Patient information: Allergy to penicillin and related antibiotics

PENICILLIN ALLERGY OVERVIEW — Serious allergies to penicillin are common, with about 10 percent of people reporting an allergy. However, about 90 percent of people who believe they are allergic can take penicillin without a problem, either because they were never truly allergic or because their allergy to penicillin diminished and resolved over time.

People who have a remote history of allergic reaction to a medication may become less allergic as time passes. Only about 20 percent of people will be allergic to penicillin 10 years after their initial allergic reaction if they are not exposed to it again during this time period.

WHAT IS PENICILLIN? — Penicillin is one of the most commonly prescribed antibiotics. It is part of a family of antibiotics known as beta lactams. Penicillins can be classified into the following categories: Penicillin G (also known as benzylpenicillin) Anti-staphylococcal penicillins (nafcillin, oxacillin, cloxacillin and dicloxacillin) Broad spectrum penicillins

- Second generation (ampicillin, amoxicillin and related agents)
- Third generation (carbenicillin and ticarcillin)
- Fourth generation (piperacillin)


Anyone who is allergic to one of the penicillins is allergic to all penicillins. One of the major differences among the penicillins is the range of bacteria against which they are active. Penicillin G and the anti-staphylococcal penicillins treat a small number of specific bacteria. On the other hand, the second, third, and fourth generation penicillins are capable of treating a wide range of bacteria, and are therefore called "broad spectrum".

REACTIONS TO PENICILLIN — A variety of unexpected reactions can occur after taking penicillin.

Adverse reactions — "Adverse reaction" is the medical term for any undesirable reaction caused by a medication. Allergic adverse reactions are less common than non-allergic adverse reactions. Stomach upset and diarrhea are examples of non-allergic adverse reactions.

It is important to distinguish non-allergic adverse reactions from true allergic reactions. Some people report that they are allergic to penicillin when actually they have had a non-allergic side effect. As a result, the person may be treated for a particular infection with a less-effective or more toxic antibiotic. This can lead to antibiotic failure or resistance, which can be costly and prolong illness.

When reporting past problems with antibiotics, it is important to provide as much detail as possible about the reaction. Anyone who is uncertain if a past allergic reaction was truly caused by allergy should avoid the antibiotic until they have discussed the situation with their healthcare provider.

Rashes — Several different types of rashes can appear while people are taking penicillin. Rashes that involve hives (raised, intensely itchy spots that come and go over hours, show picture 1) suggest a true allergy.

However, some people, especially young children, can develop flat, blotchy rashes that spread over days but do not change by the hour (show picture 2). These rashes typically start after several days of treatment. This type of rash is less likely to indicate a dangerous allergy, although it can be difficult to distinguish between different types of rashes that occurred in the past. Taking a photograph of a rash is always helpful.

Allergic reactions — An allergic reaction occurs when the immune system begins to recognize a drug as something "foreign". Several different symptoms can indicate that a person is allergic to penicillin. These include hives (raised, intensely itchy spots that come and go over hours) (show picture 1), angioedema (swelling of the tissue under the skin, commonly around the face), wheezing and coughing from asthma-like reactions (narrowing of the airways into the lungs).

A past history of these types of reactions is important because the person might develop a more severe reaction, such as anaphylaxis, if they were to take the antibiotic again. Mild to moderate allergic reactions to penicillins are common, occurring in 1 to 5 percent of people.

Anaphylaxis — Anaphylaxis is a sudden, potentially life-threatening allergic reaction. Symptoms include those of an allergic reaction, as well as very low blood pressure, difficulty breathing, abdominal pain, swelling of the throat or tongue, and/or diarrhea or vomiting. Fortunately, anaphylaxis is uncommon. (See "Patient information: Anaphylaxis symptoms and diagnosis").

PENICILLIN ALLERGY TESTING — In some situations, it is necessary to determine with certainty if a person is allergic to penicillin. Testing for allergy is recommended in the following situations: People who have a suspected penicillin (or closely related antibiotic) allergy and require penicillin to treat a life-threatening condition for which no alternate antibiotic is appropriate. People who have frequent infections but have suspected allergies to many antibiotics, leaving few options for treatment. Penicillin skin testing is suggested for anyone with a history of penicillin allergy (when penicillin skin test solutions become commercially available again). Because 90 percent of people will test negative, this type of evaluation can decrease medical costs and reduce the use of unnecessarily strong (ie, broad-spectrum) antibiotics.

Penicillin skin testing does not provide any information about certain types of reactions. This includes anyone who has experienced a severe reaction with extensive blistering and peeling of the skin (Stevens-Johnson syndrome or toxic epidermal necrolysis), a widespread sunburn-like reaction that later peeled (erythroderma), or a rash composed of small bulls-eyes or target-like spots (erythema multiforme),
People with these types of reactions should never again be given the medication that caused the reaction. This applies to all situations since a second exposure could cause a severe progressive reaction and even death.

Skin testing — Skin testing is the most reliable method to determine the risk of a serious, sudden onset allergic reaction in a person with a history of allergy to penicillin.

