title: Pharmacokinetic/pharmacodynamic evaluation of antimicrobial treatments of orofacial odontogenic infections.
abstract: OBJECTIVE
  To evaluate the efficacy of antimicrobial therapy in oral odontogenic infections using estimated pharmacokinetic/pharmacodynamic parameters or efficacy indices, and to compare pharmacokinetic/pharmacodynamic breakpoints with National Committee for Clinical Laboratory Standards' (NCCLS) breakpoints.
  
  
  METHODS
  Retrospective literature search to obtain minimum inhibitory concentration (MIC) values, pharmacokinetic parameters of antimicrobials and NCCLS breakpoints. Pharmacokinetic simulations were carried out using WinNonlin software (Pharsight Corporation, Mountain View, CA, USA).
  
  
  METHODS
  For antimicrobials with time-dependent activity, the time that the plasma drug concentration exceeds the MIC as the percentage of dose interval at steady state was calculated. For antimicrobials with concentration-dependent activity, the total area under the plasma concentration-time curve over 24 hours at steady state divided by the MIC was calculated. Pharmacokinetic/pharmacodynamic breakpoints were calculated according to these parameters.
  
  
  RESULTS
  Only amoxicillin/clavulanic acid and clindamycin showed adequate efficacy indices against the most commonly isolated bacteria in odontogenic infections. Metronidazole reached good indices against anaerobes only. Pharmacokinetic/pharmacodynamic susceptibility breakpoints do not coincide exactly with NCCLS breakpoints.
  
  
  CONCLUSIONS
  Owing to the scarcity of double-blind, clinical trials on the use of antimicrobials in endodontics, this study may be useful in determining the best antimicrobial treatment in these infections. However, as we have not used concentration data in infected tissue to determine pharmacokinetic/pharmacodynamic indices, it would be necessary to design clinical trials in order to confirm these results.
authors.affiliation: Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Isla
authors.forename: Andrés
authors.initials: A
authors.lastname: Canut
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Gascón
authors.forename: Alicia
authors.initials: A
authors.lastname: Labora
authors.forename: Bruno
authors.initials: B
authors.lastname: Ardanza-Trevijano
authors.forename: Maria Angelés
authors.initials: MA
authors.lastname: Solinís
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D001419:Bacteria / Q000187:drug effects; D006801:Humans; D007239:Infections / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000382:microbiology; D009059:Mouth Diseases / Q000188:drug therapy* / Q000382:microbiology; D014076:Tooth Diseases / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents