E. Sillerström

Antibacterial agents disrupt the ecological balance of the normal human microflora. Tigecycline, a member of a new class of antibiotics (glycylcyclines), has been shown to have a potent broad-spectrum activity against most gram-positive and gram-negative aerobic and anaerobic bacteria. The aim of the study was to investigate the ecological effects of tigecycline on the normal oropharyngeal and intestinal microflora of healthy subjects. Thirteen healthy white subjects (six females and seven males) between 20 and 31 years of age received 100 mg of tigecycline in the morning on day 1 as a 30-min intravenous infusion followed by a 50-mg dose of tigecycline every 12 h as a 30-minute infusion for 10 days. One subject was withdrawn on day 2 because of an adverse event (urticaria). Serum, saliva, and fecal samples were collected before, during, and after administration for microbiological cultivation and for assays of tigecycline. All new colonizing bacteria were tested for susceptibility (resistance of > or =8 mg/liter) during the investigation period. The fecal concentrations on day 8 were from 3.0 to 14.1 mg/kg, with a mean value of 6.0 mg/kg and a median value of 5.6 mg/kg. The saliva concentrations were generally low (0 to 0.12 mg/liter). A minor effect on the oropharyngeal microflora was observed. The numbers of enterococci and Escherichia coli cells in the intestinal microflora were reduced at day 8 (P < 0.05), while those of other enterobacteria and yeasts increased. There was a marked reduction of lactobacilli and bifidobacteria (P < 0.05) but no impact on bacteroides. No Clostridium difficile strains were isolated. Two Klebsiella pneumoniae strains and five Enterobacter cloacae strains resistant to tigecycline were found on day 8.

The aim of the present investigation was to determine the in vitro activity of HMR 3647 compared with other antimicrobial agents against anaerobic bacteria. The activity of HMR 3647 was determined against 342 clinical isolates of anaerobic bacteria by the agar dilution method and was compared with azithromycin, clarithromycin, roxithromycin, erythromycin, cefoxitin, imipenem, clindamycin and metronidazole. Among the macrolides HMR 3647 and among the beta-lactams imipenem were the most active agents tested. Anaerobic cocci (50 strains) had the following minimum inhibitory concentrations (MICs): HMR 3647, range 0.016-0.125 mg/l; imipenem, range 0.016-0.064 mg/l. Propionibacterium acnes (30 strains): HMR 3647, 0.016-1.0 mg/l; imipenem, 0.032-0.064 mg/l. Clostridium perfringens (30 strains): HMR 3647, 0.125 mg/l; imipenem, 0.016-0.5 mg/l. Clostridium difficile (50 strains): HMR 3647, 0.125-256 mg/l; imipenem, 4.0-8.0 mg/l. Bacteroides fragilis (102 strains): HMR 3647, 0.032-16 mg/l; imipenem, 0.064-0.25 mg/l. Bacteroides and Prevotella species (50 strains): HMR 3647, 0.016-4.0 mg/l; imipenem, 0.016-0.25 mg/l. Fusobacterium nucleatum (30 strains): HMR 3647, 0.016-8.0 mg/l; imipenem, 0.008-0.064 mg/l. HMR 3647 may be useful as treatment and prophylaxis for infections due to anaerobic bacteria.

LY 333328 is a new semisynthetic glycopeptide with reported activity against aerobic Gram-positive cocci such as enterococci, pneumococci, streptococci and staphylococci. The present investigation was undertaken to determine the in vitro activity of LY 333328 against 178 Gram-positive anaerobic bacteria recently isolated from human infections. The activity was compared with that of vancomycin, teicoplanin, cefoxitin, imipenem, clindamycin and metronidazole. Peptostreptococci (48 strains): LY 333328, range 0.016-1.0 mg/l; vancomycin, 0.125-2.0 mg/l; teicoplanin, 0.032-2.0 mg/l; cefoxitin, 0.064-8.0 mg/l; imipenem, 0.016-0.064 mg/l; clindamycin, 0.016-1.0 mg/l; metronidazole, 0.125-8.0 mg/l. Propionibacterium acnes (31 strains): LY 333328, range 0.032-0.125 mg/l; vancomycin, 0.25-0.5 mg/l; teicoplanin, 0.25-0.5 mg/l; cefoxitin, 0.125-1.0 mg/l; imipenem, 0.032-0.064 mg/l; clindamycin, 0.016-0.064 mg/l; metronidazole, 32-> or =64 mg/l. Clostridium difficile (50 strains): LY 333328, range 0.016-2.0 mg/l; vancomycin, 0.5-4.0 mg/l; teicoplanin, 0.064-0.5 mg/l; cefoxitin, 64-128 mg/l; imipenem, 8.0 mg/l; clindamycin, 0.25-128 mg/l; metronidazole, 0.125-0.25 mg/l. Clostridium perfringens (49 strains): LY 333328, range 0.016-2.0 mg/l; vancomycin, 0.025-4.0 mg/l; teicoplanin, 0.064-4.0 mg/l; cefoxitin, 0.5-1.0 mg/l; imipenem, 0.016-0.5 mg/l; clindamycin, 0.008-1.0 mg/l; metronidazole, 1.0-4.0 mg/l. LY 333328 had an excellent in vitro activity against anaerobic Gram-positive bacteria.