Immunology of the monobactam aztreonam

N. F. Adkinson, E. A. Swabb, A. A. Sugerman

Research output: Contribution to journalArticle

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 anti-benzylpenicilloyl (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 (<< 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 β-lactam antibiotics and may be only weakly immunogenic in humans.

Original languageEnglish (US)
Pages (from-to)93-97
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume25
Issue number1
DOIs
StatePublished - 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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