Glycopeptide Resistance in Coagulase-Negative Staphylococci

Abstract

Coagulase-negative staphylococci (CNS) were the first organisms in which acquired glycopeptide resistance was recognized. Ever since the early reports, it has been apparent that resistance to teicoplanin is more common than that to vancomycin and that resistance occurs mostly in species such as Staphylococcus haemolyticus and Staphylococcus epidermidis. The minimum inhibitory concentrations (MICs) of teicoplanin for CNS usually fall over a wide range, and, especially in some methicillin-resistant isolates of the two above-mentioned species, they can reach and even exceed the resistance breakpoint, whereas vancomycin MICs tend to remain more stable over a narrower range within the limits of susceptibility. CNS strains intermediately susceptible and even resistant not only to teicoplanin but also to vancomycin have, however, been isolated, most frequently from patients subjected to prolonged glycopeptide treatment. Laboratory detection of glycopeptide-resistant CNS may be problematic, mainly because susceptibility tests, particularly those for teicoplanin, are influenced by various technical factors, and agar diffusion tests may yield false susceptibility data. In studies with experimental glycopeptides, some molecules have exhibited improved in vitro activity compared with teicoplanin and vancomycin, but these encouraging microbiological findings have not usually been followed by in vivo trials. Stepwise and single-step exposure to teicoplanin and vancomycin has allowed stable clones for which glycopeptide MICs are increased to be obtained from susceptible CNS strains, particularly strains of Staphylococcus haemolyticus and Staphylococcus epidermidis. In these studies, resistance to teicoplanin was generally easier to obtain than resistance to vancomycin, and the levels of teicoplanin resistance were higher. Population studies have demonstrated the usually heterogeneous nature of glycopeptide resistance in CNS. Although glycopeptide-resistant CNS have been shown to differ in several features from their glycopeptide-susceptible counterparts, the exact mechanism of staphylococcal glycopeptide resistance remains unknown.

Staphylococcus haemolyticus – an emerging threat in the twilight of the antibiotics age

“…S. haemolyticus was the first Gram-positive bacteria reported as being resistant to glycopeptides, before any other staphylococci and enterococci (Kristó f et al, 2011). This species has been also suggested as being more active than other CNS in generating clones with increased glycopeptide (especially teicoplanin) MICs (Biavasco et al, 2000).…”

“…Amongst CNS, it was S. haemolyticus that was documented as being resistant to teicoplanin for the first time (Biavasco et al, 2000). It was suggested that S. haemolyticus is unique amongst CNS and especially predisposed to resistance to glycopeptides, because of its extraordinary genome plasticity and tendency to frequent DNA rearrangements (Takeuchi et al, 2005).…”

Heterogeneous resistance to vancomycin and teicoplanin among Staphylococcus spp. isolated from bacteremia

“…Resistance to glycopeptides in coagulase-negative staphylococci (CNS) comes already being shown since the end of the years 80 [2,3]. However, the interest on the acquisition of resistance to glycopeptides increased only after the isolation of Staphylococcus aureus strains presenting intermediate resistance to vancomycin (VISA strains) worldwide [4,5].…”

Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intrathecal vancomycin in an allogeneic peripheral blood stem cell transplant recipient

“…A possible explanation would be the fact that the antibacterial activity of aminoglycosides is pHdependent, with increased activity at higher pH, and it has been shown that in cases of meningitis the CSF becomes acidic. 9 The emergence of glycopeptide-resistant coagulase-negative staphylococci in patients treated for long periods with VCM and teicoplanin has been increasingly documented. 10 In vitro, linezolid, quinupristin-dalfopristin, moxifloxacin and trovafloxacin, which are new antibiotics, reveal good activity against MRSA and methicillin-resistant and teicoplaninintermediate coagulase negative staphylococci.…”