Diagnosis and management of penicillin allergy

CONCISE REVIEW FOR CLINICIANS DIAGNOSIS AND MANAGEMENT OF PENICILLIN ALLERGY Diagnosis and Management of Penicillin Allergy MIGUEL A. PARK, MD, AND JAMES T. C. LI, MD, PHD Among patients with a reported history of penicillin allergy, 8 0 % to 9 0 % have no evidence of IgE antibodies to penicillin on skin testing and thus avoid penicillin unnecessarily. M oreover, 9 7 % to 9 9 % of such patients with a penicillin skin test negative to the major and minor determinants can tolerate penicillin without risk of an immediate-type hypersensitivity reaction. A penicillin skin test is valuable for evaluating penicillin allergy in patients who need penicillin or cephalosporin. Assessment of sensitivities to penicillin is important to reduce the unnecessary use of antimicrobial agents such as vancomycin. We review the role of penicillin skin testing for evaluating penicillin allergy and the use of cephalosporin in patients with a history of penicillin allergy. M ayo Clin Proc. 2 0 0 5 ;8 0 (3 ):4 0 5 -4 1 0 ADR = adverse drug reaction; CI = confidence interval; EM = erythema multiforme minor; M DM = minor determinant mix; TEN = toxic epidermal necrolysis CLINICAL SCENARIO An 85-year-old woman with a history of penicillin allergy is hospitalized with a coagulase-negative staphylococcus line infection, and vancomycin is initiated. Blood cultures reveal that the coagulasenegative staphylococcus is susceptible to cefazolin and piperacillin. The primary medical team wants to switch the vancomycin to one of the β-lactam antimicrobial agents. Twenty years previously, the patient developed a generalized pruritic rash of a “few hours” duration, which appeared approximately 4 hours after she took the first tablet of penicillin for a “sore throat.” No other medications were taken at the time of the adverse drug reaction (ADR), and the patient has thereafter avoided all β-lactams. The following options are considered for this patient: (1) continue prescribing vancomycin, (2) prescribe piperacillin, (3) prescribe cefazolin, or (4) proceed with penicillin skin testing. humans for prophylaxis, diagnosis, or therapy.1 In 1994, an estimated 106,000 hospital patients (95% confidence interval [CI], 76,000-137,000 patients) died of ADRs,2 the fourth-leading cause of death after heart disease, cancer, and stroke. In a study of drug-related fatal anaphylactic shock,3 6 (20%) of 30 fatal drug-induced reactions were due to penicillin and ampicillin. Penicillins are the most widely used antibiotics for common infections4 and are still the treatment of choice for many infections.5 More than 80% of patients with a selfreported history of penicillin allergy have no evidence of IgE antibodies to penicillin on skin testing.6 Many patients with reported penicillin allergy are unnecessarily denied the benefits of penicillin and are given broader-spectrum antimicrobial agents. The mean antibiotic costs for patients allergic to penicillin are 63% higher than for those not allergic to penicillin.7 Moreover, patients with a history of penicillin allergy often receive prophylactic vancomycin before surgery. With the emergence of vancomycin-resistant enterococci and recent reports of Staphylococcus aureus strains with reduced susceptibility to vancomycin,8 the Hospital Infection Control Practices Advisory Committee has recommended judicious and reduced use of vancomycin.9 Therefore, appropriate identification, evaluation, and treatment of patients with a reported history of penicillin allergy have become essential. We review the role of penicillin skin testing for evaluating penicillin allergy and the use of cephalosporins in patients with a history of penicillin allergy. EPIDEM IOLOGY The prevalence of penicillin allergy in the general population is unknown. The incidence of self-reported penicillin allergy ranges from 1% to 10%,5,10 with the frequency of life-threatening anaphylaxis estimated at 0.01% to 0.05%.11 Adverse drug reaction has been defined by the World Health Organization as any noxious, unintended, and undesired effect of a drug, which occurs at doses used in Fro m the De partme nt o f Inte rnal Me dic ine and Divis io n o f Alle rgic Dis e as e s , Mayo Clinic Co lle ge o f Me dic ine , Ro c he s te r, Minn. A que s tio n-and-ans we r s e c tio n appe ars at the e nd o f this artic le . Addre s s re print re que s ts and