[Toxicological studies of talampicillin hydrochloride. (2) 7-week oral toxicity study in rats].
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OBJECTIVE: The purpose of this study was to evaluate various oral antimicrobial agent levels in tooth extraction sites. STUDY DESIGN: The concentration of dental alveolar blood in extraction wounds after the oral administration of talampicillin (500 mg), cefaclor (500 mg), cefteram pivoxil (200 mg), cefuroxime axetil (250 mg), cefdinir (200 mg), and ofloxacin (100 mg) was determined in 338 patients and was assessed on the basis of its antimicrobial activity against Streptococcus isolated in odontogenic infections. RESULTS: The percentage of patients whose concentrations exceeded the minimum inhibitory concentration for 90% of Streptococcus was 62.5% to 100% for talampicillin at 30 to 360 minutes, 0% to 12.5% for cefaclor at 30 to 360 minutes, 18.2% to 100% for cefteram pivoxil at 30 to 480 minutes, 50% to 100% for cefuroxime axetil at 30 to 480 minutes, 0% to 50% for cefdinir at 16 to 290 minutes, and 0% to 40% for ofloxacin at 30 to 480 minutes. CONCLUSION: These results indicate that talampicillin, cefteram pivoxil, and cefuroxime axetil have minimum inhibitory concentration levels for 90% of Streptococcus in tooth sockets.
The ampicillin prodrugs bacampicillin, pivampicillin, and talampicillin, the mecillinam prodrug pivmecillinam and the sulbactam prodrug sulbactam pivoxil all have a greatly improved oral availability compared to the parent drug. They show no antibacterial activity themselves until transformed into active drugs after absorption. This double advantage makes them less likely to influence the intestinal microbial ecosystem. Ampicillin has been reported to cause marked changes in the colon microflora, particularly as regards Enterobacter species, Klebsiella species, enterococci, lactobacilli, bacteroides, and clostridia, in contrast to pivampicillin, which did not exert much influence. Similarly, talampicillin has been reported to have less influence than ampicillin on the colon flora. Diarrhoea was more common after ampicillin and was accompanied by an overgrowth of Candida. Pivmecillinam has been reported to reduce the number of Escherichia coli and lactobacilli. No changes were seen in the colon flora of subjects receiving bacampicillin tablets. This was verified in a parallel group study, in which one group was given the combination of bacampicillin and sulbactam pivoxil, the other bacampicillin, for seven days. Of the subjects given the combination, five had a moderate and ten a considerable change in their colon microflora. The subjects were often heavily colonized by new aerobic strains such as enterococci, E. coli, Bacillus, Enterobacter, Aeromonas, and yeasts. Among the anaerobes, Veillonella, the bifidobacteria-lactobacillus group, and bacteroides decreased. Some strains of clostridia decreased but there was also a colonization with new strains. One subject was colonized with Clostridium difficile. Diarrhoea was seen only during the week of active drug administration in the group given the combination. The symptoms generally appeared on the second or third day of treatment and had, in most cases, subsided at the end of treatment. The results illustrate the correlation between disturbances in the intestinal microbial ecosystem and intestinal adverse reactions.
The oral administration of 300 mg of clindamycin was undertaken on 23 patients, of 500 mg of cefadroxil on 11 patients and of 250 mg of talampicillin on 12 patients, and then tooth extraction was performed under local anesthesia. Blood samples were taken from the extraction wound and the peripheral vein at the same time and assayed by the bioassay method. The blood levels of clindamycin and cefadroxil indicated a similar pattern between the extraction wound and the peripheral vein, but the blood level of talampicillin reached peek level rapider than clindamycin and cefadroxil. The blood levels of the extraction wound were 60 - 80% as compared with the venous blood levels with each antimicrobial agent.
Pivmecillinam (PMPC), semisynthetic penicillin for oral use, was studied clinically and following results were obtained. 1) Twenty-eight patients with acute simple cystitis treated with the drug 200 mg/day for 4 days, clinical results were excellent in 23 cases and moderate in 5 cases. Six patients with chronic simple cystitis treated with the drug 400 mg/day for 7 days, clinical results were excellent in 4 cases, moderate in 1 case and poor in 1 case. Eight patients with complicated urinary tract infections treated with the drug 400 mg/day for 7 days, clinical results were excellent in 2 cases, moderate in 2 cases and poor in 4 cases. Overall effectiveness amounted to 88.1%. 2) Pivmecillinam was clinically effective in patients infected by Gram-negative bacteria except Pseudomonas aeruginosa. 3) No side effects were observed in all cases. The effectiveness of PMPC for acute simple cystitis was compared with that of talampicillin (TAPC), ampicillin (ABPC), amoxicillin (AMPC) and pivampicillin (PVPC) reported previously and PMPC was assessed as the most useful agent in these. Then, pivmecillinam should be chosen firstly as a chemotherapeutic agent for acute simple cystitis.