Activity of ceftaroline against extracellular (broth) and intracellular (THP-1 monocytes) forms of methicillin-resistant Staphylococcus aureus: comparison with vancomycin, linezolid and daptomycin

作者：Melard Aurelie; Garcia Laetitia G; Das Debaditya; Rozenberg Raoul; Tulkens Paul M^*; Van Bambeke Francoise; Lemaire Sandrine

来源：Journal of Antimicrobial Chemotherapy, 2013, 68(3): 648-658.

DOI：10.1093/jac/dks442

• Hill equation
• maximal relative efficacy
• static concentration
• recursive partitioning analysis
• mass spectrometry
• VISA
• linezolid resistant
• cfr

Ceftaroline fosamil is approved for treatment of acute bacterial skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We examined the activity of its active metabolite (ceftaroline) against intracellular forms of S. aureus in comparison with vancomycin, daptomycin and linezolid. %26lt;br%26gt;Two methicillin-susceptible S. aureus (MSSA) and 11 MRSA strains with ceftaroline MICs from 0.125 to 2 mg/L [two strains vancomycin- and one strain linezolid-resistant (EUCAST interpretative criteria); VISA and cfr] were investigated. The activity was measured in broth and after phagocytosis by THP-1 monocytes in concentration-dependent experiments (24 h of incubation) to determine: (i) relative potencies (EC50) and static concentrations (C-s) (mg/L and MIC); and (ii) relative activities at human C-max (E-Cmax) and maximal relative efficacies (E-max) (change in log(10) cfu compared with initial inoculum). Ceftaroline stability and cellular accumulation (at 24 h) were measured by mass spectrometry. %26lt;br%26gt;Ceftaroline showed similar activities in broth and in monocytes compared with vancomycin, daptomycin and linezolid, with no impact of resistance mechanisms to vancomycin or linezolid. For all four antibiotics, intracellular E-Cmax and E-max were considerably lower than in broth (approximate to 0.5 log(10) versus 45 log(10) cfu decrease), but the EC50 and C-s showed comparatively little change (all values between approximate to 0.3 and approximate to 6 MIC). The mean cellular to extracellular ceftaroline concentration ratios (20 mg/L; 24 h) were 0.660.05 and 0.900.36 in uninfected and infected cells, respectively. %26lt;br%26gt;In vitro, ceftaroline controls the growth of intracellular MRSA to an extent similar to that of vancomycin, linezolid and daptomycin for strains with a ceftaroline MIC 2 mg/L.

• 出版日期2013-3