R E V I E W History and evolution of antibiotic resistance in coagulase-negative staphylococci: Susceptibility proﬁles of new anti-staphylococcal agents Joseph F John1,2 Alexander M Har vin1 1Ralph H. Johnson Department of Veterans Affairs Medical Center, 2Departments of Medicine and Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA Correspondence: Joseph F John 109 Bee Street (14), Charleston, SC 29401, USA Tel +1 843 789 7942 Email joseph.john2@va.gov Abstract: Coagulase-negative staphylococci (CNS) are a heterogenous group of Gram-positive cocci that are widespread commensals among mammalia. Unlike their coagulase-positive counterpart, Staphylococcus aureus, CNS produce few virulence patterns and normally refrain from invading tissue. Yet, not only can CNS cause infections in normal host tissue, but modern medicine has also seen their rise as opportunists that display adherence to medical device materi- als to produce a protective bioﬁlm. CNS have historically been more resistant to antimicrobials, including the β-lactam antibiotics, than S. aureus and some hospitals reveal rates of oxacillin resistance in CNS approaching 90%. Cross resistance to non-β-lactam agents has been a recurrent theme over the past 40 years in the CNS. Thus, there has been a pressing need for newer antimi- crobial agents with good antistaphylococcal activity. Those new agents tend to have excellent antistaphylococcal activity include daptomycin, linezolid, oritavancin, telavancin, tigecycline, dalbavancin, new quinolones, and ceftibiprole, several of which have unique mechanisms of action. The MIC90 for these new compounds typically ranges from 0.5–4 µ g/mL. Staphylococcal bioﬁlm formation is quite common in CNS infections and markedly increases the MIC for most older antimicrobials. Several of the newer agents offer some promise of penetration of bioﬁlm to inhibit or kill adherent staphylococci. CNS will likely remain a major cause of infections in the modern age, evolve further antimicrobial resistance mechanisms, and require development of newer antimicrobials for curative therapy. Keywords: coagulase-negative staphylococcus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus lugdenesis, bioﬁlm, new antibiotics, antibiotic resistance Introduction The group of Gram-positive bacteria identiﬁed as coagulase-negative staphylococci (CNS), usually harmless commensals, have become important, commonly isolated pathogens in clinical microbiology laboratories around the world (Kloos and Bannerman 1994; Cerca et al 2005; Arciola et al 2006; Bayram and Balci 2006; Caierão et al 2006; Widerström et al 2006). Over the last several decades, infection with CNS has been characterized as related to “medical progress” (Rupp and Archer 1994). Accordingly, CNS, as human pathogens, are usually associated with healthcare settings and occur in patients who are immunocompromised or harboring indwelling polymer or metallic devices (Bisno 1995). By 1985, there were 19 recognized species of CNS, 8 of which exhibited a pos- sible association with human infection (Kloos and Jorgensen 1985). At that time, the most commonly isolated of these pathogenic species were Staphylococcus epider- midis and S. haemolyticus. Typing of CNS in the late 1980s was primarily based on biochemical testing proﬁles such as the one proposed by Kloos and Schleifer in 1975 (Kloos and Schleifer 1975). This scheme used certain biochemical markers including novobiocin resistance; fermentation of: sucrose, fructose, galactose, ribose, lactose, Therapeutics and Clinical Risk Management 2007:3(6) 1143–1152 © 2007 Dove Medical Press Limited. All rights reserved 1143