In vivo efficacy of trovafloxacin against Bacteroides fragilis in mixed infection with either Escherichia coli or a vancomycin-resistant strain of Enterococcus faecium in an established-abscess murine model
Let. Stearne et al., In vivo efficacy of trovafloxacin against Bacteroides fragilis in mixed infection with either Escherichia coli or a vancomycin-resistant strain of Enterococcus faecium in an established-abscess murine model, ANTIM AG CH, 45(5), 2001, pp. 1394-1401
The pharmacodynamic and pharmacokinetic properties of trovafloxacin were st
udied in a standardized murine model of established subcutaneous abscesses.
Daily dosing regimens of 37.5 to 300 mg/kg every 8 h (q8h) or every 24 h (
q24h) were started 3 days after inoculation with mixtures containing either
Bacteroides fragilis-Escherichia coli-autoclaved cecal contents (ACC) or B
. fragilis-vancomycin-resistant Enterococcus faecium (VREF)-ACC, Treatment
was continued for 3 or 5 days. The efficacy of treatment was determined by
the decrease in abscess bacterial counts and abscess weights, as well as by
the reduction in inflammation (biodistribution of Tc-99m-HYNIC immunoglobu
lin G) compared to saline-treated controls. Trovafloxacin showed a signific
ant dose-response effect on the bacterial counts, weight, and inflammation
of B, fragilis-E, coli abscesses after 3 and/or 5 days of treatment. A maxi
mum 3.4 and 3.1 log(10) reduction in CFU/abscess in the respective B,fragil
is and E, coil bacterial counts was attained after 5 days of treatment with
daily doses of 300 mg/kg, The peak serum concentration was more predictive
for effect than the area under the concentration-time curve. The C-max was
the pharmacodynamic index most predictive for success, and the efficacy of
the q24h regimens was significantly better than the q8h regimens. The anti
biotic was ineffective against the VREF in mixed infection with B, fragilis
, while the kilting of the anaerobe in the same combination was significant
ly less than in the E. coli combination (P < 0.05), We conclude that this i
s a useful model for studying the activity of antimicrobials for the treatm
ent of small (< 1-cm), undrainable, mixed-infection abscesses. In addition,
we have shown for the first time that a decrease in bacterial numbers also
leads to a reduction in both abscess weight and inflammation.