Advertisement

Evaluation of Penicillin Allergy in the Hospitalized Patient: Opportunities for Antimicrobial Stewardship

  • Justin R. Chen
  • David A. KhanEmail author
Anaphylaxis and Drug Allergy (DA Khan and M Castells, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Anaphylaxis and Drug Allergy

Abstract

Purpose of Review

Penicillin allergy is often misdiagnosed and is associated with adverse consequences, but testing is infrequently done in the hospital setting. This article reviews historical and contemporary innovations in inpatient penicillin allergy testing and its impact on antimicrobial stewardship.

Recent Findings

Adoption of the electronic medical record allows rapid identification of admitted patients carrying a penicillin allergy diagnosis. Collaboration with clinical pharmacists and the development of computerized clinical guidelines facilitates increased testing and appropriate use of penicillin and related β-lactams. Education of patients and their outpatient providers is the key to retaining the benefits of penicillin allergy de-labeling.

Summary

Penicillin allergy testing is feasible in the hospital and offers tangible benefits towards antimicrobial stewardship. Allergists should take the lead in this endeavor and work towards overcoming personnel limitations by partnering with other health care providers and incorporating technology that improves the efficiency of allergy evaluation.

Keywords

Penicillin allergy Drug allergy Penicilloyl-polylysine Antimicrobial stewardship Skin test Electronic medical record 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Drug allergy. an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:259–73.CrossRefGoogle Scholar
  2. 2.
    Macy E. Penicillin and beta-lactam allergy: epidemiology and diagnosis. Curr Allergy Asthma Rep. 2014;14:476.CrossRefPubMedGoogle Scholar
  3. 3.
    del Real GA, Rose ME, Ramirez-Atamoros MT, et al. Penicillin skin testing in patients with a history of beta-lactam allergy. Ann Allergy Asthma Immunol. 2007;98:355–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Raja AS, Lindsell CJ, Bernstein JA, Codispoti CD, Moellman JJ. The use of penicillin skin testing to assess the prevalence of penicillin allergy in an emergency department setting. Ann Emerg Med. 2009;54(1):72–7.CrossRefPubMedGoogle Scholar
  5. 5.
    • Macy E, Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Pract. 2013;1(3):258–63. This study validated a protocol for penicillin allergy testing using commercially available penicilloyl-polylysine, penicillin G and amoxicillin in lieu of the unavailable minor determinants. This is the most commonly used testing protocol today. CrossRefPubMedGoogle Scholar
  6. 6.
    del Real GA, Rose ME, Ramirez-Atamoros MT, Hammel J, Gordon SM, Arroliga AC, et al. Penicillin skin testing in patients with a history of beta-lactam allergy. Ann Allergy Asthma Immunol. 2007;98(4):355–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Sagar PS, Katelaris CH. Utility of penicillin skin testing in patients 499 with a history of penicillin allergy. Asia Pac Allergy. 2013;3(2):115–99.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Rimawi RH, Cook PP, Gooch M, Kabchi B, Ashraf MS, Rimawi BH, et al. The impact of penicillin skin testing on clinical practice and antimicrobial stewardship. J Hosp Med. 2013;8(6):341–5.CrossRefPubMedGoogle Scholar
  9. 9.
    •• Chen JR, Tarver SA, Alvarez KS, Tran T, Khan DA. A proactive approach to penicillin allergy testing in hospitalized patients. J Allergy Clin Immunol Pract. 2016; doi: 10.1016/j.jaip.2016.09.045. This is the largest study of inpatient penicillin skin testing to date and outlines a protocol by which the electronic medical record is used to proactively identify patients for testing. It also describes a model for pharmacists to perform skin testing in the hospital. Β-lactam alternative use significantly declined with corresponding increases in penicillin and cephalosporin orders both during hospitalization and at discharge. PubMedCentralGoogle Scholar
  10. 10.
    Albin S, Agarwal S. Prevalence and characteristics of reported penicillin allergy in an urban outpatient adult population. Allergy Asthma Proc. 2014;Google Scholar
  11. 11.
    Caubet JC, Kaiser L, Lemaitre B, et al. The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011;127:218–22.CrossRefPubMedGoogle Scholar
  12. 12.
    • Blanca M, Torres MJ, Garcia JJ, Romano A, Mayorga C, de Ramon E, et al. Natural evolution of skin test sensitivity in patients allergic to beta-lactam antibiotics. J Allergy Clin Immunol. 1999;103:918–24. This was the first prospective study to demonstrate the waning of penicillin skin test sensitivity with time.CrossRefPubMedGoogle Scholar
  13. 13.
    Sullivan TJ, Wedner HJ, Shatz GS, et al. Skin testing to detect penicillin allergy. J Allergy Clin Immunol. 1981;68:171–80.CrossRefPubMedGoogle Scholar