Several different types of penicillin preparations are required for skin testing. These preparations can be manufactured commercially but are not currently available in the United States. Thus, the most reliable type of skin testing for penicillin allergy cannot be performed in the United States at this time. It is expected that the preparations will be available again within the next 12 to 24 months.

Until skin tests are available, options for people who may be allergic to penicillin include: Take an different antibiotic Undergo a challenge test (See "Challenge testing" below) Undergo desensitization (See "Penicillin desensitization" below)

Skin testing procedure — Skin testing should be done by an allergist in an office or hospital setting. Testing usually takes less than one hour to complete. The skin is pricked with weak solutions of the various preparations of penicillin and observed for a reaction. This may cause discomfort due to itching, but it is not painful. If there is no skin reaction, slightly stronger solutions are then used.

A positive skin reaction is an itchy, red bump that lasts about half an hour and then resolves. The testing is stopped if a skin reaction occurs since this indicates that the person is truly allergic.

If the patient completes the skin testing without a positive reaction, a single oral dose of full strength penicillin is commonly given. This confirms that the patient does not have an allergy to the medication. The oral dose is given since there is a very small risk of false negative results (when the skin test is negative although the person is actually allergic).

Interpreting results — Medical tests, including skin testing, are rarely 100 percent accurate. Most people with a positive penicillin skin test will experience an allergic reaction if given penicillin or a related antibiotic (as would be expected). However, 3 percent or less of people with a history of penicillin allergy and a negative skin test will experience an allergic reaction. These reactions are always mild, and anaphylaxis in this situation is rare.

If a person has a negative skin test and has no reaction to an oral dose of the antibiotic, no future precautions are necessary.

Challenge testing — Because skin testing is not currently available in many places, a healthcare provider may recommend a challenge test. However, this is only recommended if the person requires penicillin, no other antibiotic is available, and the chances of a true allergy are small (eg, last reaction was at least 10 years ago or allergic reaction symptoms not likely caused by true allergy). If the chances of a true allergy are high, desensitization is generally recommended.

Challenge testing is usually done in an office setting, starting with a very small dose of the antibiotic given by mouth. If the person tolerates the smallest dose, a larger dose is given every 30 to 60 minutes until he/she has signs of an allergic reaction or the full dose is given. If the person tolerates the full dose, he or she is not allergic to the antibiotic.

PENICILLIN DESENSITIZATION — Desensitization can be done for people who are truly allergic to penicillin but require treatment with it or a closely related antibiotic. Desensitization refers to a process of giving a medication in a controlled and gradual manner, which allows the person to tolerate it temporarily without an allergic reaction.

Technique — Desensitization can be performed with oral or intravenous medications, but should always be performed by an allergy specialist. There are different techniques for desensitization. Some patients undergo desensitization in an outpatient clinic under supervision while others are treated in an intensive care unit.

Limitations — While usually successful, desensitization has two important limitations. Desensitization does not work and must never be attempted for certain types of reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma, and erythema multiforme). Desensitization also does not work for other types of immunologic reactions to antibiotics, such as serum sickness, drug fever, or hemolytic anemia. Desensitization is temporary. A person is unlikely to have an allergic reaction to the medication during treatment, after undergoing desensitization, as long as the antibiotic is taken regularly. However, once the antibiotic is stopped for more than 24 hours (times differ slightly for different medications), the person is again at risk for a sudden allergic reaction. Repeat desensitization is required if the same medication is needed again.

OTHER ANTIBIOTIC ALLERGIES — Reliable skin tests are not commercially available for some antibiotics. Thus, determining if a person has an allergy to these antibiotics is more difficult, and is mostly based on the history of the reaction. Skin testing with other antibiotics is sometimes performed, but the results are much less certain than those of penicillin testing.

Cephalosporins — Cephalosporins are a class of antibiotics closely related to penicillin. There are a number of cephalosporin medications available, a few of which include cephalexin (Keflex®), cefaclor (Ceclor®), cefuroxime (Ceftin®), cefadroxil (Duricef®) , cephradine (Velocef®). cefprozil (Cefzil®), loracarbef (Lorabid®), ceftibuten (Cedax®), cefdinir (Omnicef®), cefditoren (Spectracef®), cefpodoxime (Vantin®) and cefixime (Suprax®).

People with a history of penicillin allergy have a small risk of having an allergic reaction to cephalosporins. If possible, penicillin skin testing should be performed in these individuals. Since testing will be negative in about 90 percent of these people, a negative test will allow them to take cephalosporins safely. People with a positive skin test to penicillin have a small risk of an allergic reaction to cephalosporins and may require more caution in terms of how the cephalosporin is administered.

Allergic reactions to cephalosporins are less common than reactions to penicillin. In addition, skin testing to evaluate cephalosporin allergy is not as accurate as penicillin skin testing. If a cephalosporin is required, then there are several options: Take an different antibiotic Undergo a challenge test (See "Challenge testing" above) Undergo desensitization (See "Penicillin desensitization" above)

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include: