An experimental meningitis with Streptococcus pneumoniae in rats: therapeutic effect of aspoxicillin and its penetration into CSF.
An experimental meningitis model was produced in rats with Streptococcus pneumoniae Type III and used to evaluate the therapeutic effect of aspoxicillin in comparison with piperacillin, mezlocillin and ampicillin. At the same time, their bactericidal activities and pharmacokinetics in cerebrospinal fluid (CSF) were determined. The experimental meningitis model was prepared by intracisternal inoculation of the organism. The rats in this model began to die 2 days after the infection and all died within 5 days. Histological examination also revealed that this model was a fatal pneumococcal meningitis model in rats. The concentrations of these penicillins in CSF of the infected rats determined by the high performance liquid chromatography method were significantly increased by bacterial infection. Of these drugs, ASPC gave the highest penetration into the infected CSF and the longest persistency in CSF. In a comparison of the bactericidal activity of these penicillins in this model, aspoxicillin at a dose of 20 mg/kg inhibited the regrowth of bacteria in CSF 24 h after administration, but the other three penicillins did not. To conclude, in this new experimental meningitis model in rats, aspoxicillin showed an excellent therapeutic effect due to its stronger bactericidal action and favourable pharmacokinetic properties.
Yamaguchi
T
T
Biological Research Laboratory, Tanabe Seiyaku Co. Ltd., Saitama, Japan.
Kasuga
O
O
Okuno
S
S
Maezawa
I
I
D000658:Amoxicillin / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006207:Half-Life; D008297:Male; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D051381:Rats; D011919:Rats, Inbred Strains; D013296:Streptococcus pneumoniae / Q000187:drug effects
C037485:aspoxicillin; D000658:Amoxicillin