Do you need to do a skin test for penicillin and cephalosporin? See what the authorities say!

Penicillin and cephalosporin are both β-lactam antibiotics, which are the most widely used and clinically valuable antibiotics. Due to the limitations of anti-infective drug selection for children, especially neonates, β-lactam antibiotics are more widely used in children's infectious diseases. However, this type of drug has the risk of inducing severe allergic reactions, and children often have a history of drug and food allergies, eczema, etc. Therefore, β-lactam antibiotics are widely used in various medical institutions, especially children's hospitals, to predict allergic reactions before medication.

However, how important is the skin test? A negative skin test means that there will be no allergic reaction during medication, but a positive skin test means that the drug cannot be used? Recently, the National Health Commission issued the "Guidelines for Skin Testing of β-lactam Antimicrobial Drugs (2021 Edition)" (hereinafter referred to as the "Guidelines"), which standardizes the skin testing of β-lactam antimicrobial drugs. Let's learn about it together today!

1. Purpose of skin testing

The main purpose of skin testing for β-lactam antibiotics is to predict the possibility of type I (immediate) allergic reaction by detecting whether the patient has specific IgE antibodies against this type of drug and its metabolites and degradation products in the body, thereby reducing the risk of severe allergic reactions such as anaphylactic shock.

[Tips: Type I allergic reaction, also known as immediate allergic reaction, is the most common human immune response in clinical practice. Its characteristic is that when the body is exposed to the same allergen for the second time, symptoms often appear within seconds or minutes. If the treatment is timely at this stage, the symptoms will disappear quickly. The occurrence of type I allergic reaction has obvious individual differences, but it can often cause anaphylactic shock. ]

Penicillin skin test is currently the most rapid, sensitive and effective detection method for predicting penicillin immediate allergic reaction. Studies have shown that through a complete and standardized skin test diagnostic method, the positive predictive value of penicillin skin test is 50%, and the negative predictive value is 70% to 97%.

The decomposition products of cephalosporins have not been fully identified. So far, no cephalosporin skin test reagents have been approved for marketing, and the sensitivity, specificity, positive predictive value and negative predictive value of the skin test have not been determined.

2. Which β-lactam antibiotics require skin testing before use?

1. Penicillins: Currently, the instructions for use of penicillins in my country, the "Guidelines for the Clinical Application of Antimicrobial Drugs" and the "Guidelines for Clinical Use of Drugs in the Pharmacopoeia of the People's Republic of China" all require a routine penicillin skin test before using penicillins.

2. Cephalosporins: The Guidelines do not recommend routine skin testing before using cephalosporins. Skin testing is only required in the following situations:

① Patients with a clear history of penicillin or cephalosporin type I (immediate-type) allergy. If such patients really need to use cephalosporins in clinical practice and have professional personnel and emergency conditions, after obtaining the patient's informed consent, a cephalosporin with a side chain different from that of the allergic drug can be used for skin testing, and the results have a certain reference value.

② If the drug instructions require a skin test, the drug provider should be consulted to learn more about the mechanism of drug-induced allergic reactions, the sensitivity, specificity, positive predictive value and negative predictive value of the skin test, and request the provision of the corresponding skin test reagents.

Note: Patients with a history of allergic diseases, such as allergic rhinitis, allergic asthma, atopic dermatitis, food allergies, and allergies to other drugs (non-β-lactam antibiotics) are not more likely to be allergic to cephalosporins than the general population, and routine skin tests are not required before using cephalosporins. However, if the above patients have an allergic reaction after taking the drug, the symptoms may be more severe, and observation after taking the drug should be strengthened.

3. Other β-lactams:

① For penicillins and cephalosporins, the indications and methods for skin tests of β-lactamase inhibitor combination preparations can refer to those of penicillins and cephalosporins, respectively.

② There is no evidence-based medical evidence to support the predictive effect of skin tests on other β-lactam antibiotics such as monocyclics, cephalosporins, oxacephems, carbapenems, and penems, so skin tests are not required routinely before administration. If the instructions for these types of drugs require skin tests before use, refer to cephalosporins.

③The side chain structure of aztreonam is the same as that of ceftazidime at C7. Studies have reported that there is cross-allergy between the two. Patients with a clear history of ceftazidime allergy should avoid using aztreonam.

Because skin tests cannot predict non-IgE-mediated delayed allergic reactions, and because of limited sensitivity and lack of routine positive controls, a negative skin test cannot completely rule out the possibility of an allergic reaction. Therefore, even if the skin test is negative, close observation is still required during drug use, and emergency preparations for allergic reactions should be made.

3. It is more important to ask about the allergy history in detail

Skin test is only one of the measures to prevent allergic reactions, and its predictive effect is limited to IgE-mediated immediate allergic reactions caused by a few drugs. Prevention and reduction of the risk of allergic reactions should rely more on:

① Detailed inquiry and identification of allergy history;

② Close observation during medication;

③Equipped with allergic reaction rescue medicines and equipment;

④Medical staff are familiar with the treatment measures for severe allergic reactions.

As a medical staff, paying attention to the patient's detailed medical history is more helpful in guiding the risks of medication. As a patient or a parent of a sick child, you should inform the doctor of your past allergy history in detail before taking the medication, including the specific manifestations of allergies, so that the doctor can choose the appropriate medication plan. In addition, you need to pay attention to observation after taking the medication, especially 30 minutes after the first use of the medication. If you feel uncomfortable, inform the medical staff in time.

References:

[1] “Guidelines for Skin Testing of β-lactam Antimicrobial Drugs (2021 Edition)”

[2] Zhao Xin, Zhang Haixia, Cheng Qing, et al. Survey on the current status of skin testing of β-lactam antibiotics in China[J]. Journal of Pediatric Pharmacy, 2018, 24(11):30-34.