[Combination effect of teicoplanin and various antibiotics against hetero-VRSA and VRSA]

Eleven clinical strains of MRSA which were detected as heterogeneously-resistant to vancomycin (hetero-VRSA) on Mu3-medium (a newly devised hetero-VRSA detecting medium) were subjected to a study to explore the therapeutic possibility of combination therapy. Combination effects of teicoplanin with six different beta-lactam antibiotics (imipenem, panipenem, meropenem, flomoxef, sulbactam/ampicillin, cefoselis), arbekacin, and minocycline were evaluated on the strains of Mu3, Mu50 and the above 11 strains. Combination of teicoplanin with five beta-lactam antibiotics individually (except for cefoselis) showed a synergistic effect, while that with cefoselis showed synergistic or additive effect. Neither indifference nor antagonism effect was observed in combination of seicoplanin with beta-lactam antibiotics on these MRSA strains. The degree of synergistic effect in combination with teicoplanin was the strongest in imipenem, followed by panipenem > meropenem > flomoxef > sulbactam/ampicillin > cefoselis in this order. The average FIC index of the beta-lactam antibiotics against these strains was 0.113, 0.124, 0.163, 0.230, 0.264 and 0.388, respectively. Arbekacin and minocycline showed variable of effects in combination with teicoplanine. In the case of arbekacin, the ratio of synergy, addition, indifference, and antagonism were 30.8, 30.8, 0 and 38.4%, respectively, and in the case of minocycline, they were 15.4. 7.7, 0 and 76.9%, respectively. Vancomycin activity against hetero-VRSA and VRSA is antagonized with beta-lactam antibiotics, while teicoplanin activity is synergistic or additive. It is known that MRSA is relatively easy to emerge resistance to teicoplanin. Therefore, teicoplanin is not desirable for a monotherapy. However, in a combination with beta-lactam antibiotics, teicoplanin appeared to be a promising agent for the treatment of MRSA infection.