Evaluation and Management of Penicillin Allergy

Abstract

IMPORTANCE β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events.OBSERVATIONS Approximately 10% of the US population has reported allergies to the β-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (<5%). Currently, the rate of IgE-mediated penicillin allergies is decreasing, potentially due to a decreased use of parenteral penicillins, and because severe anaphylactic reactions to oral amoxicillin are rare. IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than the 8% reported previously. Some patients have a medical history that suggests they are at a low risk for developing an allergic reaction to penicillin. Low-risk histories include patients having isolated nonallergic symptoms, such as gastrointestinal symptoms, or patients solely with a family history of a penicillin allergy, symptoms of pruritus without rash, or remote (>10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Broad-spectrum antimicrobial agents also increase the risk of developing Clostridium difficile (also known as Clostridioides difficile) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources.CONCLUSIONS AND RELEVANCE Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship.

Sustaining and spreading penicillin allergy delabelling: A narrative review of the challenges for service delivery and patient safety

“…Although most studies have shown direct oral challenges to be safe (no documented anaphylaxis or serious delayed reactions), relatively mild cutaneous reactions after a direct oral challenge 30,40,43 occur, justifying a place for such an intervention in acute care hospitals with an immediate access to management of allergic reactions. 2,44 Caution and concern about potential false negative tests for those patients where the index drug is amoxicillin-clavulanic acid or flucloxacillin has also been raised, unless these antibiotics are used for the confirmatory challenges. 45 • Patient did want to take time (9.43)…”

“…Choice of antibiotic treatment depends on the infection and patient factors including their reported or documented allergy status. Penicillins are the first‐line antibiotics for many common infections and sepsis . Six to 10% of the general population and 15–20% of hospital inpatients in the UK and USA carry a penicillin allergy (PenA) label, although emergent research shows that 90–95% of these labels are found to be incorrect following comprehensive allergy testing .…”

“…Focus on antimicrobial stewardship (AMS) and concerns of inappropriate use of antimicrobials has led to greater interest in the impact of spurious PenA labels on clinical and operational outcomes, and a call for global action . Inaccurate PenA labels are a major barrier to AMS and a patient safety concern . Large cohort studies from UK and USA show that PenA labels enhance the risk of serious hospital acquired infections such as methicillin‐resistant Staphylococcus aureus , vancomycin‐resistant Enterococci and Clostridioides difficile infections .…”

“…Whilst these studies have generated proof of concept in favour of a direct oral penicillin challenge procedure for PenA delabelling, they were limited due to: relatively small sample size; little or no assessment of views and perspectives of healthcare professionals and patients regarding their confidence in embedding such an approach into routine clinical practice; lack of exploration of reasons for patients' unwillingness to consent to direct oral challenge or re‐expose to penicillins; and failure to update medical documentation with the outcome of the direct oral challenge. Although most studies have shown direct oral challenges to be safe (no documented anaphylaxis or serious delayed reactions), relatively mild cutaneous reactions after a direct oral challenge occur, justifying a place for such an intervention in acute care hospitals with an immediate access to management of allergic reactions . Caution and concern about potential false negative tests for those patients where the index drug is amoxicillin–clavulanic acid or flucloxacillin has also been raised, unless these antibiotics are used for the confirmatory challenges …”

“…lins are the first-line antibiotics for many common infections and sepsis. 1,2 Six to 10% of the general population 3 and 15-20% of hospital inpatients in the UK and USA carry a penicillin allergy (PenA) label, although emergent research shows that 90-95% of these labels are found to be incorrect following comprehensive allergy testing. 2,[4][5][6][7] Identification and removal of inaccurate and spurious PenA labels is referred to as delabelling.…”