title: Treatment of prosthetic valve infective endocarditis due to multi-resistant Gram-positive bacteria with linezolid.
abstract: OBJECTIVE
  Clinical experience with linezolid in the treatment of infective endocarditis either alone or in combination with other agents is limited. We describe our experience in the treatment of two patients with IE due to multi-resistant Gram-positive bacteria.
  
  
  METHODS
  One patient with MRSE and one with VRE endocarditis were treated with regimens containing linezolid. The killing kinetics of linezolid in combination with gentamicin or vancomycin against isolates of Staphylococcus epidermidis and Enterococcus faecalis were analysed in vitro.
  
  
  RESULTS
  Clinical response and eradication of bacteraemia was achieved with linezolid therapy in both patients. Time-kill curve studies showed that linezolid was bacteriostatic against the MRSE and VRE isolates used. Combination with gentamicin or vancomycin did not produce synergy or antagonism but at best only marginal additive effect.
  
  
  CONCLUSIONS
  Although bacteriostatic, linezolid provides an important therapeutic option in IE due to multi-resistant Gram-positive pathogens. It challenges the conventional wisdom that bactericidal synergy is required for the effective treatment of most cases of IE due to Gram-positive organisms.
authors.affiliation: Department of Medical Microbiology, Barts and The London NHS Trust, London E1 1BB, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Wareham
authors.forename: H
authors.initials: H
authors.lastname: Abbas
authors.forename: A M
authors.initials: AM
authors.lastname: Karcher
authors.forename: S S
authors.initials: SS
authors.lastname: Das
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D016521:Electrophoresis, Gel, Pulsed-Field / Q000379:methods; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000145:classification / Q000302:isolation & purification; D005260:Female; D005839:Gentamicins / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006350:Heart Valve Prosthesis / Q000382:microbiology*; D006801:Humans; D000069349:Linezolid; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000145:classification / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome; D020713:Vancomycin Resistance
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D005839:Gentamicins; D023303:Oxazolidinones; D000069349:Linezolid