum antibiotics, which increases costs and contributes to the development and spread of
multiple drug-resistant bacteria.
In the case of penicillin, relevant allergenic determinants that elicit immune responses are
known. Hence, validated diagnostic skin testing to detect the presence of drug-specific IgE
Abstract
Index Entries:
Penicillin; cephalosporins; beta-lactams; hypersensitivity; skin testing.
Introduction Table 1
Hypersensitivity Drug Disorders Associated
Beta-lactam antibiotics are known to cause with Beta-Lactam Antibiotics
various predictable and unpredictable adverse Multisystem
reactions. Hypersensitivity reactions are a sub- Anaphylaxis
set of unpredictable reactions that are known Serum sickness-like reaction
(or presumed) to be mediated by an immuno- Drug fever
Vasculitis
logic mechanism. The term allergic reactions
Generalized lymphadenopathy
is synonymous with hypersensitivity reactions, Skin
although it is often mistakenly applied to all Maculopapular/morbilliform eruption
adverse drug reactions. Beta-lactam antibiotics Urticaria/angioedema
have been implicated in a wide variety of Stevens-Johnson syndrome
Toxic epidermal necrolysis
hypersensitivity reactions (Table 1). Although Contact dermatitis
the immune system is believed to play a role in Fixed drug eruption
all of these disorders, in many cases the under- Bone Marrow
lying mechanism does not fit into the tradi- Hemolytic anemia
tional Gell and Coombs classification scheme, Thrombocytopenia
Neutropenia
and has not yet been elucidated. This article Aplastic anemia
focuses primarily on IgE-mediated reactions, Eosinophilia
since we have considerable insight into their Lung
pathogenesis, and because physicians are often Pulmonary infiltrates with eosinophilia
faced with the evaluation and management of Kidney
Interstitial nephritis
patients with possible immediate-type beta- Nephrotic syndrome
lactam allergies. Liver
Hepatitis
Epidemiology Heart
Myocarditis
Allergies to beta-lactam antibiotics are the
most commonly reported medication allergy.
Penicillin allergy alone is reported by up to Large-scale reviews of cutaneous adverse drug
10% of patients. At the same time, when reactions have found beta-lactams to be the
patients with a history of penicillin allergy are most frequent culprit drugs. For example, the
evaluated, more than 90% of them are found to Boston Collaborative Drug Surveillance Pro-
lack penicillin-specific IgE antibodies, and can gram analyzed data from 37,665 consecutive
tolerate the antibiotic safely (1,2). The discrep- inpatients and determined the frequency of
ancy between claimed and real penicillin beta-lactam-associated cutaneous reactions to
allergy probably results from several factors, be: 5.1% of exposed patients (amoxicillin), 4.5%
including the fact that the previous reaction (ampicillin), 1.6% (penicillin G), and 1.5%
was caused by the underlying illness rather (cephalosporins) (7,8). The majority of reported
than the antibiotic, or that the reaction was pre- reactions consisted of maculopapular/morbil-
dictable rather than allergic. Penicillin-allergic liform eruptions and urticaria, but it is unknown
patients are known to lose drug-specific anti- how many were in fact caused by drug-specific
bodies over time (36), which also contributes IgE antibodies.
to the discrepancy. Retrospective data on penicillin-induced
No studies have prospectively evaluated anaphylaxis have revealed remarkably consis-
the sensitization rate during treatment courses tent results, which show that these reactions
with penicillin or other beta-lactam antibiotics. are rare. In 1968, Idsoe et al. reviewed over a
Clinical Reviews in Allergy & Immunology Volume 24, 2003
Hypersensitivity Reactions to Beta-Lactam Antibiotics 203
penicillin (9). It is also believed that allergic underlying heightened propensity to develop
sensitization is most likely to occur in individu- hypersensitivity reactions (both IgE- and non-
als who receive frequent, repeated courses of IgE-mediated) (27). According to this theory, a
similar antibiotics (22,23). Although the theo- patient who develops an allergy to one medi-
ries about route and frequency of administra- cation is more likely to develop a second allergy
tion have never been studied in prospective to an unrelated compound. Multiple drug
fashion, they are supported by the observation allergy syndrome has been described in both
that patients with cystic fibrosiswho undergo pediatric and adult patients (2831). For
frequent treatments with iv antibioticsare example, Smith et al. prospectively followed
particularly prone to developing IgE-mediated inpatients who received treatment with peni-
beta-lactam allergies (24). cillin, and found that patients who developed
an allergic reaction to the antibiotic were about
Hereditary Factors 3 times more likely to report a history of prior
There is limited evidence that genetic or fami- drug allergy (30). Similarly, hospitalized patients
lial factors may play a role in the expression of with a history of antibiotic allergy were found
antibiotic allergies, including beta-lactams. In to be 9 times more likely to develop an allergic
two separate survey-type studies, children of reaction to another antibiotic, compared with
parents who reported an antibiotic allergy inpatients without a history of antibiotic allergy
were 15 times more likely to also be antibiotic- (29). Other investigators have disputed the
allergic (25), and patients with a history of drug existence of the multiple drug allergy syn-
allergy were 9 times more likely to report a drome. Khoury et al. compared the frequency
family history of drug allergy among first- of reactions to non-beta lactam antibiotics in
degree relatives (26). The results of both age- and sex-matched groups of patients with
investigations are limited by a lack of confir- and without positive penicillin skin tests (32).
