Perspective

Beta-lactam test-dose procedures safe in patients with reported allergy

Kimberly G. Blumenthal, MD, MSc 
Kimberly G. Blumenthal
Paige G. Wickner, MD, MPH 
Paige G. Wickner

Results from a retrospective cohort study demonstrated the safety of an antimicrobial stewardship intervention that uses guideline-directed beta-lactam antibiotic test-dose procedures in hospitalized patients with reported beta-lactam allergies.

“Having a reported penicillin allergy not only decreases the likelihood that patients will be prescribed a penicillin when indicated, but very often, a penicillin allergy history will decrease the chance that a patient will be prescribed other beta-lactam drugs,” Kimberly G. Blumenthal, MD, MSc, quality and safety officer for allergy at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Infectious Disease News. “Together, this increases the risk of Clostridioides difficile infection, other hospital associated infections, and antibiotic resistance.”

Writing in Infection Control & Hospital Epidemiology, Blumenthal and colleagues explained that up to 15% of hospitalized patients report an allergy to beta-lactam antibiotics, which impacts acute-care antibiotic prescribing. Blumenthal noted that among the approximately 10% of patients in the United States who report a penicillin allergy, most will tolerate penicillin and related beta-lactams after evaluation.

Between April 2016 and December 2017, the researchers evaluated beta-lactam antibiotic test-dose outcomes within a large health care system that included two academic and three community acute-care hospitals.

“The intervention uses a guideline and clinical decision support tools to help nonspecialist providers perform test doses, a type of drug challenges where a drug is given under observation to demonstrate tolerance,” Blumenthal explained.

They assessed adverse drug reactions (ADRs), hypersensitivity reactions (HSRs) and EHR allergy record updates.

According to the study, Blumenthal and colleagues identified 1,046 test doses. Of those, 77% were identified as being to cephalosporins, 14% to penicillins and 9% to carbapenems. ADR signs and symptoms were reported by 7.5% of patients (95% CI, 5.9%-9.2%), and confirmed HSRs were reported for 3.8% (95% CI, 2.8%-5.2%). Most — 68% — of HSRs occurred at the second step of the test-dose procedure, when the patient received a full dose, the researchers reported. Of these, 58% required no treatment beyond discontinuing the drug, but three patients did require intramuscular epinephrine. The researchers found increased odds of HSR associated with a reported cephalosporin allergy history (OR = 2.96; 95% CI, 1.34-6.58).

“The guideline does not overly rely on penicillin skin testing — only 4% of test doses were

preceded by the penicillin skin test — which can be challenging to routinely perform in inpatients due to short length of stay and patient schedules,” study author Paige G. Wickner, MD, MPH, medical director of quality and safety at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, told Infectious Disease News. “To date, this guideline has been used at nine Partners HealthCare-affiliated sites, including many with no staff allergy and immunology support.”

Erica Shenoy MD, PhD
Erica Shenoy

The researchers encouraged EHR documentation to “improve this safe, effective, and practical acute-care antibiotic stewardship tool.”

“Allergy documentation strategies to improve the effectiveness of acute-care beta-lactam allergy interventions are needed,” study author Erica Shenoy MD, PhD, assistant chief of infection control at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Infectious Disease News. – by Marley Ghizzone

Disclosures: Blumenthal reports receiving royalties from UpToDate and honoraria from New England Society of Allergy, Dartmouth Medical School, and Vanderbilt Medical School, outside the submitted work. Blumenthal and Shenoy report a licensed clinical decision support tool for beta-lactam allergy evaluation that is used institutionally at Partners HealthCare System. Wickner reports no relevant financial disclosures.

Kimberly G. Blumenthal, MD, MSc 
Kimberly G. Blumenthal
Paige G. Wickner, MD, MPH 
Paige G. Wickner

Results from a retrospective cohort study demonstrated the safety of an antimicrobial stewardship intervention that uses guideline-directed beta-lactam antibiotic test-dose procedures in hospitalized patients with reported beta-lactam allergies.

“Having a reported penicillin allergy not only decreases the likelihood that patients will be prescribed a penicillin when indicated, but very often, a penicillin allergy history will decrease the chance that a patient will be prescribed other beta-lactam drugs,” Kimberly G. Blumenthal, MD, MSc, quality and safety officer for allergy at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Infectious Disease News. “Together, this increases the risk of Clostridioides difficile infection, other hospital associated infections, and antibiotic resistance.”

