Escherichia coli mutants defective in the ability to agglutinate guinea pig erythrocytes (HA-) were isolated from a nalidixic acid-resistant derivative, 31-B, of E. coli TN 675 that produces type 1 fimbriae and induces urinary tract infection in mice fed a 5% glucose solution. All nine HAmutants were defective not only in their ability to agglutinate Candida albicans cells and erythrocytes from various species, but also in their capacity to adhere to mouse bladder epithelial cells. None of the mutants were agglutinated by anti-type 1 fimbriae antiserum. Although most of the mutants were fimbriated when examined by electron microscopy, their fimbriae differed serologically from type 1 fimbriae. All of the mutants showed 100 to 1,000 times lower bacterial recovery from the bladder walls of mice 3 h after inoculation into the bladder and lacked urinary tract infectivity in mice. These results suggest that all of the HAmutants are defective in type 1 fimbriae production and that type 1 fimbriae facilitate the development of urinary tract infection in mice, probably by mediating bacterial adherence to the bladder epithelial cells.

SCE-963 {7beta-[2-(2-aminothiazol-4-yl)acetamido]-3-[({1-(2-dimethylaminoethyl)- 1H-tetrazol-5-yl}thio)methyl]-ceph-3-em-4-carboxylic acid}, a new semisynthetic cephalosporin, showed excellent antibacterial activity against gram-positive and gram-negative bacteria, including Haemophilus influenzae, indole-positive Proteus, Enterobacter species, and Citrobacter freundii. The minimum inhibitory concentrations of SCE-963 against most strains of clinically isolated Escherichia coli, Klebsiella pneumoniae, H. influenzae, and Proteus mirabilis were within the range of 0.2 to 0.78 mug/ml. These activities were about 10 times more potent than those of cefazolin, cephaloridine, and cephalothin. Variations in pH, addition of horse serum, and type of growth medium had no significant effect on the activity of the cephalosporin, but the inoculum size elicited a considerable effect on the activity of beta-lactamase-producing strains of bacteria. SCE-963 exerted bactericidal and bacteriolytic effects on Staphylococcus aureus and E. coli. The pronounced in vitro activity was reflected in the remarkable protection in mice infected with a wide range of gram-negative bacteria, such as E. coli, K. pneumoniae, P. mirabilis, Proteus vulgaris, Proteus morganii, and Proteus rettgeri. The protective effects of SCE-963 in mice infected with E. coli, K. pneumoniae, and P. vulgaris varied according to the challenge dose. The activity of SCE-963 was far more potent when the drug was administered parenterally rather than orally.

The activity of cefmenoxime (SCE-1365), 7,8-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, was compared with that of other cephalosporins. Cefinenoxime exhibited high activity against a wide variety of gram-positive and gramnegative bacteria. The in vitro activity of cefmenoxime against Streptococcus pyogenes, Haemophilus influenzae, and Enterobacteriaceae, including indolepositive Proteus, Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii, was 10 to 1,000 times greater than that of several other cephalosporins. Against Pseudomonas aeruginosa, cefmenoxime showed activity two to four times that of sulbenicillin and carbenicillin but less than that of cefsulodin. Variation in pH, addition of horse serum, and type of growth medium had definite effects on the activity of cefmenoxime, and the inoculum size affected the activity against bacterial species. In Escherichia coli cefmenoxime showed marked affinity for penicillin-binding protein 3 (PBP-3), followed by PBP-1 (1A and 1B). This affinity profile was well correlated with its filamentous cell-forming activity under extremely low drug concentrations and with its bactericidal activity against microorganisms. The high in vitro activity of cefmenoxime was reflected in the degree of protection observed in mice infected intraperitoneally with a wide variety of gram-positive and gram-negative bacteria. Furthermore, cefmenoxime showed good therapeutic activity against infection models in mice such as respiratory tract infection caused by Klebsiellapneumoniae and urinary tract infection caused by Proteus mirabilis.In recent years, with the increasing use of cephalosporins, an increasing number of infections caused by cephalosporin-resistant bacteria have been observed. The present report concerns the activity of cefmenoxime (SCE-1365),

SUMMARY.The virulence of Escherichia coli strains in ascending urinary-tract infection was studied in mice drinking a 5% glucose solution; factors determining the virulence were examined. Of 33 strains, 8 (group I) infected the bladder and kidney, 10 (group 11) infected only the bladder, while the remaining 15 strains (group 111) did not cause infection. The adherence of group-I and group-I1 strains to bladder epithelial cells in vitro was inhibited by D-mannose. In group 111, 13 strains barely adhered to the epithelial cells, while two strains showed an adherence unaffected by D-mannose. Most strains in groups I and I1 agglutinated erythrocytes of guinea-pig, chicken, and horse, and cells of Candida albicans in a mannose-sensitive manner. All strains in groups I and I1 had fimbriae. Virulence for the urinary tract was not directly related with 0-serotype, intraperitoneal virulence, ability to grow in mouse urine, ability to ferment dulcitol, production of haemolysin, susceptibility to serum bactericidal activity, or susceptibility to antibiotics. These results suggest that the adherence of the E. coli to mouse-bladder epithelial cells in a mannose-sensitive manner plays an important role in the development of urinary-tract infection in mice and that the adherence is probably mediated by type-1 or closely related fim briae.

SCE-129 [3-(4-carbamoyl-1-pyridiniomethyl)-7,8-(D-a-sulfophenylacetamido)-ceph-3-em-4-carboxylate monosodium salt], a new semisynthetic cephalosporin, shows potent in vitro antibacterial activities against Pseudomonas aeruginosa and some gram-positive bacteria, whereas it shows lower activity against many gram-negative rods. Against clinical isolates of P. aeruginosa this cephalosporin exhibited higher activity than did carbenicillin, and against the strains of Staphylococcus aureus, SCE-129 had similar activity to carbenicillin. Variations in pH, addition of horse serum, and type of growth medium had no significant effects on the activity of the cephalosporin; however, the inoculum size had some effect on the activity. SCE-129 is an effective bactericidal agent against P. aeruginosa and S. aureus. The protective effects of SCE-129 in mice infected with P. aeruginosa and S. aureus were more potent than those of carbenicillin. The protective effects of SCE-129 on Pseudomonas infection in mice varied according to the dosage schedule and the challenge dose. In a multiple dose schedule, a smaller amount of SCE-129 was necessary than that in a single dose schedule. The effects of SCE-129 after subcutaneous or intraperitoneal administration were more potent than were those by intravenous administration. No protective effect was observed by oral administration.