title: Activity of fusidic acid against extracellular and intracellular Staphylococcus aureus: influence of pH and comparison with linezolid and clindamycin.
abstract: BACKGROUND
  Emergence of multidrug-resistant Staphylococcus aureus has triggered a reassessment of fusidic acid (CEM-102, sodium fusidate).
  
  
  METHODS
  Fusidic acid was examined for (1) activity against recent methicillin-resistant S. aureus (MRSA) isolates; (2) modulation of activity by acidic pH; and (3) accumulation by phagocytic cells and intracellular activity against methicillin-susceptible S. aureus (MSSA) and MRSA.
  
  
  RESULTS
  About 96% of strains (N = 94) were susceptible (European Committee on Antimicrobial Susceptibility Testing breakpoint [≤ 1 mg/L]). Activity was enhanced at pH 5.5 (6 dilutions decrease for minimum inhibitory concentration) in parallel with an increase of drug bacterial accumulation (opposite effects for clindamycin; linezolid remained unaffected). Fusidic acid accumulated in THP-1 cells (about 5.5 fold), with further accumulation at pH 5.5 vs pH 7.4. The intracellular activity of Fusidic acid was similar to that of clindamycin and linezolid (maximal relative activity, 0.4-0.6 log(10) colony-forming unit decrease). No cross-resistance to vancomycin or daptomycin was observed.
  
  
  CONCLUSIONS
  Fusidic acid is active against S. aureus in broth as well as intracellularly, with no cross-resistance to other antibiotics.
authors.affiliation: Cellular and Molecular Pharmacology, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemaire
authors.forename: Francoise
authors.initials: F
authors.lastname: Van Bambeke
authors.forename: Denis
authors.initials: D
authors.lastname: Pierard
authors.forename: Peter C
authors.initials: PC
authors.lastname: Appelbaum
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D002981:Clindamycin / Q000494:pharmacology; D015169:Colony Count, Microbial; D003470:Culture Media; D005672:Fusidic Acid / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000069349:Linezolid; D008712:Methicillin / Q000494:pharmacology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests / Q000592:standards; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology*; D023303:Oxazolidinones / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D003470:Culture Media; D023303:Oxazolidinones; D002981:Clindamycin; D005672:Fusidic Acid; D000069349:Linezolid; D008712:Methicillin