IN-VITRO, IN-VIVO AND EX-VIVO STUDIES WITH ORAL BETA-LACTAMS AGAINST STREPTOCOCCUS-PNEUMONIAE

In-vitro killing curves, a protection model in immunocompetent mice an d an ex-vivo model in volunteers were used to evaluate the efficacy of amoxycillin, cefuroxime axetil and cefpodoxime proxetil against a pen icillin-intermediate-resistant Streptococcus pneumoniae (MIC = 1 mg/L) (PRP) and a penicillin-susceptible S. pneumoniae (MIC = 0.01 mg/L) (P SP). In vitro, the maximal bactericidal activity was obtained with amo xycillin (1 x MIC versus 2 x MIC cefpodoxime and 4 x MIC cefuroxime). Mice were challenged by intraperitoneal inoculation and treated orally every 8 h for 48 h with 2.5, 5, 7.5 and 10 mg/kg doses of these three beta-lactams. The rate of survival for the PSP strain was 100% with a ny dose of the three tested antibiotics. For the PRP strain only amoxy cillin showed 100% survival with 5, 7.5 or 10 mg/kg doses. Twelve heal thy volunteers were randomized in three groups and each received two d oses of the oral antibiotic. Blood samples were collected from each su bject 0.5 h and 2 h after drug administration and serum inhibitory and bactericidal titres were measured. Similar values were obtained with the three beta-lactams against PSP but against PRP only the serum of v olunteers that had taken amoxycillin exhibited serum bactericidal titr es of greater than or equal to 8. This study suggests a more predictab le therapeutic efficacy against pneumococcal infection with amoxycilli n than with available oral cephalosporins.