Allergy to β-lactam antibiotics
2012; Elsevier BV; Volume: 130; Issue: 6 Linguagem: Inglês
10.1016/j.jaci.2012.08.021
ISSN1097-6825
Autores Tópico(s)Chemotherapy-related skin toxicity
ResumoInstructionsCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the instructions listed below:1.Review the target audience, learning objectives and author disclosures.2.Complete the pre-test online at www.jacionline.org (click on the Online CME heading).3.Follow the online instructions to read the full version of the article, including the clinical vignette and review components.4.Complete the post-test. At this time, you will have earned 1.00 AMA PRA Category 1 CME CreditTM.5.Approximately 4 weeks later you will receive an online assessment regarding your application of this article to your practice. Once you have completed this assessment, you will be eligible to receive 2 MOC Part II Self-Assessment credits from the American Board of Allergy and Immunology.Date of Original Release: December 2012. Credit may be obtained for these courses until November 30, 2014.Copyright Statement: Copyright © 2012-2014. All rights reserved.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Roland Solensky, MD (author), and James T. Li, MD, PhD (series editor)Activity Objectives1.To understand the epidemiology and natural history of penicillin allergy.2.To recognize the utility of penicillin skin testing.3.To understand various aspects of penicillin skin testing.4.To understand the allergic cross-reactivity between penicillins and other β-lactams.Recognition of Commercial Support: This CME activity has not received external commercial support.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: R. Solensky has received grants from Merck and has received payment for lectures from GlaxoSmithKline. J. T. Li has consulted for Abbott.Clinical vignetteIn May 2009, a 66-year-old woman with a past medical history of hyperlipidemia and breast cancer is referred for seasonal allergic rhinitis and oral allergy syndrome. She also reports previous allergic reactions to penicillin and trimethoprim-sulfamethoxazole. At age 22 years, she received intramuscular penicillin for streptococcal pharyngitis and had immediate symptoms of generalized pruritic urticaria, dyspnea, wheezing, and dizziness. She was treated with injectable epinephrine and rapidly recovered. The trimethoprim-sulfamethoxazole reaction at age 45 years consisted of a maculopapular rash about a week into a treatment course for sinusitis. Penicillin skin testing could not be performed at her initial evaluation because the major penicillin determinant (Pre-Pen; ALK-Abelló, Hørsholm, Denmark) was commercially unavailable, and therefore she was instructed to return in 6 months when Pre-Pen availability was anticipated.During the following 6 months, she received levofloxacin for sinusitis and had bloody diarrhea, and although Clostridium difficile could not be confirmed, she was treated empirically with metronidazole and gradually recovered. Later, she had foot cellulitis, was treated with oral azithromycin, did not improve, and presented to an emergency department. The treating physician was reluctant to prescribe cephalosporins given her history of penicillin-induced anaphylaxis but, given the limited options, decided to administer the first dose of cephalexin in the emergency department, which she tolerated. She completed the rest of the cephalexin course uneventfully, and the culture grew methicillin-sensitive Staphylococcus aureus.In January 2010, results of penicillin skin testing were negative, and the patient tolerated a single 250-mg dose of penicillin V potassium administered in the office. The primary care physician was instructed to remove the penicillin allergy label from the patient's record and was advised that she was free to receive all β-lactam antibiotics without increased risk of having allergic reactions. In the 2½ years since evaluation, she tolerated 1 course of amoxicillin and 1 course of amoxicillin/clavulanate.The full version of this article, including a review of relevant issues to be considered, can be found online at www.jacionline.org. If you wish to receive CME or MOC credit for the article, please see the instructions above. InstructionsCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the instructions listed below:1.Review the target audience, learning objectives and author disclosures.2.Complete the pre-test online at www.jacionline.org (click on the Online CME heading).3.Follow the online instructions to read the full version of the article, including the clinical vignette and review components.4.Complete the post-test. At this time, you will have earned 1.00 AMA PRA Category 1 CME CreditTM.5.Approximately 4 weeks later you will receive an online assessment regarding your application of this article to your practice. Once you have completed this assessment, you will be eligible to receive 2 MOC Part II Self-Assessment credits from the American Board of Allergy and Immunology.Date of Original Release: December 2012. Credit may be obtained for these courses until November 30, 2014.Copyright Statement: Copyright © 2012-2014. All rights reserved.