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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This document is being maintained for historical purposes, but is now out of date.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
1998 Guidelines for Treatment of Sexually Transmitted Disease
Date: 01/23/98
Source: 47(RR-1);1-118
SUGGESTED CITATION: Centers for Disease Control and Prevention. 1998 Guidelines for Treatment of Sexually Transmitted Diseases. MMWR 1998;47(No. RR-1): {inclusive page numbers}.
The material in this report was prepared for publication by: National Center for HIV, STD and TB Prevention, Division of Sexually Transmitted Diseases Prevention
MANAGEMENT OF PATIENTS WHO HAVE A HISTORY OF PENICILLIN ALLERGY
No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women. Penicillin also is recommended for use, whenever possible, in HIV-infected patients. Of the adult U.S. population, 3%-10% have experienced urticaria, angioedema, or anaphylaxis (i.e., upper airway obstruction, bronchospasm, or hypotension) after penicillin therapy. Readministration of penicillin to these patients can cause severe, immediate reactions. 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.
An estimated 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 had a severe reaction stop expressing penicillin-specific IgE. These persons can be treated safely with penicillin. The results of many investigations indicate 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, only benzylpenicilloyl 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 identifies 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 is not available ( Table_1 ).
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 benzylpenicilloyl poly-L-lysine (i.e., the major determinant, Pre-Pen) and penicillin G. Patients who have positive test results should be desensitized. Some experts believe that persons who have negative test results should be regarded as probably allergic and should be desensitized. Others suggest that those with negative skin-test results 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., those who have a history of penicillin-related anaphylaxis, asthma, or other diseases that would make anaphylaxis more dangerous or who are being treated with beta-adrenergic blocking agents) should be tested with 100-fold dilutions of the full-strength skin-test reagents before being tested with full-strength reagents. In these situations, patients should be tested in a monitored setting in which treatment for an anaphylactic reaction is available. If possible, the patient should not have taken antihistamines recently (e.g., chlorpheniramine maleate or terfenadine during the preceding 24 hours, diphenhydramine HCl or hydroxyzine during the preceding 4 days, or astemizole during the preceding 3 weeks).
Reagents (Adapted from Beall {25}) *
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 units/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 a) 100-fold for preliminary testing if the patient has had a life-threatening reaction to penicillin or b) 10-fold if the patient has had another type of immediate, generalized reaction to penicillin within the preceding 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 ensure that results are not falsely negative because of the effect of antihistaminic drugs.
Intradermal tests. 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 greater than or equal to 2 mm larger than the initial wheal size and also is greater than or equal to 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 regarded as safer to use and easier to perform. Patients should be desensitized in a hospital setting because serious IgE-mediated allergic reactions, although unlikely, can occur. Desensitization usually can be completed in approximately 4 hours, after which the first dose of penicillin is given ( Table_1 ). STD programs should have a referral center where patients who have positive skin test results 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 (25).
** Aged penicillin is not an adequate source of minor determinants. Penicillin G should be freshly prepared or should come from a fresh-frozen source.