c o rre s po nde nc e to Jame s T. C. Li, MD, PhD, Divis io n o f Alle rgic Dis e as e s , Mayo Clinic Co lle ge o f Me dic ine , 2 0 0 Firs t St SW, Ro c he s te r, MN 5 5 9 0 5 (e -mail: li.jame s @ mayo .e du). © 2005 Mayo Foundation for Medical Education and Research Mayo Clin Proc. • CLASSIFICATIONS OF ADVERSE REACTIONS TO PENICILLIN There are several methods of classifying drug allergies.6,12,13 From a clinical standpoint, the most practical method of classifying penicillin allergy is to divide the ADRs into IgE-mediated (immediate-type) vs non–IgE-mediated hypersensitivity reactions. For example, IgE-mediated reactions include anaphylaxis, angioedema, urticaria, and bron- March 2005;80(3):405-410 • www.mayoclinicproceedings.com 405 DIAGNOSIS AND MANAGEMENT OF PENICILLIN ALLERGY TABLE 1 . Components of a History of ADR* Signs, symptoms, severity of the ADR and prior reactions Time course of the ADR Time interval from administration of the drug to initial ADR Route of drug administration Indication for the medication Other medications taken near the time of the ADR Exposure to the same medication or related medication since the ADR ADRs to other medications Alternative medications *ADR = adverse drug reaction. chospasm. Such reactions occur within minutes after drug administration but can be delayed up to 72 hours. Non– IgE-mediated hypersensitivity reactions include hemolytic anemia, interstitial nephritis, thrombocytopenia, serum sickness, drug fever, morbilliform eruptions, erythema multiforme minor (EM), Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and others. These ADRs occur most commonly at 72 hours after drug administration.14 The current penicillin skin test is applicable only in the diagnosis of IgE-mediated or immediate-type hypersensitivity reactions and plays no role in the diagnosis of the non–IgEmediated reactions. Thus, being able to classify a patient’s penicillin reaction into these categories will help in the evaluation and treatment of the patient. UTILITY OF PATIENT HISTORY Patient history is integral to the evaluation of a penicillinallergic patient (Table 1). For example, if a patient has a history consistent with EM, Stevens-Johnson syndrome, or TEN, then penicillin skin testing is not indicated because it tests only for IgE-mediated ADRs. Some physicians exclude penicillin skin testing for patients with a history of anaphylaxis because of the small risk of anaphylaxis from the skin test. However, patient history plays a limited role in predicting the outcome of the penicillin skin test. For example, the severity of ADR from penicillin is a poor predictor of a positive penicillin skin test. Gadde et al15 and Green et al16 reported that 17% to 46% of patients with a history of anaphylaxis to penicillin had a positive penicillin skin test. Among patients who experienced urticaria from penicillin, 12% had a positive penicillin skin test, and among those with exanthems, only 4% had a positive penicillin skin test. In that same study, 1.7% of patients with no history of penicillin allergy had a positive skin test. Patients with maculopapular rashes do not have a significantly higher incidence of positive skin tests than do those with a history of negative skin tests.16 Solensky et al17 showed that 33% of patients (347/1063) with a history of penicillin 406 Mayo Clin Proc. • allergy and positive penicillin skin tests had a “vague” history of prior reaction to penicillin, defined as one unlikely to be IgE-mediated (such as maculopapular rash, gastrointestinal tract symptoms, or an unknown reaction). The authors concluded that patients with a vague history of prior reaction to penicillin should still undergo penicillin skin testing because otherwise, many patients with penicillin allergy (those with evidence of IgE to penicillin on penicillin skin test) would be missed. In contrast, Salkind et al18 reported that patients with a history consistent with penicillin allergy had an increased likelihood of having penicillin allergy (positive likelihood ratio of 1.9; 95% CI, 1.5-2.5). A history of no penicillin allergy lowers the likelihood of penicillin allergy as assessed by penicillin skin testing (negative likelihood ratio of 0.5; 95% CI, 0.4-0.6). However, both the positive and negative likelihood ratios have a small effect on the pretest probability as assessed by JAMA Users’ Guides to the Medical Literature