Prevalence, Molecular Epidemiology, and Clinical Significance of Heterogeneous Glycopeptide-Intermediate Staphylococcus aureus in Liver Transplant Recipients

Abstract

We investigated the prevalence, molecular epidemiology, and clinical significance of heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA) isolates in 48 liver transplant recipients infected or colonized with methicillin-resistant S. aureus over a 5-year period. Strains were screened for hGISA on Mueller-Hinton agar containing 5 mg of teicoplanin per liter. Heterogeneous glycopeptide resistance was confirmed by the E-test method with a dense inoculum and a simplified method of population analysis. hGISA strains were found in 13 (27%) of the 48 patients studied. Eleven of the 13 strains shared a common multiresistant phenotype with homogeneous methicillin resistance and gentamicin resistance, and they were closely related according to the results of pulsed-field gel electrophoresis. Only 2 of the 13 patients infected or colonized with hGISA strains had previously received glycopeptide therapy. Most patients were successfully treated with vancomycin, but one patient who failed to respond to vancomycin subsequently died. These results suggest that the high prevalence of hGISA among our patients was due to the clonal spread of a multiresistant strain.

Comparison of Detection Methods for Heteroresistant Vancomycin-Intermediate Staphylococcus aureus , with the Population Analysis Profile Method as the Reference Method

“…Such strains are susceptible in vitro to vancomycin (MIC Ͻ 4 g/ml) and thus are classified as susceptible by standard clinical laboratory methods but contain subpopulations of 1 in 10 6 cells that can grow in the presence of Ն4 g/ml of vancomycin (9,27). Although the true prevalence of hVISA is unknown, estimates from a limited number of studies range from 1.3% to 27% of all MRSA isolates (1,4,5,8,21). Because of the increasing number of reports of vancomycin treatment failures and reports of poor outcomes for patients infected with hVISA (3,5,13,21,23,25), an accurate and practical method for the detection of hVISA among MRSA isolates in the clinical laboratory is of growing importance.…”

Effects of Alterations in Staphylococcus aureus Cell Membrane and Cell Wall in Antimicrobial Resistance

“…This phenomenon is believed to "trap" vancomycin and this, together with the thickened cell wall, may act as a barrier to the difusion of large molecules, like daptomycin (as cited below) [16,17]. In this way, the emergence of these bacterial phenotypes cited above has put into question the efectiveness of these antibiotics against S. aureus [1,18,19]. These changes in susceptibility seem to be related to the diiculty of resolving cases of S. aureus infection, leading to increased mortality of patients [20].…”

“…A thickened cell wall has been highlighted as a characteristic phenotype commonly found in clinical VISA. This feature is intimately associated with peptidoglycan-clogging theory that explains vancomycin resistance by passage delay of antibiotic molecules across the thickened The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureuspeptidoglycan layers [18]. Punctual mutations by genetic manipulation in S. aureus strains that could lead to cell wall thickening were investigated thoroughly.…”

In Vitro Activities of a Novel Cephalosporin, CB-181963 (CAB-175), against Methicillin-Susceptible or -Resistant Staphylococcus aureus and Glycopeptide-Intermediate Susceptible Staphylococci

“…In 1996, the first report of a glycopeptide-intermediate susceptible S. aureus (GISA) was described in Japan (4). Since then, other cases of GISA infections have been reported worldwide (1,2,3,4,5,8,13,16,17,20,22,24,25,27). These GISA strains are generally found in patients who been exposed to long-term vancomycin therapy with drug MICs of Ͼ4 and Ͻ32 g/ml.…”

“…These GISA strains are generally found in patients who been exposed to long-term vancomycin therapy with drug MICs of Ͼ4 and Ͻ32 g/ml. Heterogeneous GISA (hGISA) and heterogeneous glycopeptide-intermediate Staphylococcus species (hGISS) are defined as those for which vancomycin MICs are 1 to 4 g/ml but which contain subpopulations that can grow on agar plates supplemented with vancomycin (4 g/ml) (2). These strains were first described by Hiramatsu et al and may be the first step in the development of GISA strains (2).…”