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The impact of antibiotic allergy labels on antibiotic exposure, clinical outcomes, and healthcare costs: A systematic review

Published online by Cambridge University Press:  16 October 2020

Nathan M. Krah ,
Trahern W. Jones ,
Joanita Lake  and
Adam L. Hersh Open the ORCID record for Adam L. Hersh [Opens in a new window]
Nathan M. Krah
Affiliation:
Department of Pediatrics, University of Utah, Salt Lake City, Utah
Trahern W. Jones
Affiliation:
Division of Infectious Disease, Department of Pediatrics, University of Utah, Salt Lake City, Utah
Joanita Lake
Affiliation:
Department of Pharmacotherapy, University of Utah, Salt Lake City, Utah
Adam L. Hersh*
Affiliation:
Division of Infectious Disease, Department of Pediatrics, University of Utah, Salt Lake City, Utah
*
Author for correspondence: Adam L. Hersh, E-mail: [email protected]
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Abstract

Objective:

A growing body of evidence suggests that antibiotic allergy labels as documented in medical records are a risk factor for poor clinical outcomes. In this systematic review, we aimed to determine how antibiotic allergy labels influence 3 domains: antibiotic use and exposure, clinical outcomes, and healthcare-related costs.

Design:

We performed a systematic review to identify studies reporting outcomes in patients with antibiotic allergy labels compared to nonallergic counterparts. The search included PubMed, EMBASE, Cochrane CENTRAL, EBSCO, Cochrane Database of Abstracts of Reviews of Effects and Web of Science. Two reviewers independently screened studies for inclusion and abstracted data. Studies were graded using the Newcastle-Ottawa quality assessment scale. Study outcomes included antibiotic use, clinical outcomes, and economic outcomes.

Results:

In total, 41 studies met our criteria for inclusion. These studies varied in medical specialty, patient population, healthcare delivery system, and design, but most were conducted among adults age >18 years (85%) in the inpatient setting (82.5%). Among 34 studies examining antibiotic exposure, 32 (94%) found that patients with antibiotic allergy labels received more broad-spectrum antibiotics. Moreover, 31 studies examined clinical outcomes such as length of hospitalization, ICU admission, hospital readmission, multidrug-resistant or opportunistic infection, or mortality, and 27 (87%) found that allergy-labeled patients had at least 1 negative outcome. Of 9 studies examining healthcare costs, 7 (78%) found that allergy-labeled patients incurred significantly higher drug or hospital-related costs.

Conclusions:

Antibiotic allergy labels have negative effects on antibiotic use, clinical outcomes, and economic outcomes in a variety of clinical settings and populations.

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 42 , Issue 5 , May 2021 , pp. 530 - 548
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Copyright
© The Author(s), 2020. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

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Footnotes

a

Authors of equal contribution.

