title: Adaptation to vancomycin pressure of multiresistant Staphylococcus capitis NRCS-A involved in neonatal sepsis.
abstract: OBJECTIVE
  The Staphylococcus capitis clone NRCS-A has recently been described as a frequent cause of late-onset sepsis (LOS) in pre-term neonates worldwide. Representatives of this clone exhibit non-susceptibility to vancomycin, the first-line agent used in LOS. Cases of prolonged S. capitis LOS despite vancomycin treatment have been reported. We investigated whether NRCS-A strains exhibit faster adaptation to vancomycin pressure as compared with other staphylococci.
  
  
  METHODS
  Strains of S. capitis NRCS-A, S. capitis non-NRCS-A and Staphylococcus epidermidis (n = 2 each, all with vancomycin MICs ≤2 mg/L) and the prototype vancomycin-heteroresistant Staphylococcus aureus Mu3 were subcultured daily for 15 days with 0.25-32 mg/L vancomycin. Regression coefficients of daily log2 MICs on time were used to estimate the kinetics of resistance development. Changes in bacterial cell-wall thickness were measured by transmission electron microscopy. To assess the stability of resistance and the emergence of cross-resistance, vancomycin, teicoplanin, daptomycin and linezolid MICs were measured before and after vancomycin treatment, as well as after nine additional subcultures without antibiotics.
  
  
  RESULTS
  All strains developed a stable resistance to vancomycin, but this occurred significantly faster in S. capitis NRCS-A than in S. capitis non-NRCS-A (P < 0.001) and other species (P < 0.0001). Vancomycin resistance in S. capitis NRCS-A was associated with significant cell-wall thickening and an increase in MICs of daptomycin and teicoplanin, but not linezolid.
  
  
  CONCLUSIONS
  S. capitis NRCS-A rapidly adapts to vancomycin pressure as compared with potential niche competitors, a feature that might contribute to its success in neonatal ICUs where vancomycin is widely prescribed.
authors.affiliation: Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Butin
authors.affiliation: Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Martins-Simões
authors.affiliation: Neonatal Intensive Care Unit, Northern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Picaud
authors.affiliation: Public Health England, Colindale, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kearns
authors.affiliation: Neonatal Intensive Care Unit, Eastern Hospital Group, Hospices Civils de Lyon, Lyon, France.
authors.forename: O
authors.initials: O
authors.lastname: Claris
authors.affiliation: Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France frederic.laurent@univ-lyon1.fr.
authors.forename: F
authors.initials: F
authors.lastname: Laurent
authors.affiliation: Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France National Reference Center for Staphylococci, Hospices Civils de Lyon, Lyon, France Laboratory of Bacteriology, Hospices Civils de Lyon, Lyon, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Rasigade
mesh_terms: D000220:Adaptation, Biological; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002473:Cell Wall / Q000648:ultrastructure; D006801:Humans; D007231:Infant, Newborn; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology*; D012692:Serial Passage; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013210:Staphylococcus / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin