Bacteria. The 853 isolates of gram-negative species and 296 isolates of gramn-positive species were predominantly of recent clinical origin from numerous sources of broad geographical distribution. The isolates were stored as described previously (2, 4). The 3-lactamase-producing strains used to generate the data in Table 3

No abstract

BMY 28100, a new oral cephalosporin with a (Z)-propenyl side chain at the 3 position and a phydroxyphenylglycyl substituent at the 7 position, was evaluated in comparison with cefaclor and cephalexin and, when appropriate, ampicillin and vancomycin. In vitro, BMY 28100 was more active than the reference cephalosporins against streptococci, Staphylococcus aureus, Staphylococcus epidermidis, Listeria nionocytogenes, Haemophilus influenzae, Propionibacterium acnes, Clostridiunm perfrigens, and Clostridium difficile. BMY 28100 was comfparable to cefaclor and more active than eephalexin against Staphylococcus saprophyticus and ampicillin-susceptible strains of Branhamella cattarhalis; but against ampicillin-resistant strains of B. cattarhalis, BMY 28100 was comparable to cephalexin and more active than cefaclor. Against Neisseria gonorrhoeae, BMY 28100 was comparable to cephalexin, but less active than cefaclor. Members of the family Enterobacteriaceae overall were equally susceptible to BMY 28100 and cefaclor but were less susceptible to cephalexin. In human serum, BMY 28100 was 45% protein bound. After an oral dose to mice, 82% of the drug was recovered in urine. The oral therapeutic efficacy of BMY 28100 in systemically infected mice reflected its activity in vitro.Whereas parenteral cephalosporins have been prepared with an array of side chains at the 3 and 7 positions, structural requirements for good gastrointestinal absorption have limited the choice of side chains for oral cephalosporins. The number of distinct substituents at the 3 position on oral cephalosporins currently in clinical use is small, and all substituents at the 7 position are of a single design: a native or modified phenyglycyl radical. Recent attempts to deviate from this pattern have yielded compounds with a broader spectrum of activity against gram-negative organisms but reduced gastrointestinal absorption and little antistaphylococcal activity (4, 9, 13; T. Suematsu, H. Sakamoto, and K. Takai, Proc. 14th Int. Congr. Chemother., p. 1147-1148 , abstr. no. 595, 1985).BMY 28100 is a new oral cephalosporin of conventional design. It has a (Z)-propenyl side chain at the 3 position and ap-hydroxyphenylglycyl substituent at position 7 (Fig. 1)

Biological and physicochemical properties of BL-S786 were compared with those of cephalothin, cephaloridine, and cefazolin. With few exceptions, BL-S786 was more active than the reference compounds against major gram-negative pathogenic species and its antibacterial spectrum was broader than that of cephalosporins currently available for clinical use. Although BL-S786 was generally less active than the control cephalosporins against gram-positive pathogens, it inhibited their growth at concentrations that should readily be achieved in humans after standard parenteral dosage. Streptococcus faecalis, a species relatively unsusceptible to cephalosporins in general, was an exception. BL-S786 was an effective bactericidal agent for strains of various gram-negative organisms. After intramuscular administration to mice, BL-S786 achieved high concentrations in blood, and its biological half-life was longer than that of the other three cephalosporins.BL-S786 (Fig. 1) is a new semisynthetic cephalosporin with a broad spectrum of antibacterial activity. The following is a report on biological and physicochemical properties of BL-S786 in comparison with those pfcephalothin, cephaloridine, and cefazolin, three cephalosporins widely used clinically in the United States and abroad. MATERIALS AND METHODSCephalosporins. BL-S786, 7-[a-(2-aminomethylphenyl)acetamidol-3-[(1-carboxymethyltetrazol-5-ylthio)methyl]-3-cephem-4-carboxylic acid, was synthesized by members of the Product Development Department, Bristol Laboratories (W.

It is well known that the composition of the assay medium greatly affects the antimicrobial activity of aminoglycoside antibiotics. A similar response has now been observed with certain penicillins and cephalosporins. In the case of these compounds, this effect is apparently governed by the chemical nature of the penicillin 6-and cephalosporin 7-side chains. In comparison with their activity in Nutrient Broth, the activity of some of the fl-lactam antibiotics that have a weakly basic or basic group in their side chain was reduced as much as 40-fold in one or more of the following media: Mueller-Hinton, Trypticase soy, antibiotic assay, and heart infusion broths. In contrast, the assay medium had no effect on the activity of those compounds possessing an acidic or a nonionizable function in their side chain. The extent to which medium influences the antibacterial activity was also dependent upon the assay method and the organism, the effect being more pronounced in broth dilution than in agar dilution tests and occurring more frequently with gram-negative than with gram-positive organisms.