matory testing or provocative challenges and There were no significant differences in reac-
their reliance on patient history, which is tion rates between the groups, and penicillin-
known to be a poor predictor of true allergy. allergic patients were least likely to react to
Furthermore, the reactions reported by the another antibiotic.
subjects included a variety of both IgE- and non-
Beta-Lactam Immunochemistry
IgE- mediated reactions. To explain the fact that
the familial predilection occurs across different Beta-lactam antibiotics, like many medica-
classes of medications, it has been theorized tions, are structurally too small to act as complete
that these patients are more likely to mount an antigens, and therefore cannot independently
allergic immune response against drug-protein elicit an immune response (21). Instead, they
complexes that are normally formed during covalently bind to a larger carrier molecule,
therapy (27). Given the limitations of the avail- such as tissue or serum proteins, to form a
able data, further research is needed to clarify multivalent antigen that is capable of stimulat-
whether and by what mechanism hereditary ing the immune system. This process is known
factors may play a role in beta-lactam allergies. as haptenation, and the low molecular-weight
compounds are known as haptens (33). The elic-
Multiple Drug Allergy Syndrome ited immune response may be a humoral one
The term multiple drug allergy syndrome with the production of specific antibodies, a
refers to patients who have experienced aller- cellular one with the generation of specific T-
gic reactions to two or more non-crossreacting lymphocytes, or both. In general, immediate-
medications. Some investigators believe that type reactions correlate with the presence of
the syndrome is caused by an individuals specific IgE antibodies, and recent evidence
Table 2
Beta-Lactam Antibiotics with Identical R-Group Side Chains
(1 or 2 indicates number of side chains)
Modified from Poley G.E and Slater J.E (1999), Drug and vaccine allergy. Immunol. Allergy Clin. North Am. 19, 409422
testing panel of patients who report reactions immune response only to particular R-group
to these extended-spectrum penicillins. side chains present in these medications.
Although a majority of patients who are aller- Patients with selective side-chain reactivity
gic to these compounds have IgE antibodies have negative skin-test responses to PPL and
directed against the core beta-lactam portion of MDM, but test positive to non-irritating con-
the molecule, some patients (especially those centrations of the culprit extended-spectrum
with cystic fibrosis) appear to mount an penicillin (24,4144). Amoxicillin and ampicil-
Clinical Reviews in Allergy & Immunology Volume 24, 2003
208 Solensky
ize that a negative skin test with the free drug Clinical Management: Penicillins
does not rule out the presence of immediate-
type allergy. When to Skin Test
Historically, evaluation of possible penicil-
Cephalosporins lin allergy was limited to acute situations in
Skin testing with native cephalosporins has which patients with a history of penicillin
been performed since the 1960s. As part of allergy required penicillin and an alternate
many studies, a non-irritating concentration antibiotic could not be substituted (64). The
was determined in healthy, non-allergic con- Disease management of drug hypersensitiv-
trol subjects (3,5660). For intradermal testing, ity: a practice parameter of the Joint Task
concentrations of 125 mg/mL have been Force on Practice Parameters also suggests that
reported to be non-irritating. This wide range penicillin skin testing in adults be used prima-
of values probably results from the fact that, in rily when there is an acute need for the medica-
a given study, once a non-irritating concentra- tion (49). For the pediatric population, elective
tion was found, no additional attempts were testing of patients when they are well and not
made to test with higher concentrations (since in immediate need of the medication is recom-
this concentration also gave positive skin-test mended because of their frequent outpatient
responses in allergic patients). In a recent need for penicillin treatment and the impracti-
report whose sole objective was to find the cality of testing children when they are sick
highest non-irritating concentration of 16 anti- (49).
