青霉素过敏病人与头孢菌素的交叉过敏反应

目的：探讨青霉素过敏病人与头孢菌素交叉过敏反应的情况。方法：采用放射性过敏原吸附试验（RAST）检测420例青霉素过敏病人体内8种青霉素特异性IgE抗体（BPO、PVO、APO、AXO、BPA、PVA、APA和AXA）以及11种头孢菌素特异性IgE抗体（CEXO、CLO、CEZO、CPZO、CTO、CZO、CXO、CEXA、CLA、CEZA、CPZA）。结果：头孢菌素特异性IgE抗体检出阳性率随所检测抗原决定簇种类的增多而增高,并且检测5种与检测11种抗体所得阳性率无显著性差异（P〉0．05）。420例病人中有73例（t7．38％）存在青霉素与头孢菌素交叉过敏反应,有95例（22．62％）至少一种头孢菌素特异性IgE抗体呈阳性。青霉素特异性IgE抗体阳性组头孢菌素特异性IgE抗体阳性率显著高于其抗体阴性组（P〈0．01）。对具有相同或相似侧链结构抗生素的次要抗原决定簇特异性IgE抗体的相关性分析发现,APA-IgE与AXA-IgE,APA-IgE与CEXA—IgE,AXA—IgE与CEXA—IgE,BPA-IgE与CLA—IgE水平均正相关（P〈0．05）,且氨苄西林、阿莫西林抗体阳性组头孢氨苄抗体阳性率显著高于其抗体阴性组（P〈0．05）。结论：青霉素过敏病人存在与头孢菌素的交叉过敏反应,交叉过敏反应率达17．38％。     

青霉素与头孢菌素交叉过敏反应及特异性抗体

目的：探讨青霉素与头孢菌素交叉过敏反应机制,评价侧链结构在交叉过敏反应中的地位。方法：采用RAST分别检测了420例青霉素过敏病人和34例头孢菌素过敏病人体内8种青霉素特异性IgE抗体（BPO、PVO、APO、AXO、BPA、PVA、APA和AXA）以及11种头孢菌素特异性IgE抗体（CEXO、CLO、CEZO、CPZO、CTO、CZO、CXO、CEXA、CLA、CEZA、CPZA）,采用RAST抑制试验检测了4例典型过敏病人特异性抗体对多种药物及其不同侧链和母核结构的识别位点。结果：头孢菌素过敏病人血清中头孢菌素特异性IgE抗体阳性率显著高于青霉素过敏病人（P〈0．01）。特异性IgE抗体检出阳性率随所检测抗原决定簇种类的增多而增高,并且检测9种与检测19种抗体所得阳性率无显著性差异（P〉0．05）。454例病人中有90例（19．82％）存在青霉素与头孢菌素抗生素交叉过敏反应。     

头孢菌素过敏病人与青霉素的交叉过敏反应

目的：探讨头孢菌素过敏病人与青霉素交叉过敏反应的情况,并改进头孢菌素过敏反应的诊断方法,方法：采用放射性过敏原吸附试验（RAST）检测34例头孢菌素过敏病人体内8种青霉素特异性IgE抗体（BPO、PVO、APO、AXO、BPA、PVA、APA和AXA）以及11种头孢菌素特异性IgE抗体（CEXO、CLO、CEZO、CPZO、CTO、CZO、CXO、CEXA、CLA、CEZA、CPZA）。结果：特异性IgE抗体检出阳性率随所检测抗原决定簇种类的增多而增高,并且检测5种与检测11种抗体所得阳性率无显著性差异（P〉0．05）。34例病人中有32例（94．12％）至少一种头孢菌素特异性IgE抗体呈阳性,18例（52．94％）存在青霉素与头孢菌素交叉过敏反应,19例（55．88％）至少一种青霉素特异性IgE抗体呈阳性。     

