为什么头孢菌素类不需做皮试.pptx

1 为什么头孢菌素类不需做皮试为什么头孢菌素类不需做皮试为什么头孢菌素类不需做皮试为什么头孢菌素类不需做皮试?海军总医院海军总医院海军总医院海军总医院孙忠实孙忠实孙忠实孙忠实2008,6,2,2008,6,2,北京北京北京北京2为什么青霉素需要为什么青霉素需要为什么青霉素需要为什么青霉素需要/可以做皮试可以做皮试可以做皮试可以做皮试?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 population,with 500 to 1,000 deaths per year.Arch Intern Med 2001:161:15213Classification Scheme for Adverse Drug Classification Scheme for Adverse Drug Reactions Described by Gell and CoombsReactions Described by Gell and Coombs4Types of Allergic Reactions to Types of Allergic Reactions to Penicillins and CephalosporinsPenicillins and Cephalosporins5氟氯西林致过敏的斑丘疹氟氯西林致过敏的斑丘疹氟氯西林致过敏的斑丘疹氟氯西林致过敏的斑丘疹6 氨苄西林致敏的荨麻疹氨苄西林致敏的荨麻疹氨苄西林致敏的荨麻疹氨苄西林致敏的荨麻疹7为什么青霉素需要为什么青霉素需要为什么青霉素需要为什么青霉素需要/可以做皮试可以做皮试可以做皮试可以做皮试?1,青霉素过敏反应发生率较高青霉素过敏反应发生率较高,为为1%-10%;1%-10%;过敏休克率为过敏休克率为0.004%0.015%(0.04%),0.004%0.015%(0.04%),即即1/7,000-25,000,1/7,000-25,000,死亡率为死亡率为1/50,000-60,000;1/50,000-60,000;2,2,过敏反应的抗原过敏反应的抗原主要决定簇主要决定簇-青霉噻唑决定簇与次要决青霉噻唑决定簇与次要决定簇定簇-青霉烯酸决定簇非常明确青霉烯酸决定簇非常明确;3,3,皮试符合率可达皮试符合率可达70%;70%;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,皮试液的浓度与皮试方法均已定型。皮试液的浓度与皮试方法均已定型。5,80%90%5,80%90%青霉素过敏史者，再次皮试可为阴性青霉素过敏史者，再次皮试可为阴性,因因IgEIgE可逐可逐渐消失渐消失;.N Engl J Med 2006;354:601-9.8青霉素变态反应主要青霉素变态反应主要青霉素变态反应主要青霉素变态反应主要/次要决定簇明确次要决定簇明确次要决定簇明确次要决定簇明确N Engl J Med 2006;354:601-99为什么准确率仅能达到为什么准确率仅能达到为什么准确率仅能达到为什么准确率仅能达到70%?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 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 products of penicillin.10为什么准确率仅能达到为什么准确率仅能达到为什么准确率仅能达到为什么准确率仅能达到70%?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 previous reaction was not IgE-mediated Or that the antibodies are no longer present.11Safety of The Skin TestSafety 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 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青霉素皮试特别注意事项青霉素皮试特别注意事项青霉素皮试特别注意事项1,Skin testing is not generally done in people who have a strong 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 certain 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 patients 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为什么头孢菌素类不需做皮试为什么头孢菌素类不需做皮试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头孢菌素类过敏反应发生率较低,为为0.00010.10.00010.1%,%,即即1/7,000-25,000,1/7,000-25,000,死亡率为死亡率为1/50,000-60,000;1/50,000-60,000;2,2,过敏反应的半抗原过敏反应的半抗原主要决定簇与次要决定簇不明主要决定簇与次要决定簇不明确确,可能有可能有Cephalosporoyl,Cephalosporanyl;3,3,皮试准确率仅达皮试准确率仅达30%;30%;4,4,皮试液浓度与皮试方法未定型皮试液浓度与皮试方法未定型;5,20055,2005版版须知须知与与20042004年年指导原则指导原则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 results are less well established than those of penicillin.14为什么头孢菌素类为什么头孢菌素类为什么头孢菌素类为什么头孢菌素类皮试准确率很低皮试准确率很低皮试准确率很低皮试准确率很低?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 cephalosporins.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抗菌药均有过敏反应抗菌药均有过敏反应抗菌药均有过敏反应抗菌药均有过敏反应 全要做皮试吗全要做皮试吗全要做皮试吗全要做皮试吗?17CepADRsCepADRs发生率发生率发生率发生率18PenPen与与与与CepCep的交叉过敏问题的交叉过敏问题的交叉过敏问题的交叉过敏问题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 penicillin allergywas 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危险增加约4 4倍倍;有青霉素过敏史的病人对头孢菌素发生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过敏反应的危险是无过敏史病人的8 8倍倍;在有青霉素过敏在有青霉素过敏史的病人中史的病人中约约10%10%与头孢菌素发生交叉过敏反应与头孢菌素发生交叉过敏反应 虽有青霉素过敏史，但皮试阴性者，对头孢菌素的虽有青霉素过敏史，但皮试阴性者，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，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。