bioticsincluding 5 cephalosporinsin 25 This author believes that elective penicillin
non-allergic subjects, all cephalosporins were skin testing of history-positive adults as well
found to be non-irritating for intradermal test- as children makes clinical sense, in light of
ing when diluted 10-fold from the full-strength emerging new data and the increasing preva-
commercially available solution (61). Concen- lence of multiple antibiotic resistance. As men-
trations of these 10-fold dilutions ranged from tioned earlier, although penicillin allergy is
933 mg/mL. self-reported by up to 10% of the population,
the vast majority of these patients are not truly
Monobactams and Carbapenems allergic and could receive penicillin-class anti-
Skin testing with native monobactams and biotics. It is also common practice to deny these
carbapenems also may be of value in selected patients access to cephalosporins and other
patients. Aztreonam and imipenem have been beta-lactams, in addition to penicillins. Instead,
reported to be non-irritating for intradermal patients labeled as penicillin-allergic are need-
skin testing at concentrations of 6 103 M lessly treated with broad-spectrum antibiotics
(about 2.6 mg/mL) and 5 103 M (about 1.6 (65,66), and the use of these drugs contributes
to the development and spread of multiple
mg/mL), respectively (62,63). The predictive
drug-resistant bacteria (6769). Thus, an impor-
value of such skin testing is unknown, but a
tant and often under-appreciated aspect of
positive response suggests IgE-mediated
penicillin allergy is the morbidity, mortality,
allergy. Major and minor determinants (analo-
and economic cost associated with the unnec-
gous to penicillin) of aztreonam and imipenem
essary withholding of appropriate therapy in
have been synthesized and used in research patients who are assumed to be penicillin-
settings (62,63), but their relevance is unclear, allergic (70). More judicious use of broad-
and they are not available to the practicing spectrum antibiotics can help reduce the spread
allergist. of antibiotic resistance (67,69,71), and one way
to achieve this goal is to penicillin skin test and
identify the many patients erroneously labeled
Clinical Reviews in Allergy & Immunology Volume 24, 2003
210 Solensky
as penicillin-allergic. In recent years, a num- Testing Only with PPL and Penicillin G
ber of medical centers in the United States have The previous discussion assumes that the
reported on successful efforts to carry out peni- evaluating allergist has access to both major
cillin skin testing and decrease the utilization
and minor penicillin determinants. Skin test-
of broad-spectrum antibiotics (7276).
ing with PPL and penicillin G alone (without
In the real world practice setting, patients
MDM) can be successfully used to evaluate
who have negative penicillin skin tests fre-
patients with a history of penicillin allergy (52),
quently find it difficult to trust the result after
but because such testing may miss some aller-
having been told their entire lives to avoid
gic patients, it requires a more cautious
penicillin. Likewise, the referring physician or
approach. It is recommended that these skin
other future prescribing physicians may be
test-negative patients first be given a test dose
reluctant to treat patients with a beta-lactam
of approx 1/100th of the full therapeutic dose
antibiotic simply based on a skin-test result. To
alleviate patients and physicians fears and to (49). If no reaction occurs during a brief obser-
unequivocally prove the medications safety, vation period (e.g., 1 h), the full dose may be
an elective oral challenge (with the same anti- administered (49).
biotic implicated in the previous reaction) can
be performed. The Role of Allergic History
It is difficult to decide based solely on a
Penicillin Resensitization patients history (e.g., without skin testing)
Initially, elective penicillin skin testing was which patients may be safely treated with peni-
discouraged because of a fear that patients who cillin. Some patients report reactions that were
tested negative may become resensitized, or clearly mislabeled as being allergic in nature,
redevelop their allergy, following future treat- and they may not need to be skin-tested. More
ment courses with penicillin. In children, the often, patients report reactions (such as various
resensitization rate in 240 history-positive/skin skin eruptions) that could indicate allergy, or
test-negative patients was found to be about 1%, they cannot remember appropriate details of
following a course of oral penicillin (50). An their reaction because it occurred in the distant
additional 1500 unreported patients evaluated past. Often, patients simply do not recall the
by the authors of this study have confirmed reaction, but were told by their parent or
these results (Louis Mendelson, personal com-
pediatrician to always avoid penicillin.
munication). In adults, recent evidence suggests
Patients with convincing histories of penicillin
that resensitization is also rare. Solensky et al.