References

Zhou, L, Dhopeshwarkar, N, Blumenthal, KG, et al, Drug allergies documented in electronic health records of a large healthcare system. Allergy 2016;71:1305–1313.CrossRefGoogle ScholarPubMed
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;133:790–796.CrossRefGoogle ScholarPubMed
Trubiano, JA, Adkinson, NF, Phillips, EJ. Penicillin allergy is not necessarily forever. JAMA 2017;318:82–83.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Castells, M, Khan, DA, Phillips, EJ. Penicillin allergy. N Engl J Med 2019;381:2338–2351.CrossRefGoogle ScholarPubMed
Blumenthal, KG, Peter, JG, Trubiano, JA, Phillips, EJ. Antibiotic allergy. Lancet 2019;393:183–198.CrossRefGoogle ScholarPubMed
Chen, JR, Khan, DA. Evaluation of penicillin allergy in the hospitalized patient: opportunities for antimicrobial stewardship. Curr Allergy Asthma Rep 2017;17(6):40.CrossRefGoogle ScholarPubMed
Krishna, MT, Huissoon, AP, Li, M, et al, Enhancing antibiotic stewardship by tackling “spurious” penicillin allergy. Clin Exp Allergy 2017;47:1362–1373.CrossRefGoogle ScholarPubMed
Pollack, LA, Srinivasan, A. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis 2014;59 suppl 3:S97–S100.CrossRefGoogle Scholar
Ressner, RA, Gada, SM, Banks, TA. Antimicrobial stewardship and the allergist: reclaiming our antibiotic armamentarium. Clin Infect Dis 2016;62:400–401.CrossRefGoogle ScholarPubMed
Wu, JH, Langford, BJ, Schwartz, KL, et al, Potential negative effects of antimicrobial allergy labelling on patient care: a systematic review. Can J Hosp Pharm 2018;71:29–35.Google ScholarPubMed
Higgins, JPT TJ, Chandler, J, Cumpston, M, Li, T, Page, MJ, Welch, VA, editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Published 2019. Accessed April 3, 2020.CrossRefGoogle Scholar
Jones, TW HA, Lake, J. Harmful outcomes due to reported patient antibiotic allergy labels. Protocol published in PROSPERO: registration number CRD42019127971. Registered on April 11, 2019.Google Scholar
Covidence systematic review software VHI. Covidence website. www.covidence.org. Accessed September 22, 2020.Google Scholar
Wells, G, Shea, B, O’Connell, D et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. The Ottaawa Hospital Research Institute website. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Published 2013. Accessed September 22, 2020.Google Scholar
Lam, W, Staicu, ML, Conn, KM, Ramsey, AC. Is there a higher prevalence of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) colonization in patients with antibiotic allergy labels? Am J Infect Control 2020;48:663–667.CrossRefGoogle ScholarPubMed
Imlay, H, Krantz, EM, Stohs, EJ, et al, Reported beta-lactam and other antibiotic allergies in solid organ and hematopoietic cell transplant recipients. Clin Infect Dis 2019 Oct 17 [Epub ahead of print]. doi: 10.1093/cid/ciz1025.Google Scholar
Phillips, CJ, Gilchrist, M, Cooke, FJ, et al, Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts. BMJ Open 2019;9(2):e026624.CrossRefGoogle ScholarPubMed
Charneski, L, Deshpande, G, Smith, SW. Impact of an antimicrobial allergy label in the medical record on clinical outcomes in hospitalized patients. Pharmacotherapy 2011;31:742–747.CrossRefGoogle Scholar
Huang, KG, Cluzet, V, Hamilton, K, Fadugba, O. The impact of reported beta-lactam allergy in hospitalized patients with hematologic malignancies requiring antibiotics. Clin Infect Dis 2018;67:27–33.CrossRefGoogle ScholarPubMed
Trubiano, JA, Leung, VK, Chu, MY, Worth, LJ, Slavin, MA, Thursky, KA. The impact of antimicrobial allergy labels on antimicrobial usage in cancer patients. Antimicrob Resist Infect Control 2015;4:23.CrossRefGoogle ScholarPubMed
Trubiano, JA, Chen, C, Cheng, AC, et al, Antimicrobial allergy ‘labels’ drive inappropriate antimicrobial prescribing: lessons for stewardship. J Antimicrob Chemother 2016;71:1715–1722.CrossRefGoogle ScholarPubMed
van Dijk, SM, Gardarsdottir, H, Wassenberg, MW, Oosterheert, JJ, de Groot, MC, Rockmann, H. The high impact of penicillin allergy registration in hospitalized patients. J Allergy Clin Immunol Pract 2016;4:926–931.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Lucas, M, Arnold, A, Sommerfield, A, et al, Antibiotic allergy labels in children are associated with adverse clinical outcomes. J Allergy Clin Immunol Pract 2019;7:975–982.CrossRefGoogle ScholarPubMed
