The purpose of this study was to investigate the relationship between efficacy and percentage of time above the MIC (%T>MIC) in the cerebrospinal fluid (CSF) for different dosing regimens of
meropenem against an experimental lethal
meningitis model in guinea pigs with type b β-lactamase-nonproducing
ampicillin-resistant Haemophilus influenzae (Hib BLNAR). Guinea pigs were intrathecally inoculated with 10(8) CFU/head of Hib BLNAR 8 h before the start of
therapy. A single dose of 20, 40, or 80 mg/kg
meropenem or multiple doses of 40 mg/kg
meropenem were subcutaneously administered. Numbers of bacteria in CSF were counted 8 h after the start of
therapy.
Meropenem concentration in serum and CSF were determined in infected guinea pigs receiving a single dose of 40 mg/kg. In the single-dose regimen, 40 and 80 mg/kg
meropenem significantly reduced the number of bacteria in CSF compared with the control, but 20 mg/kg
meropenem did not. The %T>MIC for an 8-h period of 20, 40, and 80 mg/kg
meropenem were 41, 52, and 62, respectively. Two and four doses of 40 mg/kg
meropenem, for both of which %T>MIC was calculated as 100, had similar efficacy and were significantly superior to a single-dose of 40 mg/kg. In conclusion,
meropenem had high efficacy when %T>MIC in the CSF was increased because of the high dose level and shortening of the dosing interval in a guinea pig
meningitis model caused by Hib BLNAR, suggesting that high and frequent doses of
meropenem are useful for treatment of
meningitis with Hib BLNAR.