Journal of Antimicrobial Chemotherapy, Vol 41, 451-459, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
JD Knudsen, N Frimodt-Moller and F Espersen
The correlation between pharmacokinetic parameters and the in-vivo effect
of antibiotics in relation to bacterial growth phases was evaluated using
the mouse peritonitis model with a penicillin-resistant pneumococcus.
Different 8 h dosing regimens were applied, with different total doses and
initiated at different times during the bacterial growth phase. The effect
was measured as the decline in bacterial counts in the peritoneal cavity.
The pharmacokinetic parameters showed major changes during the phases of
growth, as the serum elimination of penicillin decreased during the
infection. The same effect of dosing regimens was observed in the
exponential and stationary phases. In two regimens where T(>MIC) (the
time the serum concentration exceeded the MIC) was 50% of the treatment
period, a significantly better effect was achieved with a 2 hourly regimen
than with a regimen with treatments every 20 min. The T(>MIC) of each
dose was shown to be a critical parameter for achieving an effect in all
growth phases. The maximum effect of penicillin, a 5-6 x log10 decline in
bacterial counts in the peritoneum of the mice, was achieved when
T(>MIC) was >50% of the treatment time or longer than approximately
40 min of each dose. The 50% effective dose for protection after a single
injection, ED50, was measured in the different phases of the infection and
found to increase with the duration of the pneumococcal infection, while
mice treated 24 h after challenge were beyond therapeutic range. The
correlation between the effect of penicillin and pharmacokinetic parameters
appears to follow the same rules during the different in- vivo growth
phases of pneumococci.
ORIGINAL ARTICLES
Pharmacodynamics of penicillin are unaffected by bacterial growth phases of Streptococcus pneumoniae in the mouse peritonitis model
Department of Research and Development, Statens Serum Institut, Copenhagen, Denmark.
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