Background: Skin testing of subjects with immediate hypersensitivity to amoxicillin
is performed using major and minor determinants of benzylpenicillin plus amoxicillin.
However, sensitivity is not optimal, and other determinants need to be considered.
We assessed the sensitivity of stable, well-characterized minor determinants of
amoxicillin in subjects with immediate allergic reactions to amoxicillin to improve
skin test sensitivity.
Methods: Amoxicillin, amoxicilloic acid, and diketopiperazine were prepared and
characterized by reverse-phase HPLC, tested in vivo by skin testing and in vitro by
basophil activation test and RAST inhibition assay.
Results: Patients with immediate hypersensitivity to amoxicillin were selected: Group
A (n = 32), skin test positive just to amoxicillin; Group B (n = 19), skin test positive
to benzylpenicillin determinants; Group C (n = 10), skin test negative and
amoxicillin drug provocation test positive. In Group A, 27 subjects (81.8%) were
skin test positive to amoxicillin, ten (30.3%) to amoxicilloic acid, two (6.1%) to
diketopiperacine, and six (18.2%) negative. In Group B, nine (50%) were positive
to amoxicillin, eight (42.1%) to amoxicilloic acid, none to diketopiperacine, and
nine (50%) negative. In Group C, skin tests were negative. BAT was positive to
amoxicillin in 26 patients (50.9%), to amoxicilloic acid in 15 (29.1%), and diketopiperazine
in four (7.8%). RAST inhibition studies showed > 50% inhibition in all
sera, with the highest concentration of amoxicillin and amoxicilloic acid.
Conclusions: The combination of minor determinants of amoxicillin, amoxicilloic
acid, and diketopiperazine seems to be of no greater value than the use of amoxicillin
alone. Further efforts are needed to find new structures to improve sensitivity in
the diagnosis of immediate hypersensitivity to betalactams.
