Mode of interaction between immunoglobulin G and mezlocillin against beta-lactamase producing bacteria

beta-Lactamase producing E. coli and Proteus spp. strains were exposed in vitro to mezlocillin (Baypen) and/or immunoglobulin G (IgG, commercially available batches of Polyglobin). Whereas each single agent exhibited no effect against these strains, the combination of both acted synergistically resulting in a pronounced reduction in viable counts. These findings were corroborated in vivo by using the granuloma pouch technique in rats. Treatment of rats with either mezlocillin (100 mg/kg b.i.d., i.v.) or IgG (single i.v. dose of 3 ml/kg) was ineffective. In contrast, simultaneous administration of both drugs exhibited a marked antibacterial effect throughout the study period of one week. Three control experiments were run in parallel in any case: firstly, albumin (3 mg/kg) served as a protein control; its application was completely ineffective. Secondly, cefoxitin and cefotaxime, respectively (40 mg/kg b.i.d., i.v.), were administered because of their beta-lactamase stability. Both cephalosporins exhibited an antibacterial effect against the beta-lactamase producing E. coli strains, but were ineffective against Proteus spp. Thirdly, beta-lactamase negative strains were not synergistically affected by the combination of mezlocillin plus IgG. These data are to be explained on the basis of beta-lactamase inactivation by antibodies being present in the IgG preparation. Antibodies were quantified by means of the ELISA (enzyme linked immunosorbent assay) technique. Furthermore, the antibody induced change in enzymic activity of various beta-lactamases was demonstrated by activity titration curves for TEM 1, TEM 2, OXA 1, OXA 2, OXA 3 beta-lactamases from E. coli.