title: The effect of dicloxacillin and fusidic acid on the extracellular and intracellular killing of Staphylococcus aureus.
abstract: The effect of dicloxacillin and fusidic acid used alone and in combination on the extracellular and intracellular killing of four isolates of Staphylococcus aureus in the presence of serum was studied. At the extracellular level, dicloxacillin (8 mg/L) had a bactericidal effect on all four isolates, whereas fusidic acid (64 mg/L) had a bacteriostatic effect on two isolates and no effect on the two other isolates. Fusidic acid significantly inhibited the extracellular bactericidal effect of dicloxacillin on two isolates. Intracellular killing was measured in human neutrophil granulocytes. Dicloxacillin (8 mg/L) significantly increased the intracellular killing of all four isolates, while fusidic acid (64 mg/L) significantly increased the intracellular killing of three isolates, but the killing was significantly lower than that of dicloxacillin. When the antibiotics were combined the intracellular killing of three of the isolates was significantly lower than that of dicloxacillin alone. The viability of the granulocytes and their ability to produce superoxide anion were not affected by the antibiotics. In conclusion, we found that the increased intracellular killing of S. aureus by dicloxacillin was inhibited by fusidic acid.
authors.affiliation: Department of Medicine and Infectious Diseases, Marselisborg Hospital, Aarhus University Hospital, Denmark.
authors.forename: S L
authors.initials: SL
authors.lastname: Nielsen
authors.forename: F T
authors.initials: FT
authors.lastname: Black
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015169:Colony Count, Microbial; D004009:Dicloxacillin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005672:Fusidic Acid / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D013481:Superoxides; D005672:Fusidic Acid; D004009:Dicloxacillin