  14. 14.
    Fishman N, Patterson J, Saiman L, et al. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp Epidemiol. 2012;33:322–7.CrossRefGoogle Scholar
  15. 15.
    Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, Srinivasan A, Dellit TH, Falck-Ytter YT, Fishman NO, et al. Implementing an Antibiotic Stewardship Program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51–77.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Picard M, Begin P, Bouchard H, Cloutier J, Lacombe-Barrios J, Paradis J, et al. Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital. J Allergy Clin Immunol Pract. 2013;1(3):252–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Lutomski DM, Lafollette JA, Biaglow MA, Haglund LA. Antibiotic allergies in the medical record: effect on drug selection and assessment of validity. Pharmacotherapy. 2008;28(11):1348–53.CrossRefPubMedGoogle Scholar
  18. 18.
    MacFadden DR, LaDelfa A, Leen J, Gold WL, Daneman N, Weber E, et al. Impact of reported beta-lactam allergy on inpatient outcomes: a multicenter prospective cohort study. Clin Infect Dis. 2016; doi: 10.1093/cid/ciw462.PubMedGoogle Scholar
  19. 19.
    McDanel JS, Perencevich EN, Diekema DJ, Herwaldt LA, Smith TC, Chrischilles EA, et al. Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals. Clin Infect Dis. 2015;61(3):361–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Jeffres MN, Narayanan PP, Shuster JE, Schramm GE. Consequences of avoiding beta lactams in patients with beta-lactam allergies. J Allergy Clin Immunol. 2016;137(4):1148–480 1153.CrossRefPubMedGoogle Scholar
  21. 21.
    •• Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J Allergy Clin Immunol. 2014;133(3):790–6. This matched cohort study showed patients with the label of penicillin allergy received significantly more fluoroquinolones, vancomycin and clindamycin and also had significantly higher rates of C difficile, MRSA and VRE infections. Cases with a penicillin allergy diagnosis averaged 0.59 more total hospital days during the study period. This study confirmed that a penicillin allergy history, although often inaccurate, was associated with significant adverse outcomes. CrossRefPubMedGoogle Scholar
  22. 22.
    US Department of Health and Human Services, Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. March 20, 2014. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
  23. 23.
    Picard M, Bégin P, Bouchard H, et al. Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital. J Allergy Clin Immunol Pract. 2013;1:252–7.CrossRefPubMedGoogle Scholar
  24. 24.
    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(4):501–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Li M, Krishna MT, Razaq S, Pillay D. A real-time prospective evaluation of clinical pharmaco-economic impact of diagnostic label of “penicillin allergy” in a UK teaching hospital. J Clin Pathol. 2014;67:1088–92.CrossRefPubMedGoogle Scholar
  26. 26.
    Macy E. Elective penicillin skin testing and amoxicillin challenge: effect on outpatient antibiotic use, cost, and clinical outcomes. J Allergy Clin Immunol. 1998 Aug;102(2):281–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Valyasevi MA, Van Dellen RG. Frequency of systematic reactions to penicillin skin tests. Ann Allergy Asthma Immunol. 2000;85:363–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Solensky R, Earl HS, Gruchalla RS. Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses. Arch Intern Med. 2002;162:822–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Lee CE, Zembower TR, Fotis MA, Postelnick MJ, Greenberger PA, Peterson LR, et al. The incidence of antimicrobial allergies in hospitalized patients: implication regarding prescribing patters and emerging bacterial resistance. Arch Intern Med. 2000;160:2819–22.CrossRefPubMedGoogle Scholar
  30. 30.
    Harris AD, Sauberman L, Kabbash L, Greineder DK, Samore MH. Penicillin skin testing: a way to optimize antibiotic utilization. Am J Med. 1999;2:166.CrossRefGoogle Scholar
  31. 31.
    Nadarajah K, Green GR, Naglak M. Clinical outcomes of penicillin skin testing. Ann Allergy Asthma Immunol. 2005;95:541–5.CrossRefPubMedGoogle Scholar
  32. 32.
    Arroliga ME, Wagner W, Bobek MB, Hoffman-Hogg L, Gordon SM, Arroliga AC. A pilot study of penicillin skin testing in patients with a history of penicillin allergy admitted to a medical ICU. Chest. 2000;4:1106.CrossRefGoogle Scholar
  33. 33.
    Arroliga ME, Radojicic C, Gordon SM, 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;5:347.CrossRefGoogle Scholar
  34. 34.
    Banks TA, Ressner RA, Gada SM. Antibiotic reclamation: penicillin allergy, antibiotic stewardship, and the allergist. Ann Allergy Asthma Immunol. 2015;115:451–2.CrossRefPubMedGoogle Scholar
  35. 35.
