Drugs as Allergens: An Immunoassay for Detecting IgE Antibodies to Cephalosporins

Harle, David G.; Baldo, B. A.

doi:10.1159/000235177

Cited by 60 publications

(46 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Employment of benzylpenicilloyl (BPO)-and the so-called cephalosporoyl (CephO)-solid phases in hapten inhibition tests with the two parent drugs, together with molecules representing their side chains viz., phenylacetic acid, benzylamine and 2-thiophene acetic acid; the β-lactam structure without side chain (6-aminopenicillanic acid); and the β-lactam ring structure (azetidinone) indicated that the methylene group in the side chains of each of the two drugs is a dominant feature of the cross-reactive IgE-binding determinant (Figure 5a,b) [19]. The results were similar to earlier quantitative inhibition findings employing an immunoassay for cephalosporin-reactive IgE in the sera of patients allergic to cephalothin [20] and further suggested that as well as the methylene structure, the thiophene ring acts as a bioisostere of the benzene ring in the side chain of benzylpenicillin [19]. Another good example of the preferential recognition of the penicillin R side chain was provided by the demonstration of IgE antibodies complementary to phenylisoxazolyl R substituents in the sera of patients who experienced anaphylaxis following the administration of flucloxacillin [17].…”

Section: Reaction Of Penicillins With Ige Antibodies and Identificatisupporting

confidence: 88%

“…Examination of the specificities of penicillin-reactive IgE antibodies in the serum from a number of allergic patients revealed a heterogeneous group of allergenic determinants consisting exclusively, or in part, of the side chain groups of penicillins, the β-lactam ring and the thiazoline ring [16][17][18][19][20]. In some patients the entire penicillin molecule comprises the IgE-binding determinant structure.…”

Section: Reaction Of Penicillins With Ige Antibodies and Identificatimentioning

confidence: 99%

See 1 more Smart Citation

IgE and Drug Allergy: Antibody Recognition of ‘Small’ Molecules of Widely Varying Structures and Activities

Baldo

2014

Antibodies

View full text Add to dashboard Cite

Abstract:The variety of chemically diverse pharmacologically-active compounds administered to patients is large and seemingly forever growing, and, with every new drug released and administered, there is always the potential of an allergic reaction. The most commonly occurring allergic responses to drugs are the type I, or immediate hypersensitivity reactions mediated by IgE antibodies. These reactions may affect a single organ, such as the nasopharynx (allergic rhinitis), eyes (conjunctivitis), mucosa of mouth/throat/tongue (angioedema), bronchopulmonary tissue (asthma), gastrointestinal tract (gastroenteritis) and skin (urticaria, eczema), or multiple organs (anaphylaxis), causing symptoms ranging from minor itching and inflammation to death. It seems that almost every drug is capable of causing an immediate reaction and it is unusual to find a drug that has not provoked an anaphylactic response in at least one patient. These facts alone indicate the extraordinary breadth of recognition of IgE antibodies for drugs ranging from relatively simple structures, for example, aspirin, to complex molecules, such as the macrolide antibiotics composed of a large macrocyclic ring with attached deoxy sugars. This wide recognition profile is borne out at the molecular level by results of quantitative immunochemical studies where hapten inhibition investigations have identified structural determinants complementary to IgE antibodies in the sera of allergic subjects. Allergenic determinants have been identified on a variety of drugs including neuromuscular blockers, penicillins, cephalosporins, opioids, thiopentone, sulfonamides, trimethoprim, quinolones, chlorhexidine and the non-steroidal anti-inflammatory drug aspirin. It is already clear that IgE can distinguish fine structural differences on a wide variety of molecules, determinants OPEN ACCESSAntibodies 2014, 3 57 may be at least as small as an amino group or encompass the whole molecule, and individual drugs may demonstrate allergenic heterogeneity.

show abstract

Section: Reaction Of Penicillins With Ige Antibodies and Identificatisupporting

confidence: 88%

Section: Reaction Of Penicillins With Ige Antibodies and Identificatimentioning

confidence: 99%

IgE and Drug Allergy: Antibody Recognition of ‘Small’ Molecules of Widely Varying Structures and Activities

Baldo

2014

Antibodies

View full text Add to dashboard Cite

show abstract

“…Despite the lack of certainty about the chemical structure of the antigenic determinant responsible for allergic reactions to cephalosporins, several studies (Pham and Baldo, 1996;Baldo, 1999;Harle and Baldo, 1990) have reported immunological results, although the conclusions have to be taken with a certain degree of speculation. Because the haptenic determinant of cephalosporins produced by their degradation is largely unknown, more definite studies require each free drug to be used as the skin test agent to detect antibodies reactive to these antibiotics (Baldo, 1999;Weiss and Adkinson, 1988).…”

Section: Immunochemical Studiesmentioning

confidence: 99%

Synthesis, characterization and immunochemical evaluation of cephalosporin antigenic determinants