青霉素类抗生素的交叉过敏反应研究

目的：探讨青霉素类抗生素交叉过敏反应的机制。方法：采用放射免疫吸附试验（radioallergosorbent test，RAST）检测142例青霉素类过敏患者和101例健康受试者血清中针对4种青霉素类药物即青霉素G（PG）、青霉素V（PV）、氨苄西林（AP）、阿莫西林（AX）的8种抗原决定簇特异性IgE抗体（BPO、BPA、APO、APA、AX0、AXA、PVO、PVA-IgE）。结果：142例抗体阳性患者中，仅对一种抗原决定簇抗体阳性的占43．66％（62例），总的交叉过敏反应率为56．34％（80例）。BPO、BPA、APO、APA、AXO、AXA、PVO、PVA分别与其他7种抗原决定簇的交叉过敏反应率为29．58％，28．17％，30．28％，16．90％，16．90％，11．27％，14．08％，28．17％。仅对一种药物抗体阳性的占46．48％（66例），总的交叉过敏反应率为53．52％（76例），PG、AP、AX、PV分别与其他3种药物的交叉过敏反应率分别为45．07％，40．85％，25．35％，36．62％。结论：特异性过敏反应在青霉素过敏反应中占有重要地位。青霉素类药物之间仅存在部分交叉过敏反应。     

青霉素过敏病人血清特异性IgE抗体与青霉素化学结构的关系

本研究采用放射过敏原吸附抑制试验研究青霉素过敏病人血清特异性IgE抗体与青霉素化学结构的关系。通过对 3例高敏病人的研究发现 ,作为青霉素G和青霉素V的侧链结构的苯乙酸 (PHA)和苯氧乙酸 (PHOA)抑制 2例高敏病人血清IgE抗体程度稍弱于青霉素G和青霉素V ,但是高于其他抑制剂。提示病人体内特异性IgE抗体的识别位点与青霉素G和青霉素V侧链关系密切。而另 1例高敏病人抑制试验显示 ,抗体识别位点与整个药物分子结构有关。研究证明 ,特异性IgE抗体在识别青霉素化学结构时 ,有的识别整个药物结构 ,而有的仅识别侧链结构     

头孢菌素和青霉素交叉过敏反应的结构基础探讨

利用亲和层析、ELISA、反向间接血凝试验和PCA试验等免疫学试验方法,证明头孢菌素和青霉素间有弱的交叉过敏反应。两类抗生素形成抗原或多价半抗原时,抗原决定簇中由β—内酰胺环形成的新抗体结合位点是交叉过敏反应的重要抗体结合位点;β—内酰胺环结构是交叉过敏反应的结构基础。 交叉过敏反应的强弱除了由抗原间的相似性所决定,还和机体中特异性抗体的抗原结合部位特异性有关。通过对18只兔抗BPO—BSA抗血清和特异性已知的青霉素单克隆抗体的比较分析,认为对青霉素和头孢菌素间的交叉过敏反应现象应有足够的重视。     

青霉素类药物皮试阴性患者发生过敏反应的临床特征及危险因素分析

目的 探讨青霉素类药物皮试阴性患者发生过敏反应的临床特征及危险因素。方法 筛选2017年1月至2022年5月衡水市4家医院ADR监测中心报告的青霉素类药物皮试阴性、用药期间发生的青霉素类药物致过敏反应的病例报道,按照患者性别与年龄、药品名称、用法用量、过敏反应发生时间、累及器官/系统及临床表现和转归等进行统计分析。结果 共纳入121例患者,男女比例为1∶1.42;发生比例最高的年龄段为> 65岁(55/121,45.45%);药品主要为阿莫西林克拉维酸钾、哌拉西林他唑巴坦钠和青霉素;给药途径以静脉滴注为主(114/121,94.21%);发生时间以用药第1天内最多(71/121,58.65%);主要表现为局部红斑或皮疹、瘙痒、胸闷气短、血压下降等。年龄(>65岁)、恶性肿瘤、慢性肾功能不全、低蛋白血症(<25 g/L)是青霉素类药物皮试阴性患者发生过敏反应的独立危险因素(P<0.05)。结论 临床医师、护师和药师应全面掌握青霉素类药物皮试阴性患者发生过敏反应的特点,对合并高危因素的患者应予以高度警惕,提高过敏反应鉴别能力。     

