John and Harvin electrophoresis similarity, that infected 21 patients. The linezolid MIC was 256 µ g/mL in 24 of the 25 isolates. In this group of patients, previous linezolid use was a risk factor for development of resistance. Tigecycline Tigecycline is a minocycline derivitative with excellent activity against resistant Gram-positive bacteria. A South American study analyzed 47 MSCNS and 180 MRCNS for tigecycline susceptibility (Gales et al 2005). Both groups displayed an MIC90 of 0.5 µ g/mL (identical for S. aureus) and 100% were susceptible to 2 µ g/mL. In a 2004 publica- tion 321 MSCNS and 1111 MRCNS mirrored Gales study with MIC90 of 0.5 µ g/mL for both groups (Frische et al 2004). In a larger study of 3574 CNS, Sader et al found tigecycline exhibited excellent activity against blood stream pathogens (Sader et al 2005). Again the demonstrated MIC90 was 0.5 µ g/mL for CNS and for S. aureus. Data supporting this level of activity were also derived in another study comparing the activity of a new quinolone, DX-619, with other Gram-positive agents (Bogdanovich et al 2005b). The MIC90 of tigecycline for 61 MRCNS and 67 MSCNS was 0.5 µ g/mL. DX-619 comparatively had an MIC90 0.06 µ g/mL. In another study, limited number of glycopeptide-intermediate susceptible isolated of CNS (22) have been studied for tigecy- cline and daptomycin susceptibility. In one small set of 8 S. epidermidis isolates and 4 S. haemolyticus isolates, the MIC was again 0.5 µ g/mL for tigecycline, 2.0 µ g/mL for arbekacin and 1.0 µ g/mL for daptomycin (LaPlante and Rybak 2004). The minimum bactericidal concentration (MBC):MIC ratio was 4 (no speciﬁcs given). Time-kill experiments for tetra- cycline at 4 times the MIC against glycopeptide-intermediate S. epidermidis revealed similar killing to daptomycin but signiﬁcantly more activity than vancomycin at 24 hours. Thus, as a tetracycline derivative, tigecycline is surprisingly active against susceptible and resistant CNS and has some bactericidal effect. Daptomycin Daptomycin, an older cyclic glycopeptide that had been studied for several decades, was recently brought back to clinical life. It made its clinical debut in 2003 for approved use in skin and soft tissue infection and has been shown recently to be clinically non-inferior to vancomycin in clini- cal trials of staphylococcal bacteremia (Fowler et al 2006). Daptomycin probably has several mechanisms of action that involve perturbation of calcium-dependent channels to disrupt the cytoplasmic membrane, perhaps ﬁrst by altering 1148 the membrane potential (Silverman et al 2001; Friedman et al 2006). One of the largest studies of daptomycin-CNS interac- tions consisted of 1126 CNS (as veriﬁed by Vitek coagulase testing) taken from 6,973 gram-positive isolates collected from patient specimens at 50 hospitals distributed throughout the nine US Bureau of the Census regions (Critchley et al 2003). Daptomycin was consistently active with an MIC range of 0.015–2.0 µ g/mL and an MIC90 of 0.5 µ g/mL. Daptomycin and quinupristin/dalfopristin were the most active agents seen in this analysis. As an anti-staphylococcal agent, daptomycin may have other advantages like a very low spontaneous resistance rates seen during serial passage, and the fact that resistant mutants had lower virulence in an animal model (Silverman et al 2001). When daptomycin was tested for in vitro activity in Mueller-Hinton broth supplemented with 50 mg of calcium per liter, MICs were about 4-fold lower (Petersen et al 2002). In a comparative study against tigecycline, and other Gram-positive agents, the MIC90 of daptomycin and tigecycline for MSCNS was 0.25 µ g/mL and 0.5 µ g/mL respectively but was 8- and 2-fold higher for MRCNS, respectively. In comparison, the MIC rose multifold for other agents like erythromycin, levoﬂoxacin, and teicoplanin. Resistance to daptomycin has been shown in the laboratory with serial passage. Elegant experiments of genome comparison revealed that the non-susceptible mutants were altered in MprF, a lysylphosphatidylglycerol synthetase (Silverman et al 2006). New ﬂuoroquinolones Several new quinolones have excellent activity against CNS. As stated above (see daptomycin), a des-F(6)-quinolone, DX-619 was compared to 6 other quinolones. For strains that had an MIC90 of 16.0 µ g/mL, the DX-619 MIC90 was 0.125 µ g/mL, one tube lower than another new quinolone agent, sitaﬂoxacin (Bogdanovich et al 2005b). Interestingly, killing for DX-619 of a vancomycin-nonsusceptible CNS was complete at 4 × MIC and log4 at 12 hours for 2 × MIC. Of the currently used ﬂuoroquinolones, moxiﬂoxacin is prob- ably the most frequently used. Its MIC90 for MSCNS was 1.0 µ g/mL and for MRCNS was MSCNS was 4.0 µ g/mL. New cephalosporins Historically, β-lactam antibiotics have produced excellent results against methicillin-susceptibile staphylococci. Pro- duction of aberrant penicillin-binding proteins like PBP-2A bypass the effect of β-lactams. Thus, there has been a search to ﬁnd β-lactams that themselves bind to PBP-2A and thus render strains susceptible. Ceftobiprole is one of a new group Therapeutics and Clinical Risk Management 2007:3(6)