Anaphylactic shock associated with cefuroxime axetil: structure-activity relationships.

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.

Informed consent for research obtained during the intensive care unit stay.

INTRODUCTION: Patients in the intensive care unit (ICU) may be in an inadequate condition to give their informed consent for research. The aim of this study was to analyse the ability to recall participation in a clinical trial for which ICU patients had given their consent. METHODS: The data presented are a two-step observational study: first, a protocolled informed consent procedure was conducted then the informed consent was given by the patient, and second, a patient interview was held 10 +/- 2 days later by the same investigator. The primary endpoints were the ability to recall their participation in the clinical trial, as well as its purpose and related risks. As secondary endpoints, we investigated whether asking questions about the clinical trial or reading the informative leaflet was related to the recall. To be included in the study, the patient had to have a Glasgow Coma Scale score of 15, be fully oriented and free of mechanical ventilation, and be judged competent by both the investigator and the attending physician. Patients admitted to the ICU after major surgery or trauma were eligible. However, patients who refused to participate, or those whose next-of-kin gave consent, were excluded. RESULTS: Of the 44 patients, 35 (80%) recognized, 10 to 12 days after informed consent had been obtained, that they had participated in the clinical trial, but only 14 out of 44 (32%) could recall the clinical trial purpose and its related risks. More patients with complete recall had read the informative leaflet or asked at least one question before signing the informed consent. Asking at least one question was associated with complete recall. CONCLUSION: Our results confirm that obtaining informed consent for research during an ICU stay is associated with poor patient recall of participation in a clinical trial and its components (purpose and risk). Whether encouraging reading the informative leaflet and asking questions about the clinical trial improves the informed consent procedure remains to be fully investigated.

Structure-activity relationships and drug allergy.

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.

Low apolipoprotein A-I level at intensive care unit admission and systemic inflammatory response syndrome exacerbation.

OBJECTIVE: Examine whether a low serum level of apolipoprotein A-I at intensive care unit (ICU) admission is associated with a further increase of the number of systemic inflammatory response syndrome (SIRS) criteria. DESIGN: Prospective observational study. SETTING: A 20-bed, university-affiliated, surgical ICU. PATIENTS: Patients admitted after major surgery, multiple trauma, or acute pancreatitis without septic shock. INTERVENTIONS: We defined as the SIRS Exacerb group patients who presented a further increase of the number of SIRS criteria during their ICU stay or, in the presence of four SIRS criteria at ICU admission, those who presented a further aggravation of organ failure. Other patients were attributed to the SIRS No Exacerb group. From day 1 to 6, we measured apolipoprotein A-I, high-density lipoprotein and total cholesterol, triglycerides, C-reactive protein, procalcitonin, serum amyloid A, interleukin 6, interleukin-1 receptor antagonist, albumin, and other nutrition-linked variables. We looked at laboratory values or factors present at ICU admission according to the two groups. MEASUREMENTS AND MAIN RESULTS: From 63 patients analyzed, 29 (46%) were assigned to the SIRS Exacerb group. Age, sex, and SAPS II and SIRS scores at ICU admission did not differ between the groups. Patients in the SIRS Exacerb group presented more often a septic event (5/29 vs. 0/34, p =.02), had a higher hospital mortality (6/29 vs. 0/34, p =.007), and had a longer ICU stay (p =.0023). At admission, inflammatory variables such as the C-reactive protein, serum amyloid A, interleukin 6, interleukin-1 receptor antagonist plasma levels, and other lipid or nutrition-linked variables were similar between the two groups. Apolipoprotein A-I levels were lower in the SIRS Exacerb group (median [interquartile range]: 68 [56-81] vs. 84 [69-94] mg/dL, p =.028). CONCLUSION: A low serum level of apolipoprotein A-I at ICU admission is associated with an increase of the number of SIRS criteria during the ICU stay.