Penicilloyl G

Code: c1

Clinical Utility

ImmunoCAP Allergen c1, Penicilloyl G, is intended as a diagnostic tool for detection of IgE sensitization to the major allergenic determinant of penicillin G, with potential cross-reactivity to other penicillins.

Allergen Description

Penicillin G (benzylpenicillin) is a natural antibiotic drug produced by industrial fermentation of Penicillium chrysogenum. Penicillins are small molecules that are not able to induce an immune response on their own. However, the β-lactam ring of penicillin is reactive and covalently binds to proteins, thereby forming hapten-carrier conjugates. Thus, penicillins react with primary amino groups in proteins to give penicilloyl amides, the major antigenic determinant of penicillin allergy (1), which is the allergen in ImmunoCAP Allergen c1, Penicilloyl G. 

Allergen Exposure

Drug therapy through parenteral administration is the main route of exposure to penicillin G.

Potential Cross-Reactivity

Extensive cross-reactivity exists between different penicillins. However, an increasing amount of evidence shows that side-chain specific reactions to especially amoxicillin have become more common (2). There are also occasional reports on specific reactions to penicillin V (3). Penicillins and cephalosporins cross-react to some extent, especially when the side-chains are identical (4).

Clinical Experience

The introduction of penicillin for treatment of bacterial infections in the 1940s was immediately followed by reports of allergic reactions. From a clinical view, penicillin allergic reactions can be classified as either immediate reactions occurring within one hour after the last penicillin administration, or as non-immediate reactions occurring at any time from 1 h to 48 h (5). Immediate reactions are usually IgE-mediated while non-immediate reactions are often induced by sensitized T cells. The longer the time before symptoms appear, the greater the possibility that a non-IgE mediated mechanism is involved. Immediate reactions are manifested clinically by urticaria, angioedema, rhinitis, bronchospasm and anaphylaxis. The main non-immediate reactions are various exanthema and delayed urticaria/angioedema.

The most comprehensive study on the performance of penicillin ImmunoCAP so far is the evaluation by Blanca and co-workers, who studied 129 patients in five groups. In the group with positive skin test to benzylpenicilloyl and amoxicillin, 68 % were positive to ImmunoCAP Allergen c1, Penicilloyl G (6). Skin testing, especially intradermal testing, has been reported to have higher sensitivity compared to in vitro testing in penicillin allergy, but the specificity of skin testing has recently been questioned. Thus, Goldberg and Confino-Cohen recently performed 137 oral challenges on patients with positive skin tests, and only 6 patients developed mild rashes in response to the challenge (7). 


  1. Levine BB, Price VH. Studies on the immunological mechanisms of penicillin allergy: II. Antigenic specificities of allergic wheal-and-flare skin responses in patients with histories of penicillin allergy. Immunology 1964; 36: 542-56.
  2. Blanca M, Mayorga C, Torres MJ, Warrington R, Romano A, Demoly P et al. Side chain specific reactions to betalactams: Twelve years later. Clin Exp Allergy 2002; 32: 192-7.
  3. Linares T, Marcos C, Gavilan M, Arenas L. Hypersensitivity to penicillin V with good tolerance to other β-lactams. J Investig Allergol Clin Immunol 2007; 17(1): 50-51.
  4. Antunez C, Blanca-Lopez N, Torres MJ, Mayorga C, Perez-Inestrosa, Montanez MI et al. Immediate allergic reactions to cephalosporins: Evaluation of cross-reactivity with a panel of penicillins and cephalosporins. J Allergy Clin Immunol 2006; 117(2): 404-10.
  5. Bousquet PJ, Kvedariene V, Co-Minh H-B, Martins P, Rongier M, Arnoux B et al. Clinical presentation and time course in hypersensitivity reactions to β-lactams. Allergy 2007; 62: 872-6.
  6. Blanca M, Mayorga C, Torres MJ, Reche M, Moya MC, Rodriguez JL et al. Clinical evaluation of Pharmacia CAP System RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy. Allergy 2001; 56: 862-70.
  7. Goldberg A, Confino-Cohen R. Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy. Ann Allergy Asthma immunol 2008; 100: 37-43.

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.