title: Vancomycin treatment is a risk factor for vancomycin-nonsusceptible Staphylococcus capitis sepsis in preterm neonates.
abstract: OBJECTIVE
  Multidrug-resistant, vancomycin-nonsusceptible Staphylococcus capitis is an emerging cause worldwide of late-onset sepsis (LOS) in preterm neonates. The pathophysiology and risk factors for S. capitis-related LOS are poorly understood, but we hypothesized that S. capitis LOS follows translocation from the gut microbiota rather than catheter invasion. The objective of this study was to investigate the risk factors of S. capitis LOS and gut colonization.
  
  
  METHODS
  We conducted a prospective single-centre cohort study of patients hospitalized in a tertiary-care unit (Lyon, France) from June 2011 to January 2012. S. capitis gut colonization was determined weekly from stool cultures. The determinants of gut colonization and LOS were established by multivariate Cox proportional hazards models.
  
  
  RESULTS
  Eighty-three (36.2%) of 229 patients had S. capitis-positive stool culture, and 28 (12.2%) developed S. capitis LOS during hospitalization. Independent risk factors for S. capitis LOS included prior administration of vancomycin independent of a previous LOS episode (hazard ratio 6.44, 95% confidence interval 2.15-19.3, p 0.001) and low birth weight (hazard ratio 0.72 per 100 g increase, 95% confidence interval 0.55-0.95, p 0.02). The prior administration of vancomycin was also an independent risk factor for S. capitis colonization (hazard ratio 3.45, 95% confidence interval 2.07-5.76, p <0.001), particularly in the first week of life and in noncolonized neonates.
  
  
  CONCLUSIONS
  Neonates treated with vancomycin are at a higher risk of LOS caused by vancomycin-nonsusceptible S. capitis. The use of vancomycin in neonates must urgently be optimized to limit the selection of vancomycin-nonsusceptible strains, for which alternative antibiotics are lacking.
authors.affiliation: International Center of Research in Infectiology, INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure, France. Electronic address: marine.butin@chu-lyon.fr.
authors.forename: M
authors.initials: M
authors.lastname: Butin
authors.affiliation: International Center of Research in Infectiology, INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure, France; Institute of Infectious Agents, France; National Reference Center for Staphylococci, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Department of Biostatistics, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, France.
authors.forename: F
authors.initials: F
authors.lastname: Subtil
authors.affiliation: International Center of Research in Infectiology, INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure, France; National Reference Center for Staphylococci, France.
authors.forename: P
authors.initials: P
authors.lastname: Martins-Simões
authors.affiliation: Institute of Infectious Agents, France.
authors.forename: C
authors.initials: C
authors.lastname: Pralong
authors.affiliation: Institute of Infectious Agents, France.
authors.forename: A-M
authors.initials: AM
authors.lastname: Freydière
authors.affiliation: International Center of Research in Infectiology, INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure, France; Institute of Infectious Agents, France; National Reference Center for Staphylococci, France.
authors.forename: F
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: Institute of Infectious Agents, France.
authors.forename: S
authors.initials: S
authors.lastname: Tigaud
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: International Center of Research in Infectiology, INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure, France; Institute of Infectious Agents, France; National Reference Center for Staphylococci, France; Department of Microbiology-Mycology, Institut des Sciences Pharmaceutiques et Biologiques de Lyon, University of Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Laurent
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D047928:Premature Birth / Q000453:epidemiology*; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D000074039:Staphylococcus capitis / Q000187:drug effects*; D014640:Vancomycin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Microbiota; Neonatal intensive care; Sepsis; Staphylococcus capitis; Vancomycin