for diagnosis articles.19,20 Hence, although patient history is an important element in evaluating penicillin allergy, clinical utility is limited. Penicillin skin testing can be useful for many patients with a history of penicillin allergy. EVALUATION OF PENICILLIN ALLERGY BY SKIN TESTING AND IN VITRO ASSAYS Penicillin skin testing, performed with prick and intradermal tests, includes both the major and minor determinants (penicillin G and/or minor determinant mix [MDM]). Benzylpenicilloyl is the major determinant and is no longer available commercially. Several different MDMs, which are not available commercially, have been used in large penicillin trials: benzylpenicilloate, benzylpenilloate, benzylpenicillin, and/or benzylpenicilloyl-N-propylamine. After a positive result with histamine as a control, the prick test is performed; if the prick test is negative, the intradermal test is performed. A wheal of 3 mm or larger with erythema greater than the control on either the prick or the intradermal test is considered a positive test.6 Penicillin skin testing with both major and minor determinants is the most reliable tool for diagnosing a penicillin allergy mediated by IgE. However, penicillin skin testing is not predictive of reactions mediated by non-IgE mechanisms such as IgG- or IgM-mediated immune complex diseases, hemolytic anemia, EM, Stevens-Johnson syndrome, and TEN.6 A patient with a history of an immediate-type hypersensitivity reaction to penicillin and skin test negative to both the major and minor determinants is at low risk of an immediate-type hypersensitivity reaction to penicillin. Gadde et al15 reported a reaction rate of 2.9% in patients March 2005;80(3):405-410 • www.mayoclinicproceedings.com DIAGNOSIS AND MANAGEMENT OF PENICILLIN ALLERGY who received penicillin and had a history of penicillin allergy and a penicillin skin test negative to both the major determinant and MDM. Two of the patients had anaphylaxis manifested by urticaria, angioedema, and difficulty breathing without cardiovascular compromise. Both patients responded promptly to epinephrine. In a multicenter study,21 566 patients with a history of penicillin allergy and negative penicillin skin test (major determinant, penicillin G, and MDM) received penicillin. Only 7 (1.2%) had an immediate-type hypersensitivity reaction, all of which were either urticaria or pruritis, and none were life-threatening. Thus, patients with a history of penicillin allergy and a skin test that is negative to the major determinant and MDM have a low occurrence of immediate-type adverse reaction on administration of penicillin. Results of skin testing with penicillin G and the major determinants can accurately predict systemic reactions to penicillin. The American Academy of Allergy16 sponsored a study in which 346 patients with a skin test that was negative to the major determinant and penicillin G were challenged with penicillin. Twelve patients (3%) had an ADR, and only 3 of the 12 (1% of total patients) were believed to be IgE-mediated. Hence, 97% to 99% of patients with negative penicillin skin tests will tolerate penicillin with no risk of an immediate reaction.18,22,23 Some physicians do not recommend penicillin skin tests for patients with a history of anaphylaxis to penicillin because of the small risk of anaphylaxis from the skin test. However, studies show that the risk of anaphylaxis to penicillin allergy skin tests is extremely low.24 A positive penicillin skin test reflects the presence of specific IgE antibodies to penicillin. Patients with a skin test that is positive to penicillin are at increased risk of an immediate-type hypersensitivity reaction to penicillin. Limited data are available about the true positive predictive value of a positive penicillin skin test. There is an approximate 50% risk of an immediate-type hypersensitivity reaction in patients with a skin test that is positive to penicillin.6,18,22 IgE antibodies specific to the MDM have been associated with acute systemic reactions.15 Patients with a positive penicillin skin test should avoid penicillin. Penicillin desensitization should be considered for patients with a positive skin test who require penicillin therapy. Use of in vitro assays (radioallergosorbent or enzymelinked immunosorbent) for IgE antibodies to penicillin is another approach to the diagnosis of IgE-mediated penicillin