Influence of LY146032 on human polymorphonuclear leucocytes in vitro

LY 146032 is a new acidic lipopeptide antibiotic with high in-vitro activity against Gram-positive bacteria. We have studied the influence of LY 146032 on the functions of polymorphonuclear leucocytes with two strains of Staphylococcus aureus, one susceptible to oxacillin and one resistant. LY 146032 (10 mg/l) was found to have no influence on superoxide generation stimulated by phorbol myristate acetate, nor on phagocytosis of opsonized Staph. aureus, furthermore there was no effect on chemotaxis in agar stimulated by opsonized zymosan. LY 146032 (MIC and MIC/4) did not modify the intracellular killing of the two strains when they were preincubated, or when the antibiotic was added either at the time or after the completion of phagocytosis both in aerobic and in strict anaerobic conditions. However, in aerobic conditions, LY 146032 was able to prevent the overgrowth of phagocytosed Staph. aureus after 24 h of incubation. The intracellular concentration of LY 146032, measured by microbiological assay, was 60% of the extracellular concentration.