title: Investigation on rifampicin administration from the standpoint of pharmacokinetics/pharmacodynamics in a neutropenic murine thigh infection model.
abstract: BACKGROUND
  The purpose of this study was to examine the pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection model.
  
  
  METHODS
  Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA [Mu50]) with rifampicin MIC 0.06 to >256 μg/mL were tested. The efficacy was calculated as the change in bacterial density. A maximum effect model was used to determine the PK/PD index that best described the dose-response data.
  
  
  RESULTS
  The area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax/MIC) were the best correlated with in vivo efficacy (AUC/MIC, R(2) = 0.96; Cmax/MIC, R(2) = 0.97) for S. aureus ATCC 25923 strain, and the dose fractionation-response study did not show significantly different antimicrobial activity (p = 0.10). The AUC/MIC values associated with stasis and 1-log kill for the S. aureus ATCC 25923 strain were 386 and 952, respectively. On the other hand, no antimicrobial efficacy was observed against two strains (MRSA and VISA) with MIC of 128 μg/mL or more.
  
  
  CONCLUSIONS
  Rifampicin demonstrated concentration-dependent killing. The AUC/MIC was a predictive PK/PD index.
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan; Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hirai
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Pharmacy, Aichi Medical University School of Hospital, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Hagihara
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Pharmacy, Aichi Medical University School of Hospital, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakanashi
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Koizumi
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamagishi
authors.affiliation: Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suematsu
authors.affiliation: Research Center for Infections and Antimicrobials, Kitasato Institute for Life Sciences, Kitasato University, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hanaki
authors.affiliation: Department of Clinical Infectious Diseases, Aichi Medical University School of Hospital, Japan; Department of Infection Control and Prevention, Aichi Medical University Hospital, Japan. Electronic address: mikamo@aichi-med-u.ac.jp.
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008813:Mice, Inbred ICR; D009503:Neutropenia / Q000188:drug therapy / Q000382:microbiology; D012293:Rifampin / Q000493:pharmacokinetics* / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000178:diet therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013848:Thigh
chemical_list: D000900:Anti-Bacterial Agents; D012293:Rifampin
keywords: Pharmacodynamics; Pharmacokinetics; Rifampicin; Staphylococcus aureus