Comparison of antibacterial activity of a new cephalosporin, ceftizoxime (FK 749) with other cephalosporin antibiotics.

clinical isolates to R-3746 was determined by the agar dilution method. Ninety percent or more of pathogens such as Staphylococcus aureus, streptococci, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, indole-positive and indole-negative Proteus spp., Providencia rettgeri, and Haemophilus influenzae were inhibited at concentrations ranging from .0.01 to 1.56 ,ug/ml. Furthermore, at a concentration of 3.13 ,ug/ml, 50% or more of Staphylococcus epidermidis, Morganella morganii, Citrobacterfreundii, and Serratia marcescens strains were also inhibited. Pseudomonas aeruginosa and Xanthomonas maltophilia were resistant to R-3746.The activity of R-3746 was scarcely influenced by several growth conditions. R-3746 was highly resistant to hydrolysis by Il-lactamases derived from various species of bacteria. Killing-curve studies demonstrated bactericidal activity of R-3746 at concentrations above the MIC. R-3746 showed high affinity for penicillinbinding proteins 1, 3, and 4 of Staphylococcus aureus and 1A, 1l$s, and 3 of Escherichia coli. Systemic infections in mice caused by various pathogens, including j3-lactamase-producing strains, responded well to therapy with oral doses of CS-807.Various oral cephem antibiotics having relatively broad antibacterial spectra have been developed and used worldwide (2, 3,15,18,19,34 Fig. 1.The present report deals with the in vitro antibacterial activity of R-3746 together with the therapeutic effect of CS-807 on systemic infections in mice compared with cefaclor, amoxicillin, cefixime, and T-2588 (T-2525).* Corresponding author. MATERIALS AND METHODSChemicals. CS-807 and R-3746 were prepared by Sankyo Co., Ltd., Tokyo, Japan. The other antibiotics were gifts: penicillin G, amoxicillin, and methicillin from Banyu Pharmaceutical Co., Ltd., Tokyo, Japan; cephaloridine from Nihon Glaxo Co., Ltd., Tokyo, Japan; cefaclor from Shionogi & Co., Ltd., Osaka, Japan; cefixime from Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan; and T-2588 and T-2525 from Toyama Chemical Co., Ltd., Tokyo, Japan. All antibiotics were prepared daily with distilled water to the desired concentrations. '4C-labeled penicillin G (potassium 6-phenyl [1-_4C]

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo antibacterial activities of CS-807, a new oral cephalosporin

Utsui¹,

Inoue²,

Mitsuhashi³

1987

“…In keeping with its superior in vitro activity, FK 027 was the most active of the agents evaluated against infections with six species of gram-negative bacteria and was especially active against infections with E. aerogenes and S. marcescens, against which the other agents tested were not active. DISCUSSION Extensive investigations of new injectable cephem antibiotics such as ceftizoxime and cefotaxime show that the introduction of the a-methoxyimino aminothiazole side chain into the 7-position of the cephem nucleus results in a significant enhancement of antibacterial activity against gram-negative bacilli and stability to ,B-lactamases (4,6,9). However, the poor absorption of these agents from the gastrointestinal tract negates their clinical usefulness in oral form.…”

mentioning

confidence: 99%

In vitro and in vivo antibacterial properties of FK 027, a new orally active cephem antibiotic