Sánchez-Sancho

Pérez‐Inestrosa

Suau

et al. 2003

J of Molecular Recognition

View full text Add to dashboard Cite

Lack of knowledge of the exact chemical structure of cephalosporin antigenic determinants has hindered clinical interpretation of adverse reactions to these drugs and delayed understanding of the mechanisms involved in the specific recognition and binding of IgE molecules to these antigenic determinants. We further resolve the relationship between structure and activity of proposed antigenic chemicals, including the rational design and synthesis of these haptenic structures. Comparative RAST inhibition studies of the synthesized molecules revealed that they were recognized by IgE antibodies induced by cephalosporin antibiotics. Thus, these data indicate that recognition is mainly directed to the acyl side chain and to the beta-lactam fragment that remains linked to the carrier protein in the cephalosporin conjugation course.

show abstract

“…Cross-reaction between penicillins and cephalosporins generally involve first and second-generation cephalosporins (9). The possibility of development of cross-reaction against penicillins in patients with advers reactions solely against thirdgeneration cephalosporins is lower compared to first-generation cephalosporins, since first-generation cephalosporins are structurally more similar to penicillins (10). The risk of allergic reactions related to ceftriaxone because of cross-reaction is expected to be higher in patients known to have a previous history of allergy against beta-lactam group of antibiotics.…”

Section: Discussionmentioning

confidence: 99%

İlk doz seftriakson enjeksiyonu sonrası anafilaksi

Arslanköylü¹,

Kuyucu²,

Balcı³

et al. 2011

tpa

View full text Add to dashboard Cite

A An na ap ph hy yl la ax xi is s a af ft te er r t th he e f fi ir rs st t d do os se e o of f c ce ef ft tr ri ia ax xo on ne e i in nj je ec ct ti io on n A Al li i E Er rt tu u¤ ¤ A Ar rs sl la an nk kö öy yl lü ü, , S Se em ma an nu ur r K Ku uy yu uc cu u* *, , S Si ib be el l B Ba al lc c› ›* ** *, , Y Yu us su uf f U Us st ta a* ** ** * IntroductionCeftriaxone is an antibiotic from the group of third-generation cephalosporins used for treatment of bacterial infections. While the incidence of allergic skin reactions related to ceftriaxone is between 1% and 3%, the incidence of anaphylaxis is lower (1). Although ceftriaxone is a frequently used antibiotic for treatment of pediatric patients, only one case of anaphylaxis occuring after the first dose of ceftriaxone has been reported in the literature (2).Herein we report a case of anaphlaxis after the first dose of ceftriaxon. Case reportA two years old male patient presented to the emergency department with fever, vomiting and abdominal pain. Personal and familial history revealed no drug allergy, atopic disease or previous use of beta-lactam antibiotics. The family started to give the patient oral cefuroxime axetyl treatment for pharyngitis.Laboratory investigations were as follows: white blood cells 22811/mm 3 , 80% segmented leucocytes, 14% lymphocytes, 6% monocytes on peripheral blood smear and CRP: 28.9 mg/L. Bacteremia was considered in the patient because of fever, leucocytosis, "shift to the left" on peripheral blood smear and high CRP. Blood culture, urine culture and urinalysis were performed.Afterwards, 500 mg ceftriaxone containing active ingredient was reconstructed with water for injection supplied with the drug by emergency department nurse and diluted to 20 cc with 0.9 % NaCl (25 mg/cc). The solution reconstructed was attached to the infusion pump to be administered in 30 minutes (1.5 mg/kg/minute). Approximately one minute after intravenous infusion of ceftriaxone was started, anaphylactic shock developed accompanied by flushing, respiratory arrest, cyanosis, circulatory failure and hypotension. Positive pressure ventilation with baloon mask was administered to the patient who had a apical heart beat of 180/minute and capillary refill time of more than 2 seconds. 0.01 ml/kg (1:1000) adrenaline was given subcutaneously. 1 mg/kg pheniraminemaleat, 1 mg/kg ranitidine and 0.6 C Ca as se e R Re ep po or rt t S Su um mm ma ar ry yCeftriaxone is a third-generation cephalosporin used for the treatment of bacterial infections. In the literature there is only one pediatric case report of anaphylaxis after first exposure to ceftriaxone. Herein we report a 2 years old boy who developed anaphylaxis after receiving the first intravenous injection of ceftriaxone. Clinicians should be aware of the risk of anaphylaxis after the first dose of ceftriaxone. (Turk Arch Ped 2011; 46: 79-80)

show abstract

Drugs as Allergens: An Immunoassay for Detecting IgE Antibodies to Cephalosporins

Cited by 60 publications

References 8 publications

IgE and Drug Allergy: Antibody Recognition of ‘Small’ Molecules of Widely Varying Structures and Activities

IgE and Drug Allergy: Antibody Recognition of ‘Small’ Molecules of Widely Varying Structures and Activities

Synthesis, characterization and immunochemical evaluation of cephalosporin antigenic determinants

İlk doz seftriakson enjeksiyonu sonrası anafilaksi

Contact Info

Product

Resources

About