Warning:

This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:

• STD Treatment Guidelines   at http://www.cdc.gov/STD/treatment

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1993 Sexually Transmitted Diseases Treatment Guidelines

09/24/1993

SUGGESTED CITATION
Centers for Disease Control and Prevention. 1993 Sexually
transmitted diseases treatment guidelines. MMWR 1993;42(No. RR-14):
{inclusive page numbers}.

CIO Responsible for this publication:
National Center for Prevention Services,
Division of Sexually Transmitted Diseases and HIV Prevention

Management of the Patient With a History of Penicillin Allergy
     
     No proven alternatives to penicillin are available for
treating neurosyphilis, congenital syphilis, or syphilis among
pregnant women. Penicillin also is recommended for use, whenever
possible, with HIV-infected patients. Unfortunately, 3%-10% of the
adult population in the United States have experienced urticaria,
angioedema, or anaphylaxis (upper airway obstruction, bronchospasm,
or hypotension) with penicillin therapy. Re-administration of
penicillin can cause severe immediate reactions among these
patients. Because anaphylactic reactions to penicillin can be
fatal, every effort should be made to avoid administering
penicillin to penicillin-allergic patients, unless the anaphylactic
sensitivity has been removed by acute desensitization.

     However, only approximately 10% of persons who report a
history of severe allergic reactions to penicillin are still
allergic. With the passage of time after an allergic reaction to
penicillin, most persons who have experienced a severe reaction
stop expressing penicillin-specific IgE. These persons can be
treated safely with penicillin. Many studies have found that skin
testing with the major and minor determinants can reliably identify
persons at high risk for penicillin reactions. Although these
reagents are easily generated and have been available in academic
centers for greater than 30 years, currently only
penicilloyl-poly-L-lysine (Pre-Pen, the major determinant) and
penicillin G are available commercially. Experts estimate that
testing with only the major determinant and penicillin G detects
90%-97% of the currently allergic patients. However, because skin
testing without the minor determinants would still miss 3%-10% of
allergic patients, and serious or fatal reactions can occur among
these minor determinant positive patients, experts suggest caution
when the full battery of skin test reagents listed in the table is
not available.

Recommendations
     If the full battery of skin-test reagents is available,
including the major and minor determinants (see Penicillin Allergy
Skin Testing), patients who report a history of penicillin reaction
and are skin-test negative can receive conventional penicillin
therapy. Skin-test positive patients should be desensitized.

     If the full battery of skin-test reagents, including the minor
determinants, is not available, the patient should be skin tested
using penicilloyl (the major determinant, Pre-Pen) and penicillin
G. Those with positive tests should be desensitized. Some experts
believe that persons with negative tests, in that situation, should
be regarded as probably allergic and should be desensitized. Others
suggest that those with negative skin tests can be test-dosed
gradually with oral penicillin in a monitored setting in which
treatment for anaphylactic reaction is possible.

Penicillin Allergy Skin Testing
     Patients at high risk for anaphylaxis (i.e., a history of
penicillin-related anaphylaxis, asthma or other diseases that would
make anaphylaxis more dangerous, or therapy with beta-adrenergic
blocking agents) should be tested with 100-fold dilutions of the
full-strength skin-test reagents before testing with full-strength
reagents. In these situations, patients should be tested in a
monitored setting in which treatment for an anaphylactic reaction
is possible. If possible, the patient should not have taken
antihistamines (e.g., chlorpheniramine maleate or terfenadine
during the past 24 hours, diphenhydramine HCl or hydroxyzine during
the past 4 days, or astemizole during the past 3 weeks).

Reagents (Adapted from Beall {14})*

     Major Determinant -

     --   Benzylpenicilloyl poly-L-lysine (Pre-Pen {Taylor Pharmacal
          Company, Decatur, Illinois}) (6 x 10-5M).

     Minor Determinant Precursors **

     --   Benzylpenicillin G (10-2M, 3.3 mg/mL, 6000 U/mL),

     --   Benzylpenicilloate (10-2M, 3.3 mg/mL),

     --   Benzylpenilloate (or penicilloyl propylamine)(10-2M, 3.3
          mg/mL).

Positive Control -

--   Commercial histamine for epicutaneous skin testing (1 mg/mL).

Negative Control -

--   Diluent used to dissolve other reagents, usually phenol
     saline.

Procedures -
     Dilute the antigens 100-fold for preliminary testing if the
patient has had a life-threatening reaction, or 10-fold if the
patient has had another type of immediate, generalized reaction
within the past year.

     Epicutaneous (prick) tests. Duplicate drops of skin-test
reagent are placed on the volar surface of the forearm. The
underlying epidermis is pierced with a 26-gauge needle without
drawing blood.

     An epicutaneous test is positive if the average wheal diameter
after 15 minutes is 4 mm larger than that of negative controls;
otherwise, the test is negative. The histamine controls should be
positive to assure that results are not falsely negative because of
the effect of antihistaminic drugs.

     Intradermal test. If epicutaneous tests are negative,
duplicate 0.02 mL intradermal injections of negative control and
antigen solutions are made into the volar surface of the forearm
using a 26- or 27-gauge needle on a syringe. The crossed diameters
of the wheals induced by the injections should be recorded.

     An intradermal test is positive if the average wheal diameter
15 minutes after injection is 2 mm or larger than the initial wheal
size and also is at least 2 mm larger than the negative controls.
Otherwise, the tests are negative.

Desensitization
     Patients who have a positive skin test to one of the
penicillin determinants can be desensitized. This is a
straightforward, relatively safe procedure that can be done orally
or IV. Although the two approaches have not been compared, oral
desensitization is thought to be safer, simpler, and easier.
Patients should be desensitized in a hospital setting because
serious IgE-mediated allergic reactions, although unlikely, can
occur. Desensitization can usually be completed in about 4 hours,
after which the first dose of penicillin is given Table_1. STD
programs should have a referral center where patients with positive
skin tests can be desensitized. After desensitization, patients
must be maintained on penicillin continuously for the duration of
the course of therapy.

* Reprinted with permission from G.N. Beall in Annals of Internal
Medicine.

** Aged penicillin is not an adequate source of minor determinants.
Penicillin G should be freshly prepared or should come from a
fresh-frozen source.

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