title: Emergence of High-Level Daptomycin Resistance in Corynebacterium striatum in Two Patients with Left Ventricular Assist Device Infections.
abstract: BACKGROUND
  We describe the clinical and microbiologic courses of two patients with ventricular assist device infections secondary to Corynebacterium striatum treated with daptomycin. In both cases, the pathogen was initially susceptible to daptomycin (minimum inhibitory concentration [MIC] <0.125 mg/L) but became resistant (MIC >256 mg/L) during therapy.
  
  
  METHODS
  The clonal nature of the isolates was determined by pulse-field gel electrophoresis (PFGE). Daptomycin binding was assessed by fluorescence microscopy using daptomycin-boron-dipyrromethene (bodipy). Induction and stability of daptomycin resistance were assessed by culturing strains in the presence of low concentrations of daptomycin or passage of resistant strains on daptomycin-free medium and repeat MIC testing, respectively.
  
  
  RESULTS
  PFGE revealed that resistant clinical isolates were genetically indistinguishable from their parent strains, but the two pairs were unrelated to each other. The resistant strains had 7.5-15 times lower binding of daptomycin-bodipy compared to the related susceptible strains (p ≤ 0.0002). High-level daptomycin resistance (MIC >256 mg/L) was generated in vitro for both susceptible parent strains after overnight culture in the presence of daptomycin. One of the resistant strains maintained a high-level resistance phenotype up to 5 days of passage on daptomycin-free medium, whereas the other strain reverted back to a susceptible phenotype (MIC = 0.38 mg/L) after one passage on daptomycin-free medium, with a concomitant increase in daptomycin binding.
  
  
  CONCLUSIONS
  High-level daptomycin resistance in C. striatum was readily generated in vitro and during the course of therapy in these patients. This resistance appears to be mediated by reduced daptomycin binding. Providers should be cautious about using long-term daptomycin monotherapy for C. striatum infections.
authors.affiliation: 1 School of Pharmacy, University of Washington , Seattle, Washington.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Werth
authors.affiliation: 2 Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington , Seattle, Washington.
authors.forename: William O
authors.initials: WO
authors.lastname: Hahn
authors.affiliation: 3 Department of Laboratory Medicine, University of Washington , Seattle, Washington.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Butler-Wu
authors.affiliation: 2 Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington , Seattle, Washington.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rakita
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003352:Corynebacterium / Q000187:drug effects* / Q000302:isolation & purification*; D003354:Corynebacterium Infections / Q000188:drug therapy / Q000382:microbiology; D017576:Daptomycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006353:Heart-Assist Devices / Q000382:microbiology*; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests / Q000379:methods; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin