Therapeutic significance of nocardicin A stimulation of phagocyte function in experimental Pseudomonas aeruginosa infection.

Nocardicin A, a monocyclic beta-lactam antibiotic with modest anti-pseudomonal activity in vitro, controlled an otherwise fatal Pseudomonas infection in mice when given in doses which produced blood levels well below the minimum bactericidal concentration. In even smaller doses, it converted the partial protection afforded by modest doses of carbenicillin into full protection. Human polymorphonuclear leucocytes exposed to low concentrations of the drug in vitro and peritoneal macrophages recovered from mice treated with nocardicin A exhibited an unusually specific form of enhanced activity. Chemotaxis and phagocytosis were not affected, but intracellular killing of Ps. aeruginosa was significantly increased. This was shown to be due to an effect on the phagocyte and not to facilitated killing of organisms damaged by extracellular exposure to the antibiotic. It is argued that the effect on phagocyte function is sufficient to contribute materially to the therapeutic effect of nocardicin A.