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Background: Hypersensitivity reactions occurring during anesthesia remain a major cause of concern for anesthesiologists. We report the results of the ninth consecutive survey of hypersensitivity reactions observed during anesthesia in France. This report will be used as an epidemiologic reference prior to this intervention., Methods: Between January 1, 2005 to December 31, 2007, 1253 patients who experienced an immune-mediated (IgE-mediated) or non-immune-mediated (non-IgE-mediated) hypersensitivity reaction were referred to one of the 40 participating centers. Diagnosis was established on the basis of clinical history, skin tests and/or specific IgE assay., Results: An IgE-mediated or non-IgE-mediated reaction was diagnosed in 786 cases (63%) and 467 cases (37%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBA) (N.=373, 47.4%), latex (N.=158, 20%), and antibiotics (N.=141, 18.1%). Succinylcholine (N.=226, 60.6%) was the most frequently incriminated NMBA, whereas the low frequency of reactions involving cis-atracurium was confirmed (N.=22, 5.9%) when market shares of each NMBA were taken into account. An increased number of reactions involving vital dyes was recorded (N.=34, 4.4%)., Conclusion: These changes in the epidemiology of allergic reactions confirm the need for regular epidemiologic surveys of anaphylaxis in the perioperative period.

Structure-activity relationships (SARs) refer to the relation between chemical structure and pharmacologic activity for a series of compounds. Since the pioneering work of Crum-Brown and Fraser in 1868, they have been increasingly used in the pharmaceutical, chemical and cosmetic industries, especially for drug and chemical design purposes. Structure-activity relationships may be based on various techniques, ranging from considerations of similarity or diversity of molecules to mathematical relationships linking chemical structures to measured activities, the latter being referred to as quantitative SAR or QSAR. This review aims at briefly reviewing the history of SARs and highlighting their interest in delayed and immediate drug allergy using selected examples from the literature. Studies of SAR are commonly conducted in the area of contact dermatitis, a delayed hypersensitivity reaction, to determine the allergenic potential of a given compound without animal testing. In immediate, immunoglobulin E-mediated drug hypersensitivity, this kind of approach remains rather confidential. It has been mainly applied to neuromuscular blocking drugs (muscle relaxants) and betalactam antibiotics (penicillins, cephalosporins). This review shows that SARs can prove useful to (i) predict the allergenic potential of a chemical or a drug, (ii) help identify putative antigenic determinants for each patient or small group of patients sharing the same cross-reactivity pattern, and (iii) predict the likelihood of adverse reactions to related molecules and select safe alternatives.

Objective: To present a predictive model of allergenicity based on a structure-activity relationship analysis of beta-lactam antibiotics using appropriate skin testing procedures., Case Summary: A 39-year-old woman was diagnosed with anaphylactic shock a few minutes after taking a 500 mg tablet cefuroxime of axetil and was admitted to the emergency department with dizziness, facial angioedema, generalized skin rash, and inferior cardiac ischemia. Skin testing confirmed the involvement of cefuroxime as the cause of the anaphylactic reaction, and the reaction was defined as probable according to the Naranjo probability scale. We then performed skin testing to study cross-reactivity between different beta-lactam antibiotics. In addition to this initial assessment, a structure-activity relationship (SAR) analysis was done. It showed that the patient was sensitized to beta-lactam antibiotics presenting a methoxyimino group, but not to similar compounds lacking this chemical group (eg, amoxicillin or penicillin G or V). Challenge with amoxicillin under intensive medical monitoring was tolerated up to a cumulated dose of 1 g, administered intravenously over 2 hours., Discussion: This study demonstrates that SAR analysis could be useful to predict potential adverse reactions to related antibiotics and to select alternative strategies when antibiotic administration is essential., Conclusions: An SAR-based approach could help physicians and pharmacists provide allergic patients with relevant advice and propose viable alternatives regarding drug therapy.

A rapid and simple method for the separation and quantitation of gentamicin sulfate by HPLC coupled with evaporative light scattering detection (ELSD) has been developed. Detection of the different components of gentamicin is problematic because of the lack of UV absorbing chromophore. The use of the universal ELSD avoids the need for sample derivatization or use of specific detector such as pulsed amperometry. Separation was performed on a highpurity C18 125 mm x 4 mm i.d., 3 microm, reversed phase column with 48.5 mM trifluoroacetic acid-methanol (97:3, v/v), as mobile phase at a flow rate of 0.7 ml/min. The influence of the gas nature, gas pressure and temperature of the drift tube of the detector on the detection response was investigated. Optimization was performed with the help of a specific experimental design software. This method allows the determination of the composition in components C1, C1a, C2, C2a and C2b of gentamicin sulfate samples. Mass spectrometry was employed to confirm the ELSD chromatographic profile. The method was validated using methodology described by the International Conference of Harmonization in the field of Medicinal Substances. Commercial samples of different sources were analyzed and results were in good agreement with specifications of both European and United States Pharmacopoeia.