Penicillin and other antibiotics are the most common source of drug allergies. Penicillin belongs to a family of antibiotic drugs known as beta–lactam antibiotics. Individuals who are allergic to one type of penicillin are usually allergic to them all (e.g., amoxicillin, ampicillin). Additionally, some people may also be allergic to the family of antibiotics known as cephalosporins (e.g., cefazolin, cephalexin), which are chemically similar to penicillins.

Penicillins are normally used to treat:

• Infectious diseases (e.g., pneumonia, tuberculosis)
• Infections of the ears, nose and throat
• Respiratory and urinary tract infections
• Prostate infections
• Sexually transmitted diseases

An allergic reaction to penicillin occurs when the drug enters the body, usually orally (a pill or liquid), intravenously (an injection) or intramuscularly (injection into a muscle). A reaction is triggered when the immune system overreacts to the penicillin, mistaking it for a dangerous substance. To combat the drug, the immune system releases IgE antibodies into the bloodstream. These antibodies interact with mast cells and basophils, and trigger these to release histamines and other chemicals.

It is the histamines and other chemicals that stimulate allergy symptoms. By causing blood vessels to swell and individual cells to leak fluid, histamines produce allergy symptoms such as itchiness, rash, hives, stomach cramps, nausea and respiratory problems. Individuals who are highly susceptible to allergic penicillin reactions can go into life–threatening anaphylactic shock, which involves difficulty breathing and lowered blood pressure.

People who suspect that they are having an allergic reaction to penicillin should immediately contact a physician. If the reaction is severe, a person should promptly contact 911 for medical help. 

The U.S. Department of Health and Human Services estimates that over 400 Americans are killed each year from anaphylactic reactions to penicillin.

It is unknown why some individuals develop penicillin allergies, while others do not. However, some experts believe heredity may be a factor.

People with allergies to penicillin generally find their reactions decrease over time. The American Academy of Allergy, Asthma and Immunology estimates that only 20 percent of individuals who have an allergic reaction to penicillin are susceptible to penicillin 10 years later (provided there is no exposure during that time period). However, individuals who have an allergic reaction to penicillin are generally advised to never use the medication again for precautionary reasons. Physicians can usually use a different form of antibiotic to treat any problems.