Activity of RP 59500, a new parenteral semisynthetic streptogramin, against staphylococci with various mechanisms of resistance to macrolide-lincosamide-streptogramin antibiotics.

RP 59500 is a semisynthetic streptogramin (Sg) composed of two synergic components: RP 57669 and RP 54476. The activities of RP 59500, RP 57669 and RP 54476 were tested against 20 strains of staphylococci susceptible to macrolide, lincosamide and streptogramin antibiotics (MLS) and against strains exhibiting different MLS resistance mechanisms. RP 59500 was active against 14 strains harbouring emrA or ermC genes which were inducibly or constitutively resistant to erythromycin (MICs of 0.5-2 mg/L). Neither RP 59500, RP 57669 nor RP 54476 induced MLSB resistance. Constitutive mutants appeared at frequencies of 10(-7)-10(-8) when two MLSB-inducible strains of staphylococci were exposed to 40 mg/L each of clindamycin and RP 57669. No such mutants appeared on plates containing RP 59500 or RP 54476. The emergence of mutants was prevented if the cultures were exposed to RP 54476 (40 mg/L), indicating that such mutants are unlikely to be selected in vivo by RP 59500. However, for some constitutive mutants, MBCs of RP 59500 were as high as 8 mg/L. Strains producing acetyltransferase and hydrolase, inactivating SgA- and SgB-type antibiotics respectively, were resistant to RP 59500, RP 57669 and RP 54476. Production of Pincosamide nucleotidyltransferase-4, which inactivates lincosamides, had no effect on the MICs of RP 59500, RP 57669 and RP 54476.