青霉素头孢菌素化学结构与交叉抗原性的探讨

迄今已开发近百种β-内酰胺类抗生素,目前临床上使用频率较高的约有二十种。由于化学结构的相似性,容易引起交叉过敏反应,这已成为此类药物在选择治疗中的一个比较重要的问题。因此进一步探讨β-内酰胺类抗生素的交叉抗原性,使其在临床化疗中最有效地发挥作用并最大限度地防止其副反应的发生,具有重要意义。     

β-内酰胺类抗生素过敏反应与其化学结构的关系

<正>β-内酰胺类抗生素在临床上应用十分广泛,但过敏反应发生率居各类药物之首,无青霉素过敏史的患者中,过敏反应发生率为0.07%～10.00%,大多为皮疹反应,严重者可引发过敏性休克而致死亡,休克发生率为0.004%～0.040%。β-内     

氨苄青霉素抗体的不均一性及对过敏反应的影响

本文由ELISA、亲和层析和PCA等实验方法证明氨苄青霉素抗血清中存在着多种抗原结合部位特异性不同的氨苄青霉素抗体。不同氨苄青霉素抗体的组合及含量的变化,决定了抗血清的表现特异性,使之表现出极大的不均一性;用DEAE葡聚糖凝胶分级分离抗血清,发现氨苄青霉素抗体的特异性和其所带电荷有关;氨苄青霉素抗体和结构不同的过敏原之间的匹配程度,直接影响着过敏反应发生的强弱。     

青霉素过敏病人血清特异性IgE和IgG抗体

采用放射过敏原吸附试验(RAST)和酶联免疫吸附试验(ELISA)测定52例青霉素过敏病人血清特异性IgE、IgG抗体，进一步探讨青霉素过敏反应机制。结果 52例过敏病人特异性IgE、IgG抗体的阳性率分别为50％和44．2％，若RAST与ELISA联合检测，IgE和IgG抗体总阳性率增至63.5％。荨麻疹组BPO—IgG水平高于过敏性休克组(P＜0.01)，过敏性休克病人BPA—IgG水平明显高于BPO—IgG(P＜0．01)，荨麻疹组内BPO—IgE水平与BPA—IgE无显著差异(P＞0．05)。但均比过敏性休克组高。研究结果提示，荨麻疹与BPO—IgE和BPA—IgE关系密切，过敏性休克与BPO—IgE和BPA—IgG关系密切；同时检测IgE和IgG抗体，可提高诊断阳性率。     

青霉素过敏病人嗜碱性粒细胞表面CD63的变化

目的评价嗜碱性粒细胞表面CD63在诊断青霉素过敏反应中的价值。方法采用流式细胞过敏原刺激试验(FAST)的方法检测43例青霉素过敏病人血中嗜碱性粒细胞在9种抗原刺激后(PG、PV、AMP、AX、6-APA、PHA、PHOA、PHPG、NPG)表面CD63的变化。采用放射免疫吸附试验(RAST)和酶联免疫吸附试验(ELISA)检测8种特异性IgE和IgG抗体。结果43例青霉素过敏病人中有28例为CD63阳性,15例健康对照受试者中有1例阳性。其敏感性为65.12%,特异性为93.33%。CD63和特异性IgE在皮试阳性组的敏感性高于特异性IgG(P<0.05),并且在IgE阳性组中,CD63的阳性率高于特异性IgG(P<0.05)。结论CD63可作为检测青霉素类过敏反应嗜碱性粒细胞特异性激活标志物。     

青霉素皮肤试验与特异性IgE抗体的相关性

目的：探讨青霉素皮肤试验（皮试）与特异性IgE的相关性，方法：采用放射过敏原吸附试验（RAST）测定青霉素过敏病人血清特异性IgE 抗体，结果：根据皮试与抗体测定时间隔分为4个时间段，即刻，30d内，30d至2年和2年以上，皮试阳性患者各时间段IgE抗体阳性率分别为42．9％，28．6％，18．8％和10．5％，当皮试阳性反应程度≥“＋”时，IgE抗体阳性率为8．3％，皮试与RAST的符合率为66．7％，当反应程度≥“＋＋”时，IgE抗体阳性率为60％，二者符合率为77．8％，皮试程度与血清特异性IgE抗体呈显著相关（P＜0．05），当皮试≥“＋＋＋”时，皮试与RAST完全相符，结论：青霉素皮试的准确性与皮试反应程度及时间有关，RAST可作为青霉素过敏反应体外诊断的一种重要辅助方法。     

