title: Pharmacodynamic assessment of vancomycin-rifampicin combination against methicillin resistant Staphylococcus aureus biofilm: a parametric response surface analysis.
abstract: OBJECTIVE
  A combination of vancomycin and rifampicin (rifampin) is commonly used to treat staphylococcal infections but its efficacy against methicillin-resistant Staphylococcus aureus (MRSA) biofilm is controversial. The objective of this study was to use a recently developed quantitative methodology to characterise the killing effect of vancomycin and rifampin combination against MRSA biofilm.
  
  
  METHODS
  MRSA biofilm was exposed to escalating concentrations of vancomycin and rifampin and the viability of the biofilm-ensconced bacteria was evaluated. ADAPT II was used to model the concentration-effect relationship and determine the optimal sampling concentrations. Combination experiments were then conducted and the observations were compared with a simulated response surface representing null interaction. Finally, the pharmacodynamic interaction index (PDI) was computed as the ratio of the volumes under the observed and simulated surfaces.
  
  
  RESULTS
  In the combination experiments, all observations showed an inferior antibacterial effect to what is expected under null interaction assumption and the PDI was estimated to be 3.36 (95% CI, 3.25 to 3.46).
  
  
  CONCLUSIONS
  The results of the study demonstrate in-vitro antagonism between vancomycin and rifampin against MRSA biofilm. The quantitative approach employed to quantify the antibacterial effect of the combination provides a scientific rationale for further in-vivo investigations that should allow a better understanding of the therapeutic potential of this combination in biofilm-associated MRSA infections.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA. sale0074@umn.edu
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Salem
authors.forename: Walid F
authors.initials: WF
authors.lastname: Elkhatib
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Noreddin
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification / Q000502:physiology; D008962:Models, Theoretical; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D012293:Rifampin