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Roland Solensky, MD (author), and James T. Li, MD, PhD (series editor)Activity Objectives1.To understand the epidemiology and natural history of penicillin allergy.2.To recognize the utility of penicillin skin testing.3.To understand various aspects of penicillin skin testing.4.To understand the allergic cross-reactivity between penicillins and other β-lactams.Recognition of Commercial Support: This CME activity has not received external commercial support.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: R. Solensky has received grants from Merck and has received payment for lectures from GlaxoSmithKline. J. T. Li has consulted for Abbott. InstructionsCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the instructions listed below:1.Review the target audience, learning objectives and author disclosures.2.Complete the pre-test online at www.jacionline.org (click on the Online CME heading).3.Follow the online instructions to read the full version of the article, including the clinical vignette and review components.4.Complete the post-test. At this time, you will have earned 1.00 AMA PRA Category 1 CME CreditTM.5.Approximately 4 weeks later you will receive an online assessment regarding your application of this article to your practice. Once you have completed this assessment, you will be eligible to receive 2 MOC Part II Self-Assessment credits from the American Board of Allergy and Immunology.Date of Original Release: December 2012. Credit may be obtained for these courses until November 30, 2014.Copyright Statement: Copyright © 2012-2014. All rights reserved.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Roland Solensky, MD (author), and James T. Li, MD, PhD (series editor)Activity Objectives1.To understand the epidemiology and natural history of penicillin allergy.2.To recognize the utility of penicillin skin testing.3.To understand various aspects of penicillin skin testing.4.To understand the allergic cross-reactivity between penicillins and other β-lactams.Recognition of Commercial Support: This CME activity has not received external commercial support.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: R. Solensky has received grants from Merck and has received payment for lectures from GlaxoSmithKline. J. T. Li has consulted for Abbott. InstructionsCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the instructions listed below:1.Review the target audience, learning objectives and author disclosures.2.Complete the pre-test online at www.jacionline.org (click on the Online CME heading).3.Follow the online instructions to read the full version of the article, including the clinical vignette and review components.4.Complete the post-test. At this time, you will have earned 1.00 AMA PRA Category 1 CME CreditTM.5.Approximately 4 weeks later you will receive an online assessment regarding your application of this article to your practice. Once you have completed this assessment, you will be eligible to receive 2 MOC Part II Self-Assessment credits from the American Board of Allergy and Immunology.Date of Original Release: December 2012. Credit may be obtained for these courses until November 30, 2014.Copyright Statement: Copyright © 2012-2014. All rights reserved.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Roland Solensky, MD (author), and James T. Li, MD, PhD (series editor)Activity Objectives1.To understand the epidemiology and natural history of penicillin allergy.2.To recognize the utility of penicillin skin testing.3.To understand various aspects of penicillin skin testing.4.To understand the allergic cross-reactivity between penicillins and other β-lactams.Recognition of Commercial Support: This CME activity has not received external commercial support.Disclosure of Significant Relationships with Relevant CommercialCompanies/Organizations: R. Solensky has received grants from Merck and has received payment for lectures from GlaxoSmithKline. J. T. Li has consulted for Abbott. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the instructions listed below:1.Review the target audience, learning objectives and author disclosures.2.Complete the pre-test online at www.jacionline.org (click on the Online CME heading).3.Follow the online instructions to read the full version of the article, including the clinical vignette and review components.4.Complete the post-test. At this time, you will have earned 1.00 AMA PRA Category 1 CME CreditTM.5.Approximately 4 weeks later you will receive an online assessment regarding your application of this article to your practice. Once you have completed this assessment, you will be eligible to receive 2 MOC Part II Self-Assessment credits from the American Board of Allergy and Immunology. Date of Original Release: December 2012. Credit may be obtained for these courses until November 30, 2014. Copyright Statement: Copyright © 2012-2014. All rights reserved. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Roland Solensky, MD (author), and James T. Li, MD, PhD (series editor) Activity Objectives1.To understand the epidemiology and natural history of penicillin allergy.2.To recognize the utility of penicillin skin testing.3.To understand various aspects of penicillin skin testing.4.To understand the allergic cross-reactivity between penicillins and other β-lactams. Recognition of Commercial Support: This CME activity has not received external commercial support. