1. J Antimicrob Chemother. 2010 Jun;65(6):1228-36. Epub 2010 Apr 8.

Activity of quinupristin/dalfopristin against extracellular and intracellular
Staphylococcus aureus with various resistance phenotypes.

Baudoux P, Lemaire S, Denis O, Tulkens PM, Van Bambeke F, Glupczynski Y.

Unité de pharmacologie cellulaire et moléculaire, Louvain Drug Research
Institute, Université catholique de Louvain, and Department of Microbiology,
Hôpital Erasme, B-1200 Brussels, Belgium.

OBJECTIVES: 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.

PMID: 20378672 [PubMed - in process]