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Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics)

Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics)
Literature review current through: Apr 2024.
This topic last updated: Jan 11, 2023.

PENICILLIN ALLERGY OVERVIEW — Overall, about 10 percent of people report some type of unwanted reaction to penicillin, and serious and even fatal allergic reactions do occur. 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 resolved over time. Among people with a convincing history of severe penicillin allergy, only about 20 percent will be allergic to penicillin a decade after their initial allergic reaction if they are not exposed to it again during this time period.

WHAT IS PENICILLIN? — Antibiotics in the penicillin class are one of the most commonly prescribed antibiotics and include many individual medications, such as penicillin G, amoxicillin, nafcillin, oxacillin, dicloxacillin, flucloxacillin, ampicillin, carbenicillin, ticarcillin, and piperacillin-tazobactam. Penicillins are part of a larger family of antibiotics known as beta-lactams.

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 avoid drugs in the penicillin family and related antibiotics unnecessarily and 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 health care 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, and 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 taking the medication.

Anaphylaxis — Anaphylaxis is a sudden, potentially life-threatening allergic reaction. Symptoms include those of an allergic reaction, such as hives and swelling, 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. Anaphylaxis is uncommon in patients taking penicillin and other beta-lactam antibiotics and occurs in 0.0005% of people starting oral penicillins. (See "Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)".)

PENICILLIN ALLERGY TESTING — Skin testing for penicillin allergy is the most reliable way to determine if a person is truly allergic to penicillin. Approximately 90 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 to it in the first place. Research has shown that patients who are labeled penicillin allergic are more likely to receive antibiotics with a broad range of activity that are not indicated for the treatment of their particular infection. These types of "broad spectrum" kill both good and bad bacteria and have more side effects than simpler antibiotics. People labeled as allergic to penicillin are also more likely to develop certain difficult-to-treat resistant infections and require longer stays in hospitals compared with patients who do not report a history of penicillin allergy. 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 (eg, syphilis).

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 "bullseyes" 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 one-half 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 not 100 percent accurate. Also, future prescribing clinicians are reluctant to treat patients with penicillins solely based on negative skin testing. About 3 percent or less of people with a history of penicillin allergy and a negative skin test will still experience an allergic reaction at some point in the future, which is often of a different type from the original 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:

Taking a different antibiotic

Undergoing a challenge test (see 'Challenge testing' below)

Undergoing desensitization (see 'Penicillin desensitization' below)

Challenge testing — If skin testing is not available, a health care provider may recommend a challenge test. However, this is only recommended if the chances of a true allergy are small (eg, last reaction was at least 10 years ago and was limited to mild, non-hive skin rashes). This scenario is most commonly encountered in children, who often develop rashes from the underlying illness while taking amoxicillin. 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 small dose of the antibiotic given by mouth. If the person tolerates the smaller dose, a larger dose is given every 30 to 60 minutes until they have signs of an allergic reaction or the full dose is given. If the person tolerates the full dose, they are 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 based on the pharmacologic properties and half-life of the drug), 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 nonpenicillin 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, including cephalexin (brand name: Keflex), cefaclor (brand name: Ceclor), cefuroxime (brand name: Ceftin), cefadroxil (brand name: Duricef), cefprozil (brand name: Cefzil), ceftibuten (brand name: Cedax), cefdinir (brand name: Omnicef), cefpodoxime, and cefixime (brand name: Suprax). These medications are also sold under other brand names in different countries.

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 are at higher risk of an allergic reaction, particularly to some cephalosporins that share an additional part of their chemical structure with specific penicillins, and may require more caution in terms of how the cephalosporin is administered.

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 health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Penicillin allergy (The Basics)
Patient education: Anaphylaxis (The Basics)
Patient education: Angioedema (The Basics)
Patient education: What you should know about antibiotics (The Basics)
Patient education: Allergy skin testing (The Basics)
Patient education: Drug allergy (The Basics)
Patient education: Medication safety (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Anaphylaxis symptoms and diagnosis (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Penicillin allergy: Immediate reactions
Anaphylaxis: Emergency treatment
Fatal anaphylaxis
Overview of cutaneous small vessel vasculitis
Allergy evaluation for immediate penicillin allergy: Skin test-based diagnostic strategies and cross-reactivity with other beta-lactam antibiotics

The following organizations also provide reliable health information.

American Academy of Allergy, Asthma, and Immunology (AAAAI) (https://www.aaaai.org/Conditions-Treatments/Allergies/Drug-Allergy)

National Library of Medicine (medlineplus.gov/ency/article/003519.htm)

Mayo Clinic (www.mayoclinic.org/diseases-conditions/penicillin-allergy/symptoms-causes/syc-20376222)

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Disclaimer: This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms. 2024© UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.
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