It is clearly stipulated in the Instructions for Clinical Use that a penicillin skin test must be performed before penicillin sodium injection and is prohibited for positive reactions; and there is no provision for skin test for cephalosporins. It is also pointed out that cephalosporins can be used in patients who are allergic to penicillin. However, it should be used with caution after weighing the pros and cons. So, what kind of β-lactam antibiotics should be injected and how should they be tested? Is a skin test required? To discuss the need for skin testing, it is important to first understand the cause of allergy. Generally speaking, the allergens of β-lactam antibiotics can be divided into two categories, one is the protein peptide impurities remaining in the biosynthesis stage – exogenous allergens; the second is the residual in the chemical synthesis stage and its products after the β-lactam ring opening in the storage and use process through their own polymerization, generated by polymer – endogenous allergens. It has been found that penicillin itself is not an allergen, what causes allergy to patients is the impurities introduced during the production, storage and use process, such as penicillin thiazole and other polymers. The quality of their products varies from manufacturer to manufacturer, and even if different batches of products are produced successively by the same manufacturer, it is required to re-skin test penicillin when the batch number is changed because it is impossible to have all conditions identical in the process of production. In addition, the main antigenic determinant cluster in penicillin is the penicillothiazole group, and since different side chains of penicillin can form the same structural antigenic determinant cluster penicillothiazole group, strong cross-allergic reactions can occur between penicillin antibiotics. The cephalosporin β-lactam ring cannot form a stable cefotaxime group after ring opening, but generate different antigenic clusters with mainly side chains, so cross-allergic reactions between cephalosporins and penicillins are not possible as long as the side chains are different. How to skin test? Since there is a strong cross-allergic reaction between penicillin antibiotics, solid before using any other penicillin drugs can use penicillin skin test solution (50 ug/ml) for skin test, and positive reaction is prohibited. Since the allergenicity of cephalosporin antibiotics depends on their side chains, there is no cross-allergy if the side chains are different. And cephalosporins with the same side chain are not rare, and it is impossible to require physicians to master their structure. Therefore, it is recommended to use the original solution of its drug (300-500 ug/ml) for skin testing, which is prohibited in positive cases. Discussion Although the incidence of β-lactam allergy is low, it is extremely harmful because it is not related to the drug dosage and has a high mortality rate, so the skin test should be conducted in strict accordance with the relevant requirements, and as far as possible, all β-lactam drugs should be skin test negative before application. Penicillin drugs can use penicillin skin test solution, the concentration of 50 ug/ml is appropriate, cephalosporins are applied to the original solution for skin test, the concentration of 500 ug/ml is appropriate. Do not blindly use higher level drugs, should be in line with the principle of disease need to choose antibacterial drugs. Drugs containing antimicrobial potentiators such as sulbactam and tazobactam are also recommended to use the original solution skin test.