Table 4 Ideal characteristics of anti-coagulase-negative staphylococcal antimicrobials • Ease of synthesis, isolation • Evidence that bactericidal concentration (MBC) closely approaches the inhibitory concentrations (MIC) • Excellent extracellular and intracellular activity • Pharmacokinetics/pharmacodynamics favorable to long intermittent dosing • Prolonged post-antibiotic effect • Good bioﬁlm penetration • Potential bioﬁlm inhibition • Lack of antagonism with other anti-staphylococcal agents • Slow evolution of in vitro and in vivo resistance • Low indices of systemic and organ toxicity and ciproﬂoxacin resistance (92% and 83% respectively) in 20 ICU patients were correlated with longer lengths of stay. Genotyping of the ICU CNS isolates found 32 pulse ﬁeld types involved, but 16 genotypes colonized more than 1 individual suggesting some clonality among these CNS isolates. In a study from Greece of intravenous catheter infec- tions associated with bacteremia, over a 2-year period CNS were responsible for nearly 60% of infections (Paragioudaki et al 2004). For these pathogens, in 1999, the resistance rate was 72% for ampicillin, oxacillin, ceftazidime, ceftriaxone, cefaclor, amoxicillin/clavulanate, and impenem, with slightly lower rates for SXT, ciproﬂoxacin, and amikacin. There was no vancomycin resistance. Rates dropped slightly in the year 2000 for the same antimicrobials. The redundancy of resistance rates may be due to spread of virulent CNS clones as was observed earlier at the University of Patras (Spiliopoulou et al 2003). Several studies combined automated species identiﬁca- tion with antimicrobial susceptibility testing. From Italy, Ariciola et al reported resistance levels in 15 species of 193 isolates found to colonize orthopedic implants (Arciola et al 2006). In the 5 most prevalent species – S. hominis, S. haemolyticus, S. capitis, S. warnerii, S. cohenii – resis- tance to penicillin was similar (51%–66%). Most oxacillin resistance was seen in S. haemolyticus whereas no oxacillin resistance was present in S. warneri. Multiple antibiotic resis- tance genes were most likely to be found in S. haemolyticus, averaging 2.8 for that species. Though the data are small in number, this study suggests that both careful susceptibility testing along with species identiﬁcation is helpful in certain device-related infections. CNS remain the major cause of postcataract endophthal- mitis. Recchia et al found that nearly 60% of pathogens from such cases were CNS and 91% of these were S. epidermidis (Recchia et al 2006). In analyzing 2 groups, for the 5 years Therapeutics and Clinical Risk Management 2007:3(6) Antibiotic resistance in coagulase-negative staphylococci before and after 1994, a signiﬁcant increase in resistance was seen for ciproﬂoxacin (20 to 38%) and cefazolin (19 to 40%). TMP/SMZ resistance stated relative stable, around 27%. The study of device-related antimicrobial resistance has been hampered by lack of good models. Work with newer models has determined activity of various antibacterial solutions activity against different bacteria after adherence to silicone catheter segments (Sherertz et al 2006). Results showed that S. epidermidis was the most susceptible in terms of log kill over 24 hours to most antimicrobials tested and, in particular, to a complex solution of minocycline, EDTA, and ethanol. New individual agents Several new antimicrobials with good anti-staphylococcal activity have been marketed recently or will likely soon be marketed: ceftobiprole, dalbavancin, daptomycin, linezolide, tigecycline and telavancin. We will discuss the reports that have included CNS in the susceptibility proﬁle. Linezolid This oxazolidinone was introduced into clinical practice (in the US) in 2000. Its mechanism of action involves the binding of N-formylmethionyl-tRNA to the ribosome with the 50s subunit, but not the 30s subunit of the ribosome (Shinabarer 1999). There are no comparative trials of linezolid therapy for CNS infections. With an MIC90 = 1–4 µ g/mL, it has become a major option for therapy in resistant and recalcitrant staphy- lococcal infections including those due to CNS (Davidson and Low 2004). In the largest in vitro experience as of its 1999 publication, Noskin et al studied 365 oxacillin-susceptible and 441 oxcillin-resistant CNS (Noskin et al 1999). Both groups had the same MIC50 and MIC90, 2 and 4 µ g/mL respectively. At that time, only vancomycin of the agents studied was more active. Data submitted for US registration of linezolid showed MIC90 values of both methicillin-resistant and methicillin-resistant S. epidermidis of 1–4 µ g/mL (Pﬁzer data on ﬁle). Postmarketing surveillance programs reported for 870 CNS isolates an MIC90 of 1 µ g/mL (Ross et al 2005). Only one isolate had an MIC 8 µ g/mL. In vitro development of resistance occurs very slowly with serial passage but when it does occur, it is related to two independently isolated point mutations at G2447U and G2576U of the 23S rRNA (Shinabarger 1999). Resis- tance in the clinical setting, interestingly, has involved a report of linezolid-resistant CNS (Potoski et al 2006). The University of Pittsburgh Medical Center experienced this cluster of 25 linezolid-resistant CNS isolates with a single S. epidermidis clone, shown by pulse-ﬁeld gel 1147