CHEMOTHERAPY OCT Fig. 1 Chemical structure of CVA-K
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1 OCT Fig. 1 Chemical structure of CVA-K
2 VOL.34 S-4 heart infusion broth (Difco) 37.0 g, Resazurin 0.1% alcoholic solution (Wako) 1.0 ml, L-Cystein-HCl H2O (Wako) 0.5 g, Bact agar (Difco) 1.0 g, Deionized tion buffer A CKH2PO4 special grade (Wako) 4. 5 g, Na2HPO4 special grade 6.0 g, L-Cystein-HC1 H2O (Wako) 0.5 g, Polysorbate-80 (Katayama) 0.5 g, Resazurin 0.1% alcoholic solution (Wako) 1.0 ml,
3 OCT Table 1 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2, i.v.)
4 VOL.34 S-4 Table 2 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2, i.v.) -just before administration- Table 3 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2, i.v.) -3 days under administration-
5 OCT Table 4 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2, iv.) -5 days undei. administration- Table 5 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2, i.v.) -3 days after administration-
6 VOL.34 S-4 Table 6 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2, i.v.) -5 days after administration- Table 7 Bacterial flora in feces of healthy volunteers administered BRL28500 (3,200mg ~2,i.v.) -10 days after administration
7 OCT Table 8 Toxin production of C. difficile in feces of healthy volunteers administered Fig. 2 Bacterial flora in feces of healthy volunteers administered BRL (3, 200 mg ~2, i. v.)
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9 OCT. 1986
10 VOL. 34 S-4 Tables 7, 8, Fig. 2) B Table 9 Bacterial flora in feces of healthy volunteers administered TIPC (3,000mg ~2, i.v.)
11 OCT Table 10 Bacterial flora in feces of healthy volunteers administered TIPC (3,000mg ~2,,i.v.) -just before administration- Tale 11 Bacterial flora in feces of healthy volunteers administered TIPC (3,000mg ~2,i.v.) -3 days under administration-
12 34 S-4 Table 12 Bacterial flora in feces of healthy volunteers administered TIPC (3,000mg ~2, i.v.) -5 days under administration. Table 13 Bacterial flora in feces of healthy volunteers administered TIPC (3,000mg ~2, i.v.) - 3days after administration-
13 OCT Table 14 Bacterial flora in feces of healthy volunteers j administered TIPC (3,000mg ~2, i.v.) -5 days after administration - Table 15 Bacterial flora in feces of healthy volunteers administered TIPC (3,000mg ~2, i.v.) -10 days after administration-
14 VOL.34 S-4 Table 16 Toxin production of C. difficile in feces of healthy volunteers administered TIPC (3,000mg ~2,i.v.) Fig. 3 Bacterial flora in feces of healthy volunteers administered TIPC
15 OCT. 1986
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17 OCT Table 17 Fecal concentration of BRL28500 after administration in healthy volunteers (3,200mg ~ 2, i.v.) ND.: Not detected Table 18 Fecal concentration of TIPC after administration in healthy volunteers (3,000rng ~ 2,i.v.) ND.: Not detected
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19 OCT. 1986
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21 OCT. 1986
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23 OCT. 1986
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25 OCT. 1986
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27 OCT. 1986
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29 OCT. 1986
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31 OCT. 1986
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33 OCT Table 44 Laboratory findings administered BRL28500 (3,200mg ~2,i.v.) Table 45 Laboratory findings administered TIPC (3,000mg ~2,i.v.)
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35 OCT. 1986
36 VOL.34 S-4 1) READING, C. & M. COLE: Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob. Agents Chemother. 11 (5): 852 `857, ) ALLEN, S. D: Manual of Clinical Microbiology, 4th ed., Edited by LENNETTE, E. D., A. BA- LOWS, W. J. HAUSLERS JR, and H. J. SHADOMY, p.434 `444, American Society for Microbiology, Washington, 1985 EFFECT OF BRL (CLAVULANIC ACID-TICARCILLIN) ON BACTERIAL FLORA IN HUMAN FECES TAKASHI MOTOHIRO, AKIRA KAWAKAMI, MASASHI ARAMAKI, KOICHI TANAKA, TATSUHIKO KOGA, YASUSHI SHIMADA, SHOBUN TOMITA, YASUTAKA SAKATA, TAMOTSU FUJIMOTO, TOHRU NISHIYAMA, NAOKI KUDA, KOJI ISHIMOTO, KAORU TOMINAGA and FUMIO YAMASHITA Department of Pediatrics, School of Medicine, Kurume University BRL 28500, a formulation of clavulanic acid (CVA 1 part) and ticarcillin (15 parts) and ticarcillin alone (TIPC) (as a control) were administered to healthy volunteers, aged 20 `26 years. Volunteers were separated into 2 groups of 6 and each drug was administered intravenously twice a day for 5 days. The fecal flora were studied before dosage, during administration and after the administration course was completed. Fecal concentrations of TIPC and CVA and the susceptibility of the bacteria to TIPC, CVA and BRL were measured. Side effects and laboratory findings were also checked. The results obtained were as follows: 1. In the group receiving BRL (3, 200mg ~2/day), the fecal population of E. coli increased by 2 or 3 logarithms both 5 days after initiation and 3 days after end of administration. At the same time, the number of subjects from whom Klebsiella spp. were detected, increased whilst for Staphylococcus spp. the number decreased. These changes returned to initial levels 5 or 10 days after the end of administration. No consistent changes in the fecal population were noted for the other Gram-negative bacilli, Gram-positive organisms or anaerobic bacteria. In the TIPC (3, 000mg ~2/day) group, the number of cases from which Klebsiella spp. and Staphylococcus spp. were detected changed in the same manner as with BRL but no consistent changes in population were noted for E. coli, the other Gramnegative bacilli, Gram-positive organisms or anaerobic bacteria. 2. The fecal concentrations of TIPC and CVA were below the detection limit in all cases. 3. The MICs of TIPC and BRL against fecal isolates from the volunteers, using inoculum sizes of 106 cells/m1. The results were similar to those reported in other publications and in particular BRL was found to have a stronger effect than TIPC against many Gram -negative bacilli. 4. No side effects were noted in either group. Slight GPT elevation was noted in 2 cases in the BRL group but no abnormal finding was noted i n any subject of the TIPC group.
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