allergy are more likely to have positive skin
challenged 46 skin test-negative patients with a
tests than those with vague histories (1,16,53).
convincing history of penicillin allergy with
However, vague allergic histories should not
three separate courses of oral penicillin, and
be disregarded, because, as a recent review of
none converted to a positive skin test (77).
the literature revealed, one-third of all history-
Although resensitization following oral penicil-
positive/penicillin-skin test-positive patients
lin appears to be low, limited data indicate that
had a vague history of a previous reaction (80).
it may be more common following parenteral
administration (78,79). Therefore, pending
additional studies, history-positive patients
Skin Test-Positive Patients
who have tolerated a parental course of penicil- Patients who have a positive penicillin-skin
lin should have skin testing repeated prior to test to any antigenic determinant should avoid
receiving additional penicillin. all penicillin-class compounds and be treated
with alternate antibiotics that do not crossreact
Clinical Reviews in Allergy & Immunology Volume 24, 2003
Hypersensitivity Reactions to Beta-Lactam Antibiotics 211
Table 4
Administration of Cephalosporins to Patients with Positive Penicillin Skin Tests
No. of No. of
Ref. Patients Reactions (%) Comment
Girard (56) 23 2 (8.7) Both reactions to
cephaloridine*
Assem (82) 3 3 All reactions to
cephaloridine*
Warrington (88) 3 0
Solley (43) 27 0
Saxon (89) 62 1 (1.6) Specific cephalosporin not reported
Blanca (90) 17 2 (11.8) Both reactions to
cefamandole*
Shepherd (91) 9 0
Audicana (92) 12 0
Novalbos (60) 23 0
TOTAL 179 8 (4.5)
*
These cephalosporins have side chains similar to benzylpenicillin. All patients had positive skin-
test responses to PPL, penicillin G, and/or MDM. Patients negative to the major and minor determi-
nants but positive to amoxicillin/ampicillin are not included.
with penicillin. The only exception to this rule history of penicillin allergy revealed allergic
is if a patient has a positive response only to an reactions in 8.11.9% of patients, respectively
extended-spectrum penicillin. For example, if (86). In 1975 Dash reviewed the international
a patient tests positive to amoxicillin but is literature for allergic reactions to first-
negative to PPL, penicillin G, and MDM, he/ generation cephalosporins and found similar
she can likely tolerate other penicillins that do resultsa reaction rate of 7.7% in penicillin
not share the same side chain (to which the IgE allergy history-positive patients, and 0.8% in
is presumably directed) (41,42,44). When skin history-negative patients (87). Neither report
test-positive patients require treatment with commented on the type of penicillin allergy
penicillin, they should undergo desensitization history the participants had or on the type of
(discussed in detail later in this article). reactions elicited by the cephalosporins, and
none of the patients underwent penicillin
Clinical Management: Cephalosporins skin testing. In contrast to these findings, a
review of over 600 hospitalized inpatients
Patients with a History of Penicillin Allergy with a history of penicillin allergy who
In vitro studies with penicillin and cepha- received cephalosporins revealed only one
losporins have shown a high degree of immu- non-immediate reaction (unpublished obser-
nologic crossreactivity that is suggested by the vation by author).
presence of a common beta-lactam ring (81 The major weakness of the studies dis-
85). Although clinical crossreactivity occurs cussed here is a lack of confirmation of penicil-
much less frequently, the exact incidence is still lin allergy by skin testing, since it is likely that
not known. A retrospective review of treat- the vast majority of these patients did not have
ment courses with first-generation cepha- penicillin-specific IgE antibodies. There are a
losporins in 701 patients with a history of limited number of reports of penicillin-skin
penicillin allergy and 15,007 patients without a test-positive patients challenged with cepha-
Clinical Reviews in Allergy & Immunology Volume 24, 2003
212 Solensky
losporins, and they reveal a very low reaction mental challenges depend on the side chain
rate (Table 4). Additionally, the frequency of similarity (or lack thereof) between the cepha-
reactions to cephalosporins in skin test-positive losporin and the penicillin to which the patient
patients does not appear to differ from that reacted previously. In the absence of penicil-
in penicillin history-positive/skin test-negative lin-skin testing, since less than 1% of patients
patients (3,43,91,92). It is also important to will have a reaction, direct administration of
point out that in virtually all reported positive the cephalosporin can be considered (Fig. 3),
cephalosporin challenges, the culprit cepha- but is generally discouraged (49). Under these
losporin shares a similar R-group side chain circumstances, this author recommends an ini-
with benzylpenicillin (Table 4). Therefore, the tial test dose or a graded-dose challenge.
