• Centers for Disease Control and Prevention, Workowski KA, Berman SM. Management of patients who have a history of penicillin allergy. Sexually transmitted diseases treatment guidelines 2006. MMWR Morb Mortal Wkly Rep 2006 Aug 4;55(RR-11):33-5. [222 references]

This is the current release of the guideline.

This guideline updates a previous version: Centers for Disease Control and Prevention. Management of patients who have a history of penicillin allergy. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2002 May 10;51(RR-6):28-30.

Penicillin allergy in patients with sexually transmitted diseases

Evaluation
Management
Treatment

Allergy and Immunology
Family Practice
Infectious Diseases
Internal Medicine
Obstetrics and Gynecology
Pediatrics
Preventive Medicine

Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Managed Care Organizations
Nurses
Physician Assistants
Physicians
Public Health Departments

• To update the Sexually Transmitted Diseases Treatment Guidelines 2002 (MMWR 2002;51[No. RR-6])
• To assist physicians and other health-care providers in preventing and treating sexually transmitted diseases (STDs)

Patients with sexually transmitted diseases who have a history of penicillin allergy

1. Full battery of skin-test agents: major determinant benzylpenicilloyl poly-L-lysine (Pre-Pen®) and minor determinant precursors (benzylpenicillin G, benzylpenicilloate or penicilloyl propylamine)
   • Epicutaneous (prick) test
   • Intradermal test
2. Desensitization to penicillin (oral or intravenous)

Allergic reaction to penicillin

Searches of Electronic Databases

Not stated

Not stated

Subjective Review

Not applicable

Systematic Review with Evidence Tables

Beginning in 2004, the Centers for Disease Control and Prevention (CDC) personnel and professionals knowledgeable in the field of sexually transmitted diseases (STDs) systematically reviewed evidence (including published abstracts and peer-reviewed journal articles) concerning each of the major STDs, focusing on information that had become available since publication of the Sexually Transmitted Diseases Treatment Guidelines, 2002. Background papers were written and tables of evidence constructed summarizing the type of study (e.g., randomized controlled trial or case series), study population and setting, treatments or other interventions, outcome measures assessed, reported findings, and weaknesses and biases in study design and analysis. A draft document was developed on the basis of the reviews.

Expert Consensus (Consensus Development Conference)

In April 2005, the Centers for Disease Control and Prevention (CDC) staff members and invited consultants assembled in Atlanta, Georgia, for a 3-day meeting to present the key questions regarding sexually transmitted disease (STD) treatment that emerged from the evidence-based reviews and the information available to answer those questions. When relevant, the questions focused on four principal outcomes of STD therapy for each individual disease: 1) microbiologic cure, 2) alleviation of signs and symptoms, 3) prevention of sequelae, and 4) prevention of transmission. Cost-effectiveness and other advantages (e.g., single-dose formulations and directly observed therapy of specific regimens) also were discussed. The consultants then assessed whether the questions identified were relevant, ranked them in order of priority, and attempted to arrive at answers using the available evidence. In addition, the consultants evaluated the quality of evidence supporting the answers on the basis of the number, type, and quality of the studies.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

Peer Review

Not stated

No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women. Penicillin is also recommended for use, whenever possible, in human immunodeficiency virus (HIV)-infected patients. Of the adult U.S. population, 3%-10% have experienced an immunoglobulin E (IgE) mediated allergic response to penicillin such as urticaria, angioedema, or anaphylaxis (i.e., upper airway obstruction, bronchospasm, or hypotension). Re-administration 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 they undergo acute desensitization to eliminate anaphylactic sensitivity.

An estimated 10% of persons who report a history of severe allergic reactions to penicillin remain allergic. With the passage of time after an allergic reaction to penicillin, the majority of persons who have had a severe reaction to penicillin 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 of penicillin can reliably identify persons at high risk for penicillin reactions. Although these reagents are easily generated and have been available for >30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen® [i.e., the major determinant]) and penicillin G have been available commercially. Testing with only the major determinant and penicillin G identifies an estimated 90%-97% of the currently allergic patients. However, because skin testing without the minor determinants would still miss 3%-10% of allergic patients and because serious or fatal reactions can occur among these minor-determinant-positive patients, specialists suggest exercising caution when the full battery of skin-test reagents is not available. An additional challenge has occurred with the recent unavailability of Pre-Pen®; however, plans for future availability of this product have been made, as well as a companion minor determinant mixture.

Skin-test Reagents for Identifying Persons at Risk for Adverse Reactions to Penicillin

Major Determinant

• Benzylpenicilloyl poly-L-lysine (Pre-Pen® [Taylor Pharmacal Company, Decatur, Illinois]) (6 x 10^-5M).

Minor Determinant Precursors (Note: Aged penicillin is not an adequate source of minor determinants. Penicillin G should be freshly prepared or should come from a fresh-frozen source.)

• Benzylpenicillin G (10^-2M, 3.3 mg/mL, 6,000 units/mL)
• Benzylpenicilloate (10^-2M, 3.3 mg/mL)
• Benzylpenicilloate (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

Recommendations

If the full battery of skin-test reagents is available, including the major and minor determinants (see section on Penicillin Allergy Skin Testing below), 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) and penicillin G. Patients who have positive test results should be desensitized. Some specialists suggest 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 can be provided.

If the major determinant (Pre-Pen®) is not available for skin testing, all patients with a history suggesting IgE mediated reactions (anaphylaxis, angioedema, bronchospasm, or urticaria) to penicillin should be desensitized in a hospital setting. In patients with reactions not likely to be IgE mediated, outpatient oral desensitization or monitored test doses may be considered.

Penicillin Allergy Skin Testing

Patients at high risk for anaphylaxis, including those who 1) have a history of penicillin-related anaphylaxis, asthma, or other diseases that would make anaphylaxis more dangerous or 2) 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 hydrochloride (HCl) or hydroxyzine during the preceding 4 days, or astemizole during the preceding 3 weeks).

Procedures

Dilute the antigens either 1) 100-fold for preliminary testing if the patient has had a life-threatening reaction to penicillin or 2) 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 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 larger than the initial wheal size and also is >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 (see Table 1 in the original guideline for an oral desensitization protocol). This is a straightforward, relatively safe procedure that can be performed orally or intravenously. 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 can occur. Desensitization usually can be completed in approximately 4 hours, after which the first dose of penicillin is administered. After desensitization, patients must be maintained on penicillin continuously for the duration of the course of therapy.

None provided

The type of supporting evidence is not specifically stated for each recommendation.

Throughout the 2006 guideline document, the evidence used as the basis for specific recommendations is discussed briefly. More comprehensive, annotated discussions of such evidence will appear in background papers that will be published in a supplement issue of the journal Clinical Infectious Diseases.

• Skin testing can reliably identify persons at high risk for allergic reactions to penicillin, which can sometimes be fatal.
• Desensitization allows penicillin-allergic patients to receive penicillin therapy.

Subgroups Most Likely to Benefit

• Patients with neurosyphilis, congenital syphilis, or syphilis in pregnant women, as there are no proven alternatives to penicillin available for treatment.
• Patients with HIV infection, for whom penicillin is recommended, whenever possible.

• Anaphylaxis can occur during skin testing in high-risk patients.
• Serious immunoglobulin E-mediated allergic reactions, although unlikely, can occur during desensitization procedures.

Subgroups Most Likely to be Harmed

Patients at high risk for anaphylaxis are 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.

• These recommendations were developed in consultation with public- and private-sector professionals knowledgeable in the treatment of patients with sexually transmitted diseases (STDs). The recommendations are applicable to various patient-care settings, including family planning clinics, private physicians' offices, managed care organizations, and other primary-care facilities.
• These recommendations are meant to serve as a source of clinical guidance: health-care providers should always consider the individual clinical circumstances of each person in the context of local disease prevalence. These guidelines focus on the treatment and counseling of individual patients and do not address other community services and interventions that are important in STD/human immunodeficiency virus (HIV) prevention.