Assessing the prevalence and characteristics of self-reported penicillin allergy in Saudi Arabian population: A nationwide cross-sectional study

IntroductionBeing allergic to penicillin can lead to the overuse of broad-spectrum antibiotics, contributing to the growing problem of multidrug resistance. Knowing the exact allergy history is essential as some circumstances may allow reinitiating penicillin. This study focused on assessing the prevalence and characteristics of self-reported penicillin allergy in the Saudi Arabian population.MethodsWe conducted a nationwide cross-sectional study via an electronic self-administered questionnaire directed toward the Saudi Arabian general adult population. Variables about respondent demographics as well as type and characteristics of the allergy were collected.ResultsOne hundred ninety-three out of 2022 participants who completed the survey (9.5%) reported allergy to penicillin, with the most reported reaction being anaphylaxis in 89 participants (46.1%), non-anaphylaxis reported by 69 participants (35.8%). Twenty-two participants (11.4%) were identified as not having a true allergy due to reporting a tolerability issue or a non-penicillin-type agent. About 38% reported that the allergy occurred more than ten years ago.ConclusionThis is the first study to report the prevalence and characteristics of self-reported penicillin allergy in Saudi Arabia. The data from this study provides valuable information to consider starting in-hospital penicillin de-labeling programs and providing evidence for healthcare providers to consider re-challenging certain qualified patients.     

Assessing the risk of type 1 allergy to enzymes present in laundry and cleaning products: Evidence from the clinical data

Microbial enzymes have been used in laundry detergent products for several decades. These enzymes have also long been known to have the potential to give rise to occupational type 1 allergic responses. A few cases of allergy among consumers using dusty enzyme detergents were reported in the early 1970s. Encapsulation of the enzymes along with other formula changes were made to ensure that consumer exposure levels were sufficiently low that the likelihood of either the induction of IgE antibody (sensitization) or the elicitation of clinical symptoms be highly improbable. Understanding the consumer exposure to enzymes which are used in laundry and cleaning products is a key step to the risk management process. Validation of the risk assessment conclusions and the risk management process only comes with practical experience and evidence from the marketplace. In the present work, clinical data from a range of sources collected over the past 40 years have been analysed. These include data from peer reviewed literature and enzyme specific IgE antibody test results in detergent manufacturers’ employees and from clinical study subjects. In total, enzyme specific IgE antibody data were available on 15,765 individuals. There were 37 individuals with IgE antibody. The majority of these cases were from the 1970s where 23 of 4687 subjects (0.49%) were IgE positive and 15 of the 23 were reported to have symptoms of allergy. The remaining 14 cases were identified post-1977 for a prevalence of 0.126% (14/11,078). No symptoms were reported and no relationship to exposure to laundry and cleaning products was found. There was a significant difference between the pre- and post-1977 cohorts in that the higher rates of sensitization with symptoms were associated with higher exposure to enzyme. The clinical testing revealed that the prevalence of enzyme specific IgE in the population is very rare (0.126% since 1977). This demonstrates that exposure to these strong respiratory allergens via use of laundry and cleaning products does not lead to the development of sensitization and disease. These data confirm that the risk to consumers has been properly assessed and managed and support the concept that thresholds of exposure exist for respiratory allergy. Expansion of enzyme use into new consumer product categories should follow completion of robust risk assessments in order to continue ensuring the safe use of enzymes among consumers.     