observed crossreactivity may have been the
result of side chain-specific determinants Patients with a History of Cephalosporin
rather than the core beta-lactam portion of Allergy
the molecules. Several investigators have The lack of standardized validated skin
described selective allergic crossreactivity testing makes evaluation of possible cepha-
between particular penicillins and cephalo- losporin allergy more difficult than penicillin
sporins that share similar or identical side allergy. As stated previously, skin testing with
chains (46,47). native cephalosporins can be of some value,
Another factor to consider when evaluating but its predictive value is unknown. A positive
early reports of reactions to cephalosporins in skin-test response using a non-irritating con-
patients with a history of penicillin allergy centration is suggestive of IgE-mediated aller-
(56,9398) is that initial cephalosporin prepa- gy, but a negative result does not rule out
rations contained trace amounts of penicillin sensitivity.
(99). Such contamination may have con- Little is known about the extent of cross-
founded the findings and resulted in an reactivity among different cephalosporins, and
overestimate of the allergic crossreactivity. thus the safety of administering a particular
Furthermore, as mentioned previously, cephalosporin to a patient who has previously
patients who are allergic to one medication experienced an allergic reaction to another
may be more likely to react to a non-cross- cephalosporin. Case reports of patients who
reacting agent (2831). Thus, in some penicillin- are allergic to a particular cephalosporin being
allergic patients, multiple drug allergy able to tolerate other cephalosporins seem to
syndrome, rather than immunologic cross- suggest that the immune response is directed
reactivity, may be responsible for their cepha- against R-group side chains, rather than the
losporin allergy. core portion of the molecules (45,57,58,100).
The approach to patients with a history of These data and clinical experience led to the
penicillin allergy who require treatment with recommendation that patients with a history of
cephalosporins is outlined in Fig. 3. Ideally, if cephalosporin allergy may safely receive other
penicillin-skin testing is available, it should be cephalosporins as long as they have dissimilar
utilized in the evaluation. Patients whose skin- side chains (Fig. 3). The results of a recent study
test responses are negative can receive any by Romano et al. places some doubt on this
cephalosporin safely. Alternatively, if skin test- practice, however (59). The investigators skin-
ing is positive, the practice parameter sug- tested 30 cephalosporin-allergic patients with
gests one of three options (Fig. 3). Based several different cephalosporins. About half of
on the evidence discussed here, this author the subjects reacted only to the culprit cepha-
recommends a graded challenge. The pace and losporin, and the other half had positive skin
degree of caution exercised in such incre- responses to various cephalosporins, including
Clinical Reviews in Allergy & Immunology Volume 24, 2003
Hypersensitivity Reactions to Beta-Lactam Antibiotics 213
Fig. 3. Algorithms for the evaluation and management of patients with histories of penicillin/cephalosporin
allergies. Adapted from Bernstein, I. L., et al. (1999), Disease management of drug hypersensitivity: a prac-
tice parameter. Ann. Allergy Asthma Immunol. 83, 665700.
Clinical Reviews in Allergy & Immunology Volume 24, 2003
214 Solensky
ones with different side chains. These results and aztreonam (104106). The only exception
suggest that some cephalosporin-allergic to this was ceftazidime, which shares an
patients form IgE antibodies to crossreacting identical side-chain R group with aztreonam
core deter-minants (rather than R groups), but (105,106). These findings indicate that the
none of the patients was challenged to confirm immunologic response to aztreonam is direc-
this suspicion. ted at its side chain, rather than the core beta-
The management of patients with a history lactam portion of the molecule.
