RP 59500, a streptogramin derivative, is effective in murine listeriosis

RP 59500 (Synercid) a streptogramin derivative, is a mixture of two water-soluble substances, RP 57669 (quinupristin), and RP 54476 (dalfopristin). It was tested in vitro and in vivo against Listeria strains. All strains were sensitive in vitro. The MICs of 60 strains of Listeria monocytogenes, L. seeligeri, L. ivanovii, and L. innocua were between 0.156 and 0.625 mg/l. Strains of L. grayi were inhibited by 1.25 mg/l of RP 59500. In contrast to its bactericidal effect against other gram-positive bacteria, RP 59500 was bacteriostatic against L. monocytogenes in all concentrations tested (up to 16 x MIC). However, it exerted a pronounced postantibiotic effect. RP 59500 was ineffective against intracellular L. monocytogenes multiplying in L929 mouse fibroblast cells. When it was included in the supernatant of the cells in nontoxic concentrations of below 12.5mg/l alone or in combination with gentamicin (50mg/l) it was not able to inhibit the growth of the listeriae in the cells. However, when tested in peritoneal exudate cells, it was bacteriostatic against L. monocytogenes. In spite of its relatively poor effects on listeriae in vitro, RP 59500 was as active as erythromycin in a mouse model of listeriosis. When mice iv infected with L. monocytogenes were treated ip with 2mg/animal every 12 hours with either erythromycin or RP 59500, both substances prevented growth of the bacteria in the organs, but were unable to eradicate the listeriae. We conclude that RP 59500 is a candidate substance for the treatment of human listeriosis which might be used when therapy with ampicillin is not feasible.