Trubiano, JA, Cairns, KA, Evans, JA, et al, The prevalence and impact of antimicrobial allergies and adverse drug reactions at an Australian tertiary centre. BMC Infect Dis 2015;15:572.CrossRefGoogle ScholarPubMed
Su, T, Broekhuizen, BDL, Verheij, TJM, Rockmann, H. The impact of penicillin allergy labels on antibiotic and health care use in primary care: a retrospective cohort study. Clin Transl Allergy 2017;7:18.CrossRefGoogle ScholarPubMed
Kraemer, MJ, Caprye-Boos, H, Berman, HS. Increased use of medical services and antibiotics by children who claim a prior penicillin sensitivity. West J Med 1987;146:697–700.Google ScholarPubMed
Desai, SH, Kaplan, MS, Chen, Q, Macy, EM. Morbidity in pregnant women associated with unverified penicillin allergies, antibiotic use, and group B Streptococcus infections. Perm J 2017;21:16-080.CrossRefGoogle ScholarPubMed
MacFadden, DR, LaDelfa, A, Leen, J, et al, Impact of reported beta-lactam allergy on inpatient outcomes: a multicenter prospective cohort study. Clin Infect Dis 2016;63:904–910.CrossRefGoogle ScholarPubMed
Blumenthal, KG, Ryan, EE, Li, Y, Lee, H, Kuhlen, JL, Shenoy, ES. The impact of a reported penicillin allergy on surgical site infection risk. Clin Infect Dis 2018;66:329–336.CrossRefGoogle ScholarPubMed
Blumenthal, KG, Shenoy, ES, Huang, M, et al, The impact of reporting a prior penicillin allergy on the treatment of methicillin-sensitive Staphylococcus aureus bacteremia. PLoS One 2016;11(7):e0159406.CrossRefGoogle ScholarPubMed
Conway, EL, Lin, K, Sellick, JA, et al, Impact of penicillin allergy on time to first dose of antimicrobial therapy and clinical outcomes. Clin Ther 2017;39:2276–2283.CrossRefGoogle ScholarPubMed
Ponce, B, Raines, BT, Reed, RD, Vick, C, Richman, J, Hawn, M. surgical site infection after arthroplasty: comparative effectiveness of prophylactic antibiotics: do surgical care improvement project guidelines need to be updated? J Bone Joint Surg Am 2014;96:970–977.CrossRefGoogle ScholarPubMed
Tan, TL, Springer, BD, Ruder, JA, Ruffolo, MR, Chen, AF. Is vancomycin-only prophylaxis for patients with penicillin allergy associated with increased risk of infection after arthroplasty? Clin Orthop Relat Res 2016;474:1601–1606.CrossRefGoogle ScholarPubMed
Sousa-Pinto, B, Cardoso-Fernandes, A, Araujo, L, Fonseca, JA, Freitas, A, Delgado, L. Clinical and economic burden of hospitalizations with registration of penicillin allergy. Ann Allergy Asthma Immunol 2018;120:190–194.CrossRefGoogle ScholarPubMed
Irawati, LH, J.D.; Keen N, Golledge CL, Joyce AW. Influence of penicillin allergy on antibiotic prescribing patterns and costs. J Pharm Pract Res 2006;36:286–290.CrossRefGoogle Scholar
Saunders, S, Reese, S, Lam, J, Wulu, J, Jalisi, S, Ezzat, W. Extended use of perioperative antibiotics in head and neck microvascular reconstruction. Am J Otolaryngol 2017;38:204–207.CrossRefGoogle ScholarPubMed
Sousa-Pinto, B, Araujo, L, Freitas, A, Delgado, L. Hospitalizations in children with a penicillin allergy label: an assessment of healthcare impact. Int Arch Allergy Immunol 2018;176:234–238.CrossRefGoogle ScholarPubMed
Turner, NA, Moehring, R, Sarubbi, C, et al, Influence of reported penicillin allergy on mortality in MSSA bacteremia. Open Forum Infect Dis 2018;5(3):ofy042.CrossRefGoogle ScholarPubMed
Khumra, S, Chan, J, Urbancic, K, et al, Antibiotic allergy labels in a liver transplant recipient study. Antimicrob Agents Chemother 2017;61(5):e00078-17.CrossRefGoogle Scholar
Knezevic, B, Sprigg, D, Seet, J, et al, The revolving door: antibiotic allergy labelling in a tertiary care centre. Intern Med J 2016;46:1276–1283.CrossRefGoogle Scholar
Blumenthal, KG, Lu, N, Zhang, Y, Li, Y, Walensky, RP, Choi, HK. Risk of meticillin-resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ 2018;361:k2400.Google ScholarPubMed
Sun, Y, Wang, H, Tang, Y, et al, Incidence and risk factors for surgical site infection after open reduction and internal fixation of ankle fracture: a retrospective multicenter study. Medicine (Baltimore) 2018;97(7):e9901.CrossRefGoogle ScholarPubMed
