EFFECT OF BRL 25000 (CLAVULANIC ACID-AMOXICILLIN) ON BACTERIAL FLORA IN HUMAN FECES

• Published in: Japanese journal of antibiotics Vol. 38; no. 2; pp. 441 - 480
• Main Authors: YAMASHITA, FUMIO, TOMINAGA, KAORU, TANAKA, KOICHI, ISHIMOTO, KOJI, TOMITA, NAOFUMI, KUDA, NAOKI, MOTOHIRO, TAKASHI, FUJIMOTO, TAMOTSU, KOGA, TATSUHIKO, NISHIYAMA, TOHRU, SHIMADA, YASUSHI, SAKATA, YASUTAKA
• Format: Journal Article
• Language: Japanese
• Published: Japan Japan Antibiotics Research Association 01.02.1985
• Subjects: Administration, Oral; Adult; Amoxicillin - administration & dosage; Amoxicillin - metabolism; Amoxicillin - pharmacology; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Bacteria - drug effects; Clavulanic Acids - administration & dosage; Clavulanic Acids - metabolism; Clavulanic Acids - pharmacology; Drug Combinations - administration & dosage; Drug Combinations - metabolism; Drug Combinations - pharmacology; Enterobacteriaceae - drug effects; Feces - analysis; Feces - microbiology; Gram-Positive Bacteria - drug effects; Humans; Male; Penicillin Resistance
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.38.441

BRL 25000 (187.5 and 375mg tablets), a formulation of CVA-K and AMPC in the ratio of 1: 2, and AMPC (as control drug) were administered to healthy volunteers, aged 20-28 years and weighing 60-85kg (68.8kg, on average). Each drug was administered 3 times a day (after meals) for 5 days and the volunteers were separated into 3 groups of 4 subjects each. The effect on the fecal flora was studied before dosage, during administration (day 3 and 5) and day 3 and 5 after the administration course was completed. Studies were undertaken to isolate C. difficile on the last day of administration and 3 and 5 days after administration had ceased. Fecal concentrations and the susceptibility of the isolates to AMPC, CVA-K and BRL 25000 were measured. Side effects and laboratory findings were studied. The results obtained were as follows: 1. In BRL 25000 (187.5mg × 3/day) group, the population of E. coli was on average, 1 × 106-9 × 106 cells/g feces before initiation of administration and it increased by 2 logarithms 3 and 5 days after initiation of administration. By 3 and 5 days after end of administration, the E. coli population was similar to the initial population. The population of Klebsiella sp. was 1 × 106-9 × 108 cells/g feces on average before commencement of dosage and it increased by 2 logarithms 3 days after initiation of administration but there was no consistent change in the Klebsiella sp. population thereafter. The Enterobacter sp., population was not consistent neither was the population of other Enterobacteriaceae. In total, the mean Enterobacteriaceae population was 1 × 107-9 × 107 cells/g feces before initiation of administration and increased by 2 logarithms 3 days after initiation of administration, and then returned to the initial level 5 days after end of administration. No consistent changes in population were noted for the other Gram-negative bacilli. The Staphylococcus sp. population was 1×106-9×106 cells/g feces on average before initiation of administration. This organism was detected in only 1 case 3 days after initiation of administration and in another 5 days after initiation of administration, thereafter, the population was similar to the initial population. The population of Enterococcus sp. was 1×106-9×106 cells/g feces on average before initiation of administration and there was no remarkable change in population 3 and 5 days after initiation of administration, but it increased by 2 logarithms 3 and 5 days after administration had ceased. No consistent changes were found for other Gram-positive organisms. Throughout the study the population of Bacteroides sp., and the total population of anaerobic organisms, was 1×109-9×109 cells/g feces and 1×109-9×1010 cells/g feces (average results) respectively, and no effect on these organisms was found. C. difficile was not found in any of the volunteers. 2. In BRL 25000 (375mg×3/day) group, the population of E. coli was 1×106-9×106 cells/g feces on average before initiation of administration, similar to the BRL 25000 (187.5mg×3/day) group, and it also increased by 2 logarithms 3 and 5 days after initiation of administration. Three and 5 days after the end of administration, the population was similar to the initial population. The number of cases from which Klebsiella sp. were detected gradually increased with time; i. e. 1 case before initiation of administration, 2 cases 3 days after initiation of administration and 4 cases 5 days after initiation administration.