Bay Y 3118, a new quinolone derivative, rapidly eradicates Listeria monocytogenes from infected mice and L929 cells

Abstract

Bay Y 3118 is a new quinolone derivative with pronounced activity against gram-positive bacteria including the facultatively intracellular bacterium Listeria monocytogenes. Bay Y 3118 was tested in vitro and in animal models of listeriosis. All strains of L. monocytogenes and other Listeria spp. were highly susceptible in vitro; the MICs for these organisms ranged from 0.062 to 0.25 micrograms/ml. Bay Y 3118 was rapidly bactericidal in vitro, with a postantibiotic effect occurring for 3 h after removal of the antibiotic. L. monocytogenes was eliminated from infected L929 cells treated with Bay Y 3118, suggesting a bactericidal effect on the listeriae in these cells. Immunocompetent mice were rapidly cured by treatment with 4 mg every 12 h. Concomitantly, the levels of interleukin 6 and gamma interferon in mouse sera declined rapidly. In immunocompetent mice, treatment with 2 mg of Bay Y 3118 every 12 h resulted in a greater initial reduction in the listerial counts in the organs than treatment with 2 mg of ampicillin every 12 h. Bay Y 3118 completely eliminated L. monocytogenes from the livers and spleens of chronically infected nude mice. However, some of the bacteria reappeared after the cessation of therapy. In conclusion, Bay Y 3118 is an excellent candidate substance for the therapy of infections caused by facultatively intracellular gram-positive bacteria such as L. monocytogenes.