Synergy between acylureidopenicillins and immunoglobulin G in experimental animals

The interaction of a commercially available 7S modified immunoserumglobulin and beta-lactam antibiotics was studied in animal experiments (granuloma pouch model) as well as an ex vivo system (rat polyvinyl sponge model). Infections of the pouches were caused by gram-negative rods and gram-positive cocci, respectively. Therapy of pouches being infected with beta-lactamase-producing strains with beta-lactam antibiotics and immunoserumglobulin was as effective as beta-lactam antibiotic monotherapy of beta-lactamase-negative strains. This synergistic effect between immunoserumglobulin and beta-lactam antibiotics against beta-lactamase-producing bacteria is due to inactivation of enzymic beta-lactamase activity by specific antibodies against beta-lactamases. Immune phagocytosis was studied by adopting the in vivo and ex vivo models, respectively. Immune phagocytosis was most effectively stimulated by immunoserumglobulin whereas a pepsin-degraded product or a preparation obtained by pH4 treatment caused only minor effects. Furthermore, immunoserumglobulin stimulated phagocytosis and intracellular killing of gram-negative bacteria even in the absence of specific antibodies against these strains. Analogous effects were obtained with spermidine and albumin. These results indicate that immunoserumglobulin may stimulate phagocytosis nonspecifically, too. Thus, immunoserumglobulin may play a dual role in host defense mechanisms; in addition immunoserumglobulin acts as a beta-lactamase inhibitor, thus protecting beta-lactam antibiotics from hydrolysis.