title: Antimicrobial interactions (synergy) of teicoplanin with two broad-spectrum drugs (cefotaxime, ofloxacin) tested against gram-positive isolates from Germany and the United States.
abstract: Teicoplanin, a glycopeptide, has been widely used in some nations alone and in empiric therapy combinations to address infections caused by Gram-positive cocci. However, glycopeptide resistance and the increasing incidence of oxacillin-resistant staphylococci have compromised contemporary chemotherapy. In this study, teicoplanin was tested in combinations with ampicillin, cefotaxime with and without desacetylcefotaxime, and ofloxacin against 151 Gram-positive cocci to assess the potential for enhanced action. The strains included recent isolates from the United States and Germany having well-characterized resistance mechanisms (oxacillin-resistant staphylococci, vancomycin-resistant enterococci), each tested by NCCLS methods, checkerboard synergy tests, and kill-curves. Teicoplanin alone was active (MIC90s, 0.25-2 micrograms/mL) against all species except vanA enterococci. Drug interactions of teicoplanin with beta-lactams revealed synergy and partial synergy versus oxacillin-resistant Staphylococcus spp. (67-100%) and vancomycin-resistant enterococci (70-100%), many at clinically achievable drug concentrations. 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 viable alternative to vancomycin, especially in combination therapy with selected broad-spectrum cephalosporins or fluoroquinolones. Many emerging pathogens that test resistant to individual drugs appear to be inhibited by tested combinations, extending their potential clinical utility.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: S A
authors.initials: SA
authors.lastname: Marshall
authors.forename: H
authors.initials: H
authors.lastname: Grimm
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D002439:Cefotaxime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D005858:Germany; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D017334:Teicoplanin / Q000494:pharmacology*; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002511:Cephalosporins; D017334:Teicoplanin; D015242:Ofloxacin; D002439:Cefotaxime