No abstract

The bactericidal activities of ABT-773, a new ketolide, were compared to those of cefuroxime and amoxicillinclavulanate against 10 strains of Streptococcus pneumoniae containing the ermB gene. MICs and time-kill curves were determined in duplicate per NCCLS guidelines with cation-adjusted Mueller-Hinton broth with 3% lysed horse blood. Viable counts were done at 0, 2, 6, and 24 h. Antibiotic concentrations tested were two and eight times the MIC. ABT-773 MICs ranged from 0.008 to 1.0 g/ml. Bactericidal activity was observed with ABT-773 at eight times the MIC against 4 of 10 strains at 24 h compared to 10 of 10 strains with the beta-lactam antibiotics.The ketolides, semisynthetic 14-membered ring macrolides, represent a new subclass of agents in the macrolide-lincosamide-streptogramin group. The substitution of the L-cladinose sugar with a 3-keto group on the erythronolide A ring is the major differing structural component of the ketolides (2). Despite structural similarity, the ketolides maintain in vitro activity against macrolide-resistant strains of Streptococcus pneumoniae. One of the newest agents, ABT-773, has demonstrated higher rates of accumulation as well as stronger ribosome binding than erythromycin with macrolide-sensitive strains of S. pneumoniae (2). ABT-773 has also demonstrated the ability to accumulate in S. pneumoniae isolates containing the mef gene. Even in the presence of the erm gene, ABT-773 was shown to bind to methylated ribosomes, although binding was less than that to the wild type. It is these properties that allow the ketolide to remain active against macrolide-resistant organisms (2). The MIC of ABT-773 at which 90% of the isolates tested are inhibited has been reported previously to be 0.125 g/ml for 78 ermB-and 44 mefE-containing strains (3).With in vitro activity against macrolide-resistant S. pneumoniae (1), the ketolides are prime candidates for the treatment of community-acquired respiratory tract infections. The purpose of this study was to compare the in vitro bactericidal activities of ABT-773, amoxicillin-clavulanate, and cefuroxime against ermB-containing strains of S. pneumoniae. MIC and time-kill assays were performed on 10 clinical isolates of S. pneumoniae containing the ermB gene. PCR was used to determine the genes present in the macrolide-resistant strains of S. pneumoniae. Bacterial DNA was prepared with the Wizard genomic DNA purification kit (Promega, Madison, Wis.). Primers (mefE and ermB) were prepared at the University of Illinois at Chicago Protein Research Laboratory as previously described (8, 9).The isolates were stored at Ϫ70°C and underwent three subcultures prior to MIC and time-kill studies. The control strain, S. pneumoniae ATCC 49619, was used for validation of MIC results (5). For each experiment, the organisms were freshly subcultured on blood agar plates (Remel, Lenexa, Kans.) and incubated overnight at 35°C with 5% CO 2 . Each inoculum was prepared by direct suspension and adjusted with sterile saline until the turbidity matched a 0.5 McFarlan...

The in vitro activity of ABT-773, a new ketolide, was compared with those of clarithromycin, amoxicillin, metronidazole, and tetracycline against 15 strains of Helicobacter pylori. The MIC of ABT-773 at which 90% of isolates were inhibited was 0.25 g/ml, which was 3 dilutions higher than that of the most active agent, clarithromycin. Synergy and antagonism were not seen with any combinations. Additive activity was seen with tetracycline, metronidazole, and amoxicillin in 100, 60, and 40% of the combinations, respectively.Infections with Helicobacter pylori have been successfully treated with several different regimens. Combination therapy with a proton pump inhibitor, bismuth salt or ranitidine bismuth citrate, and two antibiotics is most commonly used, with no optimum regimen yet determined. The antimicrobial agents used in the treatment of H. pylori infections consist primarily of clarithromycin, metronidazole, amoxicillin, and tetracycline. While these antibiotics have demonstrated good in vitro activities and high cure rates, there is concern about increasing resistance and adverse effects associated with these agents. New antibiotics are needed to augment the current arsenal of agents effective against H. pylori. ABT-773 is a novel ketolide possessing a spectrum of activity similar to the macrolide class of antibiotics. The purpose of this study was to determine the in vitro activity of ABT-773 alone and in combination with the other antibiotics commonly used against H. pylori.(This work was presented in part at the poster session of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, Calif., 1999.) Fourteen clinical isolates of H. pylori were obtained from the University of Illinois Hospital Microbiology Laboratory (Chicago, Ill.), Abbott Laboratories (Abbott Park, Ill.), and D. Y. Graham (Houston, Tex.). Most of the isolates were collected prior to 1995. One control strain, ATCC 43504, was obtained from the American Type Culture Collection (Manassas, Va.). The isolates were kept frozen at Ϫ70°C in skim milk and 17% glycerol. Prior to the susceptibility studies the organisms were plated on 5% sheep blood agar and incubated at 37°C in 10% CO 2 for 3 days. The isolates were subcultured once to ensure reliable growth.ABT-773, clarithromycin (Abbott Laboratories), amoxicillin, metronidazole, and tetracycline (U.S. Pharmacopeia, Rockville, Md.) powders were prepared according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines or per the manufacturer's recommendation (7). Agar dilution procedures were used for the MIC and checkerboard assays. The agar medium used for MIC and checkerboard determinations was Mueller-Hinton (Difco, Detroit, Mich.) supplemented with 10% defibrinated horse blood (Remel, Lenexa, Kans.) at a neutral pH. The final inoculum of the H. pylori strains was 10 5 CFU/spot. The inocula were prepared by suspending organisms in Mueller-Hinton broth (Difco) and adjusting the turbidity to that of a 2.0 McFarland standard using a spectr...

The bactericidal activity of ABT-773 was compared with amoxicillin against 10 clinical isolates of S. pyogenes (six erythromycin susceptible and four erythromycin resistant). The MIC ranges (mg/L) were 0.004-0.25 of ABT-773 and 0.015-0.12 of amoxicillin. At 24 h, ABT-773 concentrations of 2 x MIC and 8 x MIC were bactericidal against three and six organisms, respectively. In comparison, amoxicillin was bactericidal against all 10 organisms at both test concentrations.

In vitro bactericidal activity and post-antibiotic effect of ABT-773 versus co-amoxiclav against anaerobes