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: R. Solensky has received grants from Merck and has received payment for lectures from GlaxoSmithKline. J. T. Li has consulted for Abbott. Clinical vignetteIn May 2009, a 66-year-old woman with a past medical history of hyperlipidemia and breast cancer is referred for seasonal allergic rhinitis and oral allergy syndrome. She also reports previous allergic reactions to penicillin and trimethoprim-sulfamethoxazole. At age 22 years, she received intramuscular penicillin for streptococcal pharyngitis and had immediate symptoms of generalized pruritic urticaria, dyspnea, wheezing, and dizziness. She was treated with injectable epinephrine and rapidly recovered. The trimethoprim-sulfamethoxazole reaction at age 45 years consisted of a maculopapular rash about a week into a treatment course for sinusitis. Penicillin skin testing could not be performed at her initial evaluation because the major penicillin determinant (Pre-Pen; ALK-Abelló, Hørsholm, Denmark) was commercially unavailable, and therefore she was instructed to return in 6 months when Pre-Pen availability was anticipated.During the following 6 months, she received levofloxacin for sinusitis and had bloody diarrhea, and although Clostridium difficile could not be confirmed, she was treated empirically with metronidazole and gradually recovered. Later, she had foot cellulitis, was treated with oral azithromycin, did not improve, and presented to an emergency department. The treating physician was reluctant to prescribe cephalosporins given her history of penicillin-induced anaphylaxis but, given the limited options, decided to administer the first dose of cephalexin in the emergency department, which she tolerated. She completed the rest of the cephalexin course uneventfully, and the culture grew methicillin-sensitive Staphylococcus aureus.In January 2010, results of penicillin skin testing were negative, and the patient tolerated a single 250-mg dose of penicillin V potassium administered in the office. The primary care physician was instructed to remove the penicillin allergy label from the patient's record and was advised that she was free to receive all β-lactam antibiotics without increased risk of having allergic reactions. In the 2½ years since evaluation, she tolerated 1 course of amoxicillin and 1 course of amoxicillin/clavulanate.The full version of this article, including a review of relevant issues to be considered, can be found online at www.jacionline.org. If you wish to receive CME or MOC credit for the article, please see the instructions above. In May 2009, a 66-year-old woman with a past medical history of hyperlipidemia and breast cancer is referred for seasonal allergic rhinitis and oral allergy syndrome. She also reports previous allergic reactions to penicillin and trimethoprim-sulfamethoxazole. At age 22 years, she received intramuscular penicillin for streptococcal pharyngitis and had immediate symptoms of generalized pruritic urticaria, dyspnea, wheezing, and dizziness. She was treated with injectable epinephrine and rapidly recovered. The trimethoprim-sulfamethoxazole reaction at age 45 years consisted of a maculopapular rash about a week into a treatment course for sinusitis. Penicillin skin testing could not be performed at her initial evaluation because the major penicillin determinant (Pre-Pen; ALK-Abelló, Hørsholm, Denmark) was commercially unavailable, and therefore she was instructed to return in 6 months when Pre-Pen availability was anticipated. During the following 6 months, she received levofloxacin for sinusitis and had bloody diarrhea, and although Clostridium difficile could not be confirmed, she was treated empirically with metronidazole and gradually recovered. Later, she had foot cellulitis, was treated with oral azithromycin, did not improve, and presented to an emergency department. The treating physician was reluctant to prescribe cephalosporins given her history of penicillin-induced anaphylaxis but, given the limited options, decided to administer the first dose of cephalexin in the emergency department, which she tolerated. She completed the rest of the cephalexin course uneventfully, and the culture grew methicillin-sensitive Staphylococcus aureus. In January 2010, results of penicillin skin testing were negative, and the patient tolerated a single 250-mg dose of penicillin V potassium administered in the office. The primary care physician was instructed to remove the penicillin allergy label from the patient's record and was advised that she was free to receive all β-lactam antibiotics without increased risk of having allergic reactions. In the 2½ years since evaluation, she tolerated 1 course of amoxicillin and 1 course of amoxicillin/clavulanate. The full version of this article, including a review of relevant issues to be considered, can be found online at www.jacionline.org. If you wish to receive CME or MOC credit for the article, please see the instructions above. ReviewPenicillin allergy: BackgroundPenicillin allergy is the most commonly reported medication allergy, with a prevalence rate of 5% to 10%. In older large-scale studies 80% to 90% of patients with a history of penicillin allergy are found not to be allergic, but recent data suggest this has increased to 95%.E1Jost B.C. Wedner H.J. Bloomberg G.R. Elective penicillin skin testing in a pediatric outpatient setting.Ann Allergy Asthma Immunol. 