Cephalosporins’ Cross-Reactivity and the High Degree of Required Knowledge. Case Report and Review of the Literature

Abstract

Antibiotic cross-reactivity represents a phenomenon of considerable interest as well as antibiotic resistance. Immediate reactions to cephalosporins are reported in the literature with a prevalence of only 1–3% of the population, while anaphylactic reactions are rarely described (approximately 0.0001–0.1%) as well as fatalities. Allergic reaction to cephalosporins may occur because of sensitization to unique cephalosporin haptens or to determinants shared with penicillins. Cross-reactivity between cephalosporins represents, in fact, a well-known threatening event involving cephalosporins with similar or identical R1- or R2-side chains. The present report describes the case of a 79-year-old man who suddenly died after intramuscular administration of ceftriaxone. Serum dosage of mast cell tryptase from a femoral blood sample at 3 and 24 h detected values of 87.7μg/L and 93.5μg/L, respectively (cut-off value 44.3 μg/L); the serum-specific IgE for penicillins, amoxicillin, cephaclor and also for the most common allergens were also determined. A complete post-mortem examination was performed, including gross, histological and immunohistochemical examination, with an anti-tryptase antibody. The cause of death was identified as anaphylactic shock: past administrations of cefepime sensitized the subject to cephalosporins and a fatal cross-reactivity of ceftriaxone with cefepime occurred due to the identical seven-position side chain structure in both molecules. The reported case offers food for thought regarding the study of cross-reactivity and the need to clarify the predictability and preventability of the phenomenon in fatal events.

Drug-Induced Anaphylaxis: National Database Analysis

“…Cephalosporins are associated with the full spectrum of HSRs and their immunogenicity is mainly defined by the presence of R1 side chains in the structure of the molecule [ 26 ]. Cephalosporins have been proven to be common triggers of ARs in adults and children [ 26 , 27 , 28 , 29 ], and third-generation agents including ceftriaxone were among the main inducers of allergic reactions reported in hospitals in South Korea [ 30 ]. An analysis of the Korean Adverse Event Reporting System (KAERS) and HIRA database revealed incidence rates for hypersensitivity reactions including anaphylaxis to cefaclor, other second-generation cephalosporins, and third-generation cephalosporins to be 1.17/10,000 persons (0.38/10,000 persons), 3.57/10,000 persons (0.38/10,000 persons), and 5.82/10,000 persons (0.61/10,000 persons), respectively [ 31 ].…”

Ceftriaxone-Induced Hemolytic Anemia: A Rare and Fatal Reaction

“…These reactions occur against the R1 side chain and, less commonly, the R2 chain. One case in 2020 reported a similar example of cephalosporin cross-reactivity where a patient was potentially sensitized by cefepime 10 months prior to a fatal episode of CTX-induced anaphylactic shock [ 12 ]. Similarly, our patient may have been sensitized to CTX after cefepime administration, thereby developing antibodies to the R1 side chain.…”

Potential Factors of Primary Hospital Healthcare Professionals in Hindering the Abolition of Routine Skin Test for Cephalosporin: A Cross-Sectional Study

“…5 Serious allergic shock due to cephalosporin is very rare, with rates of 0.0001%-0.1%, 2,3 and some deaths were even reported in extreme cases. [6][7][8] Due to their increasing use in hospitals, the number of reports concerning the adverse reaction of cephalosporin has also been increasing. Therefore, in most hospitals in China, especially primary hospitals where medical and pharmaceutical professional skill level are relatively low and training is relatively less, a routine skin test would be carried out before cephalosporin is administered, but whether the routine skin test is required before the use of cephalosporin is controversial.…”