Neo-antigens for the serological diagnosis of IgE-mediated drug allergic reactions to antibiotics cephalosporin, carbapenem and monobactam.

New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for ß-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty ß-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-ß-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-ß-lactam IgE antibodies with high sensitivity (< 0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of ß-lactam antibiotics renders improved molecular recognition events when the 4-member ß-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.

[Anaphylaxis as part of a clinical diagnosis of mastocytosi - case demonstration]. / Anafilaksja jako kliniczny element rozpoznania mastocytozy--demonstracja przypadku.

Mastocytosis is a heterogeneous group of diseases characterized by excessive proliferation and accumulation of mast cells--in one or more organs. The number of symptoms and clinical prognosis vary depending on the disease. One of the most severe potential outcome of mastocytosis is anaphylactic shock. Early diagnosis and identification of triggers enables education and avoidance them. We describe the case of a 31-year-old woman with systemic mastocytosis (SM) without skin symptoms with multiple anaphylactic reactions, including two severe. Systemic mastocytosis was confirmed in bone marrow and genetic studies. We identify allergic triggers: latex and cefuroxime and also other non-immunological triggers as non-steroidal anti-inflammatory drugs (NSAIDs). The patient never had any allergic reaction after Hymenoptera stings. Only one result of serum tryptase was elevated. There was a need to determine the safety of antibiotic use and anesthetic drugs before cesarean. The moment when the disease was diagnosed and triggers were identifie, helped avoid further severe reactions.

Safety of cefuroxime as an alternative in patients with a proven hypersensitivity to penicillins: a DAHD cohort survey.

OBJECTIVE: In patients sensitized to beta-lactams, a safe beta-lactam alternative is often needed. The objective was to assess the safety of cefuroxime in patients with a proven beta-lactam allergy. DESIGN: Using the Drug Allergy and Hypersensitivity Database cohort, patients with a proven beta-lactam allergy and tested for cefuroxime between September 1996 and April 2007 were selected. The European Network of Drug Allergy recommendations were followed. Prevalence of sensitization to cefuroxime (as an alternative) was established in patients with a proven beta-lactam allergy. RESULTS: Amongst the 650 subjects tested, 143 (22.0%) presented at least one beta-lactam sensitization other than cefuroxime [39-27.3% male, median age at test 44.0 (32.0-56.0) years]. One hundred and eighteen (82.5%) were sensitized to penicillins, 8 (5.6%) to cephalosporins and 17 (11.9%) to both penicillins and cephalosporins. Nine (6.3%) patients were sensitized to cefuroxime (6 diagnosed by provocation test): 5 (55.6%) in the penicillin-only allergic group and 4 (44.4%) in the penicillin and cephalosporin allergic group. Prevalence of cefuroxime hypersensitivity reaction in patients sensitized to beta-lactams was 6.3% (95% CI 2.3-10.3%) and in those sensitized to penicillin 4.2% (95% CI 0.6-7.9). This rate decreased to 2.9% (95% CI 0-6.9) in patients with prior histories involving a penicillin only (without any history involving an unknown beta-lactam). CONCLUSION: Cefuroxime appeared to be a safe alternative in beta-lactam-allergic patients after testing. The risk of giving cefuroxime being not null, a thorough drug allergy work-up, including provocation test, is still needed.

Prophylactic subconjunctival cefuroxime during cataract surgery in patients with a penicillin allergy.

The incidence of cross-reaction after subconjunctival cefuroxime following cataract surgery in penicillin allergy patients is not common and therefore cefuroxime with its better spectrum of action and lower toxicity is probably a better choice than gentamycin.

Antigen specific quantification of sulfidoleukotrienes in patients allergic to Betalactam antibiotics.

BACKGROUND: After in vitro allergen-specific stimulation, basophils become activated and release sulfidoleukotrienes LTC4, LTD4 and LTE4. This can be detected by means of the CAST assay. We assessed the positivity criteria and the reliability of antigen-specific sulfidoleukotriene production (CAST) in the in vitro diagnosis of betalactam (BL) allergic patients. MATERIAL AND METHODS: We studied a sample of 67 patients (age 48.94 +/- 15.76 years) who had presented with anaphylaxis or urticaria-angioedema within the first 60 minutes after administration of Amoxicillin (54/67), Penicillin G (7/67), Cefuroxime (5/67) or Cefazoline (1/67). All of them had a positive skin test to at least one of the antigenic determinants of Penicillin. As control group 30 adults with negative skin tests who tolerated BL were included. All of them underwent skin tests, oral provocation tests, specific IgE (CAP-FEIA, Pharmacia) and CAST. RESULTS: Positivity criteria were established by means of ROC curves: a sLT release induced by Betalactams of at least 100 pg/ml and greater than or equal to 3 times the basal value. The overall sensitivity of CAST is 47.7% and specificity 83.3%. Sensitivity of specific IgE is 37.8% and specificity 83.3%. CONCLUSIONS: We have established validated positivity criteria for the CAST technique in patients allergic to Betalactams. This technique is a useful in vitro diagnostic method in patients with IgE-mediated allergy to Betalactam antibiotics.

Cefuroxime-induced immune hemolysis.

Drug-induced immune hemolytic anemia (IHA) is rare but is being reported with increasing frequency. The most commonly cited cause of drug-induced IHA has been receipt of second and third generation cephalosporin antibiotics. We report the first case of IHA associated with cefuroxime administration.

Boosted IgE response after anaphylaxis reaction to cefuroxime with cross-reactivity with cefotaxime.

BACKGROUND: Cefuroxime is a second-generation lactamase-stable cephalosporin. Its use is on the increase, and in recent years several reactions to this compound have been reported. OBJECTIVE: To describe a case of selective reaction to cefuroxime, showing a boosted immunoglobulin (Ig)E response after administration of this drug. METHODS: Specific serum IgE antibodies to several cephalosporins were monitored in a 52-year-old man after a selective systemic anaphylaxis attributable to cefuroxime, who showed a good tolerance to penicillin V during a single-blind, placebo-controlled challenge. RESULTS: Specific IgE levels to cefuroxime were not detected at the moment of the reaction but became positive 1 day after, increasing to peak at day 51, and still positive after 115 days. Through radioallergosorbent test inhibition, cross-reactivity between cefuroxime and cefotaxime was demonstrated. CONCLUSIONS: IgE-mediated reaction attributable to cefuroxime with cross-reactivity to cefotaxime was reported. A prompt evaluation undertaking skin tests and additional radioallergosorbent test studies with different betalactam derivatives improves the evaluation of subjects with allergic reactions to betalactams.

An assessment of antigenic potential of beta-lactam antibiotics, low molecular weight drugs, using guinea pig models.

Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight beta-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.