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To investigate if colonization with heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA) is associated with hGISA bacteraemia.Isolates of methicillin-resistant S. aureus (MRSA) from blood cultures and from swabs to detect MRSA colonization were screened for reduced susceptibility to glycopeptides by an agar incorporation method. Isolates detected by this screen were tested for glycopeptide resistance by MacroEtest, standard MIC Etest methods and population analysis profile–AUC (PAP–AUC) analysis. S. aureus isolates with and without reduced glycopeptide susceptibility were characterized by PFGE and spa typing.MRSA isolates with reduced susceptibility to glycopeptides, as identified by the MacroEtest method, were detected in the colonization screens of 86 of 2550 MRSA-positive patients. The isolates were confirmed by Etest MIC and PAP–AUC analysis as hGISA. A total of 82/86 of the hGISA colonizing isolates were EMRSA-16 by PFGE; the remainder were EMRSA-15. Bacteraemia with hGISA was identified in five patients during the study period; two isolates were EMRSA-16 and three were EMRSA-15. hGISA colonization could not be linked to hGISA bacteraemia and hGISA bacteraemia could not be linked to hGISA colonization. Four of the five hGISA bacteraemias developed following teicoplanin therapy for a central venous catheter-associated MRSA bacteraemia.Laboratory strategies to reduce morbidity associated with hGISA should focus on testing for hGISA in bacteraemic (rather than colonizing) MRSA isolates in patients with recurrent S. aureus bacteraemia following glycopeptide exposure.