of cephalosporin allergy who require treat- In vivo studies and challenges of penicil-
ment with penicillin is straightforward, and it lin-allergic patients have confirmed a lack of
is based on the result of penicillin-skin testing crossreactivity between these agents (62,102
(Fig. 3). Skin test-negative patients may receive 104,107). Of 41 penicillin-skin test-positive
penicillin, whereas skin test-positive patients patients, none had a reproducible positive skin
should receive an alternate agent or undergo test to aztreonam determinants analogous
desensitization. If penicillin-skin testing is not to penicillin major and minor determinants
available, penicillin can be given via a graded (which were synthesized for research purposes
challenge. only) (62). Subsequently, these investigators
challenged 20 penicillin skin test-positive
Clinical Management:
patients with aztreonam, and none experi-
Other Beta-Lactams enced an adverse reaction (103), a finding
Monobactams confirmed by Vega et al. in 19 additional pen-
Aztreonam is a newer beta-lactam anti- icillin-skin test-positive patients (102). Graninger
biotic that contains a monocyclic ring structure, and colleagues treated 23 penicillin and/or
in contrast to the other bicyclic core beta-lactams cephalosporin-allergic patients (by history
(Fig. 2). There are no standardized aztreonam only) with aztreonam; 22 tolerated the medica-
skin-test reagents, making evaluation of pos- tion, and one patient developed urticaria after
sible allergy difficult. Native aztreonam is non- 3 wk of treatment (108). Finally, there is a case
irritating for intradermal skin testing up to a report of a penicillin-allergic patient who failed
concentration of 2.6 mg/mL (62,101,102), but penicillin desensitization but was able to toler-
its predictive value is unknown. Patients with ate aztreonam (109).
a history of immediate reactions to aztreonam To summarize, available data indicate a
who require re-administration should undergo lack of allergic crossreactivity between
desensitization. aztreonam and other beta-lactam antibiotics.
The immunogenicity of aztreonam and its
Therefore, patients who report previous reac-
potential allergic crossreactivity with penicillin
tions to penicillins and cephalosporins can
and cephalosporins were extensively studied in
safely receive aztreonam, with the exception of
cooperation with the drugs manufacturer dur-
ing the preclinical development and early clini- patients who are allergic to ceftazidime (which
cal trials (103). A prospective and comparative has an identical side chain). Conversely,
randomized trial of aztreonam, cefotaxime, patients who have experienced Type I allergic
and procaine penicillin in the treatment of reactions to aztreonam are able to tolerate
gonococcal urethritis showed aztreonam to be penicillins and cephalosporins (except for
least immunogenic (e.g., least likely to result in ceftazidime) (101,110,111).
the development of drug-specific IgG and IgE
antibodies) (104). In vitro studies demonstrated
virtually no immunologic crossreactivity
between either penicillin or cephalosporins
Clinical Reviews in Allergy & Immunology Volume 24, 2003
Hypersensitivity Reactions to Beta-Lactam Antibiotics 215
Table 5
Penicillin Oral Desensitization Protocol
Penicillin Amount Dose given Cumulative dose
Step* (mg/mL) (mL) (mg) (mg)
1 0.5 0.1 0.05 0.05
2 0.5 0.2 0.1 0.15
3 0.5 0.4 0.2 0.35
4 0.5 0.8 0.4 0.75
5 0.5 1.6 0.8 1.55
6 0.5 3.2 1.6 3.15
7 0.5 6.4 3.2 6.35
8 5 1.2 6 12.35
9 5 2.4 12 24.35
10 5 5 25 49.35
11 50 1 50 100
12 50 2 100 200
13 50 4 200 400
14 50 8 400 800
Observe patient for 30 mins, then give full therapeutic dose by the desired route.
*Interval between doses is 15 min.
Adapted from Sullivan, T. J. Drug allergy, in Allergy: Principles and Practice.
4th ed. Middleton, E., Reed, C. E., Ellis, E. F., Adkinson, N. F., and Yunginger, J.
W., eds. Mosby, St. Louis, 1993, pp. 17261746.
Table 6
Penicillin iv Desensitization Protocol with Drug Added
by Piggyback Infusion
Penicillin Amount Dose given Cumulative dose
Step* (mg/mL) (mL) (mg) (mg)
1 0.1 0.1 0.01 0.01
2 0.1 0.2 0.02 0.03
3 0.1 0.4 0.04 0.07
4 0.1 0.8 0.08 0.15
5 0.1 1.6 0.16 0.31
6 1 0.32 0.32 0.63
7 1 0.64 0.64 1.27
8 1 1.2 1.2 2.47
9 10 0.24 2.4 4.87
10 10 0.48 4.8 10
11 10 1 10 20
12 10 2 20 40
13 100 0.4 40 80
14 100 0.8 80 160
15 100 1.6 160 320
16 1000 0.32 320 640
17 1000 0.64 640 1280
Observe patient for 30 min, then give full therapeutic dose by the desired route.
*Interval between doses is 15 min.
Adapted from Sullivan T. J. Drug allergy, in Allergy: Principles and Practice.
4th ed. Middleton, E., Reed, C. E., Ellis, E. F., Adkinson, N. F., and Yunginger, J.
W., eds. Mosby, St. Louis, 1993, pp. 17261746.
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