Activity of quinupristin/dalfopristin against extracellular and intracellular Staphylococcus aureus with various resistance phenotypes.
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.
Baudoux
Pierre
P
Unité de pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, and Department of Microbiology, Hôpital Erasme, B-1200 Brussels, Belgium.
Lemaire
Sandrine
S
Denis
Olivier
O
Tulkens
Paul M
PM
Van Bambeke
Françoise
F
Glupczynski
Youri
Y
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*
D000900:Anti-Bacterial Agents; D014769:Virginiamycin; C062940:quinupristin-dalfopristin