Kamimura¹,

Kojo²,

Matsumoto³

et al. 1984

FK 027 was more active than cefaclor, cephalexin, and amoxicillin against stock strains of a wide variety of gram-negative bacteria, including such opportunistic pathogens as Citrobacter and Enterobacter species and Serratia marcescens. FK 027 was significantly more active than the three reference drugs against clinical isolates of Escherichia coli, Klebsiella pneumoniae, indole-positive and -negative Proteus species, Providencia species, Haemophilus influenzae, and Neisseria gonorrhoeae. It was less active than cefaclor, cephalexin, and amoxicillin against staphylococci, but it was similar to cefaclor in its activity against streptococci. With few exceptions, FK 027 was active against strains of E. coli, K. pneumoniae, and Proteus mirabilis that were resistant to the reference agents. The bactericidal activity of FK 027 against various gram-negative bacteria, including Proteus species, Citrobacterfreundii, Enterobacter aerogenes, and S. marcescens, was greater than that of cefaclor, cephalexin, and amoxicillin. The therapeutic activities of FK 027 in mice infected with gram-negative bacilli were far superior to the activities of cefaclor, cephalexin, and amoxicillin, but they were inferior to the activities of these reference drugs against infection with Staphylococcus aureus.Various orally active cephem antibiotics with broad antibacterial spectra have been developed (1,3,5,7,8,10,12) and used extensively in the treatment of bacterial infections. The clinical usefulness of these agents is limited, however, because of their relatively low activity against infections with gram-negative bacilli. We recently succeeded in developing FK 027 (Fig. 1) Gani agar (Nissui, Tokyo, Japan) was used for testing anaerobic bacteria. Nonfastidious aerobic organisms were prectiltured in Mueller-Hinton broth (Difco), streptococci were precultured in Mueller-Hinton broth plus 1O0o horse serum, H. influenzae was precultured in Mueller-Hinton broth plus 5% Fildes enrichment, Neisseria species were precultured in Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.), and anaerobic bacteria were precultured in Gam broth (Nissui). Overnight cultures of these organisms were diluted 100-fold with the respective medium, and 0.025 ml of an inoculum containing 104 CFU was applied with a multipoint replicating apparatus to agar plates containing serial 2-fold dilutions of each antibiotic. For the testing of N. gonorrhoeae, 0.025 ml of an overnight culture was applied to agar plates. These plates were incubated at 37°C for 18 h. For streptococci, Haemophilus influenzae, and Neisseria species, incubation was carried out in an atmosphere of 5% C02, and.for anaerobic bacteria, incubation was carried out at 37°C for 24 h by the GasPak method (BBL). The MIC was the lowest antibiotic concentration that inhibited macroscopic colonial growth during this incubation. Broth dilution MICs were determined with overnight broth cultures of the test strains in Mueller-Hinton broth (Difco). The cultures were diluted in this broth to give an inocu...

“…Numerous modifications of the cephem betalactam molecule have resulted in cephalosporin, cephamycin, and 1-oxa-beta lactam drugs with remarkable antimicrobial activities and spectra (2,3,6,7,11,12,(19)(20)(21)(22)(23). Many of these compounds also possess stability to the most frequently isolated microbe-mediated beta-lactamases (1,4,5,11,19).…”

mentioning

confidence: 99%

In vitro antimicrobial activity evaluation of cefodizime (HR221), a new semisynthetic cephalosporin

Jones¹,

Barry²,

Thornsberry³

et al. 1981

Cefodizime (HR221) is a new a-methoxyimino cephalosporin developed by Hoechst-Roussel with a reported serum half-life of over 2 h. In vitro susceptibility studies showed that the cefodizime spectrum includes all those Enterobacteriaceae, staphylococci, Streptococcus spp., Haemophilus spp., and Neisseria spp. normally susceptible to cefotaxime (HR756) or ceftizoxime (FK749) or both. Cefodizime was less active (two-to eightfold) than cefotaxime or ceftizoxime against some enteric species, but was the most potent drug against some strains of Morganella spp. and Proteus vulgaris. Enterococci, methicillin-resistant Staphylococcus aureus, and most Pseudomonas spp. were resistant to cefodizime (median minimum inhibitory concentrations, 264 Ag/ml). Acinetobacter spp. and Pseudomonas aeruginosa strains required cefodizime concentrations of 32 ,tg/ml to inhibit 50% of tested strains. Cefodizime was very stable to hydrolysis by Richmond-Sykes type I, II, III, and IV beta-lactamases, as well as the enzyme derived from Bacillus cereus. The reference PADAC and nitrocefin substrate hydrolysis by a type I beta-lactamase was markedly inhibited (>80%) by cefodizime at concentrations 0.4 to 4% of substrate concentration. Cefodizime was active against 43% of bacteria which were resistant to cephalothin and cefamandole and against 58% of those resistant to aminoglycosides.