Kazuo Numata

The susceptibility of Campylobacter pylori to antiulcer agents and antibiotics

The antibacterial activities of antiulcer agents and antibiotics against Campylobacter pylori were studied. The MC90 values of three kinds of antibiotics—macrolides, β-lactams, and metronidazole—were 0.05–0.78, 0.39–1.56, and 12.5 μg/ml, respectively. They were more active than antiulcer agents such as H2blockers and cetraxate with MIC90 values of ≥1,600 and >1,600 μg/ml, respectively. Especially, clarithromycin, a new derivative of erythromycin, showed an MIC90 of 0.05 μg/ml. However, the other antiulcer agents such as sofalcone and tripotassium dicitrate bismuthate (TDB) also had MIC90 values of 50 and 6.25 μg/ml, respectively, Clarithromycin, sofalcone, and TDB showed bactericidal activity against C. pylori CLO2. The bactericidal actions of these drugs could be observed under electron microscopy.

In vitro and in vivo Antibacterial Activity and Pharmacokinetics of SC-002 and Its Derivative, SC-004: New Oral Cephalosporins

SC-002 is a novel oral cephalosporin possessing a unique thiadiazolylethenyl moiety at the 3 position. In the present study, it was the most active against gram-positive bacteria among oral cephalosporins such as cefdinir (CFDN), cefpodoxime, cefditoren and cefaclor (CCL). It was equal to or 16 times more active than CFDN against standard and clinical strains. In particular, against clinical isolates of Morganella morganii and Haemophilus influenzae, SC-002 was 8–64 times more active than CFDN. The antibacterial activity of SC-002 against some β-lactam-resistant strains was superior to that of CFDN. The in vivo antibacterial activity of SC-004, a pivaloyloxymethyl ester of SC-002, was 1.2–8 times more protective against systemic infections due to Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae than that of CFDN. The therapeutic effects of SC-004 on experimental respiratory tract infections caused by S. pneumoniae or H. influenzae were superior to those of CFDN and CCL. SC-004 showed higher and longer-lasting blood levels and higher urinary excretion in pharmacokinetics in mice.

In vitro and in vivo Antibacterial Activities of Clarithromycin

The in vitro and in vivo antibacterial activities of clarithromycin (CAM), a new oral macrolide antibiotic, were compared with those of erythromycin (EM), josamycin (JM) and rokitamycin (RKM). The antibacterial spectrum and in vitro activities of CAM were similar to those of EM. Therapeutic efficacies of CAM against various experimental infections in mice--including systemic infections caused by gram-positive bacteria such as Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, and subcutaneous abscess due to S. aureus, and bacterial pneumonia caused by S. pneumoniae--were superior to those of EM, JM and RKM. CAM exhibited higher serum levels than EM in mice after a single oral dose of 50 mg/kg.

Synthesis and biological properties of 3-[(Z)-2-(1,2,3-Thiadiazolyl)ethenyl]-substituted cephalosporins and related compounds: new oral cephalosporins

A series of cephalosporins possessing a [(Z-2-(1,2,3-thiadiazolyl)ethenl] moiety at C-3 were synthesized and their biological properties were examined. SC-002 (1a) exhibited excellent activity against both Gram-positive and Gram-negative bacteria. The ester SC-004 (1b) showed good bioavailability after oral administration in mice and rats.

Studies on cephalosporin antibiotics. VI. Synthesis, antibacterial activity and oral efficacy in mice of new 7.BETA.-((Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)-acetamido)-3-(substituted alkylthio)cephalosporins.

A series of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetamido] cephalosporins (1) having various substituted alkylthio groups at the C-3 position of the cephem nucleus were prepared and evaluated for antibacterial activity and oral absorption in rats. Of these, the cephalosporin with a cyanomethylthio group (1a) showed the greatest activity against Staphylococcus aureus and Gram-negative bacteria. Its pivaloyloxymethyl ester (6a), a representative prodrug, exhibited good in vivo efficacy in mice by oral administration. The structure-activity relationships of 1 are also presented.