The influence of cefoperazone, cefotaxime, ceftaridime and aztreonam on phagocytosis by human neutrophils in vitro

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Abstract
The uptake and intracellular breakdown of Escherichia coli by human neutrophils was studied under the influence of cefoperazone, cefotaxime, ceftazidime and aztreonam. Non-opsonized as well as serum- and IgG-opsonized bacteria were used, and bacteria and neutrophils were exposed both separately before phagocytosis and together during uptake and in the postingestion phase. Preincubation of the neutrophils with the drugs stimulated their subsequent uptake of untreated serum-opsonized and non-opsonized E. coli in an antibiotic-free medium. With serum-opsonized bacteria this stimulating effect was reversed when the drugs were also present during phagocytosis. The uptake of IgG-opsonized bacteria was largely unaffected both after preincubation of the neutrophils and when the antibiotics were present during phagocytosis. With all four drugs, pre-exposure of bacteria before IgG-opsonization gave a much higher uptake than exposure after IgG-opsonization. Contrary to this, preincubation of the bacteria followed by serum-opsonization inhibited (cefotaxime, ceftazidime) or did not influence (cefoperazone, aztreonam) subsequent uptake in the absence of the drugs. The release of bacterial breakdown products from the cells in the postingestion phase was also inhibited by cefotaxime and ceftazidime after serum-opsonization. With non-opsonized and IgG-opsonized bacteria, however, a stimulation of intracellular breakdown was induced by the presence of these drugs during phagocytosis. Aztreonam and cefoperazone did not significantly influence this phase of phagocytosis. These observations suggest that the drugs bind to both neutrophils and bacteria in an individual manner and modify the binding and function of opsonins.

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