VOL.36 S-I CHEMOTHERAPY Tabl 1 List of healthy male volunteers

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VOL.36 S-I CHEMOTHERAPY Tabl 1 List of healthy male volunteers

CHEMOTHERAPY MAY 1988 Table 2 Experimental schedule of CS-807 administration and sampling of feces Table 3 Isolation of aerobic and anaerobic bacteria from fecal flora Medium (abbreviation, manufacturer) Selection for aerobes GAM agar (GAM, NISSUI) Trypticase soy blood agar (TSBA, base BBL) DHL agar (DHL, EIKEN) SF agar (SF, EIKEN) PEA blood agar (PEA, base NISSUI) NAC agar (NA, EIKEN) Aerobic spores Total aerobes Enterobacteriactue Enterococcus spp. Streptococcus spp., Enterococcus spp. Pseudomonas aeruginosa No.110 agar (No. 110, NISSUI) Staphylococcus spp., Micrococc-uspp. Candida GE agar (GE, NISSUI) for anaerobes GAM agar (GAM, NISSUI) BL agar (BL, NISSUI) KM VC Brucella blood agar (KM VC, base BBL) Bacteroides bile esculin agar (BBE, KYOKUTO) Modified FM agar (FM, NISSUI) BS agar (BS, base NISSUI) Yeasts Total anaerobes, anaerobic spores Total anaerobes, Bifidobactenum spp. Bacteroides spp. Bacteroides fragilis group Fusobacterium spp. Bifidobacteriupn spp. Bacteroides agar ( Bacteroides, NISSUI) Clostridium spp. CCMA agar (CCMA) Clostridium difficile PO agar (PO, base NISSUI) Clostridium spp. PNC agar (PNC, base NISSUI) Clostridium spp. CW egg yolk agar (CW, base NISSUI) Lecithinase (+) Clostridium spp. Lactobacillus selective medium (LHS, BBL) PS agar (PS, base NISSUI) PMS agar (PMS, base NISSUI) Lactobacillus spp. Anaerobic cocci Anaerobic cocci Veillonella agar (VS) Veillonella spp. for identification Mueller Hinton agar (MHA, BBL) Columbia blood agar (BBL) BL agar (NISSUI) GAM agar (NISSUI) GAM semi-solid agar (NISSUI)

VOL.36 S-1 CHEMOTHERAPY Table 4 Effect of CS-807 on fecal flora of volunteer A

CHEMOTHERAPY MAY. 1988 Table 5 Effect of CS-807 on fecal flora of volunteer C Table 6 Effect of CS-807 on fecal flora of volunteer D

VOL.36 S-1 CHEMOTHERAPY Table 7 Effect of CS-807 on fecal flora of volunteer E Fig. 1 Effect of CS-807 on total bacteria of fecal flora Fig. 2 Effect of CS-807 on total aerobes of fecal flora Symbols: ( ), volunteer A; ( œ), volunteer C;(ƒ ) (ƒ ), volunteer F; ( ), volunteer F, volunteer D, Symbols: ( ), volunteer A; ( œ), volunteer C;(ƒ ), volunteer D, (ƒ ), volunteer E; ( ), volunteer F Fig. 3 Effect of CS-807 on total anaerobes of fecal flora Symbols: ( ), volunteer A; ( œ), volunteer C;(ƒ ), volunteer D, (ƒ ), volunteer E; ( ), volunteer F

CHEMOTHERAPY MAY. 1988 Table 8 Effect of CS.807 on fecal flora of volunteer F *:Counts are expressed as logio per g wet feces, 0: No organisms detected. Table 9 Effect of CS-807 on Enterobacteriaceae of volunteer A Table 10 Effect of CS-807 on Enterobacteriaceae of volunteer C

VOL.36 S-1 CHEMOTHERAPY Table 11 Effect of CS-807 on Enterobacteriaceae of volunteer D *:Counts are expressed as logio per g wet feces, 0: No organisms detected. Table 12 Effect of CS-807 on Enterobacteriaceae of volunteer E *:Counts are expressed as logio per g wet feces, 0: No organisms detected. Table 13 Effect of CS-807 on Enterobacteriaceae of volunteer F Table 14 Effect of CS-807 on anaerobic Gram-negative rods of volunteer A

CHEMOTHERAPY MAY, 1988 Table 15 Effect of CS-807 on anaerobic Gram negative rods of volunteer C Fig. 4 Effect of CS-807 on fecal flora of volunteer A Fig. 5 Effect of CS-807 on fecal flora of volunteer C Symbols:( ), total bacteria ;( œ), total aerobes; (ƒ ), total anaerobes Symbols:( ). total bacteria ;( œ). total aerobes; (ƒ ). total anaerobes

