Allergy to Penicillin

by Michael_Koger

Of all drug allergies which patients in the United States inform their physician, penicillin is the most common.

People in the United States report allergy to penicillin more commonly than any other medication. However, not all of them are truly sensitive to that drug. The reports suggest that a tenth of the general population in that country cannot tolerate this well-known antibiotic, but clinical observation shows that hypersensitivity is less present than that [1, 2].

In fact, those who are really allergic to it eventually lose their sensitivity with the passage of time [1]. Within five years of an immediate hypersensitivity immune response from penicillin, nearly half of these clients will be able to tolerate administration of the antibiotic. Ten years after this type of immune response to that medication, four-fifths will be able to receive it without the occurrence of an allergic reaction [1].

Cross-Reactivity with Other Agents

There are many antibiotics with chemical structures similar to that of penicillin, and this may lead to cross-reactivity in which the penicillin allergic client cannot tolerate the other antibiotics.  Cephalosporins are an example of this, and it has to do with the beta-lactam ring of the chemical structure which is present in both agents [1]. 

Aminopenicillins, monobactams, and carbapenems also carry the beta-lactam ring in their chemical structures and therefore can pose a risk for individuals who are allergic to penicillin.  Nevertheless, the cross-reactivity between penicillin and cephalosporins is not as common as physicians have believed.  The previous assumption has been that this cross-reactivity is 10 percent, but current research shows that it is three percent [1].

On the other hand, cross-reactivity between aminopenicillins and cephalosporins may range from 10 to 40 percent in those who cannot tolerate beta-lactam antibiotics [1].

It is possible to exclude the presence of allergy to the family of antimicrobial agents which have the beta-lactam ring.  Specifically, the absence of a hypersensitivity immune response upon the administration of some of these drugs will eliminate the possibility of allergy to any medication in that family [1].

Other Risk Factors for Allergic Reaction

The risk of allergic reaction to penicillin has to do with the frequency, amount, and mode of administration.  For example, intravenous infusion in high doses may increase the possibility of a hypersensitivity immune response.  Moreover, frequent doses increase the risk of reaction [1].

It is also true that the different types of cephalosporins will not have the same risk as each other.  First and second generation agents in this class of antimicrobials will present more risk of allergic reaction than those of the third or fourth generations [1].


The possibility of hypersensitivity immune response to penicillin or similar drugs is a complex question as many factors determine its occurrence.


  1. Gonzalez-Estrada, A.  M.D. and Radojicic, C. M.D.  (2015).  Penicillin allergy:  A practical guide for clinicians.  Cleveland Clinic Journal of Medicine, 82, 295-300.
  2. National Institute of Allergy and Infectious Diseases.  (2015).  Anaphylaxis.  Retrieved May 14, 2015.
  3. The photo shows allergen skin testing.  Reprinted with permission from Centers for Disease Control and Prevention/Dr. Frank Perlman/M.A. Parsons.


The information contained in this article is for educational purposes only and should not be used for diagnosis or to guide treatment without the opinion of a health professional. Any reader who is concerned about his or her health should contact their physician for advice.

Updated: 05/18/2015, Michael_Koger
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