In vitro activity of an oral iminomethoxy aminothiazolyl cephalosporin, R-3746.
The in vitro activity of R-3746, an iminomethoxy aminothiazolyl cephalosporin with a CH2OCH3 moiety at position 3, was compared with those of other antibiotics. R-3746 inhibited the majority of hemolytic streptococci (groups A, B, C, F, and G) and Streptococcus pneumoniae at less than 0.06 micrograms/ml, which was comparable to the activity of amoxicillin, 2- to 8-fold more active than cefixime, and 16- to 64-fold more active than cefaclor and cephalexin. Ninety percent of beta-lactamase-producing Haemophilus influenzae and Neisseria gonorrhoeae were inhibited at a concentration 0.25 micrograms/ml, but it was less active against Branhamella spp. It did not inhibit (MIC, greater than 16 micrograms/ml) enterococci, viridans group streptococci, or methicillin-resistant staphylococci. The MICs of R-3746 for 90% of strains tested for Escherichia coli; Klebsiella pneumoniae; Citrobacter diversus; Proteus mirabilis; and Salmonella, Shigella, and Yersinia spp. were less than or equal to 1 micrograms/ml. It was two- to eightfold less active than cefixime but was markedly superior to cefaclor, cephalexin, amoxicillin-clavulanate, and trimethoprimsulfamethoxazole. R-3746 inhibited 50% of Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Morganella spp., Providencia spp., Proteus vulgaris, and Serratia marcescens at less than or equal to 8 micrograms/ml. Pseudomonas spp. were resistant. Fifty percent of Clostridium spp. were inhibited by 0.5 micrograms/ml, but MICs for Bacteroides spp. were greater than 128 micrograms/ml. R-3746 was not appreciably hydrolyzed by most chromosomal and plasmid-mediated beta-lactamases.
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Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
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D000658:Amoxicillin / Q000494:pharmacology; D019980:Amoxicillin-Potassium Clavulanate Combination; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002433:Cefaclor / Q000494:pharmacology; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000494:pharmacology; D015296:Ceftizoxime / Q000031:analogs & derivatives*; D002444:Cefuroxime / Q000494:pharmacology; D002506:Cephalexin / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D002969:Clavulanic Acids / Q000494:pharmacology; D003470:Culture Media; D004338:Drug Combinations / Q000494:pharmacology; D004355:Drug Stability; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D013420:Sulfamethoxazole / Q000494:pharmacology; D014295:Trimethoprim / Q000494:pharmacology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D001618:beta-Lactamases / Q000378:metabolism; D000097623:Cefpodoxime
D000658:Amoxicillin; D019980:Amoxicillin-Potassium Clavulanate Combination; D000900:Anti-Bacterial Agents; D002433:Cefaclor; D020682:Cefixime; D002439:Cefotaxime; D015296:Ceftizoxime; D002444:Cefuroxime; D002506:Cephalexin; D002511:Cephalosporins; D002969:Clavulanic Acids; D003470:Culture Media; D004338:Drug Combinations; D013420:Sulfamethoxazole; D014295:Trimethoprim; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D001618:beta-Lactamases; D000097623:Cefpodoxime