VOL.36 S-1 CHEMOTHERAPY Table 16 Effect of CS-807 on anaerobic Gram-negative rods of volunteer D *:Counts are expressed as logic per g wet feces, 0: No organisms detected. Table 17 Effect of CS-807 on anaerobic Gram-negative rods of volunteer E Fig. 6 Effect of CS-807 on fecal flora of volunteer D Fig. 7 Effect of CS-807 on fecal flora of volunteer E Symbols:( ), total bacteria:( œ), total aerobes;(ƒ ), total anaerobes Symbols:( ), total bacteria ;( œ), total aerobes;(ƒ ), total anaerobes Fusobacterium spp. B. thetaiotaomicron Fusobacterium spp. Clostridium spp. Bifidobacterium spp.

CHEMOTHERAPY MAY. 1988 Table 18 Effect of CS-807 on anaerobic Gram-negative rods of volunteer F *:Counts are expressed as logio per g wet feces, 0: No organisms detected. Table 19 Effect of CS-807 on anaerobic Gram-positive rods of volunteer A *:Counts are expressed as logio per g wet feces, 0: No organisms detected. Table 20 Effect of CS-807 on anaerobic Gram-positive rods of volunteer C *:Counts are expressed as logio per g wet feces, 0: No organisms detected. family Enterobacteriaceae Enterococcus spp. P. aeruginosa Staphylococcus spp. ily Enterobacteriace Citrobacter freundii

VOL.36 S-1 CHEMOTHERAPY Table 21 Effect of CS-807 on anaerobic Gram-positive rods of volunteer D *:Counts are expressed as logio per g wet feces, 0: No organisms detected. Table 22 Effect of CS-807 on anaerobic Gram-positive rods of volunteer E Table 23 Effect of CS-807 on anaerobic Gram-positive rods of volunteer F Bacteroides spp. B. fragilis nocuum C. thetaiotaomicron difficile Fusobacterium spp F. mortzferum Clostridium spp.

CHEMOTHERAPY Table 24 Ĉ-lactamase activity n mol nitrocefin hydrolysed/min/g Table 25 Fecal concentration of R-3763 Fig. 8 Effect of CS-807 on fecal flora of volunteer F

CHEMOTHERAPY -lactamase by using a chromogenic cephalospor- in substrate. Antimicrob. Agents Chemother. 1: 6) BUCHANAN, R, E.; & N. E. GIBBONS ed.: Bergey's manual of Determinative Bacteriology, 8ed., Williams & Wilkins, Baltimore, 1974 7) KRIEG, N, R. ; & J. G. HOET ed.: Bergey's manual of Systematic Bacteriology Vol. 1., Williams & Wilkins, Baltimore, 1985 8) HOLDEMAN, V. L.; E. P. CATO & W. E. C. MORE: Anaerobe laboratory manual, 4th ed., Virginia Polytechnic Institute and State University, Blacksburg, 1977 9) O'CALLAGHAN C. H.; A. MORRIS, S. M. KIRBY & A. H. SHINGLAR : Novel method for detection of beta 283 `288, 1972 11) TAJIMA M. ; K. SAWA, K. WATANABE & K. UENO: The fl-lactamases of Genus Bacteroides. J. Antibiotics 36: 423-428, 1983

CHEMOTHERAPY MAY. 1988 THE EFFECTS OF ORALLY ADMINISTERED CS-807 ON HUMAN FECAL MICROFLORA MASAZO TAJIMA, KUNITOMO WATANABE and KAZUE UENO Institute of Anaerobic Bacteriology, Gifu University, School of Medicine, Gifu HARUKI DOMON, KIYOMI SAKAO, YUKIO UTSUI, SATOSHI TAKENOUCHI, TERUO MAGARIBUCHI, YUMIKO TSUKADA, SUMIE YURUGI and MASAYUKI IWATA Biological Research Laboratories, Sankyo Co. Ltd., Tokyo Influence of CS-807 on the human fecal microflora was studied, in 5 healthy male volunteers who were given the drug in an oral dose of 200mg b.i.d. for 14 consecutive days. The total counts of fecal organisms slighly decreased in one volunteer. Enterobacteriaceae and Bacteroidaceae were decreased, but returned to normal soon after the end of treatment. Clostridium difficile was detected in one volunteer at the end of treatment. No diarrhoea occurred in any of the 5 volunteers during the period of study.

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