Bactericidal activity of cefotaxime and fosfomycin in cerebrospinal fluid during the treatment of rabbit meningitis experimentally induced by methicillin-resistant Staphylococcus aureus.
The purpose of this study was to evaluate the therapeutic effect of cefotaxime (CTX) and fosfomycin (FOS), alone or in combination, in an experimental meningitis, with cerebrospinal fluid (CSF) concentrations of the two antibiotics reproducing those obtained in human CSF during bacterial meningitis. With a dose of 50 mg/kg of CTX and 100 mg/kg of FOS injected i.v. (CTX over 0.5 h and FOS over 3 h), CSF concentrations were comparable to those observed in man. In a series of five rabbits per treatment group, the bacterial population was counted before and after treatment (two doses with a six-hour interval) with CTX, FOS or CTX + FOS (CTX over 0.5 h before the end of FOS infusion). By the 12th hour of treatment, the percentage of bacteria surviving in CSF compared to the initial population was 4.35% for CTX, 0.20% for FOS and 0.19% for CTX + FOS. Thus, it seemed that CTX + FOS was not more active than FOS alone. In another series of four rabbits per group, the bactericidal effect was followed at T0, T6, T12, T24 and T48 after treatment (two doses with a six-hour with a six-hour interval). With CTX, a variable drop in bacterial count from one rabbit to the other occurred during the first 12 h, and then a bacteriostasis followed. With FOS, a quick bactericidal effect was observed during the first 12 h, becoming slower during the following 36 h (0.03% of bacteria surviving at the 48th hour). With CTX and FOS in combination, a quick bactericidal effect was achieved, remaining steady over a 48-hour period (0.001% of bacteria surviving at the 48th hour).
D000368:Aged; D000818:Animals; D002439:Cefotaxime / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005578:Fosfomycin / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D006801:Humans; D008581:Meningitis / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D008712:Methicillin / Q000494:pharmacology*; D010403:Penicillin Resistance; D011817:Rabbits; D013203:Staphylococcal Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
D005578:Fosfomycin; D002439:Cefotaxime; D008712:Methicillin