为什么头孢菌素类不需做皮试.ppt

1、1,为什么头孢菌素类不需做皮试?,海军总医院 孙忠实 2008,6,2,北京,2,为什么青霉素需要/可以做皮试?,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 0.002% among the general popu

2、lation, with 500 to 1,000 deaths per year. Arch Intern Med 2001:161:1521,3,Classification Scheme for Adverse Drug Reactions Described by Gell and Coombs,4,Types of Allergic Reactions to Penicillins and Cephalosporins,5,氟氯西林致过敏的斑丘疹,6,氨苄西林致敏的荨麻疹,7,为什么青霉素需要/可以做皮试?,1,青霉素过敏反应发生率较高,为1%-10%;过敏休克率为0.004%0.0

3、15%(0.04%),即1/7,000-25,000,死亡率为1/50,000-60,000; 2,过敏反应的抗原主要决定簇-青霉噻唑决定簇与次要决定簇-青霉烯酸决定簇非常明确; 3,皮试符合率可达70%; 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,皮试液的浓度与皮试方法

4、均已定型。 5,80%90%青霉素过敏史者，再次皮试可为阴性,因IgE可逐渐消失;,.,N Engl J Med 2006;354:601-9.,8,青霉素变态反应主要/次要决定簇明确,N Engl J Med 2006;354:601-9,9,为什么准确率仅能达到70%?,The breakdown products of penicillin include the penicilloyl group, known as the major determinant because it is the major penicillin metabolic product (approxima

5、tely 85% to 90% of the penicillin 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 product

6、s of penicillin.,10,为什么准确率仅能达到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

7、indicates that the previous reaction was not IgE-mediated Or that the antibodies are no longer present.,11,Safety of The Skin Test,If 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. Se

8、rious reactions to the penicillin 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,青霉素皮试特别注意事项,1,Skin testing is not generally done in people who have a s

9、trong history of 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 c

10、ertain medications, 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 pati

11、ents with an extensive skin rash since it would be difficult to judge if skin test results were positive or negative.,13,为什么头孢菌素类不需做皮试?,1,头孢菌素类过敏反应发生率较低,为0.00010.1%, 即1/7,000-25,000,死亡率为1/50,000-60,000; 2,过敏反应的半抗原主要决定簇与次要决定簇不明确,可能有Cephalosporoyl ,Cephalosporanyl; 3,皮试准确率仅达30%; 4,皮试液浓度与皮试方法未定型; 5,200

12、5版须知与2004年指导原则均不要求做; 6,Skin testing for cephalosporins has been undertaken in a number of studies, but the positive and negative predictive values of the results are less well established than those of penicillin .,14,为什么头孢菌素类皮试准确率很低?,We use radioimmunoassays to measure major determinants (penicillo

13、yl and cephalosporoyl) and minor determinants (penicillanyl and cephalosporanyl) for up to six different penicillins and six different cephalosporins. The higher incidence of IgE antibodies against cephalosporins was not anticipated and most likely reflects both increased use of cephalosporins and g

14、reater parenteral exposure to these drugs. N Engl J Med, 2002 ;346:380,15,N Engl J Med 2002 ;346; 5 ,16,抗菌药均有过敏反应全要做皮试吗?,17,CepADRs发生率,18,Pen与Cep的交叉过敏问题,Penicillins and cephalosporins share a -lactam ring structure, making cross-reactivity a concern. Although a rate of cross-reactivity of more than

15、10 percent has been reported, this figure must be interpreted with caution since it is based on retrospective studies in which penicillin allergy was not routinely confirmed by skin testing,19,在对青霉素过敏的病人中，发生头孢菌素过敏反应的危险增加约4倍;有青霉素过敏史的病人对头孢菌素发生过敏反应的危险是无过敏史病人的8倍;在有青霉素过敏史的病人中约10%与头孢菌素发生交叉过敏反应 虽有青霉素过敏史，但皮

16、试阴性者，对头孢菌素的过敏危险性并不增加，故皮试后，可以使用头孢菌素，反之亦然。 大约有80%90%有青霉素过敏史者，再次皮试可为阴性,因IgE可逐渐消失; N Engl J Med 2001;345:804809,Pen与Cep的交叉过敏问题,20,有Pen过敏史者选用Cep危险性增加,In a review combining data from 11 studies of cephalosporin administration in patients with a history of penicillin allergy, cephalosporin reactions were f