Writing in Infection Control & Hospital Epidemiology, Blumenthal and colleagues explained that up to 15% of hospitalized patients report an allergy to beta-lactam antibiotics, which impacts acute-care antibiotic prescribing. Blumenthal noted that among the approximately 10% of patients in the United States who report a penicillin allergy, most will tolerate penicillin and related beta-lactams after evaluation.

Between April 2016 and December 2017, the researchers evaluated beta-lactam antibiotic test-dose outcomes within a large health care system that included two academic and three community acute-care hospitals.

“The intervention uses a guideline and clinical decision support tools to help nonspecialist providers perform test doses, a type of drug challenges where a drug is given under observation to demonstrate tolerance,” Blumenthal explained.

They assessed adverse drug reactions (ADRs), hypersensitivity reactions (HSRs) and EHR allergy record updates.

According to the study, Blumenthal and colleagues identified 1,046 test doses. Of those, 77% were identified as being to cephalosporins, 14% to penicillins and 9% to carbapenems. ADR signs and symptoms were reported by 7.5% of patients (95% CI, 5.9%-9.2%), and confirmed HSRs were reported for 3.8% (95% CI, 2.8%-5.2%). Most — 68% — of HSRs occurred at the second step of the test-dose procedure, when the patient received a full dose, the researchers reported. Of these, 58% required no treatment beyond discontinuing the drug, but three patients did require intramuscular epinephrine. The researchers found increased odds of HSR associated with a reported cephalosporin allergy history (OR = 2.96; 95% CI, 1.34-6.58).

“The guideline does not overly rely on penicillin skin testing — only 4% of test doses were

preceded by the penicillin skin test — which can be challenging to routinely perform in inpatients due to short length of stay and patient schedules,” study author Paige G. Wickner, MD, MPH, medical director of quality and safety at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School, told Infectious Disease News. “To date, this guideline has been used at nine Partners HealthCare-affiliated sites, including many with no staff allergy and immunology support.”

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Erica Shenoy MD, PhD
Erica Shenoy

The researchers encouraged EHR documentation to “improve this safe, effective, and practical acute-care antibiotic stewardship tool.”

“Allergy documentation strategies to improve the effectiveness of acute-care beta-lactam allergy interventions are needed,” study author Erica Shenoy MD, PhD, assistant chief of infection control at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Infectious Disease News. – by Marley Ghizzone

Disclosures: Blumenthal reports receiving royalties from UpToDate and honoraria from New England Society of Allergy, Dartmouth Medical School, and Vanderbilt Medical School, outside the submitted work. Blumenthal and Shenoy report a licensed clinical decision support tool for beta-lactam allergy evaluation that is used institutionally at Partners HealthCare System. Wickner reports no relevant financial disclosures.

    Perspective

    Every day in health care, we are faced with the patient who presents with a beta-lactam allergy. Penicillin allergies specifically are reported in approximately 10% of the population, and even higher rates are reported in patients who present to the hospital. It is also known that 90% of these allergies are not true allergies. The biggest question is how to properly assess and treat these patients when many times a subjective history is all that is available. Using available resources to stratify interventions in these patients would allow for optimal therapy in many cases, as well as avoidance of unnecessary or broad-spectrum therapy.

    In this study, Blumenthal and colleagues incorporate allergy intervention for patients presenting with a beta-lactam allergy into daily antimicrobial stewardship activities. Patients received test doses of penicillin or cephalosporin and overall less than 4% of patients had a hypersensitivity reaction. Of interest, most of these test doses were ordered and performed by nonallergists. This was in spite of the fact that 20% of patients reported a severe immunoglobulin E-mediated history in the penicillin group.

    Many facilities are challenged with the Infectious Diseases Society of America recommendation to incorporate beta-lactam allergy evaluation as part of antimicrobial stewardship. Penicillin skin testing is recommended where appropriate, but it can be challenging from a logistical and financial perspective at some facilities. A thorough allergy history with either a full-dose or test-dose challenge is appropriate in many situations.

    Beta-lactam allergy evaluation should be a part of all antimicrobial stewardship programs. It is hoped that continued real-world data from a study such as this one will continue to support broad tools to be created to standardize how patients who present with a beta-lactam allergy are treated.

    • Bruce M. Jones, PharmD, BCPS
    • Infectious diseases clinical pharmacy specialist,
      St. Joseph's/Candler Health System
      Clinical adjunct assistant professor,
      University of Georgia College of Pharmacy

    Disclosures: Jones reports receiving grant funding from and consulting for ALK-Abelló.