為什么頭孢菌素類不需做皮試

1、1 為什么頭孢菌素類不需做皮試為什么頭孢菌素類不需做皮試?海軍總醫(yī)院海軍總醫(yī)院孫忠實孫忠實2008,6,2,北京北京2為什么青霉素需要為什么青霉素需要/可以做皮試可以做皮試?Approximately 300 deaths can be attributed to penicillin allergy each year in the United States. Allergy to Beta Lactam Antibiotics July 26, 2007 Fatal penicillin-induced anaphylaxis has been reported at a rate of

2、 0.002% among the general population, with 500 to 1,000 deaths per year.Arch Intern Med 2001:161:15213Classification Scheme for Adverse Drug Reactions Described by Gell and Coombs4Types of Allergic Reactions to Penicillins and Cephalosporins5氟氯西林致過敏的斑丘疹氟氯西林致過敏的斑丘疹6 氨芐西林致敏的蕁麻疹氨芐西林致敏的蕁麻疹7為什么青霉素需要為什么青霉

3、素需要/可以做皮試可以做皮試?1,青霉素過敏反應(yīng)發(fā)生率較高青霉素過敏反應(yīng)發(fā)生率較高, ,為為1%-10%;1%-10%;過敏休克率為過敏休克率為0.004%0.015%(0.04%),0.004%0.015%(0.04%),即即1/7,000-25,000,1/7,000-25,000,死亡率為死亡率為1/50,000-60,000; 1/50,000-60,000; 2, 2,過敏反應(yīng)的抗原過敏反應(yīng)的抗原主要決定簇主要決定簇- -青霉噻唑決定簇與次要決青霉噻唑決定簇與次要決定簇定簇- -青霉烯酸決定簇非常明確青霉烯酸決定簇非常明確; ;3, 3,皮試符合率可達皮試符合率可達70%; 70%;

4、 但是但是Penicillin skin testing does not provide any information about certain types of reactions; skin tests show that only a small percentage actually are reactive to these antibiotics. 4, 4,皮試液的濃度與皮試方法均已定型。皮試液的濃度與皮試方法均已定型。5,80%90%5,80%90%青霉素過敏史者，再次皮試可為陰性青霉素過敏史者，再次皮試可為陰性, ,因因IgEIgE可逐可逐漸消失漸消失; ;.N Eng

5、l J Med 2006;354:601-9.8青霉素變態(tài)反應(yīng)主要青霉素變態(tài)反應(yīng)主要/次要決定簇明確次要決定簇明確N Engl J Med 2006;354:601-99為什么準確率僅能達到為什么準確率僅能達到70%?The breakdown products of penicillin include the penicilloyl group, known as the major determinant because it is the major penicillin metabolic product (approximately 85% to 90% of the penici

6、llin breakdown products).The minor haptenic determinants or minor determinant mixture, so called because they are formed in smaller quantities, are composed of the parent penicillin molecules, penicilloate, penicilloylamine, penilloate, and other simple chemical products of penicillin. 10為什么準確率僅能達到為

7、什么準確率僅能達到70%?A penicillin skin test does not predict non-IgE-mediated reactions caused by other immune mechanisms, such as cytotoxic antibody-mediated reactions, antibody-antigen immune complex-mediated reactions, and delayed-type cell-mediated reactions. Negative skin testing indicates that the pre

8、vious reaction was not IgE-mediated Or that the antibodies are no longer present.11Safety of The Skin TestIf done properly, the skin test is safe, with a rate of systemic reaction of less than 1%. Nevertheless, severe reactions such as anaphylaxis and death have occurred. Serious reactions to the pe

9、nicillin skin test are usually a result of violations of the skin test protocol, such as administering too high a dosage or performing intracutaneous testing without prick/puncture testing beforehand.12青霉素皮試特別注意事項青霉素皮試特別注意事項1,Skin testing is not generally done in people who have a strong history of

10、severe allergy, especially if the reaction happened within the past year. In such patients, an alternate antibiotic should be used, or desensitization to penicillin should be performed if no alternates are acceptable or available. 2,Skin testing should not be done in people taking certain medication

11、s, such as beta-blockers (eg, atenolol, propranolol, nadolol, esmolol, carvedilol, metoprolol, and sotalol). These medications can interfere with treatment of a severe allergic reaction, were it to unexpectedly occur during testing. 3,Finally, skin testing should not be done in patients with an exte

