Synergy between spiramycin and metronidazole in the treatment of polymicrobial infections

The in-vitro and in-vivo activity of metronidazole and spiramycin, singly or in combination, was tested in the eradication of infection caused by Bacteroides spp. alone and in combination with Neisseria gonorrhoea, Staphylococcus aureus, Streptococcus pyogenes or Str. faecalis. The in-vitro tests consisted of determinations of the MICs with or without the addition of a constant amount of the other antimicrobials. The MICs of metronidazole for B. melaninogenicus, B. fragilis and B. bivius were significantly reduced by the addition of 0.125 mg/l spiramycin. The in-vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the bacterial contents of abscesses induced by subcutaneous injection of bacterial suspension. Combined therapy of mixed infections showed further significant reduction of the numbers of Bacteroides spp. in seven of 12 combinations and of the aerobic and facultative bacteria in four of 12 combinations. Furthermore, a reduction in the number of facultative anaerobes was noted in mixed infections with Bacteroides spp. which were treated with metronidazole alone. The synergy in vitro and in vivo between metronidazole and spiramycin may have important clinical implications in the treatment of polymicrobial aerobic-anaerobic infections.