allergy.25 In the United States, these tests are available only for the major determinants of penicillin G, penicillin V, amoxicillin, and ampicillin.26 A history of an immediatetype hypersensitivity reaction to penicillin with a positive in vitro test suggests an IgE-mediated penicillin allergy. However, a negative test does not exclude a penicillin Mayo Clin Proc. • allergy because these tests are relatively insensitive and do not test for minor determinants.6 Hence, the most reliable means of diagnosing an IgE-mediated penicillin allergy is by penicillin skin testing. At the time of writing this article, the major determinant (benzylpenicilloyl) for penicillin skin testing is no longer available commercially. However, some medical centers are able to produce their own major and minor determinants. Hence, we recommend that patients with a history of penicillin allergy who need penicillin should ask their allergist or medical center about the center’s capability to evaluate patients with penicillin skin testing. SAFETY OF PENICILLIN SKIN TESTS Systemic reactions to penicillin skin testing are uncommon when performed with the correct reagents and proper technique.6 Ressler and Mendelson27 suggested that less than 1% of the patients who underwent cautious stepwise scratch/intradermal penicillin skin testing had an adverse reaction. No severe reactions or fatalities were noted. In a retrospective study of 1710 patients with a history of penicillin allergy who underwent penicillin skin testing by puncture (bifurcated needle) with or without intradermal testing, only 2 patients (0.12%) had a systemic reaction (1 dyspnea/urticaria and 1 urticaria); there were no deaths.24 Although systemic reactions to penicillin skin tests are rare, fatalities have been reported.28 From 1973 to 1983, 1 fatality after penicillin skin testing was reported in a survey of practicing allergists sponsored by the American Academy of Allergy and Immunology.29 The fatality may have been due to an incorrect dose of penicillin G or penicilloyl polylysine and failure to perform a prick test before the intradermal test.29 Hence, penicillin skin testing has a low risk of systemic reactions and fatalities if correct reagents and proper techniques are used. If a patient has a history consistent with EM, StevensJohnson syndrome, or TEN, then penicillin skin testing is of limited usefulness14 because such tests poorly predict non–IgE-mediated drug reactions. Some physicians also exclude penicillin skin testing in patients with a history of anaphylaxis because of the small risk of anaphylaxis from the skin test. Patients taking antihistamines and tricyclic antidepressants (because of their antihistamine properties) should not undergo penicillin skin testing because antihistamines suppress the skin test response. CEPHALOSPORIN USE IN PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY In vitro tests have shown moderate cross-reactivity between cephalosporin and penicillins,6,30,31 which may be March 2005;80(3):405-410 • www.mayoclinicproceedings.com 407 DIAGNOSIS AND MANAGEMENT OF PENICILLIN ALLERGY due to the shared β-lactam ring and similar side chains.30 Up to 10% of patients with a history of penicillin allergy can have an adverse reaction to cephalosporins.32 No validated skin test or anticephalosporin IgE antibody assays are available clinically.32 In one review,32 an adverse reaction rate of 4.4% (6/135) was noted in patients with a positive penicillin skin test challenged with a cephalosporin. When patients with a history of penicillin allergy and a negative penicillin skin test were given a cephalosporin, only 2 (0.6%) of 351 patients had an adverse reaction.32 Daulat et al33 reviewed the medical records of 606 selected patients with a reported history of penicillin allergy who received a cephalosporin. Penicillin skin tests were not performed in most of these patients. Only 1 (0.17%) of 606 patients experienced an ADR (worsening of eczema). Other studies showed that patients with a history of penicillin allergy are at low risk of drug reaction when given cephalosporins.34,35 These studies suggest a low risk of adverse reaction in patients with a history of penicillin allergy challenged with a cephalosporin. However, caution is advised. Pumphrey and Davis,36 in a study of fatal anaphylaxis in the United Kingdom from 1992 to 1997, revealed that 6 of 12 deaths were from