title: Treating Gram-positive infections: vancomycin update and the whys, wherefores and evidence base for continuous infusion of anti-Gram-positive antibiotics.
abstract: OBJECTIVE
  The role of vancomycin for treating serious methicillin-resistant Staphylococcus aureus infections and the optimal method of administration of anti-Gram-positive antibiotics have been recently questioned. This review summarizes the current literature concerning the use of vancomycin and the role of continuous infusion antimicrobials for treatment of Gram-positive infections.
  
  
  RESULTS
  Although vancomycin-resistant S. aureus due to acquisition of vanA from vancomycin-resistant enterococci remains rare (11 cases to date), heterogeneous vancomycin-intermediate S. aureus and vancomycin-intermediate S. aureus have now been reported from many countries around the world. Laboratory studies have demonstrated subtle, but potentially significant differences in vancomycin susceptibility depending on the methods used, meaning clinicians need to liaise closely with their local microbiology laboratories. Higher vancomycin minimum inhibitory concentrations within the accepted susceptible range and the presence of vancomycin-intermediate S. aureus are associated with vancomycin treatment failure. It is likely that heterogeneous vancomycin-intermediate S. aureus contributes to treatment failure in patients with serious, high bacterial load infections. Despite the potential limitations of vancomycin, no clinical trials have demonstrated superiority of alternative agents.Administration of antibiotics by continuous infusion is supported by in-vitro and animal studies for the classes of antibiotic that demonstrate time-dependent killing. However, few, limited clinical studies have been performed to date.
  
  
  CONCLUSIONS
  Vancomycin remains an important first-line antimicrobial for treatment of serious methicillin-resistant S. aureus infections; however, a detailed analysis of isolate susceptibility and appropriate dosing are important. Although continuous infusion of some anti-Gram-positive antimicrobials may provide theoretical benefits, clinical trials demonstrating superiority in outcomes are uncommon. Use of continuous infusion may, however, provide practical advantages in patients on home intravenous antibiotics.
authors.affiliation: Department of Infectious Diseases, Australia.
authors.forename: Kyra
authors.initials: K
authors.lastname: Chua
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Howden
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage*; D020713:Vancomycin Resistance / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin