Sexually Transmitted Diseases Treatment Guidelines, 2006

Kimberly A. Workowski, MD; Stuart M. Berman, MD

Morbidity and Mortality Weekly Report. 2006;55(30):1-94.

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 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, 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 ( Box 1 ). 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.

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 who 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.

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 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 by using a 26- or 27-gauge needle on a syringe. The 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 ( Table 1 ). This is a straightforward, relatively safe procedure that can be performed orally or IV. Although the two approaches have not been compared, oral desensitization is regarded as safer 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.

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Cite this: Sexually Transmitted Diseases Treatment Guidelines, 2006 - Medscape - Aug 04, 2006.

Sidebar: Terms and Abbreviations Used in This Report

Terms and Abbreviations Used in This Report

AIDS = Acquired immunodeficiency syndrome	IFA = Immunofluorescence assay
ALT = Alanine aminotransferase	IgE = Immunoglobulin E
anti-HBc = Antibody to hepatitis B core antigen	Ig = Immune globulin
anti-HCV = Hepatitis C antibodies	IgG = Immunoglobulin G
ASC-US = Atypical squamous cells of undetermined significance	IgM = Immunoglobulin
BCA = Bichloroacetic acid	IM = Intramuscularly
BV = Bacterial vaginosis	IUD = Intrauterine device
CBC = Complete blood count	IV = Intravenous or intravenously
CI = Confidence interval	KOH = Potassium hydroxide
CIN = Cervical intraepithelial neoplasia	LGV = Lymphogranuloma venereum
CLIA = Clinical Laboratory Improvement Amendments	MAC = Mycobacterium avium complex
CNS = Central nervous system	MIC = Minimum inhibitory concentration
CI = Confidence interval	MSM = Men who have sex with men
CSF = Cerebrospinal fluid	N-9 = Nonoxynol-9
DFA = Direct fluorescent antibody	NAAT = Nucleic acid amplification test
DGI = Disseminated gonococcal infection	NGU = Nongonococcal urethritis
dL = Deciliter	Pap = Papanicolaou
DNA = Deoxyribonucleic acid	PCR = Polymerase chain reaction
EC = Emergency contraception	PEP = Postexposure prophylaxis
EIA = Enzyme immunoassay	PID = Pelvic inflammatory disease
ELISA = Enzyme-linked immunosorbent assay	PO = By mouth
EPT = Expedited partner therapy	PPV = Positive predictive value
FDA = Food and Drug Administration	QRNG = Quinolone resistant Neisseria gonorrhoeae
FTA-ABS = Fluorescent treponemal antibody absorbed	RNA = Ribonucleic acid
gG = Glycoprotein G	RPR = Rapid plasma reagin
GNID = Gram-negative intracellular diplococci	RT-PCR = Reverse transcriptase polymerase chain reaction
HAART = Highly active antiretroviral therapy	RVVC = Recurrent vulvovaginal candidiasis
HAV = Hepatitis A virus	SIL = Squamous intraepithelial lesion
HBIG = Hepatitis B immune globulin	STD = Sexually transmitted disease
HBsAg = Hepatitis B surface antigen	TCA = Trichloroacetic acid
HBV = Hepatitis B virus	TE = Toxoplasmic encephalitis
HCC = hepatocellular carcinoma	TP-PA = Treponema pallidum particle agglutation
HCV = Hepatitis C virus	VDRL = Venereal Disease Research Laboratory
HIV = Human immunodeficiency virus	VVC = Vulvovaginal candidiasis
HPV = Human papillomavirus	WB = Western blot
HSV = Herpes simplex virus	WBC = White blood count
	WSW = Women who have sex with women

Sidebar: Sexually Transmitted Diseases Treatment Guidelines, 2006 Consultants

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

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.

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Sexually Transmitted Diseases Treatment Guidelines, 2006

Management of Patients Who Have a History of Penicillin Allergy

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Authors and Disclosures

Authors and Disclosures

Sidebar

Sidebar: Terms and Abbreviations Used in This Report

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Sidebar: Sexually Transmitted Diseases Treatment Guidelines, 2006 Consultants

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