Using beta-lactam antibiotics in patients with a history of beta-lactam allergy: current concepts

Abstract

ABSTRACTβ-lactams are the most widely used antibiotic family, but they are also the most common cause of drug-induced hypersensitivity reactions. The estimated prevalence of reported penicillin allergy ranges between 9% and 12%, although a high percentage of patients with a history of penicillin allergy have no subsequent reactions on reexposure to β-lactams. A self-reported penicillin allergy has been associated with antimicrobial resistance, increased cost, intensive care admission, and death, making it essential to establish an accurate diagnosis. In addition to a thorough clinical history, diagnostic methods include skin tests, in vitro tests, and drug-challenge tests. In this review, the diagnosis and management of patients with self-reported penicillin allergy is discussed, including the recently introduced antimicrobial stewardship strategy.REVIEW ARTICLE Use of β-lactam antibiotics in patients with a history of β-lactam allergy 541Antigenic determinants of β-lactams Penicillins and βlactams are generally considered immuno logically haptens and need to bind to carrier mol ecules to acquire complete immunogenic poten cy. The binding of the antibiotic to amino groups of autologous proteins induces a conformational modification that causes the immune system to recognize them as strange. The βlactam rings and the side group are all potentially immunogenic.Penicillins have been the most studied antibiot ics. The βlactam ring is intrinsically reactive and does not need prior metabolism. The instability of its structure makes it open quickly, allowing the carbonyl groups to form amidetype linkages with the amino groups of the lysine residues of the nearby proteins. 26 As approximately 95% of the penicillin molecules are bound to proteins in this manner, the antigenic determinant formed, benzylpenicilloyl (BPO), has been known as the major antigenic determinant of penicillin. BPO has been attached to a weakly immunogenic car rier molecule, called polylysine, to form benzyl penicilloyl polylysine (BPOPPL), which is used in making skin tests. The remaining part of the penicillin molecule degrades to a range of deriv atives which can also act as haptens. 27 These are minor determinants accounting for allergic reac tions in approximately 10% to 20% of patients. 23 The minor determinant mixture (MDM) has been also used in skin tests.The progressive increase in the consumption of amoxicillin (AX) has led to an increase in the detection of patients allergic to AX who tolerate benzylpenicillin (BP).28 These reactions are called selective reactions to AX. The major antigenic de terminant of AX is the amoxicilloyl amide, which results from the opening of the βlactam ring by amino groups. 29 Although the structure of the possible antigen ic elements of cephalosporins is not well known, different experimental studies have proved that they can generate structures able to provoke spe cific immune response. 30 IgE antibodies that re act with cephalosporins have been shown to de tect a wide range of specificities, although the f...

Antibiotic Skin Testing in the Intensive Care Unit: A Systematic Review

“…Articles included in the review (n = 23) adverse events. 18 Similarly, Moreno et al 19 emphasized the importance of allergy history in the diagnosis of b-lactam allergy. In contrast, other interventional studies indicated that patient-reported penicillin allergies can be unreliable and may result in needless changes in antibiotic therapy.…”

“…Thus, some researchers concluded that PST to confirm or rule out penicillin allergy should be a routine procedure. 19,23 If the allergy to penicillin is ruled out, patients can receive b-lactam antibiotics. 19,23,24 However, if the allergy to penicillin is confirmed, patients will be given non-b-lactam antimicrobials.…”

“…19,23 If the allergy to penicillin is ruled out, patients can receive b-lactam antibiotics. 19,23,24 However, if the allergy to penicillin is confirmed, patients will be given non-b-lactam antimicrobials. 19,23 Many studies suggest that PST is a safe, reliable, and effective strategy to rule out penicillin allergy and reduce the use of non-b-lactam antibiotics in patients who are labeled as penicillin allergic.…”

“…19,23,24 However, if the allergy to penicillin is confirmed, patients will be given non-b-lactam antimicrobials. 19,23 Many studies suggest that PST is a safe, reliable, and effective strategy to rule out penicillin allergy and reduce the use of non-b-lactam antibiotics in patients who are labeled as penicillin allergic. 14,19,23,24 Furthermore, antibiotic skin testing has been found to be safe for use in the pediatric population to rule out or confirm antibiotic allergy.…”

“…19,23 Many studies suggest that PST is a safe, reliable, and effective strategy to rule out penicillin allergy and reduce the use of non-b-lactam antibiotics in patients who are labeled as penicillin allergic. 14,19,23,24 Furthermore, antibiotic skin testing has been found to be safe for use in the pediatric population to rule out or confirm antibiotic allergy. 25 In addition, PST can be performed safely in pregnant women.…”