Section of Clinical Immunology and Allergy, Department of Pediatrics, Alberta Children's Hospital and University of Calgary, 2888 Shaganappi Trail NW, Calgary, Alberta T3B 6A8, Canada.
Allergy Asthma Clin Immunol. 2013 Jun 14;9(1):22. doi: 10.1186/1710-1492-9-22.
Diagnostic testing to antibiotics other than to penicillin has not been widely available, making the diagnosis of antibiotic allergy difficult and often erroneous. There is often reluctance in performing challenges to antibiotics when standardized testing is lacking. However, while the immunogenic determinants are not known for most antibiotics, a skin reaction at a non-irritating concentration (NIC) may mean that antibodies to the native form are present in the circulation. While the NIC's for many non penicillin antibiotics have been determined in adults, the use of these concentrations for skin testing pediatric subjects prior to provocative challenge has not been done. Our objective was to determine if we could successfully uncover the true nature of antibiotic allergy in children using these concentrations for testing.
Children were included between 2003-2009 upon being referred to the Drug and Adverse Reaction/Toxicology (DART) clinic of the Hospital for Sick Children in Toronto, Ontario Canada. The referral needed to demonstrate that clinical care was being compromised by the limitation in antibiotic options or there was a significant medical condition for which the label of antibiotic allergy may prove detrimental. Patients were not seen if there was a suggestion of serum like sickness, Stevens Johnson Syndrome or Toxic Epidermal Necrolysis. Patients were excluded from testing if there was objective evidence of anaphylaxis. All other patients were consented to receive testing and/or challenges. A retrospective chart review was then performed of the results.
We were able to exclude an antibiotic allergy in the majority of our patients who had a negative intradermal test result and were then challenged (>90%). Only one patient was challenged with a positive intradermal test to Cotrimoxazole because of a questionable history and this patient failed the provocative challenge. While we did not challenge more patients with positive testing, we did note that 10/11 (91%) patients with positive intradermal testing had some aspect of a Type 1 reaction in their history.
Through testing with NIC's of various antibiotics in children and providing provocative challenges based on negative skin testing results, we were able to advance the medical care of the majority of our patients by increasing their antibiotic options in order to successfully treat future infections. While challenging patients with positive testing was not deemed ethically appropriate at this stage of our study, it would be a useful future step to reaching statistical validity of testing to these antibiotics.
除青霉素外,其他抗生素的诊断检测手段并不广泛,这使得抗生素过敏的诊断变得困难且常常出现错误。当标准化检测缺乏时,人们往往不愿意对抗生素进行挑战。然而,虽然大多数抗生素的免疫原性决定因素尚不清楚,但在非刺激性浓度(NIC)下出现皮肤反应可能意味着循环中有针对天然形式的抗体。虽然许多非青霉素类抗生素的 NIC 已在成人中确定,但在进行激发性挑战之前,尚未在儿科患者中使用这些浓度进行皮肤测试。我们的目的是确定是否可以使用这些浓度成功揭示儿童抗生素过敏的真实性质。
2003 年至 2009 年间,加拿大安大略省多伦多 SickKids 医院的药物和不良反应/毒理学(DART)诊所收治的患者被纳入研究。该转诊需要表明,由于抗生素选择有限,临床治疗受到限制,或者存在可能因抗生素过敏标签而对患者产生不利影响的严重疾病。如果存在血清样疾病、史蒂文斯-约翰逊综合征或中毒性表皮坏死松解症的迹象,患者则不进行皮肤测试。如果有过敏反应的客观证据,患者则被排除在测试之外。所有其他患者都同意接受测试和/或挑战。然后对结果进行回顾性图表审查。
我们能够排除大多数皮内试验结果阴性且随后接受挑战的患者(>90%)的抗生素过敏。只有一名患者因可疑病史而对 Cotrimoxazole 皮内试验呈阳性而接受挑战,该患者在激发性挑战中失败。虽然我们没有对更多皮内试验阳性的患者进行挑战,但我们注意到,10/11(91%)皮内试验阳性的患者在其病史中有某种 1 型反应。
通过对儿童使用各种抗生素的 NIC 进行测试,并根据阴性皮肤测试结果提供激发性挑战,我们能够通过增加抗生素选择来改善大多数患者的医疗护理,从而成功治疗未来的感染。虽然在我们研究的现阶段,对皮内试验阳性的患者进行挑战被认为在伦理上不合适,但对这些抗生素进行测试的统计有效性是未来的有用步骤。