Roland Solensky, MD
N Franklin Adkinson, Jr, MD
Anna M Feldweg, MD
Disclosures
PENICILLIN ALLERGY OVERVIEW — Serious allergies to penicillin are common, with about 10 percent of people reporting an allergy. However, most 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 has 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, and there are many individual medications in this family: Penicillin G, nafcillin, oxacillin, cloxacillin and dicloxacillin, ampicillin, amoxicillin, carbenicillin, ticarcillin, and piperacillin.
Anyone who is allergic to one of the penicillins should be presumed to be allergic to all penicillins and should avoid the entire group, unless they have been specifically evaluated for this problem.
REACTIONS TO PENICILLIN — A variety of unexpected reactions can occur after taking penicillin. When reporting past problems with antibiotics, it is important to provide as much detail as possible about the reaction.
Adverse reactions — “Adverse reaction” is the medical term for any undesirable reaction caused by a medication. Both allergic and nonallergic adverse reactions can occur. Nonallergic reactions are much more common. Examples of common nonallergic adverse reactions include upset stomach and diarrhea.
It is important to distinguish nonallergic adverse reactions from true allergic reactions. Some people report that they are allergic to penicillin when actually they have had a nonallergic 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.
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 a penicillin medication:
- Rashes that involve hives (raised, intensely itchy spots that come and go over hours), or occur with other allergic symptoms like wheezing or swelling of the skin or throat, suggest a true allergy (picture 1).
- Rashes that are flat, blotchy, spread over days but do not change by the hour are less likely to represent a dangerous allergy (picture 2). These rashes typically start after several days of treatment.
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) (picture 1), angioedema (swelling of the tissue under the skin, commonly around the face), throat tightness, wheezing, coughing, and trouble breathing 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 occur 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 — Skin testing for penicillin allergy is the most reliable way to determine if a person is truly allergic to penicillin. Approximately ninety percent of people will test negative (meaning they do NOT have a penicillin allergy), because they either lost the allergy over time, or they were never allergic in the first place. There are some situations in which penicillin, which is generally safe and inexpensive, would be a suitable antibiotic, but a person with possible allergy is given a stronger drug with more side effects because their allergic status is unclear. Therefore, determining if someone can safely take penicillin can be useful.
Testing for penicillin allergy is especially important 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 and have suspected allergies to many antibiotics, leaving few options for treatment.
Penicillin skin testing does NOT provide any information about certain types of reactions. This includes severe reactions 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 should be done by an allergist in an office or hospital setting. Testing usually takes about one hour to complete. The skin is pricked and injected with weak solutions of the various preparations of penicillin and observed for a reaction. This may cause discomfort due to itching, although it is not painful.
A positive skin reaction is an itchy, red bump that lasts about half an hour and then resolves. A positive test indicates that the person is truly allergic. People with a positive test should continue to avoid penicillins.
If the patient completes the skin testing without a positive reaction, a single oral dose of full strength penicillin is commonly given to confirm that the patient does not have an allergy to the medication. The oral dose is needed because medical tests, including skin testing, are rarely 100 percent accurate. About three percent or less of people with a history of penicillin allergy and a negative skin test will still experience an allergic reaction. However, these reactions are very mild. If a person has a negative skin test and has no reaction to an oral dose of the antibiotic, no future precautions are necessary.
If skin testing is NOT available, options for people who may be allergic to penicillin include:
- Take a different antibiotic
- Undergo a challenge test (see ‘Challenge testing’ below)
- Undergo desensitization (see ‘Penicillin desensitization’ below)
Challenge testing — If skin testing is not available, 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 (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma, erythema multiforme, and some others). 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 a 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.
This article will be updated as needed every four months on our web site (www.uptodate.com/patients).
Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient Level Information:
Patient information: Anaphylaxis symptoms and diagnosis
Professional Level Information:
Allergy to penicillins
Anaphylaxis: Rapid recognition and treatment
Fatal anaphylaxis
Hypersensitivity vasculitis in adults
Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams
The following organizations also provide reliable health information.
- American Academy of Allergy Asthma and Immunology
(www.aaaai.org/patients/publicedmat/tips/adversereactions.stm)
- National Library of Medicine
(www.nlm.nih.gov/medlineplus/ency/article/003519.htm)
- Mayo Clinic
(www.mayoclinic.com/health/penicillin-allergy/DS00620)
REFERENCES
- Solensky R, Earl HS, Gruchalla RS. Clinical approach to penicillin-allergic patients: a survey. Ann Allergy Asthma Immunol 2000; 84:329.
- Solensky R. Drug desensitization. Immunol Allergy Clin North Am 2004; 24:425.
- Forrest DM, Schellenberg RR, Thien VV, et al. Introduction of a practice guideline for penicillin skin testing improves the appropriateness of antibiotic therapy. Clin Infect Dis 2001; 32:1685.
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