title: In vitro microdialysis membrane efficiency of broad-spectrum antibiotics in combination and alone.
abstract: OBJECTIVE
  Microdialysis is a valuable technique for studying the distribution of drugs into interstitial fluid, the target site for a pharmacologic effect. Due to incomplete equilibrium, retrodialysis is a method used to correct for relative recovery. The impact of two-drug combinations on probe recovery, however, remains unknown.
  
  
  METHODS
  In vitro microdialysis was conducted for five antibiotics (avibactam, cefepime, ceftaroline, piperacillin-tazobactam, and vancomycin), representing three empiric antimicrobial regimens, to assess the impact of two-drug combinations on probe recovery. Recoveries were compared between single and two-drug treatments.
  
  
  RESULTS
  Recoveries by gain and loss were linear with their molecular weight. During all gain experiments, recoveries were similar when tested alone or in combination with another antibiotic. Unacceptable differences in recovery by loss were observed for cefepime in the presence of vancomycin (-21%) and vancomycin in the presence of piperacillin-tazobactam (-22%).
  
  
  CONCLUSIONS
  Differences among in vitro recovery by loss suggest two-drug combinations may impact dialysate recovery during in vivo retrodialysis procedures, particularly when larger molecular weight drugs (ie, vancomycin) are involved. Importantly, there were no differences during gain experiments. In vitro studies, as performed here, should be conducted for each potential two-drug combination, prior to their combined use for in vivo retrodialysis.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford, CT, USA.
authors.forename: Shawn H
authors.initials: SH
authors.lastname: MacVane
authors.affiliation: Center for Anti-Infective Research and Development, Hartford, CT, USA.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Housman
authors.affiliation: Center for Anti-Infective Research and Development, Hartford, CT, USA ; Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
keywords: combination therapy; microdialysis; retrodialysis