MacLaughlin, EJ, Saseen, JJ, Malone, DC. Costs of beta-lactam allergies: selection and costs of antibiotics for patients with a reported beta-lactam allergy. Arch Fam Med 2000;9:722–726.CrossRefGoogle ScholarPubMed
Trubiano, JA, Beekmann, SE, Worth, LJ, et al, Improving antimicrobial stewardship by antibiotic allergy delabeling: evaluation of knowledge, attitude, and practices throughout the Emerging Infections Network. Open Forum Infect Dis 2016;3(3):ofw153.CrossRefGoogle ScholarPubMed
Frost, HM, Knepper, BC, Shihadeh, KC, Jenkins, TC. A novel approach to evaluate antibiotic utilization across the spectrum of inpatient and ambulatory care and implications for prioritization of antibiotic stewardship efforts. Clin Infect Dis 2020;70:1675–1682.CrossRefGoogle ScholarPubMed
Suda, KJ, Hicks, LA, Roberts, RM, Hunkler, RJ, Matusiak, LM, Schumock, GT. Antibiotic expenditures by medication, class, and healthcare setting in the United States, 2010–2015. Clin Infect Dis 2018;66:185–190.CrossRefGoogle ScholarPubMed
Baggs, J, Fridkin, SK, Pollack, LA, Srinivasan, A, Jernigan, JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med 2016;176:1639–1648.CrossRefGoogle ScholarPubMed
Tabak, YP, Srinivasan, A, Yu, KC, et al, Hospital-level high-risk antibiotic use in relation to hospital-associated Clostridioides difficile infections: retrospective analysis of 2016–2017 data from US hospitals. Infect Control Hosp Epidemiol 2019;40:1229–1235.CrossRefGoogle ScholarPubMed
Metlay, JP, Waterer, GW, Long, AC, et al, Diagnosis and treatment of adults with community-acquired pneumonia: an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200(7):e45–e67.CrossRefGoogle ScholarPubMed
Infectious Diseases Society of A, Spellberg B, Blaser M, et al, Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis 2011;52 suppl 5:S397–S428.Google Scholar
Ross, RK, Hersh, AL, Kronman, MP, Newland, JG, Gerber, JS. Cost of antimicrobial therapy across US children’s hospitals. Infect Control Hosp Epidemiol 2015;36:1242–1244.CrossRefGoogle ScholarPubMed
Butler, DF, Lee, BR, Suppes, S, et al, Variability of surgical prophylaxis in penicillin-allergic children. Infect Control Hosp Epidemiol 2018;39:1480–1483.CrossRefGoogle ScholarPubMed
Dewart, CM, Gao, Y, Rahman, P, et al, Penicillin allergy and association with ciprofloxacin coverage in community-onset urinary tract infection. Infect Control Hosp Epidemiol 2018;39:1127–1128.CrossRefGoogle ScholarPubMed
Fernandez-Rubio, ME, Cuesta-Rodriguez, T, Urcelay-Segura, JL, Cortes-Valdes, C. Beta-lactamic antibiotics allergy in cataract surgery. Prevalence and preoperative characteristics of allergic patients. Arch Soc Esp Oftalmol 2014;89:92–98.Google ScholarPubMed
French, D, Noroozi, M, Shariati, B, Larjava, H. Clinical retrospective study of self-reported penicillin allergy on dental implant failures and infections. Quintessence Int 2016;47:861–870.Google ScholarPubMed
Lee, CE, Zembower, TR, Fotis, MA, et al, The incidence of antimicrobial allergies in hospitalized patients: implications regarding prescribing patterns and emerging bacterial resistance. Arch Intern Med 2000;160:2819–2822.CrossRefGoogle ScholarPubMed
Powell, N, West, R, Sandoe, J. Impact of penicillin allergy records on carbapenem prescribing: an observational retrospective cohort study. J Hosp Infect 2019;101:467–470.CrossRefGoogle Scholar
Schroeck, JL, Ruh, CA, Sellick, JA Jr, Ott, MC, Mattappallil, A, Mergenhagen, KA. Factors associated with antibiotic misuse in outpatient treatment for upper respiratory tract infections. Antimicrob Agents Chemother 2015;59:3848–3852.CrossRefGoogle ScholarPubMed
Trinh, JV, Chen, LF, Sexton, DJ, Anderson, DJ. Risk factors for gram-negative bacterial surgical site infection: do allergies to antibiotics increase risk? Infect Control Hosp Epidemiol 2009;30:440–446.CrossRefGoogle ScholarPubMed
Trubiano, JA, Pai Mangalore, R, Baey, YW, et al, Old but not forgotten: antibiotic allergies in general medicine (the AGM Study). Med J Aust 2016;204:273.CrossRefGoogle Scholar
Turnbull, BR, Zoutman, DE, Lam, M. Evaluation of hospital and patient factors that influence the effective administration of surgical antimicrobial prophylaxis. Infect Control Hosp Epidemiol 2005;26:478–485.CrossRefGoogle ScholarPubMed
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