the first course of a cephalosporin. Three of the 6 patients were known to be allergic to amoxicillin and 1 to penicillin. Hence, some caution is still advised if a cephalosporin is to be given to patients with a history of penicillin allergy. The Joint Task Force on Practice Parameters6 recommends that if a substitute with a non–β-lactam antimicrobial agent is unavailable for patients who need a cephalosporin, patients with a history of an immediate-type hypersensitivity reaction to penicillin should undergo penicillin skin testing. If penicillin skin tests are negative, a cephalosporin can be administered with a less than 1% risk of immediate adverse reaction. However, if penicillin skin tests are positive, then the patient should either avoid β-lactam antimicrobials or be considered for cephalosporin desensitization. Patients with a history of penicillin allergy who subsequently have tolerated a cephalosporin agent generally do not need to undergo penicillin skin testing before readministration of the same cephalosporin drug. An analogue of cephalosporin, cefazolin is the preferred prophylactic antibiotic in many surgical specialties for prevention of postoperative surgical site infection.37 Some expert panels have recommended vancomycin as an alternative for patients with a history of penicillin allergy who need perioperative prophylactic antibiotics to decrease postoperative surgical site infections6,38; thus, such patients often receive vancomycin before surgery. However, S aureus strains with reduced susceptibility to vancomycin have been reported.8 The Hospital Infection Control 408 Mayo Clin Proc. • Practices Advisory Committee has recommended judicious and reduced use of vancomycin.9 In a practice improvement study at our institution,39 60 patients with a history of penicillin or cephalosporin allergies who underwent elective orthopedic surgery were evaluated by an allergy consultation and penicillin skin test. We were able to substantially decrease prophylactic vancomycin use in patients with a history of penicillin allergy. In an extended study (P. Markus, RN; M.A.P.; and J.T.C.L., unpublished data, 2005), more than 1000 surgical patients with a history of penicillin allergy reported a decrease in vancomycin use to only 16% compared with 30% in historical controls. Hence, an allergy consultation and penicillin skin testing can reduce prophylactic vancomycin use in surgical patients. March 2005;80(3):405-410 CLINICAL SCENARIO DISCUSSION RECOM M ENDED OPTION The recommended option for the 85-year-old patient discussed previously, who had a coagulase-negative staphylococcus infection susceptible to piperacillin or cefazolin and a history of penicillin allergy, is to proceed with penicillin skin testing with the major and minor determinants. RATIONALE The pruritic rash that appeared 4 hours after the patient took penicillin is suggestive of an IgE-mediated hypersensitivity reaction; thus, the patient has an increased risk of an immediate-type adverse reaction if given piperacillin. Serious and even fatal reactions to cephalosporins have been reported, especially in the setting of prior reaction to penicillin. The Joint Task Force on Practice Parameters has recommended penicillin skin testing in patients with a history of penicillin allergy who need cephalosporins.6 Because only 10% to 20% of patients with reported history of penicillin allergy have evidence of IgE antibodies to penicillin on skin testing, the patient would benefit by further evaluation with penicillin skin testing. Hence, penicillin skin testing with a major and minor determinant is the best option. If penicillin skin testing is unavailable, an antibiotic with no β-lactam ring such as vancomycin is a reasonable alternative to cefazolin. CONCLUSION The penicillin skin testing with major and minor determinants was negative with a good histamine control. The patient was given cefazolin and had no ADR. • www.mayoclinicproceedings.com DIAGNOSIS AND MANAGEMENT OF PENICILLIN ALLERGY SUM M ARY A detailed history of a prior reaction to penicillin is integral to patient evaluation but is not accurate for predicting a positive penicillin skin test. A patient with a history of penicillin allergy and a penicillin skin test that is negative to the major and minor determinants is at low risk of an immediate-type hypersensitivity reaction to penicillin or cephalosporins. Patients with a positive penicillin skin test should undergo desensitization to penicillin and/or cephalosporins, or an alternative antibiotic should be considered. REFERENCES 1. World Health Organization. International Drug Monitoring: The Role of the Hospital. Geneva, Switzerland: World Health Organization; 1969. Technical Report Series, No. 425. 