An implementation strategy was not provided.

Getting Better

Effectiveness
Safety

• Centers for Disease Control and Prevention, Workowski KA, Berman SM. Management of patients who have a history of penicillin allergy. Sexually transmitted diseases treatment guidelines 2006. MMWR Morb Mortal Wkly Rep 2006 Aug 4;55(RR-11):33-5. [222 references]

Not applicable: The guideline was not adapted from another source.

1993 (revised 2006 Aug 4)

Centers for Disease Control and Prevention - Federal Government Agency [U.S.]

These guidelines for the treatment of persons who have sexually transmitted diseases (STDs) were developed by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta, Georgia, during April 19–21, 2005.

United States Government

Not stated

Chairpersons: David Atkins, MD, Agency for Healthcare Research and Quality, Rockville, Maryland; Kimberly A. Workowski, MD, National Center for HIV, STD, and TB Prevention, CDC, and Emory University, Atlanta, GA

Presenters: Heidi Bauer, MD, California Sexually Transmitted Disease Control Branch, Oakland, California; Emily J. Erbelding, MD, Johns Hopkins University School of Medicine, Baltimore, Maryland; William M. Geisler, MD, Department of Medicine, University of Alabama, Birmingham, Alabama; Margaret Hammerschlag, MD, State University of New York, Downstate Medical Center, Brooklyn, New York; Peter Leone, MD, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Jenne Marrazzo, MD, University of Washington, Harborview Medical Center, Seattle, Washington; Kenneth Hugh Mayer, MD, Brown University Medical School, Providence, Rhode Island; Pablo Sanchez, MD, University of Texas Southwestern Medical Center, Dallas, Texas; Bradley Stoner, MD, PhD, Washington University, St. Louis, Missouri; Anna Wald, MD, University of Washington, Harborview Medical Center, Seattle, Washington; George Wendel, MD, University of Texas Southwestern Medical School, Dallas, Texas; Karen Wendel, MD, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma; Harold C. Wiesenfeld, MD, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Moderators: Willard Cates, Jr., MD, Family Health International, Durham, North Carolina; King K. Holmes, MD, PhD, University of Washington, Harborview Medical Center, Seattle, Washington; David Martin, MD, Louisiana State University Medical Center, New Orleans, Louisiana

Rapporteurs: Hunter Handsfield, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia, University of Washington, Seattle, Washington; William McCormack, MD, State University of New York Health Science Center, Brooklyn, New York; Anne Rompalo, MD, Johns Hopkins School of Medicine, Baltimore, Maryland

Consultants: Michael Augenbraun, MD, State University of New York Health Science Center, Brooklyn, New York; Gail Bolan, MD, California Department of Health, Oakland, California; Carolyn Deal, PhD, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Kenneth H. Fife, MD, PhD, Indiana University School of Medicine, Indianapolis, Indiana; J. Dennis Fortenberry, MD, Indiana University School of Medicine, Indianapolis, Indiana; Edward Hook, III, MD, Department of Medicine, University of Alabama, Birmingham, Alabama; Franklyn Judson, MD, University of Colorado Department of Medicine and Preventive Medicine, Denver, Colorado; Alice A. Kraman, PharmD; Emory Healthcare, Atlanta, Georgia; Roberta B. Ness, MD, University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania; Paul Nyirjesy, MD, Drexel University College of Medicine, Philadelphia, Pennsylvania; Jeffrey Peipert, MD, Women and Infants Hospital, Providence, Rhode Island; Jane R. Schwebke, MD, Department of Medicine, University of Alabama, Birmingham, Alabama; Mary Ann Shafer, MD, University of California, San Francisco Department of Medicine, San Francisco, California; David Soper, MD, Medical University of South Carolina, Charleston, South Carolina; Lawrence Stanberry, MD, PhD, University of Texas Medical Branch, Galveston, Texas; Heather Watts, MD, National Institute of Child Health and Development, National Institutes of Health, Bethesda, Maryland; Jonathan M. Zenilman, MD, Johns Hopkins Bayview Medical Center, Baltimore, Maryland

