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Original Article


Prospective, Multicenter Clinical Trial to Validate New Products for Skin Tests in the Diagnosis of Allergy to Penicillin


J Fernández,1 MJ Torres,2 J Campos,3 F Arribas-Poves,3 M Blanca,2 on behalf of the DAP-Diater group*

1Allergy Section, General University Hospital, UMH, Alicante, Spain
2Allergy Service, Carlos Haya Hospital, Málaga, Spain
3Research Unit, Diater laboratory, Madrid, Spain
*V Soriano, P Gamboa, A Vega, T Lobera, S Millán, L Sánchez, MI Montañez, C Martínez, E Moreno, J Quiralte, N Blanca-López, R González, MT Audícana, MA Padial, MJ Barasona, C Colas, M Boquete, B García, and MC García-Aviles

J Investig Allergol Clin Immunol 2013; Vol. 23(6): 398-408



Allergy to penicillin is the most commonly reported type of drug hypersensitivity. Diagnosis is currently confirmed using skin tests with benzylpenicillin reagents, ie, penicilloyl-polylysine (PPL) as the major determinant of benzylpenicillin and benzylpenicillin, benzylpenicilloate and benzylpenilloate as a minor determinant mixture (MDM).

Objective: To synthesize and assess the diagnostic capacity of 2 new benzylpenicillin reagents in patients with immediate hypersensitivity reactions to ß-lactams: benzylpenicilloyl octa-L-lysine (BP-OL) as the major determinant and benzylpenilloate (penilloate) as the minor determinant.

Methods: Prospective multicenter clinical trial performed in 18 Spanish centers. Efficacy was assessed by detection of positive skin test results in an allergic population and negative skin test results in a nonallergic, drug-exposed population. Sensitivity, specificity, and negative and positive predictive values were determined.

Results: The study sample comprised 94 allergic patients: 31 (35.23%) presented anaphylaxis, 4 (4.55%) anaphylactic shock, 51 (58.04%) urticaria, and 2 (2.27%) no specific condition. The culprit ß-lactams were amoxicillin in 63 cases (71.60%), benzypencillin in 14 cases (15.89%), cephalosporins in 2 cases (2.27%), other drugs in 3 cases (3.42%), and unidentified agents in 6 cases (6.82%). The results of testing with BP-OL were positive in 46 cases (52.3%); the results of testing with penilloate were positive in 33 cases (37.5%). When both reagents were taken into consideration, sensitivity reached 61.36% and specificity 100%. Skin testing with penilloate was significantly more often negative when the interval between the reaction and the study was longer.

Conclusions: The sensitivity of BP-OL and penilloate was 61%. Considering that amoxicillin was the culprit drug in 71% of reactions, these results indicate that most patients were allergic to the whole group of penicillins. These data support the use of benzylpenicillin determinants in the diagnosis of allergy to ß-lactams, even in predominantly amoxicillin-allergic populations.

Key words: Hypersensitivity. ß-Lactams. Penicillin determinants. Skin tests. Clinical trial.