Table 2 List of antimicrobial classes potentially active against coagulase-negative staphylococci Class Aminoglycosides Carbapenems Cephalosporins Choramphemicols Diaminopyrimidines Fluoroquinolones Fusidic acid Glycopeptides Lincomycins Lipopeptides Macrolides Oxazolidinones Polymyxins Rifampicins Semi-synthetic penicillins Sulfonamides Tetracyclines Dihydrofolate reductase inhibitors (trimethoprim) are highly active against planktonic cultures. The problem of antibiotic bioﬁlm interaction has recently become a stimulus to develop antibiotics that can inhibit initial microbial adhe- sion to polymer surfaces as well as growth on planktonic cultures (Cerca et al 2005). In this paper we will review the general problem of antibiotic resistance in CNS and discuss the susceptibility and resistance, where data are available, for speciﬁc species. Additionally, in view of a recent expansion in new anti staphylococcal agents, we will address the susceptibility proﬁles of some of these newer agents. Pre-1994 susceptibility literature Antimicrobial susceptibility in CNS became an issue in the 1970s when these species were isolated as pathogens in prosthetic valve endocarditis infections of cerebrospinal ﬂuid shunt infections (Keys and Hewitt 1973; Shoenbaum et al 1975). There were earlier harbingers that new resistance genes were emerging, speciﬁcally those whose products would inhibit the binding of semisynthetic penicillins, agents that had been developed to resist the effects of extracellular staphylococcal β-lactamases. Methicillin was the predomi- nant semisynthetic penicillin used in early therapy so the term “methicillin resistance” became a generic term for resis- tance to β-lactam antibiotics based on the inability of these agents to bind to the new penicillin-binding protein product of mecA, PBP-2a (Sutherland and Rollison 1964; Bentley et al 1967). During the 1970s it became clear that methicil- lin resistance was more prevalent in CNS (MRCNS) than in Therapeutics and Clinical Risk Management 2007:3(6) Antibiotic resistance in coagulase-negative staphylococci methicillin-resistant S. aureus (MRSA), an observation that continues to be true today. During the 1970s and early 1980s, the problem of multi- resistance in CNS was reported primarily in cases of device related infections particularly prosthetic valve endocarditis (Archer 1978). In a group of S. epidermidis associated with device infections, 56% were resistant to methicillin and 70% were resistant to cefoxitin and cephardine (Archer 1978). For the subsequent period through 1994, Archer and Climo have reviewed the literature (Archer and Climo 1994) in which they report an escalation of resistance for almost all antimicrobial classes excluding glycopeptides: β-lactams aminoglycosides, trimethoprim, rifampin, ﬂuoroquinolones, macrolides, and tetracyclines. Therefore, in this current paper we will review the post-1994 literature on the subject. Post-1994 susceptibility literature The trends in resistance in CNS over the last 13 years have continued to show escalation in the frequency and expression of resistance determinants. Resistance to β-lactam agents (methicillin resistance) has remained the foremost strain determinant. Strains of MRCNS are often linked to multi- resistance, like their MRSA counterparts, thus presenting an ongoing therapeutic challenge. The discovery of speciﬁc chromosomal cassettes carrying the mecA gene as well as multiple other genes has provided a new backdrop against which evolution of CNS species and their respective SCCmec can be measured (Mongkolrattanothai et al 2004; Noto and Archer 2006). A dichotomy between methicillin-susceptible CNS (MSCNS) and MRCNS permeates the literature on susceptibility testing. In fact, these groups are usually tested and reported separately. For example the analysis of US key bloodstream bacterial isolates from 1995, 1996, and 1997 showed that among 43,789 CNS, 42% were MSCNS and 58% were MRCNS (Sahm et al 1999). Moreover, in this group of MRCNS the rate of vancomycin minimum inhibi- tory concentration (MIC) of 4 µ g/mL increased from 1.8% to 4.8% from 1995 to 1997. That database, SENTRY, was expanded to other countries during 1997–1999 (Diekema 2001). Interestingly, while rates of methicillin resistance among CNS varied widely among 13 European countries, the rate was around 70% for 5 global locations; Canada, USA, Latin America, Europe, and the West Pacific. Co-resistance patterns were also reported for the ﬁve regions based on oxacillin resistance. For example in the US trimethoprim-sulfamethoxazole (SXT) resistance was about 17% in MSCNS compared with nearly 57% in MRCNS. Similar trends were seen for gentamicin, 1145