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 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 beta-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 beta-lactams against PSP but against PRP only the serum of volunteers that had taken amoxycillin exhibited serum bactericidal titres of > or = 8. This study suggests a more predictable therapeutic efficacy against pneumococcal infection with amoxycillin than with available oral cephalosporins.
Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Hospital NS Aránzazu, San Sebastián, Spain. labmikro@teleline.es
E
E
Pérez-Trallero
M
M
Alkorta
J M
JM
García-Arenzana
A
A
Iturzaeta
M
M
Gomariz
D000284:Administration, Oral; D000328:Adult; D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015296:Ceftizoxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002444:Cefuroxime / Q000031:analogs & derivatives / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D011897:Random Allocation; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D000097627:Cefpodoxime Proxetil
D000658:Amoxicillin; D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D002444:Cefuroxime; D002511:Cephalosporins; D000097627:Cefpodoxime Proxetil; C040738:cefuroxime axetil