12、nsive skin rash since it would be difficult to judge if skin test results were positive or negative. 13為什么頭孢菌素類不需做皮試為什么頭孢菌素類不需做皮試?1,頭孢菌素類過敏反應(yīng)發(fā)生率較低頭孢菌素類過敏反應(yīng)發(fā)生率較低, ,為為0.00010.10.00010.1%,%, 即即1/7,000-25,000,1/7,000-25,000,死亡率為死亡率為1/50,000-60,000;1/50,000-60,000;2, 2,過敏反應(yīng)的半抗原過敏反應(yīng)的半抗原主要決定簇與次要決定簇不明主要決定簇與

13、次要決定簇不明確確, ,可能有可能有Cephalosporoyl ,Cephalosporanyl; ;3, 3,皮試準確率僅達皮試準確率僅達30%;30%;4, 4,皮試液濃度與皮試方法未定型皮試液濃度與皮試方法未定型; ;5,20055,2005版版須知須知與與20042004年年指導(dǎo)原則指導(dǎo)原則均不要求做均不要求做; ; 6,Skin testing for cephalosporins has been undertaken in a number of studies, but the positive and negative predictive values of the re

14、sults are less well established than those of penicillin .14為什么頭孢菌素類為什么頭孢菌素類皮試準確率很低皮試準確率很低? We use radioimmunoassays to measure major determinants (penicilloyl and cephalosporoyl) and minor determinants (penicillanyl and cephalosporanyl) for up to six different penicillins and six different cephalos

15、porins. The higher incidence of IgE antibodies against cephalosporins was not anticipated and most likely reflects both increased use of cephalosporins and greater parenteral exposure to these drugs. N Engl J Med, 2002 ;346:380 15N Engl J Med 2002 ;346; 5 , 16抗菌藥均有過敏反應(yīng)抗菌藥均有過敏反應(yīng)全要做皮試嗎全要做皮試嗎?17CepADRs

16、發(fā)生率發(fā)生率18Pen與與Cep的交叉過敏問題的交叉過敏問題Penicillins and cephalosporins share a -lactamring structure, making cross-reactivity a concern.Although a rate of cross-reactivity of more than10 percent has been reported, this figure mustbe interpreted with caution since it is based onretrospective studies in which p

17、enicillin allergywas not routinely confirmed by skin testing,19 在對青霉素過敏的病人中，發(fā)生頭孢菌素過敏反應(yīng)的在對青霉素過敏的病人中，發(fā)生頭孢菌素過敏反應(yīng)的危險增加約危險增加約4 4倍倍; ;有青霉素過敏史的病人對頭孢菌素發(fā)生有青霉素過敏史的病人對頭孢菌素發(fā)生過敏反應(yīng)的危險是無過敏史病人的過敏反應(yīng)的危險是無過敏史病人的8 8倍倍; ;在有青霉素過敏在有青霉素過敏史的病人中史的病人中約約10%10%與頭孢菌素發(fā)生交叉過敏反應(yīng)與頭孢菌素發(fā)生交叉過敏反應(yīng) 雖有青霉素過敏史，但皮試陰性者，對頭孢菌素的雖有青霉素過敏史，但皮試陰性者，對頭孢

18、菌素的過敏危險性并不增加，故皮試后，可以使用頭孢菌素，過敏危險性并不增加，故皮試后，可以使用頭孢菌素，反之亦然。反之亦然。 大約有大約有80%90%80%90%有青霉素過敏史者，再次皮試可為有青霉素過敏史者，再次皮試可為陰性陰性, ,因因IgEIgE可逐漸消失可逐漸消失; ; N Engl J Med 2001;345:804809Pen與與Cep的交叉過敏問題的交叉過敏問題20有有Pen過敏史者選用過敏史者選用Cep危險性增危險性增加加 In a review combining data from 11 studies of cephalosporin administration in

19、patients with a history of penicillin allergy, cephalosporin reactions were found to have occurred in 6 of 135 patients with positive skin-test results for penicillin allergy (4.4 percent), as compared with only 2 of 351 with negative skin tests (0.6 percent). 有過敏史者的危險性增加了有過敏史者的危險性增加了7.3倍倍 ! 21Cep用于

