Activity of quinupristin/dalfopristin against extracellular and intracellular Staphylococcus aureus with various resistance phenotypes.
(2010) Journal of Antimicrobial Chemotherapy — Vol. 65, n° 6, p. 1228-1236 (2010)
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- 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 (E(min)) and the pharmacodynamic response [maximal relative efficacy (E(max)), relative potency (EC(50)) and apparent static concentration (C(static))]. 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 log(10) cfu decrease in broth and a 1.3 [erm(A) strain] to 2.6 [fully susceptible, vat(B) and msr(A/B) strains] log(10) 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.
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Baudoux, P., Lemaire, S., Denis, O., Tulkens, P. M., Van Bambeke, F., & Glupczynski, G. (2010). Activity of quinupristin/dalfopristin against extracellular and intracellular Staphylococcus aureus with various resistance phenotypes. Journal of Antimicrobial Chemotherapy, 65(6), 1228-1236. https://doi.org/10.1093/jac/dkq110 (Original work published 2010)