Commentary

Time to get it right. Consequences of mislabeled penicillin allergies

by Lisa Infanti, PharmD

Penicillin is the most commonly implicated medication reported as the source of a drug allergy, with a reported incidence of up to 10% in the United States. However, only about 1% of the reported population has a confirmed anaphylactic reaction and is therefore appropriately labeled with a penicillin allergy. Commonly, children who experience a rash or diarrhea after receiving a dose of penicillin are labeled as having a penicillin allergy, even though the rash or diarrhea are likely a side effect of the medication rather than an immune-mediated reaction. However, this label is rarely questioned through future treatment courses. This is exemplified by a retrospective study of 65,000 patients with a documented history of penicillin allergy who received a total of 127,000 courses of cephalosporins: Only three patients experienced a true anaphylaxis reaction. This lifetime label attached incorrectly to patients has several consequences that must be identified and addressed.

In many cases, patients report penicillin allergies without having a clear understanding or memory of the reaction to the medication. The current practice of allowing patients and family members without medical knowledge to report penicillin allergies leads to an increase in alternative antibiotics for the most common infectious diseases. The use of alternative antibiotics leads to increased risk for future resistance due to broader coverage, costs with utilization of second-line agents, risk for toxic or adverse effects, and ultimately decreased efficacy. A large cohort study showed that patients who reported a penicillin allergy had a 69% increased risk for MRSA infection and a 26% greater risk for Clostridium difficile compared with those patients who did not report a penicillin allergy. Specifically for inpatient populations, patients who receive alternative antibiotics for perioperative management or complications have a significant risk of these adverse outcomes as well.

Surgical site infections result in significant morbidity and mortality, costing upwards of $25,000 per case. Cefazolin is typically the beta-lactam antibiotic of choice for surgical procedures due to its quick onset of action and short half-life, as well as its bactericidal activity and spectrum of coverage against gram positive organisms. Surgical patients who receive beta-lactam alternative antibiotics for surgical management, such as clindamycin or vancomycin, are subject to an increased risk for C. difficile infection, up to a 30% increased risk for vancomycin-resistant Enterococcus (VRE) colonization, and overall increased risk for surgical site infections. A retrospective study involving 8,385 surgery patients reported a 50% increased risk for developing a surgical site infection due to utilization of alternative antibiotics as surgical prophylaxis therapy, and such infections may increase length of stay by up to 7 to 10 days. Additionally, there have been concerns surrounding the timing in which alternative antibiotics are administered, considering that vancomycin requires a longer infusion time and thus a longer time to achieve peak concentrations. Although these concerns surrounding the utilization of alternative antibiotics are well documented and published, many anesthesiologists report that they would choose an alternative antibiotic if a penicillin allergy was documented, rather than clarifying the history and severity of the reaction.

One solution to address this issue is to utilize perioperative patient review as an opportunity to clarify allergies, to provide a referral for patients to undergo allergy testing, or to perform penicillin testing. According to the 2016 American Academy of Allergy, Asthma, & Immunology recommendations, routine penicillin allergy testing should be performed in those patients with a history of a penicillin allergy. The most feasible and reliable way to test is by performing an oral challenge, which only requires 1 hour of observation after the challenge. Tolerance of oral penicillin testing is the gold standard test for absence of an IgE-mediated penicillin allergy, and may help to de-label patients with a documented allergy. However, if a patient has a history of anaphylaxis reaction, performing skin testing first is most appropriate. An example of how to identify patients that may require penicillin testing is demonstrated by the Medical College of Wisconsin, who developed a 17-item questionnaire for parents to complete to determine if the patient has a true penicillin allergy. If the survey responses are not indicative of a true allergy, they would then offer penicillin testing to the patient. Another benefit of penicillin allergy testing demonstrated by the Medical College of Wisconsin ED is an estimated cost savings of $192,223 over the course of a year. By taking these necessary steps to clarify penicillin allergies and increase penicillin allergy testing, institutions will not only experience improved patient outcomes but also significant cost savings.

The mislabeling of penicillin allergies, although seemingly benign, can negatively impact patient care outcomes. Increased risk of resistant infections, adverse effects, and costs associated with utilizing alternative agents, along with increased risk of surgical site infections that may prolong hospital length of stay, are all consequences of a mislabeled penicillin allergy. Identifying cases in which these allergies can be properly identified and documented is increasingly becoming the responsibility of health care providers, whether by penicillin testing, questionnaires, or screening prior to surgical procedures. By developing institutional processes for identifying and clarifying documented penicillin allergies, patients may be afforded the opportunity for improved outcomes.

References:

Blumenthal KG, et al. BMJ. 2018;doi:10.1136/bmj.k2400.

Blumenthal KG, et al. Clin Infect Dis. 2018;doi:10.1093/cid/cix794.

Macy E, Contreras R. J Allergy Clin Immunol. 2015;doi:10.1016/j.jaci.2014.07.062.

Penicillin Allergy in Antibiotic Resistance Workgroup. J Allergy Clin Immunol Pract. 2017;doi:10.1016/j.jaip.2016.12.010.

Rubin R. JAMA. 2018;doi:10.1001/jama.2018.14358.

Vaisman A, et al. JAMA Intern Med. 2017;doi:10.1001/jamainternmed.2016.8185.

Vorobeichik L, et al. Anesth Analg. 2018;doi:10.1213/ANE.0000000000003419.