    Abbo LM, Beekmann SE, Hooton TM, et al. Management of antimicrobial allergies by infectious diseases physicians. JAMA Intern Med. 2013;173:1376–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Heil EL, Bork JT, Schmalzle SA, et al. Implementation of an infectious disease fellow-managed penicillin allergy skin testing service. Open Forum Infect Dis. 2016:3–ofw155.Google Scholar
  37. 37.
    Chandrasekar PH. Bad news to worse news: 2015 infectious diseases fellowship match results. Clin Infect Dis. 2015;60:1438.PubMedGoogle Scholar
  38. 38.
    Macy ER, Roppe LB, Schatz M. Routine penicillin skin testing in hospitalized patients with a history of a penicillin allergy. Perm J. 2004;8(3):20–4.PubMedPubMedCentralGoogle Scholar
  39. 39.
    • King EA, Challa S, Curtin P, Bielory L. Penicillin skin testing hospitalized patients with β-lactam allergies: effect on antibiotic selection and cost. Ann Allergy Asthma Immunol. 2016;117(1):67–71. This study featured clinical pharmacist identification of patients on high cost beta lactam alternatives and demonstrated clear antibiotic cost savings when penicillin allergy testing was applied to this population. CrossRefPubMedGoogle Scholar
  40. 40.
    Wall GC, Peters L, Leaders CB, Wille JA. Pharmacist-managed service providing penicillin allergy skin tests. Am J Health Syst Pharm. 2004;61(12):1271–5.PubMedGoogle Scholar
  41. 41.
    Chen JR, Tarver SA, Alvarez KS, Nguyen C, Khan DA. Reflexive penicillin allergy testing with in-hospital aztreonam use. J Allergy Clin Immunol. 2017;139(2): Suppl):AB30.CrossRefGoogle Scholar
  42. 42.
    Prematta T, Shah S, Ischmael FT. Physician approaches to beta-lactam use in patients with penicillin hypersensitivity. Allergy and Asthma Proceedings. 2012;33:145–51.CrossRefPubMedGoogle Scholar
  43. 43.
    Puchner TC, Zacharisen MC. A survey of antibiotic prescribing and knowledge of penicillin allergy annals of allergy. Asthma and Immunology. 2002;88:24–9.CrossRefGoogle Scholar
  44. 44.
    Blumenthal KG, Shenoy ES, Hurwitz S, Varughese CA, Hooper DC, Banerji A. Effect of a drug allergy educational program and antibiotic prescribing guideline on inpatient clinical providers’ antibiotic prescribing knowledge. J Allergy Clin Immunol Pract. 2014;2(4):407–13.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    • Blumenthal KG, Shenoy ES, Varughese CA, Hurwitz S, Cooper DC, Banerji A. Impact of a clinical guideline for prescribing antibiotics to patients reporting penicillin or cephalosporin allergy. Ann Allergy Asthma Immunol. 2015;115(4):294–300. Introduces a clinical guideline for general inpatient providers that promotes taking a detailed allergy history and prescribing the proper antibiotic for a patient reporting a β-lactam allergy. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    •• Blumenthal KG, Wickner PG, Hurwitz S, Pricco N, Nee AE, Laskowski K, et al. Tackling penicillin allergies: assessing tools for antimicrobial stewardship. J Allergy Clin Immunol. doi: 10.1016/j.jaci.2017.02.005. This study evaluates the effect of a computerized clinical guideline available on mobile devices intended to guide inpatient providers on evaluating penicillin allergy and performing test doses or consulting an allergist if indicated. This approach yielded significant increases in penicillin and cephalosporin use compared to standard-of-care where evaluation was performed through formal consultation alone. In comparison, a proactive approach to penicillin skin testing by a specialized team resulted in significant increases in β-lactam use in the per-protocol analysis, but did not yield dramatic changes in the cohort as a whole due to difficulty in coordinating skin tests for many hospitalized patients. The approaches described in this paper may be useful in environments without penicillin skin testing on-site.
  47. 47.
    Warrington RJ, Lee KR, McPhillips S. The value of skin testing for penicillin allergy in an inpatient population: analysis of the subsequent patient management. Allergy Asthma Proc. 2000;21:297–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Rimawi RH, Shah KB, Cook PP. Risk of redocumenting penicillin allergy in a cohort of patients with negative penicillin skin tests. J Hosp Med. 2013 Nov;8(11):615–8.Google Scholar
  49. 49.
    Bourke J, Pavlos R, James I, Phillips E. Improving the effectiveness of penicillin allergy de-labeling. J Allergy Clin Immunol Pract. 2015;3:365–74.Google Scholar
  50. 50.
    Patel SV, Tarver SA, Alvarez KS, Lutek KE, Schlebus J, Khan DA. Effectiveness of interventions to maintain penicillin allergy label removal as part of an inpatient penicillin allergy testing protocol. J Allergy Clin Immunol. 2017;139(2): Suppl.):AB183.Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Allergy & ImmunologyThe University of Texas Southwestern Medical CenterDallasUSA

Personalised recommendations