In-vitro characteristics of glycopeptide resistant strains of Staphylococcus epidermidis isolated from patients on CAPD

Abstract

The low-level resistance of three clinical isolates of Staphylococcus epidermidis to glycopeptide antibiotics was found to be constitutive, not inducible, and was not increased by passage in the presence of either vancomycin or teicoplanin. There was no loss of resistance on repeated passage in antibiotic-free broth. In contrast, the susceptibility to these antibiotics declined for S. epidermidis NCTC 6513 that been sequentially passaged in either vancomycin or teicoplanin whereas the variants reverted to being susceptible on further passage in antibiotic-free broth. Antibiotic activity was almost completely abolished when cultures of the resistant S. epidermidis strains were exposed overnight to sub-MIC concentrations. No evidence of drug-modifying activity was obtained. Experiments of antibiotic-binding activity indicated that the resistant strains exhibited an increased ability to sequester antibiotics which was particularly rapid in stationary phase cultures when most of the antibiotic activity disappeared from the growth medium within 30 min of exposure to the drugs. Teicoplanin was sequestered more efficiently than vancomycin and some loss of activity was also observed when stationary phase cultures of S. epidermidis NCTC 6513 were exposed to glycopeptides. These results suggest that glycopeptide-resistant isolates of S. epidermidis are able to bind large amounts of these antibiotics, possibly at sites unassociated with the D-alanyl-D-alanine target, and that teicoplanin is bound more avidly than vancomycin.

Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus

“…Some of the properties of the highly vancomycin-resistant S. aureus mutant VM described in this communication have also been seen in other bacteria, such as binding of vancomycin to bacterial cell walls (1,4,24,27), abnormal morphology and the appearance of amorphous material on the surface of glycopeptide-treated bacteria (29,41), and the capacity of some lowlevel vancomycin-resistant laboratory mutants and/or clinical isolates of coagulase-negative staphylococci to remove vancomycin from the growth medium (25,30). Whether the mechanism of resistance of these low-level vancomycin-resistant staphylococci is similar to the mechanism we propose for the highly vancomycin-resistant S. aureus described in this communication remains to be tested.…”

Glycopeptide Susceptibility Profiles of Staphylococcus haemolyticus Bloodstream Isolates

“…Glycopeptide-resistant cells of clinical and laboratory-derived strains of S. haemolyticus and S. epidermidis have been shown to differ from their glycopeptidesusceptible counterparts in several features, including ultrastructural morphology (3,11,20,24), glycopeptide-binding capacity (21,28), membrane proteins (18), cell wall synthesis and composition (5), and susceptibility to cell wall-active antibiotics and enzymes (7,9). Reduced and heterogeneous susceptibility to teicoplanin in methicillin-resistant coagulase-negative staphylococci appears to be on the increase in some hospital settings (28).…”

An electronmicroscope study of glycopeptide antibiotic-resistant strains of Staphylococcus epidermidis

“…22 The evident increase in the amount of cell-wall peptidoglycan and the presence of extracellular material observed in S. epidermidis strains SP4 and JS2 after exposure to teicoplanin, provide morphological support for the view that some glycopeptide-resistant strains of coagulase-negative staphylococci possess an excess of glycopeptide binding sites by virtue of overproduction of cell-wall peptidoglycan material. The nature of the extracellular material observed after exposure to teicoplanin remains conjectural.…”