03127nas a2200265   4500008004100000020001400041024001700055245020200072210006900274260038300343300001600726490000700742520185600749653003602605653001002641653002802651100002002679700001902699700001802718700001802736700001602754700002102770700002102791856004902812       2013                        eng d  a0305-7453  ahd7, 751361700aGenomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases.0 aGenomic analysis of teicoplanin resistance emerging during treat  a(C) British Society for Antimicrobial Chemotherapy 2013. Published by Oxford University Press. All rights reserved.b(1)Austin Centre for Infection Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC 3084, Australia(2)Department of Medicine, University of Melbourne, Parkville, VIC 3052, Australia(3)Department of Microbiology and Immunology, Univec2013  a2134 - 21390 v683 aObjectives: We noted four cases of apparent in vivo emergence of teicoplanin resistance during failed therapy for initially teicoplanin-susceptible vanB vancomycin-resistant Enterococcus faecium (VREfm) infections in solid organ transplant recipients at our institution over a 12 month period. We investigated if in vivo emergence of resistance had occurred, if transplant-related vancomycin-resistant Enterococcus (VRE) infections had occurred and identified clinical predictors of resistance emergence., Methods: Whole genome sequencing was performed on nine VREfm isolates for phylogenetic analysis and to identify determinants of teicoplanin resistance. Clinical treatment details were compared with other patients who received teicoplanin for confirmed vanB VRE infections but did not develop resistance during the same year at our institution., Results: A high-resolution, core genome phylogeny was inferred for nine VREfm isolates and confirmed in vivo development of resistance during failed therapy in four cases. Four different non-synonymous single nucleotide polymorphisms (SNPs) were observed in the vanRS genes of teicoplanin-resistant strains compared with the index teicoplanin-susceptible strains, and these SNPs were predicted to confer teicoplanin resistance. VREfm within a cluster of early transplant-related infections were phylogenetically identical at the core genome level, indicating a common source donor. Focus eradication and absence of prosthetic material were characteristics of those patients treated successfully., Conclusions: Clinicians should be cautious of resistance emerging during teicoplanin therapy for vanB VRE, particularly in immunosuppressed patients or where source control is difficult., (C) British Society for Antimicrobial Chemotherapy 2013. Published by Oxford University Press. All rights reserved.10asingle nucleotide polymorphisms10avanRS10awhole genome sequencing1 aHolmes, Natasha1 aBallard, Susan1 aLam, Margaret1 aJohnson, Paul1 aGrayson, M.1 aStinear, Timothy1 aHowden, Benjamin  uhttps://www.notifylibrary.org/reference/4161