In-vitro, in-vivo and ex-vivo studies with oral β-lactams against Streptococcus pneumoniae

Abstract

In-vitro killing curves, a protection model in immunocompetent mice and an ex-vivo model in volunteers were used to evaluate the efficacy of amoxycillin, cefuroxime axetil and cefpodoxime proxetil against a penicillin-intermediate-resistant Streptococcus pneumoniae (MIC = 1 mg/L) (PRP) and a penicillin-susceptible S. pneumoniae (MIC = 0.01 mg/L) (PSP). In vitro, the maximal bactericidal activity was obtained with amoxycillin (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 β-lactams. The rate of survival for the PSP strain was 100% with any dose of the three tested antibiotics. For the PRP strain only amoxycillin showed 100% survival with 5, 7.5 or 10 mg/kg doses. Twelve healthy volunteers were randomized in three groups and each received two doses of the oral antibiotic. Blood samples were collected from each subject 0.5 h and 2 h after drug administration and serum inhibitory and bactericidal titres were measured. Similar values were obtained with the three β-lactams against PSP but against PRP only the serum of volunteers that had taken amoxycillin exhibited serum bactericidal titres of ≤ 8. This study suggests a more predictable therapeutic efficacy against pneumococcal infection with amoxycillin than with available oral cephalosporins.