HMR 3647 human-like treatment of experimental pneumonia due to penicillin-resistant and erythromycin-resistant Streptococcus pneumoniae

An experimental Streptococcus pneumoniae pneumonia model in rabbits was use d to assess the efficacy of amoxycillin, erythromycin and a new ketolide, t elithromycin (HMR 3647), The MICs of amoxycillin, erythromycin and HMR 3647 for the three clinical S. pneumoniae strains used were, respectively, (mg/ L): 0.01, 16 and 0.02 (strain 195); 2, 0.25 and 0.02 (strain 16089); 8, >64 and 0.02 (strain 11724), Antibiotic therapy reproduced human serum pharmac okinetics (amoxycillin 1 g iv tds or erythromycin 500 mg qds or HMR 3647 80 0 mg bd), Forty-eight hours of therapy with HMR 3647 and amoxycillin result ed in significant bacterial clearance in the lungs and spleen of rabbits in fected by S, pneumoniae strain 195 and strain 16089 (at least 3 log(10) cfu /g decrease, P < 0.001). Erythromycin was active against only the erythromy cin-susceptible strain (3 log(10) cfu/g decrease at 48 h, P < 0.001). None of the antibiotics showed significant efficacy with strain 11724, All agent s produced significant bacterial clearance when time above MBC was >33%, an d microbiological failure when it was <25%, whereas MIC was not correlated with microbiological outcome with HMR 3647, Our findings suggest that pharm acodynamic data integrating MBC may be predictive of microbiological succes s or failure with greater accuracy than with MIC. HMR 3647 produced signifi cant bacterial clearance in both penicillin- and erythromycin-resistant pne umonia, but was less effective against the highly erythromycin-resistant S. pneumoniae strain.