2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279:1200-1205. 3. Lenler-Petersen P, Hansen D, Andersen M, Sorensen HT, Bille H. Drugrelated fatal anaphylactic shock in Denmark 1968-1990: a study based on notifications to the Committee on Adverse Drug Reactions. J Clin Epidemiol. 1995;48:1185-1188. 4. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States [published correction appears in JAMA. 1998;279:434]. JAMA. 1995;273:214-219. 5. Kerr JR. Penicillin allergy: a study of incidence as reported by patients. Br J Clin Pract. 1994;48:5-7. 6. Joint Task Force on Practice Parameters. Executive summary of disease management of drug hypersensitivity: a practice parameter. Ann Allergy Asthma Immmunol. 1999;83(6, pt 3):665-700. 7. Sade 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;33:501-506. 8. Hiramatsu K, Aritaka N, Hanaki H, et al. Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet. 1997;350:1670-1673. 9. Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). Am J Infect Control. 1995;23:87-94. 10. Ahlstedt S. Penicillin allergy—can the incidence be reduced? Allergy. 1984;39:151-164. 11. Idsoe O, Guthe T, Willcox RR, de Weck AL. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ. 1968;38:159-188. 12. Adkinson NF Jr. Drug allergy. In: Adkinson NF Jr, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FE, eds. Middleton’s Allergy Principles & Practice. Vol 2. 6th ed. Philadelphia, Pa: Mosby; 2003:1679-1694. 13. Gruchalla RS. Drug allergy. J Allergy Clin Immunol. 2003;111(2, suppl 2):548-559. 14. Greenberger PA. Part B: allergic reactions to individual drugs: low molecular weight. In: Grammer LC, Greenberger PA, eds. Patterson’s Allergic Diseases. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2002:335359. 15. Gadde J, Spence M, Wheeler B, Adkinson NF Jr. Clinical experience with penicillin skin testing in a large inner-city STD clinic. JAMA. 1993;270: 2456-2463. 16. Green GR, Rosenblum AH, Sweet LC. Evaluation of penicillin hypersensitivity: value of clinical history and skin testing with penicilloyl-polylysine and penicillin G: a cooperative prospective study of the penicillin study group of the American Academy of Allergy. J Allergy Clin Immunol. 1977;60:339345. 17. Solensky R, Earl HS, Gruchalla RS. Penicillin allergy: prevalence of vague history in skin test-positive patients. Ann Allergy Asthma Immunol. 2000;85:195-199. 18. Salkind AR, Cuddy PG, Foxworth JW. Is this patient allergic to penicillin? an evidence-based analysis of the likelihood of penicillin allergy. JAMA. 2001;285:2498-2505. Mayo Clin Proc. • 19. Jaeschke R, Guyatt G, Sackett DL, Evidence-Based Medicine Working Group. Users’ guides to the medical literature, III: how to use an article about a diagnostic test, A: are the results of the study valid? JAMA. 1994;271:389391. 20. Jaeschke R, Guyatt GH, Sackett DL, Evidence-Based Medicine Working Group. Users’ guides to the medical literature, III: how to use an article about a diagnostic test, B: what are the results and will they help me in caring for my patients? JAMA. 1994;271:703-707. 21. Sogn DD, Evans R III, Shepherd GM, et al. Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults. Arch Intern Med. 1992;152:1025-1032. 22. Weiss ME, Adkinson NF. Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy. 1988;18:515-540. 23. Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med. 1987;107:204-215. 24. Valyasevi MA, Van Dellen RG. Frequency of systematic reactions to penicillin skin tests. Ann Allergy Asthma Immunol. 2000;85:363-365. 25. Wide L, Juhlin L. Detection of penicillin allergy of the immediate type by radioimmunoassay of reagins (IgE) to penicilloyl conjugates. Clin Allergy. 1971;1:171-177. 26. Thethi AK, Van Dellen RG. Dilemmas and controversies in penicillin allergy. Immunol Allergy Clin North Am. 2004;24:445-461, vi. 27. Ressler C, Mendelson LM. Skin test for diagnosis of penicillin allergy— current status. Ann Allergy. 1987;59:167-170. 28. Van Dellen RG. Skin testing for penicillin allergy. J Allergy Clin Immunol. 1981;68:169-170. 29. Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol. 1987;79: 660-677. 30. Blanca M, Fernandez J, Miranda A, et al. Cross-reactivity between penicillins and cephalosporins: clinical and immunologic studies. J Allergy Clin Immunol. 1989;83(2, pt 1):381-385. 31. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol. 1995;74:167-170. 32. Kelkar PS, Li JT. Cephalosporin allergy. N Engl J Med. 2001;345:804809. 33. Daulat S, Solensky R, Earl HS, Casey W, Gruchalla RS. Safety of cephalosporin administration to patients with histories of penicillin allergy [letter]. J Allergy Clin Immunol. 2004;113:1220-1222. 34. Macy E, Burchette RJ. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up. Allergy. 2002;57:1151-1158. 35. Novalbos A, Sastre J, Cuesta J, et al. Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins. Clin Exp Allergy. 2001; 31:438-443. 36. Pumphrey RS, Davis S. Under-reporting of antibiotic anaphylaxis may put patients at risk [letter]. Lancet. 1999;353:1157-1158. 37. Osmon DR. Antimicrobial prophylaxis in adults. Mayo Clin Proc. 2000; 75:98-109. 38. American Society of Health-System Pharmacists. ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 1999;56:1839-1888. 39. Li JT, Markus PJ, Osmon DR, Estes L, Gosselin VA, Hanssen AD. Reduction of vancomycin use in orthopedic patients with a history of antibiotic allergy. Mayo Clin Proc. 2000;75:902-906. Questions About Penicillin and Cephalosporin Allergy 1. Which one of the following represents the percentage of patients with a history of penicillin allergy who have a positive penicillin skin test? a. 3% to 15% b. 16% to 25% c. 26% to 35% d. 36% to 45% e. 46% to 55% March 2005;80(3):405-410 • www.mayoclinicproceedings.com 409 DIAGNOSIS AND MANAGEMENT OF PENICILLIN ALLERGY 2. A 21-year-old patient with a history of penicillin allergy comes to your office for an antibiotic for group A streptococcal pharyngitis. You determine that penicillin is the best treatment. When the patient was 5 years old, he received oral penicillin and developed ulcers and blistering in his mouth and on his genitals. Penicillin was discontinued, and the patient recovered without sequela. No further exposures to β-lactam antibiotics have been noted. Which one of the following is the next-best step? a. Administer the full dose of penicillin b. Desensitize to penicillin c. Give a test dose of penicillin and if the patient has no ADRs in your office, give the full dose d. Administer a non–β-lactam antibiotic e. Perform a penicillin skin test 3. A 50-year-old patient with a history of penicillin allergy comes to your office for an antibiotic for group A streptococcal pharyngitis. You determine that penicillin is the best treatment. When the patient was 5 years old, he experienced an ADR to penicillin but does not remember the type of reaction. The patient has strictly avoided penicillin since the reaction. Which one of the following is the next-best step? a. Administer the full dose of penicillin b. Perform a penicillin skin test c. Give a test dose of penicillin and if the patient has no ADRs in your office, give the full dose d. Administer a non–β-lactam antibiotic e. Desensitize to penicillin 410 Mayo Clin Proc. • 4. A 35-year-old patient with a history of penicillin allergy is hospitalized for cellulitis. You determine that cefazolin is the best treatment. An ADR to penicillin occurred when the patient was 5 years old, which he believes was a rash that lasted a few days. The patient’s medical record reveals that he tolerated cefazolin 2 years previously. Which one of the following is the next-best step? a. Administer cefazolin b. Avoid cephalosporins c. Perform a penicillin skin test and if negative, give cefazolin d. Desensitize to cefazolin e. Avoid all β-lactam antibiotics 5. A 42-year-old patient with a history of penicillin allergy is hospitalized for cellulitis. You determine that cefazolin is the best treatment. When the patient was 5 years old, he experienced an ADR to penicillin, which he believes was a rash that lasted a few days. He has since avoided all β-lactam antibiotics. Which one of the following is the nextbest step? a. Administer cefazolin b. Avoid cephalosporins c. Perform a penicillin skin test and if negative, give cefazolin d. Desensitize to cefazolin e. Avoid all β-lactam antibiotics Correct answers: 1. a, 2. d, 3. b, 4. a, 5. c March 2005;80(3):405-410 • www.mayoclinicproceedings.com