1997 Volume 50 Issue 10 Pages 844-853
RP 59500 (Quinupristin-Dalfopristin) is the first semisynthetic injectable streptogramin anti-microbial agent, which is a combination of quinupristin and dalfopristin in a 30: 70 ratio. The components of RP 59500 act synergically to provide bactericidal activity through action at different Oct. 1997 THE JAPANESE JOURNAL OF ANTIBIOTICS 50-10 853 (47) sites on bacterial ribosomes.
In the present study, the antimicrobial activity of RP 59500 was compared with those of four macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin). Susceptibility testing was carried out by microdilution method on 303 strains of 10 species, especially antibiotic-resistant Gram-positive cocci.
RP 59500 was active against a wide range of Gram-positive cocci including methicillin-resistant Staphylococci and penicillin-resistant Streptococcus pneumoniae. The MICs90 of RP 59500 against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis were both 0.25μ9/ml, although those of four macrolides were higher than 32μg/ml. The MICs90 of RP 59500 against penicillin-sensitive, -intermediate and -resistant S. pneumoniae were all 0.5μg/ml, although those of four macrolides against penicillin-resistant S. pneumoniae were higher than 32μg/ml. RP 59500 also exhibited equivalent activities to the four macrolides against strains of Streptococcus pyogenes, Streptococcus agalactiae and Moraxella catarrhalis. RP 59500 exhibited the highest activities against Enterococcus faecalis, Enterococcus faecium and Enterococcus avium strains which are intrinsically resistant to most antimicrobial agents.
No cross-resistance was observed between RP 59500 and the four macrolides, which will merit attention in future clinical trials of the agent.
The effect of human serum on the MIC of RP 59500 was studied with strains of S. aureus, S. epidermidis and E. faecalis. The presence of 20% (V/V) serum had little or no effect on the MIC, although 50% (V/V) serum increased MICs by 4-8 folds.
Laboratory-induced resistance to RP 59500 occurred in a stepwise fashion in broth cultures of S. aureus, S. epidermidis and E. facalis strains and the induction rate was slow and no more than four fold increases were observed.
Population analysis was performed on RP 59500 and the reference macrolides against S. aureus ATCC 25923 strain. Although low frequencies (less than 0.01%) of resistant sub-population were detected with EM, CAM, AZM and RXM, no RP 59500-resistant sub-population was detected in this study.
