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Title: Genomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases.
Austin Authors: Holmes, Natasha E ;Ballard, Susan A;Lam, Margaret M C;Johnson, Paul D R ;Grayson, M Lindsay ;Stinear, Timothy P;Howden, Benjamin P 
Affiliation: Infectious Diseases
Issue Date: 23-Apr-2013
Publication information: The Journal of Antimicrobial Chemotherapy 2013; 68(9): 2134-9
Abstract: 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.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.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.Clinicians should be cautious of resistance emerging during teicoplanin therapy for vanB VRE, particularly in immunosuppressed patients or where source control is difficult.
DOI: 10.1093/jac/dkt130
Journal: The Journal of Antimicrobial Chemotherapy
Type: Journal Article
Subjects: single nucleotide polymorphisms
whole genome sequencing
Anti-Bacterial Agents.administration & dosage.pharmacology
Bacterial Proteins.genetics
Drug Resistance, Bacterial
Enterococcus faecium.drug effects.genetics.isolation & purification
Genome, Bacterial
Gram-Positive Bacterial Infections.drug therapy.microbiology
Middle Aged
Organ Transplantation
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
Teicoplanin.administration & dosage.pharmacology
Treatment Failure
Appears in Collections:Journal articles

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