Abstract
To assess the immunological cross-reactivity of the monobactam antibiotic aztreonam (AZ), rabbits were immunized with protein conjugates of benzylpenicillin, cephalothin (CEPH), and AZ. The resulting antibenzylpenicilloyl (BPO) and anti-CEPH rabbit antibodies showed negligible cross-reactivity with AZ conjugated to human serum albumin (AZ-HSA), whereas anti-AZ showed negligible cross-reactivity with BPO-HSA and CEPH-HSA. Unlike benzylpenicillin and CEPH, unconjugated AZ was as effective as AZ conjugated to epsilon aminocaproic acid (AZ-EACA) in inhibiting the binding of homologous antibody. Studies with various analogs of AZ confirmed that immunoglobulin G (IgG) anti-AZ was entirely side-chain specific. The inhibition of the binding of human IgE anti-penicilloyl to BPO-HSA was studied in the presence of AZ-EACA, BPO-formyl lysine, and CEPH-EACA. Whereas CEPH-EACA displayed 3% cross-reactivity with BPO-lysine, AZ-EACA showed little or no cross-reactivity (much less than 0.9%). To assess the immunogenicity of AZ in humans, IgE and IgG antibodies were measured in sera from 36 healthy male volunteers receiving 0.5 or 1 g intravenously or intramuscularly every 8 h for 7 days. None of the subjects had detectable preexisting IgE reactive with AZ or demonstrated an IgE response to antibiotic administration. Four subjects gave evidence for naturally occurring IgG cross-reactive with AZ, but only one subject demonstrated a rise in IgG levels after exposure to AZ. This anti-AZ IgG did not cross-react with BPO or CEPH conjugates of bovine thyroglobulin and was completely side-chain specific. These studies suggest that AZ displays very low immunological cross-reactivity with other beta-lactam antibiotics and may be only weakly immunogenic in humans.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BRANDRISS M. W., SMITH J. W., STEINMAN H. G. COMMON ANTIGENIC DETERMINANTS OF PENICILLIN G, CEPHALOTHIN AND 6-AMINOPENICILLANIC ACID IN RABBITS. J Immunol. 1965 May;94:696–704. [PubMed] [Google Scholar]
- Batchelor F. R., Dewdney J. M., Weston R. D., Wheeler A. W. The immunogenicity of cephalosporin derivatives and their cross-reaction with penicillin. Immunology. 1966 Jan;10(1):21–33. [PMC free article] [PubMed] [Google Scholar]
- Levine B. B. Antigenicity and cross-reactivity of penicillins and cephalosporins. J Infect Dis. 1973 Oct;128(Suppl):S364–S366. doi: 10.1093/infdis/128.supplement_2.s364. [DOI] [PubMed] [Google Scholar]
- Levine B. B. Immunochemical mechanisms of drug allergy. Annu Rev Med. 1966;17:23–38. doi: 10.1146/annurev.me.17.020166.000323. [DOI] [PubMed] [Google Scholar]
- PARKER C. W., THIEL J. A. STUDIES IN HUMAN PENICILLIN ALLERGY: A COMPARISON OF VARIOUS PENICILLOYL-POLYLYSINES. J Lab Clin Med. 1963 Sep;62:482–491. [PubMed] [Google Scholar]
- Swabb E. A., Sugerman A. A., McKinstry D. N. Multiple-dose pharmacokinetics of the monobactam azthreonam (SQ 26,776) in healthy subjects. Antimicrob Agents Chemother. 1983 Jan;23(1):125–132. doi: 10.1128/aac.23.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sykes R. B., Bonner D. P., Bush K., Georgopapadakou N. H. Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob Agents Chemother. 1982 Jan;21(1):85–92. doi: 10.1128/aac.21.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sykes R. B., Cimarusti C. M., Bonner D. P., Bush K., Floyd D. M., Georgopapadakou N. H., Koster W. M., Liu W. C., Parker W. L., Principe P. A. Monocyclic beta-lactam antibiotics produced by bacteria. Nature. 1981 Jun 11;291(5815):489–491. doi: 10.1038/291489a0. [DOI] [PubMed] [Google Scholar]