反之亦然。大约有大约有80%90%80%90%有青霉素过敏史者，再次皮试可为有青霉素过敏史者，再次皮试可为阴性阴性,因因IgEIgE可逐渐消失可逐渐消失;N Engl J Med 2001;345:804809PenPen与与与与CepCep的交叉过敏问题的交叉过敏问题的交叉过敏问题的交叉过敏问题20有有有有PenPen过敏史者选用过敏史者选用过敏史者选用过敏史者选用CepCep危险性增加危险性增加危险性增加危险性增加 In a review combining data from 11 studies of cephalosporin administration in patients with a history of penicillin allergy,cephalosporin reactions were 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).有有过敏史者的危敏史者的危险性增加了性增加了7.3倍倍!21CepCep用于有用于有用于有用于有PenPen过敏史过敏史过敏史过敏史者时过敏反应发生率者时过敏反应发生率者时过敏反应发生率者时过敏反应发生率22CepCep用于有用于有用于有用于有/无无无无PenPen过敏史过敏史过敏史过敏史者时过敏反应发生率者时过敏反应发生率者时过敏反应发生率者时过敏反应发生率23CepCep用于用于用于用于PenPen过敏史者的过敏发生率过敏史者的过敏发生率过敏史者的过敏发生率过敏史者的过敏发生率24为什么为什么为什么为什么CepCep与与与与PenPen交叉反应较少交叉反应较少交叉反应较少交叉反应较少?Cephalosporins and penicillins differ in that the 5-membered thiazolidine ring of penicillin is replaced with a 6-membered dihydrothiazine ring in the cephalosporins.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-lactam rings of these compounds might be minimal,a finding supported by clinical and monoclonal antibody analysis 25CepCep致过敏休克反应的报告致过敏休克反应的报告致过敏休克反应的报告致过敏休克反应的报告N Engl J Med,2001;345:80480926英国英国英国英国1992199719921997年只发生了年只发生了年只发生了年只发生了3 3例例例例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能否应用能否应用能否应用能否应用CepCep取决于是否取决于是否取决于是否取决于是否为为为为IgEIgE介导的过敏反应介导的过敏反应介导的过敏反应介导的过敏反应For patients with a history of penicillin allergy who require a cephalosporin,treatment depends on whether the previous reaction was mediated by IgE(I I型反应型反应).28Evidence Supporting the Use of Cephalosporin Evidence Supporting the Use of Cephalosporin Antibiotics in Penicillin-Allergic PatientsAntibiotics 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 articles 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 molecular 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%)and 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 generation 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!35CepCep皮试和变态反应发生率的调查皮试和变态反应发生率的调查皮试和变态反应发生率的调查皮试和变态反应发生率的调查 目的目的:了解头孢菌素的皮试及变态反应情况了解头孢菌素的皮试及变态反应情况,为是否需做皮试提为是否需做皮试提供客观资料供客观资料.方法方法:采用分层系统抽样方法采用分层系统抽样方法,对住院期间使用头孢菌素的对住院期间使用头孢菌素的1,0841,084例病人进行皮试和变态反应情况的调查例病人进行皮试和变态反应情况的调查.结果结果:用青霉素皮试的有用青霉素皮试的有203203例例,用头孢菌素原液皮试的有用头孢菌素原液皮试的有9 9例例,未未做皮试做皮试872872例例.皮试人数占皮试人数占19.5619.56.196196例青霉素皮试阴性者使例青霉素皮试阴性者使用头孢菌素有用头孢菌素有5 5例发生变态反应例发生变态反应,872,872例未做皮试者发生例未做皮试者发生7 7例例,两两者之间变态反应发生率的差异无统计学意义者之间变态反应发生率的差异无统计学意义(P(P0.05);0.05);有和无有和无青霉素过敏史之间变态反应发生率的差异也无统计学意义青霉素过敏史之间变态反应发生率的差异也无统计学意义(P(P0.05).0.05).头孢菌素变态反应发生率头孢菌素变态反应发生率1.111.11.结论结论:头孢菌素用药前皮试头孢菌素用药前皮试可不列为常规可不列为常规,用青霉素皮试代替头用青霉素皮试代替头孢菌素试敏不敏感孢菌素试敏不敏感药物流行病学物流行病学杂志志 2005年年2期期36头孢菌素皮试究竟怎样做头孢菌素皮试究竟怎样做头孢菌素皮试究竟怎样做头孢菌素皮试究竟怎样做?20052005版须知版须知:凡使用青霉素类抗生素时凡使用青霉素类抗生素时,均应按规定均应按规定:“注射前必须先做青霉素皮肤试验注射前必须先做青霉素皮肤试验”;这里可以理解为这里可以理解为“口服口服”时可以不做。时可以不做。头孢菌素是否皮试应遵从说明书。迄今临床所用全头孢菌素是否皮试应遵从说明书。迄今临床所用全部十余种制剂中部十余种制剂中,仅头孢美唑仅头孢美唑(Cefmetazole)1(Cefmetazole)1种在说明种在说明书中有书中有“用药前进行皮肤过敏试验为宜用药前进行皮肤过敏试验为宜”的要求的要求,其其他均注明他均注明“对青霉素过敏者慎用对青霉素过敏者慎用”。37CepCep皮试液的浓度是多少皮试液的浓度是多少皮试液的浓度是多少皮试液的浓度是多少?Cephalosporin skin tests at a concentration of 2 mg per mL seem to be reliable indicators of immediate hypersensitivity.Ann Intern Med 2004;141:16-22.38结结结结 语语语语千万不要因噎废食千万不要因噎废食,由于不正确的或似由于不正确的或似是而非的原因是而非的原因,而将临床抗感染的主力军而将临床抗感染的主力军头孢菌素类抗生素搁置一边头孢菌素类抗生素搁置一边,从而耽误从而耽误患者的及时治疗患者的及时治疗!39谢谢谢谢 谢谢谢谢!