Antimicrobial synergy resulting from combined antibiotic therapy is often important in the treatment of serious bacterial infections. To investigate the interactions between cefotaxime (CTX), desacetylcefotaxime (DES), and ofloxacin (OFL), 247 recent clinical isolates were tested for in vitro susceptibility to each antibiotic alone by an agar dilution technique and retested with the various antibiotic combinations using a checkerboard protocol. Fractional inhibitory concentrations were calculated for all organisms with all drug combinations. Time kill kinetic studies were performed on selected isolates to examine the bactericidal activity of the various antimicrobial combinations. Of the 110 gram-negative organisms tested, synergy or partial synergy between CTX, DES and OFL was demonstrable for 89 (81%). Included in the study were 70 members of the Enterobacteriaceae family, 20 isolates of Pseudomonas aeruginosa, 10 strains of Acinetobacter baumannii, and 10 isolates of Xanthomonas maltophilia. Additive activity was observed against an additional 13 (11%) isolates. Findings were similar for the 89 gram-positive isolates examined. Organisms tested included methicillin-resistant Staphylococcus aureus (20), methicillin-susceptible Staphylococcus aureus (20), methicillin-resistant Staphylococcus epidermidis (9), methicillin-susceptible S. epidermidis (10), Enterococcus faecalis (10), and Streptococcus pneumoniae (20). Synergy or partial synergy was observed against 81 (91%). Less synergistic activity was detected, however, with members of the Bacteroides fragilis group. Of the 48 organisms tested, synergy or partial synergy was noted for only 27 (57%). Isolates representative of each major group of organisms included in the study were tested to determine whether synergistic bactericidal activity was also demonstrable with the three drugs. Time kill studies supported the checkerboard results.(ABSTRACT TRUNCATED AT 250 WORDS)

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Fifteen clinical isolates of Fusobacterium species were studied to determine their quality of growth on five agar media, their susceptibility to penicillin, cephalothin, cefoxitin, and cefotaxime, the inoculum effect, and the presence of L forms and beta-lactamase. Wilkins-Chalgren agar supported confluent growth best, but Fusobacterium nucleatum exhibited poor growth on all agar media. Most isolates exhibited poor reproducibility of MIC results with repeated agar dilution testing. However, most isolates were susceptible to all antibiotics at the breakpoint concentrations. No inoculum effect was observed, but preparation of an inoculum at a 0.5 McFarland nephelometric standard produced a lower than expected number of CFU (10(6) CFU) in some isolates. L forms were frequently seen. No beta-lactamase was found. The variability in MICs seen with beta-lactam antibiotics was not found when clindamycin was tested. MIC studies with Fusobacterium spp. may be complicated by poor growth on agar media, poor reproducibility, and small inoculum size.