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

Cefadroxil is a new semisynthetic cephalosporin with a broad antibacterial spectrum and a high chemotherapeutic potential when administered orally. The inhibitory activity of this compound was similar to that of cephalexin and cephradine when tested against 602 clinical isolates on Mueller-Hinton medium. In the oral treatment of experimental infections of mice, cefadroxil was more effective than cephalexin against Streptococcus pyogenes, and comparably effective against Streptococcus pneumoniae, Staphylococcus aureus, and several gram-negative species. Administered orally to mice, at doses ranging from 25 to 100 mg/kg, cefadroxil attained peak concentrations in the blood similar to those of cephalexin. At a dose of 200 mg/kg, however, higher peak levels were noted with cefadroxil than with cephalexin. In regard to other properties which were investigated, the behavior of cefadroxil compared favorably to that of cephalexin.

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)

Ceragenins are small molecule mimics of endogenous antimicrobial peptides (AMPs), and as such display broadspectrum antimicrobial activity. These molecules are derived from a common bile acid and can be prepared at a large scale. Because ceragenins are not peptide based, they are not substrates for proteases. Gram-negative and positive bacteria are susceptible to ceragenins, including drug resistant organisms. Although ceragenins and colistin have common features, ceragenins retain full antibacterial activity against colistin-resistant Gram-negative bacteria. Bactericidal activity of ceragenins involves selective association with bacterial membranes followed by membrane depolarization. Due to this mechanism of action, which provides bactericidal activity against sessile bacteria, ceragenins eradicate established biofilms. Lipid-enveloped viruses (e.g. vaccinia) are deactivated by ceragenins, and topical application of a lead ceragenin decreases transmission of the virus in skin in a murine model. More recently, the activities of ceragenins against fungal pathogens have been reported, with minimum inhibition concentrations comparable to clinically used anti-fungal agents. In addition to antimicrobial activities, ceragenins have been shown to display some of the "secondary" activities attributed to AMPs. In vivo use of ceragenins to eradicate biofilms, prevent infection and accelerate bone growth demonstrate some of the types of applications in which ceragenins may be used to augment or replace activities of endogenous AMPs.

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.

No abstract

BL-S 640 was evaluated in vitro by comparison with cephalothin, cephaloridine, cefazolin, and cephalexin. The new compound was more active than the control cephalosporins against most major gram-negative and some gram-positive species. Moreover, its antibacterial spectrum included strains of Enterobacter, Proteus morganii, P. rettgeri , and Providencia stuartii , species generally resistant to the other cephalosporins. BL-S 640 was an effective bactericidal agent for strains of various species of Enterobacteriaceae . In human plasma, the compound was 58% protein bound.

No abstract