Allergic Reactions and Cross-Reactivity Potential with Beta-Lactamase Inhibitors

Abstract

Although beta-lactam allergies are an emerging focus of stewardship programs and interventions, less is publicly released regarding allergies to beta-lactamase inhibitors. This review presents and evaluates the data regarding allergic reactions with beta-lactamase inhibitors. Clavulanate, sulbactam, and tazobactam are beta-lactam-based beta-lactamase inhibitors that are combined with several penicillins or cephalosporins in order to preserve antimicrobial activity in the presence of beta-lactamases. Avibactam, relebactam, and vaborbactam are non-beta-lactam beta-lactamase inhibitors that are combined with cephalosporins or carbapenems in order to expand the antimicrobial activity against broader-spectrum beta-lactamases. Case reports document hypersensitivity reactions to clavulanate, sulbactam, and tazobactam, but not to avibactam, relebactam, or vaborbactam. Based on these reports and considering the chemical structures, cross-allergenicity with beta-lactams is likely with sulbactam and tazobactam. Considering the slightly altered beta-lactam structure, cross-allergenicity is less likely with clavulanate, but still possible. It appears that cross-allergenicity between beta-lactam antimicrobials and the newer, non-beta-lactam beta-lactamase inhibitors is unlikely. It is important for clinicians to perform allergy testing to both the beta-lactam and the beta-lactamase inhibitor in order to confirm the specific allergy and reaction type.

Prevalence of Antibiotic Allergy Labels in a Tertiary Referral Center in Belgium

“…Case reports also document hypersensitivity reactions to the BLI clavulanate (37,38), and one nonimmunological hypersensitivity reaction to tazobactam was previously reported (39,40). However, the latter is not tested separately in our center.…”

The Chemical Relationship Among Beta-Lactam Antibiotics and Potential Impacts on Reactivity and Decomposition

“…The low rate of cross-reactivity seen between penicillin and carbapenems (<1%), which possess a unique hydroxyethyl side chain, further supports the hypothesis that not only does the R 1 bioisosterism play a dominant role, but aromatic end group chemistry appears causative ( Romano et al, 2006 , 2007 ; Atanaskovic-Markovic et al, 2008 ; Gaeta et al, 2015 ; Buonomo et al, 2016 ). Although not utilized on their own as an antibacterial therapy, β-lactam based β-lactam inhibitors also have been implicated in allergic reactions ( Stover et al, 2019 ). The authors concluded that cross-allergenicity with β-lactams is likely with sulbactam and tazobactam.…”

Infection prevention requirements for the medical care of immunosuppressed patients: recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute

“…In haemato-oncology, professional associations have already developed comprehensive evidence-based guidelines for diagnosis and treatment in certain clinical situations involving infectious diseases, on which a local interdisciplinary ABS programme can be based. Immunosuppressed patients with a history indicating penicillin intolerance (but not clear immediate anaphylactic reactions) must undergo further evaluation to rule out a (very rare) penicillin allergy of the immediate type so as not to be unjustifiably denied the most effective treatment with penicillins or other beta-lactam antibiotics for their indication [ 422 ], [ 423 ], [ 424 ], [ 425 ], [ 426 ], [ 427 ], [ 428 ].…”