17、ound 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). 有过敏史者的危险性增加了7.3倍 !,21,Cep用于有Pen过敏史者时过敏反应发生率,22,Cep用于有/无Pen过敏史者时过敏反应发生率,23,Cep用于Pen过敏史者的过敏发生率,24,为什么Cep与Pen交叉反应较少?,Ce

18、phalosporins and penicillins differ in that the 5-membered thiazolidine ring of penicillin is replaced with a 6-membered dihydrothiazine ring in the cephalosporins. However, after degradation, penicillin forms a stable penicilloate ring, with preservation of the thiazolidine ring, whereas cephalospo

19、rins undergo rapid fragmentation of the -lactam and dihydrothiazine rings. On the basis of these differences in degradation, immunologic cross-reactivity between -lactam rings of these compounds might be minimal, a finding supported by clinical and monoclonal antibody analysis,25,Cep致过敏休克反应的报告,N Eng

20、l J Med, 2001;345:804809,26,英国19921997年只发生了3例,Among 12 cases of fatal anaphylaxis caused by antibiotics in the United Kingdom from 1992 to 1997, 6 cases occurred after the first dose of a cephalosporin, and 3 of the 6 patients were known to have penicillin allergy.,27,能否应用Cep取决于是否为IgE介导的过敏反应,For pat

21、ients with a history of penicillin allergy who require a cephalosporin, treatment depends on whether the previous reaction was mediated by IgE (I型反应).,28,Evidence Supporting the Use of Cephalosporin Antibiotics in Penicillin-Allergic Patients,The objective was to review the frequency of allergic cro

22、ss-reactivity between penicillins and cephalosporin antibiotics. MEDLINE and EMBASE databases were searched for all English language articles relevant to penicillin and cephalosporin cross-sensitivity. Among 219 retrieved articles, 103 were included in the review. Based on 38 studies, the evidence s

23、uggests that the crossreactive, immunoglobulin E (IgE)-mediated immune responses between penicillins and cephalosporins are based on molecular side chain similarities of the antibiotics rather than similarities in lactam rings. Twenty-eight studies examined 5420 patients with a history of penicillin

24、 allergy compared to 47,976 without such a history who received cephalosporins; possible allergic reactions were noted in 138 (2.55%) and 654 (1.36%) patients respectively (p 0.0001). However, the risk of a cross-allergic reaction occurred predominantly among patients receiving first-generation ceph

25、alosporins with related chemical side chains to penicillin or amoxicillin. The proportion of patients with a cross-allergy to a first generation cephalosporin was increased by 6.1% (95% confidence interval CI for difference between penicillin allergic and nonallergic = 5.4%6.9% p 0.0001),29,Evidence

26、 Supporting the Use of Cephalosporin Antibiotics in Penicillin-Allergic Patients,While to second- and third-generation cephalosporins with unrelated chemical side chains, the proportion was decreased by 0.45% (95% CI = 1.2%0.3%; p = 0.25). Cephalosporin skin testing, described in 21 articles, predic

27、ts hypersensitivity to the specific cephalosporin skin test reagents or those with similar side chains and based on 3 studies a positive skin test is 10%38% predictive of a clinical reaction. Experimental and clinical studies suggest that side-chainspecific antibodies predominate in the allergic imm

28、une response to cephalosporins thereby explaining the lack of cross-sensitivity between second- and third-generation cephalosporins and penicillins. Pediatr Asthma Allergy 18:230246,30,1#与2 # 、3 #Cep与Pen-7位侧链异同的交叉反应比较,31,1#与2 # 、3 #Cep与Pen- 3位侧链异同的交叉反应比较,32,A Review of Evidence Supporting the Americ

29、an Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients,Anaphylaxis with penicillins was 0.015% to 0.004%, with a fatality rate of 0.002% to 0.0015%.More limited data suggested that the rate of anaphylaxis with cephalosporins was 0.1% to 0.0

30、001%. Cases of anaphylaxis induced by cephalosporins are summarized in Table Of course. PEDIATRICS 2005:115: 1048-1057,33,Cep用于有/无Pen过敏史者时过敏反应发生率,PEDIATRICS Vol. 115 No. 4 April 2005, pp. 1048-1057,PEDIATRICS Vol. 115 No. 4 April 2005, pp. 1048-1057,PEDIATRICS Vol. 115 No. 4 April 2005, pp. 1048-1057,PEDIATRICS Vol. 115 No. 4 April 2005, pp. 1048-1057,34,是否选用Cep必须强调Pen过敏史,According to a review of the literature on allergy to penicillin, 28 of 15,987 patients who were treated with cephaloridine, cephalexin, cephalothin, cefazolin, or