2006; 97: 807-812Abstract Full Text PDF PubMed Scopus (41) Google Scholar, E2Macy E. Schatz M. Lin C.K. Poon K.-Y. The falling rate of positive penicillin skin tests from 1995 to 2007.Perm J. 2009; 13: 12-18Crossref PubMed Google Scholar Potential reasons why most patients with a label of "penicillin allergy" are able to tolerate penicillins include the following: (1) the reaction was mislabeled as allergic, (2) the symptoms were attributable to the underlying illness or an interaction between the illness and the antibiotic, and (3) levels of penicillin-specific IgE wane over time and penicillin allergy is commonly (but not always) outgrown.The medical costs of patients labeled as having penicillin allergy are higher compared with those of patients without a history of penicillin allergy.E3Sade K. Holtzer I. Levo Y. Kivity S. The economic burden of antibiotic treatment of penicillin-allergic patients in internal medicine wards of a general tertiary care hospital.Clin Exp Allergy. 2003; 33: 501-506Crossref PubMed Scopus (134) Google Scholar One reason for this discrepancy is that patients with a history of penicillin allergy are more likely to be treated with more expensive broad-spectrum antibiotics, such as quinolones and vancomycin. In addition to financial costs, clinical care can be compromised because quinolones and vancomycin are risk factors for the development of multiple drug-resistant bacteria, such as vancomycin-resistant Enterococcus species,E4Martinez J.A. Ruthazer R. Hansjosten K. Barefot L. Snydman D.R. Role of environmental contamination as a risk factor for acquisition of vancomycin-resistant enterococci in patients treated in a medical intensive care unit.Arch Intern Med. 2003; 163: 1905-1912Crossref PubMed Scopus (173) Google Scholar and quinolones are strongly associated with development of aggressive forms of Clostridium difficile–induced colitis.E5Loo V.G. Poirier L. Miller M.A. Oughton M. Libman M.D. Michaud S. et al.A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.N Engl J Med. 2005; 353: 2442-2449Crossref PubMed Scopus (1667) Google Scholar In several medical centers penicillin skin testing of inpatients with a history of penicillin allergy resulted in large decreases in the use of vancomycin and quinolones (Table E1).E6Harris A.D. Sauberman L. Kabbash L. Greineder D.K. Samore M.H. Penicillin skin testing: a way to optimize antibiotic utilization.Am J Med. 1999; 107: 166-168Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, E7Arroliga M.E. Radojicic C. Gordon S.M. Popovich M.J. Bashour A. Melton A.L. et al.A prospective observational study of the effect of penicillin skin testing on antibiotic use in the intensive care unit.Infect Control Hosp Epidemiol. 2003; 24: 347-350Crossref PubMed Scopus (67) Google Scholar, E8Nadarajah K. Green G.R. Naglak M. Clinical outcomes of penicillin skin testing.Ann Allergy Asthma Immunol. 2005; 95: 541-545Abstract Full Text PDF PubMed Scopus (41) Google Scholar, E9Park M.A. Markus P.J. Matesic D. Li J.T.C. Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy.Ann Allergy Asthma Immunol. 2006; 97: 681-687Abstract Full Text PDF PubMed Scopus (108) Google Scholar, E10del Real G.A. Rose M.E. Ramirez-Atamoros M.T. Hammel J. Gordon S.M. Arroliga A.C. et al.Penicillin skin testing in patients with a history of beta-lactam allergy.Ann Allergy Asthma Immunol. 2007; 98: 355-359Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar, E11Frigas E. Park M.A. Narr B.J. Volcheck G.W. Danielson D.R. Markus P.J. et al.Preoperative evaluation of patients with history of allergy to penicillin: comparison of 2 models of practice.Mayo Clin Proc. 2008; 83: 651-657PubMed Scopus (42) Google Scholar This is to be expected because the vast majority of patients with a history of penicillin allergy have negative penicillin skin test results and are able to have antibiotic coverage changed to β-lactams.Penicillin skin testingThe immunochemistry of penicillin was characterized in the 1960s, and subsequently, penicillin skin test reagents were developed (Table E2). The major penicillin determinant is commercially available for skin testing as penicilloyl-polylysine (PPL; ie, Pre-Pen), which is penicilloyl conjugated to a polylysine carrier molecule to produce a multivalent antigen. The minor determinants penicilloate and penilloate are not commercially available but are synthesized by various medical centers around the United States for local use. Penicillin G is used for skin testing at a concentration of 10,000 U/mL. Amoxicillin and ampicillin have been used for skin testing at concentrations ranging from 3 to 25 mg/mL, with no consensus regarding the appropriate concentration. The diagnostic utility of skin testing with amoxicillin or ampicillin has not been established. Penicillin skin testing has an excellent record of safety.On the basis of studies conducted in the United States, the negative predictive value (NPV) of penicillin skin testing is greater than 95%, and when challenge reactions occur, they are generally mild.E12Macy E. Mangat R. Burchette R.J. Penicillin skin testing in advance of need: multiyear follow-up in 568 test result-negative subjects exposed to oral penicillins.J Allergy Clin Immunol. 