ANTIMICROBIAL INTERACTIONS (SYNERGY) OF TEICOPLANIN WITH 2 BROAD-SPECTRUM DRUGS (CEFOTAXIME, OFLOXACIN) TESTED AGAINST GRAM-POSITIVE ISOLATES FROM GERMANY AND THE UNITED-STATES

Teicoplanin, a glycopeptide, has been widely used in some nations alon e and in empiric therapy combinations to address infections caused by Gram-positive cocci. However, glycopeptide resistance and the increasi ng incidence of oxacillin-resistant staphylococci have compromised con temporary chemotherapy. In this study, teicoplanin was tested in combi nations with ampicillin, cefotaxime with and without desacetylcefotaxi me, and ofloxacin against 151 Gram-positive cocci to assess the potent ial for enhanced action. The strains included recent isolates from the United States and Germany having well-characterized resistance mechan isms (oxacillin-resistant staphylococci, vancomycin-resistant enteroco cci), each tested by NCCLS methods, checkerboard synergy tests, and ki ll-curves. Teicoplanin alone was active (MIC(90)s, 0.25-2 mu g/mL) aga inst all species except vanA enterococci. Drug interactions of teicopl anin with beta-lactams revealed synergy and partial synergy versus oxa cillin-resistant Staphylococcus spp. (67-100%) and vancomycin-resistan t enterococci (70-100%), many at clinically achievable drug concentrat ions. However, confirming kill-curve experiments showed static action and no significant bactericidal effect. Combinations of ofloxacin with teicoplanin or cefotaxime plus desacetylcefotaxime showed a dominant additive and indifferent interaction. Teicoplanin continues to be a vi able alternative to vancomycin, especially in combination therapy with selected broad-spectrum cephalosporins or fluoroquinolones. Many emer ging pathogens that test resistant to individual drugs appear to be in hibited by tested combinations, extending their potential clinical uti lity. (C) 1997 Elsevier Science Inc.