The ketolide antibiotic HMR 3647, a candidate substance for the treatment of systemic and intracerebral infections with Listeria monocytogenes

HMR 3647 is a novel macrolide derivative with a broad spectrum of activity against grampositive bacteria and some fastiduous gramnegative bacteria, an aerobes and Toxoplasma gondii. In this work, its activity against the facul tatively intracellular bacterium, Listeria monocytogenes, was examined in v itro, in tissue culture and in animal models of systemic and intracerebral infection and compared with that of erythromycin. All strains of L. monocyt ogenes were susceptible to the substance, with minimal inhibitory concentra tions (MICs) that were consistently lower than the MICs of erythromycin. HM R 3647 was bacteriostatic against L. monocytogenes since concentrations of up to 64 times the MIC did not kill the bacteria within 24 hours. HMR 3647 produced a pronounced postantibiotic effect (PAE) and was bacteriostatic in tissue culture cells infected with L. monocytogenes. In animal models of s ystemic and intracerebral infection, HMR 3647 was slightly more effective t han erythromycin in the livers and spleens and comparably effective in the brains when given in the same dosage. In conclusion, HMR 3647 is a candidat e substance for the treatment of infections with L. monocytogenes in immuno competent subjects.