应用核糖体展示技术高效筛选人源抗IgE单链抗体

本研究从哮喘患者外周血分离淋巴细胞、提取总mRNA,采用RT-PCR技术分别构建重链可变区VH(variable region of heavy chain)和轻链可变区VL(variable region of light chain)cDNA库,然后通过连接肽(Gly4Ser)3和特定引物将VH和VL cDNA基因组装成人源单链抗体(scFv)核糖体展示模板基因库。应用兔网织红细胞核糖体展示技术,单引物原位反转录技术,经3轮展示富集并回收针对人源IgE蛋白(免疫球蛋白E)的目的单链抗体基因;回收的抗体基因经双酶切后与pET22b(+)载体连接,转化至E.coli Rosseta(DE3)宿主细胞,应用菌落PCR结合Dot blotting技术快速鉴定阳性克隆,抗原ELISA法进一步鉴定阳性克隆。VH和VL基因库得到正确的构建,长度分别为400和710 bp,库容为1013。核糖体展示模板构建正确,长度为1 100 bp。该基因库经过3轮针对IgE蛋白的核糖体展示,目的基因得到了有效富集和回收。经过高效克隆、表达和鉴定,确定1株针对人IgE蛋白显示最强亲和力的阳性克隆菌pET-IgE-6。经测序和序列分析证实该单链抗体为人源抗体,序列未见国内外报道。结果表明,采用患者外周血构建人源抗体基因库,结合核糖体展示技术,可以成功获得高亲和力的人源单链抗体分子。该技术路线为快速获得具有药用价值的人源抗体提供了参考。     

青霉素侧链结构对其聚合反应的影响探讨

摘要：目的 青霉素是临床中应用最广泛的抗生素之一。控制青霉素中的聚合物含量对保证药品安全具有重要的意义,但目前对青霉素类抗生素聚合反应的认知尚不全面,因此需对其相关机制进行分析。方法 本文选择苯唑西林钠和磺苄西林钠,分别作为侧链为苯甲异恶唑类青霉素和侧链具有较强的吸电子基团青霉素的代表,采用理论计算进一步验证前期文献提出的基于青霉素母核的聚合反应途径,并探讨侧链结构对其聚合反应的影响。结果 聚合反应Ⅰ(青霉素母核的羧基与另一分子β-内酰胺环的反应)是优势聚合反应途径,但侧链具有较强吸电子基团的青霉素如磺苄西林不易发生聚合反应,提示青霉素侧链结构对聚合反应具有明显影响。结论 理论分析聚合反应途径结合强制聚合反应验证是聚合物分析的理想方案;采用LC-MS方法,根据聚合物的质谱裂解途径,结合聚合反应机理,可以较好地推断聚合物的结构。     

Effects of penicillins on binding of phenytoin to plasma proteins in vitro and in vivo

Effects of penicillins on the binding of phenytoin to plasma proteins were examined in vitro and in vivo. The results from in vitro studies showed that the penicillins including oxacillin and dicloxacillin were effective in displacing phenytoin from its binding sites. In vivo, the total phenytoin concentration in serum decreased during penicillin administration, while the free phenytoin concentration increased. As a result, penicillins caused a significant increase in the apparent volume of distribution and in the total body clearance of phenytoin. These results can be explained on the basis of the displacement of phenytoin from its plasma protein binding site by penicillins.     

Clinical pharmacokinetics of penicillins in the neonate: a review of the literature

Background

Sepsis is common in neonates and a major cause of morbidity and mortality. Sixty percent of preterm neonates receive at least one antibiotic during the first week of life, with penicillins being the most frequently administered antibiotics. The clearance (Cl), serum half-life (t_½) and volume of distribution (Vd) of penicillins are different in the neonate than in the adult. As such, the pharmacokinetics of penicillins need be studied in neonates in order to optimise therapy in this age class with these drugs.

Objectives

The aim of this study was to review the published data on the pharmacokinetics of penicillins in the neonate in order to provide a critical analysis of the literature and, consequently, a useful tool in the hands of the physician.

Methods

The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines. An initial search was performed with the keywords “pharmacokinetics”, “penicillins” and “neonates”. Secondly, other searches were performed using the keywords “pharmacokinetics” and “neonates”, followed by the name of a single antibiotic. The search included articles up to 2007.

Results

There have been few pharmacokinetic studies on the use of penicillins in neonates. The results from those few studies that have been carried out suggest that the Cl is reduced and t_½ prolonged in the neonate as compared with the more mature infant. There is little variation in Vd during the first week of life. In the premature neonate, Cl is reduced compared to the full-term infant. As postnatal age proceeds, the Cl of penicillins increases.

Conclusions

More pharmacokinetic studies are required to provide a sound scientific basis for planning a dosage regimen with penicillins in the neonate.