Liaison Participants: Joanne Armstrong, MD, Women's Health, Aetna, Sugar Land, Texas; James R. Allen, MD, American Social Health Association, Durham, North Carolina; Margaret J. Blythe, MD, American Academy of Pediatrics, Indianapolis, Indiana; Sherry R. Crump, MD, American College of Preventive Medicine, Atlanta, GA; Carolyn D. Deal, PhD, National Institutes of Health, Bethesda, Maryland; Jordon Dimitrakov, MD, PhD, American Urological Association, Boston, Massachusetts; Mark FitzGerald, MD, British Association for Sexual Health and HIV, Southampton, United Kingdom; Edward Harrison, National Commission on Correctional Health Care, Chicago, Illinois; Edward W. Hook, III, MD, Infectious Disease Society of America, Birmingham, Alabama; Michel Janier, MD, PhD, International Union Against Sexually Transmitted Infections Europe, Paris, France; Abe Macher, MD, HIV/AIDS Bureau, Rockville, Maryland; Francis J. Ndowa, MD, World Health Organization, Geneva, Switzerland; Jeffrey F. Peipert, MD, American College of Obstetricians and Gynecologists, Providence, Rhode Island; Kees A. Rietmeijer, MD, PhD, Denver Public Health Department, Denver, Colorado; Richard Rothman, MD, American College of Emergency Physicians, Baltimore, Maryland; David Soper, MD, Infectious Diseases Society for Obstetrics and Gynecology, Charleston, South Carolina; Litjen Tan, PhD, American Medical Association, Chicago, Illinois; Bruce Trigg, MD, National Coalition for Sexually Transmitted Disease Directors, Albuquerque, New Mexico; Julia Valderrama, MD, Pan American Health Organization, Washington, DC; Tom Wong, MD, Public Health Agency of Canada, Ottawa, Ontario, Canada; Miriam Zieman, MD, Association of Reproductive Health Professionals, Atlanta, Georgia

CDC, Division of Sexually Transmitted Disease Prevention Treatment Guidelines 2006 Project. Coordinator: Kimberly A. Workowski, MD, National Center for HIV, STD, and TB Prevention, CDC, and Emory University, Atlanta, GA

Project Manager: Donald F. Dowda, ORISE, Oakridge, Tennessee; Richard Voigt, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia

Co-Moderators: Lyn Finelli, Ph.D., DSTDP; Robert Johnson, M.D., DSTDP; Lauri Markowitz, M.D., DSTDP

CDC Presenters: Joanna Buffington, MD, National Center for Infectious Diseases; Eileen Dunne, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Matthew Hogben, PhD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Emily Koumans, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Hershel Lawson, MD, National Center for Chronic Disease Prevention and Health Promotion, Atlanta, Georgia; Catherine McLean, MD, National Center for HIV, STD, and TB Prevention, Atlanta, Georgia; Juliette Morgan, MD, National Center for Infectious Diseases, CDC, Atlanta, Georgia; Lori Newman, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Madeline Sutton, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia

CDC Consultants: Sevgi O. Aral, PhD, Stuart M. Berman, MD, John Douglas, MD, Susan J. DeLisle, Kathleen Ethier, PhD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Kevin Fenton, MD, National Center for HIV, Hepatitis, Sexually Transmitted Diseases and Tuberculosis Prevention, CDC, Atlanta, Georgia; John Moran, MD, National Immunization Program, CDC, Atlanta, Georgia; Julia Schillinger, MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia

Support Staff: Valerie Barner, Winda Graves, Garrett Mallory, Deborah McElroy, National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Eboney Walker, NAI Personnel, Washington, DC

Not stated

This is the current release of the guideline.

This guideline updates a previous version: Centers for Disease Control and Prevention. Management of patients who have a history of penicillin allergy. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2002 May 10;51(RR-6):28-30.

None available

This summary was completed by ECRI on August 19, 2002. This summary was updated by ECRI on October 10, 2006.

No copyright restrictions apply.