title: Activity of quinupristin/dalfopristin against extracellular and intracellular Staphylococcus aureus with various resistance phenotypes.
abstract: OBJECTIVE
  Treatment of chronic or recurrent Staphylococcus aureus infections may require using antibiotics with activity against intracellular multiresistant organisms. Quinupristin/dalfopristin (3:7) has been examined in this context.
  
  
  METHODS
  Quinupristin and dalfopristin were used separately or mixed. Strains used were: (i) methicillin-susceptible and -resistant S. aureus (MSSA and MRSA); (ii) one vat(B) MSSA and msr(A/B) MRSA; (iii) erm(A)+ [MSSA, MRSA, vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA)]; and (iv) one erm(A/B)+ cfr+ MRSA resistant to quinupristin, dalfopristin and their combination. Assessment of activity was determined by: (i) MICs (CLSI method); and (ii) concentration-response curves in broth and after phagocytosis by THP-1 macrophages, with descriptors of the model (Emin) and the pharmacodynamic response [maximal relative efficacy (Emax), relative potency (EC50) and apparent static concentration (Cstatic)].
  
  
  RESULTS
  erm(A)-positive strains were all susceptible to quinupristin/dalfopristin (except strain CM05), with MICs not adversely influenced by acid pH or by the MRSA, VISA or VRSA character of the strain. In concentration-response experiments, quinupristin/dalfopristin showed similar patterns for all strains (except strain CM05), with a >3 log10 cfu decrease in broth and a 1.3 [erm(A) strain] to 2.6 [fully susceptible, vat(B) and msr(A/B) strains] log10 cfu decrease for intracellular bacteria at the maximal extracellular concentration tested (25 mg/L). Maximal extracellular and intracellular activity was obtained for a quinupristin/dalfopristin ratio of 3:7. For strain CM05, quinupristin/dalfopristin was static in all conditions.
  
  
  CONCLUSIONS
  Based on historical comparisons with rifampicin, fluoroquinolones, lipoglycopeptides and other antistaphylococcal drugs with a large accumulation in eukaryotic cells, quinupristin/dalfopristin appears to be one of the most active antibiotics against intracellular S. aureus studied in this model so far, largely irrespective of its resistance phenotype.
authors.affiliation: Unité de pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, and Department of Microbiology, Hôpital Erasme, B-1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baudoux
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemaire
authors.forename: Olivier
authors.initials: O
authors.lastname: Denis
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
authors.forename: Youri
authors.initials: Y
authors.lastname: Glupczynski
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010587:Phagocytosis; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D014769:Virginiamycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014769:Virginiamycin; C062940:quinupristin-dalfopristin