In vitro activity of cefbuperazone compared with that of other new beta-lactam agents against anaerobic gram-negative bacilli and contribution of beta-lactamase to resistance

Abstract

Cefbuperazone was compared with other currently available and investigational antibiotics against 278 clinical isolates of anaerobic gram-negative bacilli by an agar dilution method. Cefbuperazone and cefotetan were equally active against Bacteroides fragiis, with 8% of the organisms tested found to be resistant to 32 ,ug of either drug per ml, Cefoperazone, cefotaxime, ceftriaxone, and cefmetazole were less active against these strains; cefoxitin, moxalactam, piperacillin, clindamycin, and metronidazole were more active. None of the agents were consistently active against any of the other anaerobic gram-negative bacilli except imipenem, for which the minimum concentration required to inhibit 90% of all strains tested was 4 ,ug/ml. A 10,000-fold increase in inoculum size caused an increase in the MIC of ceftriaxone, cefotaxime, and cefoperazone bUt not of-cefbuperazone, cefotetan, or cefoxitin. Investigation of the mechanism of resistance to cephalosporin-like agents demonstrated a correlation between the level of resistance and Il-lactamase activity. Cefbuperazone, cefotetan, and cefoxitin were not hydrolyzed, had lower MICs, and were less affected by changes in inoculum size than were cefotaxime, ceftriaxone, and cefoperazone.This study was undertaken to evaluate the activity of cefbuperazone, several new penicillins and cephalosporins, moxalactam, and imipenem against clinically important, frequently occurring anaerobic gram-negative bacilli and compare them with currently available agents which have useful activity against anaerobic bacteria. Anaerobic gramnegative bacilli were chosen for the evaluation for the following reasons: (i) these organisms are the major pathogenic anaerobes isolated in the clinical laboratories of the Medical University of South Carolina teaching hospitals; (ii) antimicrobial susceptibility of these organisms is not frequently tested in routine hospital laboratories; and (iii) there is great confusion as to which antimicrobial agents are most effective against these organisms in vitro. MIC, inoculum size effects, stability of the compounds to Bacteroides fragilis ,B-lactamase, and contribution of ,-lactamase to resistance were also investigated. Thirty-one strains of Bacteroides species which did not fit into any particular designation were also studied. Fifteen strains of B. melaninogenicus and 15 strains of Fusobacterium species were also studied. Organisms were stored at -70°C on glass beads coated with 1% brain heart infusion agar. B. fragilis ATCC 25285 and B. thetaiotaomicron ATCC 29741 were used throughout the study as control organisms. MATERIALS AND METHODS AntibioticsSusceptibility studies. MICs for the organisms tested were determined by the agar dilution method described by Sutter et al. (14). Overnight cultures of test organisms were diluted to the optical density of a 0.5 McFarland standard. These suspensions were inoculated with a Steers-Foltz replicator onto brain heart infusion agar supplemented with cysteine, hemin, and menadione and containing serial twofold d...

Factors affecting antimicrobial susceptibility of Fusobacterium species

“…Beta-lactamase. Each strain was examined for the presence of beta-lactamase by using a nitrocefin solution and PADAC strips (4,6,8). Two B. fragilis strains were used as controls; one was always strongly positive, and one was never positive.…”

“…The median differences from the low MIC to the high MIC for each strain expressed in log2 dilutions were as follows: penicillin, 4; cephalothin, 5; cefoxitin, 3; and cefotaxime, 4. This variability did not affect antimicrobial agent susceptibility when it was defined by susceptibility at the following breakpoints: penicillin, 12.5 U/ml; cephalothin, 16 p.g/ml; cefoxitin, 16 ,ug/ml; cefotaxime, 16 pLg/ml; and clindamycin, 4 1Lg/ml (6,10). When these breakpoints were used, no isolate was resistant during any measurement for penicillin or clindamycin, and none varied between susceptible and resistant to cefotaxime.…”

“…on various agar media have been reported, but the reliability of results obtained for Fitsob(a(îter-iium spp. has not been addressed previously (1,5,6,10,(14)(15)(16)19).…”