20、有用于有Pen過敏史過敏史者時過敏反應(yīng)發(fā)生率者時過敏反應(yīng)發(fā)生率22Cep用于有用于有/無無Pen過敏史過敏史者時過敏反應(yīng)發(fā)生率者時過敏反應(yīng)發(fā)生率23Cep用于用于Pen過敏史者的過敏發(fā)生率過敏史者的過敏發(fā)生率24為什么為什么Cep與與Pen交叉反應(yīng)較少交叉反應(yīng)較少?Cephalosporins and penicillins differ in that the 5-membered thiazolidine ring of penicillin is replaced with a 6-membered dihydrothiazine ring in the cephalosporins.

21、However, after degradation, penicillin forms a stable penicilloate ring, with preservation of the thiazolidine ring, whereas cephalosporins undergo rapid fragmentation of the -lactam and dihydrothiazine rings. On the basis of these differences in degradation, immunologic cross-reactivity between -la

22、ctam rings of these compounds might be minimal, a finding supported by clinical and monoclonal antibody analysis 25Cep致過敏休克反應(yīng)的報告致過敏休克反應(yīng)的報告N Engl J Med, 2001;345:80480926英國英國19921997年只發(fā)生了年只發(fā)生了3例例Among 12 cases of fatal anaphylaxis caused by antibiotics in the United Kingdom from 1992 to 1997, 6 cases

23、 occurred after the first dose of a cephalosporin, and 3 of the 6 patients were known to have penicillin allergy.27能否應(yīng)用能否應(yīng)用Cep取決于是否取決于是否為為IgE介導(dǎo)的過敏反應(yīng)介導(dǎo)的過敏反應(yīng)For patients with a history of penicillin allergy who require a cephalosporin, treatment depends on whether the previous reaction was mediated by

24、 IgE (I I型反應(yīng)型反應(yīng)).28Evidence Supporting the Use of Cephalosporin Antibiotics in Penicillin-Allergic PatientsThe objective was to review the frequency of allergic cross-reactivity between penicillins and cephalosporin antibiotics. MEDLINE and EMBASE databases were searched for all English language art

25、icles relevant to penicillin and cephalosporin cross-sensitivity. Among 219 retrieved articles, 103 were included in the review. Based on 38 studies, the evidence suggests that the crossreactive, immunoglobulin E (IgE)-mediated immune responses between penicillins and cephalosporins are based on mol

26、ecular side chain similarities of the antibiotics rather than similarities in lactam rings. Twenty-eight studies examined 5420 patients with a history of penicillin allergy compared to 47,976 without such a history who received cephalosporins; possible allergic reactions were noted in 138 (2.55%) an

27、d 654 (1.36%) patients respectively (p 0.0001). However, the risk of a cross-allergic reaction occurred predominantly among patients receiving first-generation cephalosporins with related chemical side chains to penicillin or amoxicillin. The proportion of patients with a cross-allergy to a first ge

28、neration cephalosporin was increased by 6.1% (95% confidence interval CI for difference between penicillin allergic and nonallergic = 5.4%6.9% p 4倍倍!35Cep皮試和變態(tài)反應(yīng)發(fā)生率的調(diào)查皮試和變態(tài)反應(yīng)發(fā)生率的調(diào)查 目的目的: :了解頭孢菌素的皮試及變態(tài)反應(yīng)情況了解頭孢菌素的皮試及變態(tài)反應(yīng)情況, ,為是否需做皮試提為是否需做皮試提供客觀資料供客觀資料. .方法方法: :采用分層系統(tǒng)抽樣方法采用分層系統(tǒng)抽樣方法, ,對住院期間使用頭孢菌素的對住院期間使用頭孢菌素的1, 0841, 084例病人進行皮試和變態(tài)反應(yīng)情況的調(diào)查例病人進行皮試和變態(tài)反應(yīng)情況的調(diào)查. .結(jié)果結(jié)果: :用青霉素皮試的有用青霉素皮試的有203203例例, ,用頭孢菌素原液皮試的有用頭孢菌素原液皮試的有9 9例例, ,未未做皮試做皮試872872例例. .皮試人數(shù)占皮試人數(shù)占19.5619.56. .196196例青霉素皮試陰性者使例青霉素皮試陰性者使用頭孢菌素有用頭孢