2003; 111: 1111-1115Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, E13Gadde J. Spence M. Wheeler B. Adkinson N.F. Clinical experience with penicillin skin testing in a large inner-city STD Clinic.JAMA. 1993; 270: 2456-2463Crossref PubMed Scopus (276) Google Scholar In Europe some investigators reported the NPV to be as low as 70%, and reactions in patients with negative skin test responses were sometimes severe.E14Torres M.J. Romano A. Mayorga C. Moya M.C. Guzman A.E. Reche R. et al.Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.Allergy. 2001; 56: 850-856Crossref PubMed Scopus (221) Google Scholar The reason for these differences is unknown.The importance of minor determinants in penicillin skin testing remains unclear. In large-scale studies about 10% of patients with positive skin test responses have positive results to penicilloate, penilloate, or both (and negative results to PPL and penicillin G).E1Jost B.C. Wedner H.J. Bloomberg G.R. Elective penicillin skin testing in a pediatric outpatient setting.Ann Allergy Asthma Immunol. 2006; 97: 807-812Abstract Full Text PDF PubMed Scopus (41) Google Scholar, E15Macy E. Burchette R. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.Allergy. 2002; 57: 1151-1158Crossref PubMed Scopus (78) Google Scholar Because of ethical concerns, these patients are not challenged with penicillins, and therefore the positive predictive value of penicilloate/penilloate skin testing is unknown. When patients with a history of penicillin allergy underwent skin testing with only PPL and penicillin G (without other minor determinants), the NPV in several studies was greater than 95%,E10del Real G.A. Rose M.E. Ramirez-Atamoros M.T. Hammel J. Gordon S.M. Arroliga A.C. et al.Penicillin skin testing in patients with a history of beta-lactam allergy.Ann Allergy Asthma Immunol. 2007; 98: 355-359Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar, E16Green G.R. Rosenblum A.H. Sweet L.C. Evaluation of penicillin hypersensitivity: value of clinical history and skin testing with penicilloyl-polylysine and penicillin G.J Allergy Clin Immunol. 1977; 60: 339-345Abstract Full Text PDF PubMed Scopus (188) Google Scholar which is comparable with that seen when all reagents are used. However, the patient populations might have differed, and it might not be appropriate to compare the results with those of studies that used all penicillin skin test reagents. It is possible that some patients with severe penicillin reaction histories were not challenged in studies using only PPL and penicillin G.Another difference between the United States and Europe is the frequency of selective IgE-mediated allergy to semisynthetic penicillins, such as amoxicillin. These patients react (or elicit positive results on skin testing) to amoxicillin but are able to tolerate penicillin V potassium (and have negative skin test results to PPL, penicillin G, penicilloate, and penilloate). The immune reaction is likely directed at the R-group side chain rather than the core β-lactam portion of the molecule. Selective amoxicillin reactors are rarely found in the United States (3% to 6% of positive penicillin skin test results),E15Macy E. Burchette R. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.Allergy. 2002; 57: 1151-1158Crossref PubMed Scopus (78) Google Scholar whereas in Europe they represent a percentage of positive penicillin skin test results that is an order of magnitude larger.E14Torres M.J. Romano A. Mayorga C. Moya M.C. Guzman A.E. Reche R. et al.Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.Allergy. 2001; 56: 850-856Crossref PubMed Scopus (221) Google Scholar The reason for these differences is unknown.Evaluation of patients with a history of penicillin allergyThe evaluation of patients with a history of penicillin allergy with penicillin skin testing is ideally performed electively before the need for antibiotic therapy. Patients with histories of severe non–IgE-mediated reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, and hemolytic anemia, are not candidates for skin testing or challenge and should avoid penicillins indefinitely. Patients with reaction histories compatible with a potential IgE-mediated mechanism (eg, pruritic rashes, urticaria, angioedema, and anaphylaxis) might undergo penicillin skin testing with PPL, penicillin G, amoxicillin, or ampicillin and, if available, penicilloate or penilloate. Reaction history is known to be a poor predictor of skin test results, and therefore penicillin allergy cannot be diagnosed accurately solely based on the history. Prick puncture skin testing should be performed first, and if results are negative, they should be followed by intradermal skin testing. Negative penicillin skin test results are ideally followed by oral challenge to unequivocally prove lack of allergy; otherwise, there is a reluctance by future treating physicians to prescribe β-lactams. The challenge can be administered stepwise (graded challenge) or as a single dose, depending on the reaction history and the skin test reagents used.Penicillin resensitization is a theoretic concern in patients with a history of penicillin allergy who have negative skin test results and tolerate a course of penicillin. However, on the basis of
Referência(s)