For more information:

Lisa Infanti, PharmD, is a pharmacy resident at Norton Children’s Hospital in Louisville, Kentucky. She can be reached at Lisa.infanti@nortonhealthcare.org.

by Lisa Infanti, PharmD

Penicillin is the most commonly implicated medication reported as the source of a drug allergy, with a reported incidence of up to 10% in the United States. However, only about 1% of the reported population has a confirmed anaphylactic reaction and is therefore appropriately labeled with a penicillin allergy. Commonly, children who experience a rash or diarrhea after receiving a dose of penicillin are labeled as having a penicillin allergy, even though the rash or diarrhea are likely a side effect of the medication rather than an immune-mediated reaction. However, this label is rarely questioned through future treatment courses. This is exemplified by a retrospective study of 65,000 patients with a documented history of penicillin allergy who received a total of 127,000 courses of cephalosporins: Only three patients experienced a true anaphylaxis reaction. This lifetime label attached incorrectly to patients has several consequences that must be identified and addressed.

In many cases, patients report penicillin allergies without having a clear understanding or memory of the reaction to the medication. The current practice of allowing patients and family members without medical knowledge to report penicillin allergies leads to an increase in alternative antibiotics for the most common infectious diseases. The use of alternative antibiotics leads to increased risk for future resistance due to broader coverage, costs with utilization of second-line agents, risk for toxic or adverse effects, and ultimately decreased efficacy. A large cohort study showed that patients who reported a penicillin allergy had a 69% increased risk for MRSA infection and a 26% greater risk for Clostridium difficile compared with those patients who did not report a penicillin allergy. Specifically for inpatient populations, patients who receive alternative antibiotics for perioperative management or complications have a significant risk of these adverse outcomes as well.

Surgical site infections result in significant morbidity and mortality, costing upwards of $25,000 per case. Cefazolin is typically the beta-lactam antibiotic of choice for surgical procedures due to its quick onset of action and short half-life, as well as its bactericidal activity and spectrum of coverage against gram positive organisms. Surgical patients who receive beta-lactam alternative antibiotics for surgical management, such as clindamycin or vancomycin, are subject to an increased risk for C. difficile infection, up to a 30% increased risk for vancomycin-resistant Enterococcus (VRE) colonization, and overall increased risk for surgical site infections. A retrospective study involving 8,385 surgery patients reported a 50% increased risk for developing a surgical site infection due to utilization of alternative antibiotics as surgical prophylaxis therapy, and such infections may increase length of stay by up to 7 to 10 days. Additionally, there have been concerns surrounding the timing in which alternative antibiotics are administered, considering that vancomycin requires a longer infusion time and thus a longer time to achieve peak concentrations. Although these concerns surrounding the utilization of alternative antibiotics are well documented and published, many anesthesiologists report that they would choose an alternative antibiotic if a penicillin allergy was documented, rather than clarifying the history and severity of the reaction.

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One solution to address this issue is to utilize perioperative patient review as an opportunity to clarify allergies, to provide a referral for patients to undergo allergy testing, or to perform penicillin testing. According to the 2016 American Academy of Allergy, Asthma, & Immunology recommendations, routine penicillin allergy testing should be performed in those patients with a history of a penicillin allergy. The most feasible and reliable way to test is by performing an oral challenge, which only requires 1 hour of observation after the challenge. Tolerance of oral penicillin testing is the gold standard test for absence of an IgE-mediated penicillin allergy, and may help to de-label patients with a documented allergy. However, if a patient has a history of anaphylaxis reaction, performing skin testing first is most appropriate. An example of how to identify patients that may require penicillin testing is demonstrated by the Medical College of Wisconsin, who developed a 17-item questionnaire for parents to complete to determine if the patient has a true penicillin allergy. If the survey responses are not indicative of a true allergy, they would then offer penicillin testing to the patient. Another benefit of penicillin allergy testing demonstrated by the Medical College of Wisconsin ED is an estimated cost savings of $192,223 over the course of a year. By taking these necessary steps to clarify penicillin allergies and increase penicillin allergy testing, institutions will not only experience improved patient outcomes but also significant cost savings.

The mislabeling of penicillin allergies, although seemingly benign, can negatively impact patient care outcomes. Increased risk of resistant infections, adverse effects, and costs associated with utilizing alternative agents, along with increased risk of surgical site infections that may prolong hospital length of stay, are all consequences of a mislabeled penicillin allergy. Identifying cases in which these allergies can be properly identified and documented is increasingly becoming the responsibility of health care providers, whether by penicillin testing, questionnaires, or screening prior to surgical procedures. By developing institutional processes for identifying and clarifying documented penicillin allergies, patients may be afforded the opportunity for improved outcomes.

References:

Blumenthal KG, et al. BMJ. 2018;doi:10.1136/bmj.k2400.

Blumenthal KG, et al. Clin Infect Dis. 2018;doi:10.1093/cid/cix794.

Macy E, Contreras R. J Allergy Clin Immunol. 2015;doi:10.1016/j.jaci.2014.07.062.

Penicillin Allergy in Antibiotic Resistance Workgroup. J Allergy Clin Immunol Pract. 2017;doi:10.1016/j.jaip.2016.12.010.

Rubin R. JAMA. 2018;doi:10.1001/jama.2018.14358.

Vaisman A, et al. JAMA Intern Med. 2017;doi:10.1001/jamainternmed.2016.8185.

Vorobeichik L, et al. Anesth Analg. 2018;doi:10.1213/ANE.0000000000003419.

For more information:

Lisa Infanti, PharmD, is a pharmacy resident at Norton Children’s Hospital in Louisville, Kentucky. She can be reached at Lisa.infanti@nortonhealthcare.org.