In vitro activity of trovafloxacin against Bacteroides fragilis in mixed culture with either Escherichia coli or a vancomycin-resistant strain of Enterococcus faecium determined by an anaerobic time-kill technique

To determine the efficacy of trovafloxacin as a possible treatment for intr a-abdominal abscesses, we have developed an anaerobic time-kill technique u sing different inocula to study the in vitro killing of Bacteroides fragili s in pure culture or in mixed culture,vith either Escherichia coli or a van comycin-resistant strain of Enterococcus faecium (VREF). With inocula of 5 x 10(5) CPU/ml and trovafloxacin concentrations of less than or equal to2 m ug/ml, a maximum observed effect (E-max) of greater than or equal to6.1 (lo g(10) CFU/ml) was attained with all pure and mixed cultures within 24 h. Wi th inocula of 10(8) CFU/ml, a similar E-max and a similar concentration to produce 50% of E-max (EC50) for B. fragilis were found in both pure culture s and mixed cultures with E. coli. However, to produce a similar killing of B. fragilis in the mixed cultures with VREF, a 14-fold increase in the con centration of trovafloxacin was required. A vancomycin-susceptible strain o f E. faecium and a trovafloxacin-resistant strain off. coli were also found to confer a similar "protective" effect on B. fragilis against the activit y of trovafloxacin. Using inocula of 10(9) CFU/ml, the activity of trovaflo xacin was retained for E. coli and B. fragilis and was negligible against V REF. We conclude that this is a useful technique to study the anaerobic kil ling of mixed cultures in vitro and may be of value in predicting the killi ng of mixed infections in vivo. The importance of using mixed cultures and not pure cultures is clearly shown by the difference in the killing of B. f ragilis in the mixed cultures tested. Trovafloxacin will probably be ineffe ctive in the treatment of infections involving large numbers of enterococci . However, due to its ability to retain activity against large cultures of B. fragilis and E. coli, trovafloxacin could be beneficial in the treatment of intra-abdominal abscesses.