John and Harvin Table 3 New agents with good antibacterial activity against coagulase-negative staphylococci Agent Year introduced Mechanism of action MIC90 CNS MSCNS/MRCNS Ceftibiprole N.A. Binds to abberant penicillin binding 1.0/2.0 protein,PBP-2A Daptomycin 2003 Cell membrane lysis 0.5/0.5 Dalbavancin Linezolid Moxiﬂoxacin Televancin Tigecycline N.A. 2000 2002 N.A. 2003 Blocks cell-wall synthesis like teichoplanin Binds to tRNA Interferes with topoisomerase II and IV Blocks the synthesis of phospholipids in cell membranes Blocks 30s ribosome 0.06/0.06 4.0/4.0 0.12/4.0 0.5/1.0 0.5/0.5 MIC90 S. aureus MSSA/MRSA 0.5/2.0 Reference Bogdanovich et al 2005a 0.5/0.5 0.06/0.06 4.0/4.0 0.12/4.0 0.5/0.5 0.5/0.5 Critchley et al 2003 Petersen et al 2002 Lin et al 2005 Noskin et al 1999 Hardy et al 2000 King et al 2004 Frische et al 2004 Gales et al 2005 Sader et al 2005 Abbreviations: CNS, coagulase-negative staphylococci; MSCNS/MRCNS, methicillin-susceptible/methicillin-resistant CNS; MSSA/MRSA, methicillin-susceptible S. aureus/ methicillin-resistant S. aureus. ciproﬂoxacin, clindamycin, and erythromycin both in US and global sites (Diekema et al 2001). For most antimicrobials, intensive care units (ICUs) tend to show the highest rates of antimicrobial resistance (Fridkin et al 1999). In a massive study to determine the focus of antibiotic resistance in dif- ferent areas for over 80 hospitals, the rates of MRCNS were signiﬁcantly higher in ICU – than in non-ICU patients and were higher in non-ICU patients than in outpatients. These data suggest that the major risk for MRCNS is associated with more complex hospital environments. A similar large study was conducted in which staphy- lococci were collected from 20 regional health centers in several countries across Europe, Asia, and Latin America (Sanches et al 2000). The CNS were divided into methicil- lin-resistant S. epidermidis (MRSE), methicillin-resistant S. haemolyticus (MRSH), and other MRCNS and their susceptible counterparts. Cross resistance was most com- mon in the methicillin-resistant groups. For example, rates of SXT, ciproﬂoxacin, and gentamicin were 64%, 50.5%, and 72.3% respectively. MRSH showed even higher frequencies of cross resistance. These trends in cross resistance among CNS were different than those for MRSA, suggesting that different selection pressures are at work for the two groups. Another study tested susceptibility of only skin and soft tissue isolates in 283 US hospitals and 301 hospitals in Europe for 9 antimicrobials, including amoxicillin- clavulanate, cefotaxime, cetriaxone, ciprofloxacin, erythromycin, gentamicin, levofloxacin, trimethoprim (TMP)/sulfamethoxazole (SMX), and vancomycin. For MSCNS almost all isolates were susceptible to amoxicillin- clavulanate, suggesting that clavulanate remains very 1146 active against staphylococcal β-lactamase (Jones et al 2003). For the ﬂuoroquinolones, ciproﬂoxacin averaged about 90% susceptibility and, where tested, levoﬂoxacin was active against slightly more strains. For example, in Italy 83.3% of isolates were susceptible to ciproﬂoxacin versus 85.7% for levoﬂoxacin. Ranges of activity for gen- tamicin (86.1%–96.4%) and TMP/sulfamethizole (SMZ) (88.1%–92.7%) were active in a similar range. Over 25% of isolates were resistant to erythromycin whereas all isolates were susceptible to vancomycin. For MRCNS the resis- tance trends were, in general, similar in European and US isolates with some exception. For example, ciproﬂoxacin resistance was 65.0%–66.7% across four European coun- tries (France, Germany, Italy, and Spain) versus a range of 38.1%–47.0% in the US. Gentamicin resistance was higher in Europe (range of 50.2%–61.3%) in the US (32.4%). No vancomycin resistance was detected. Cuevas et al studied the trends of resistance in clinical isolates of CNS in Spain for ﬁve periods from 1986 to 2002 (Cuevas et al 2004). For all years together, 28% of strains were community in origin and 72% were nososcomial. Oxacillin resistance rose steadily from 32.5% in 1986 to 61.3% in 2002. Gentamicin resistance rates peaked in 1994 at 41.4% but dropped to 27.85% in 2002. Most interestingly, ciproﬂoxacin resistance rose from 1.1% in 1986 to 44.9% in 2002. Although there was no vancomycin resistance, there was one isolate in the 1996 study resistant to teichoplanin, an observation made earlier in one isolate of S. epidermidis from a corneal infection (Pinna et al 1999). Nosocomial strains were more likely to demonstrate resistance. In another study done in Uppsala, Sweden to determine more speciﬁcally how an ICU stay would inﬂuence CNS resistance, high rates of oxacillin Therapeutics and Clinical Risk Management 2007:3(6)