title: Distribution of metronidazole in muscle tissue of patients with septic shock and its efficacy against Bacteroides fragilis in vitro.
abstract: OBJECTIVE
  Studies investigating the target site concentration of antibiotics, such as beta-lactams and fluoroquinolones, have demonstrated differences between the drug concentrations in healthy volunteers and septic patients. The aims of this study were (i) to evaluate the muscle tissue concentration of metronidazole in patients with septic shock and (ii) to test the efficacy of metronidazole in an in vitro pharmacodynamic model at different single doses.
  
  
  METHODS
  Six patients admitted to the ICU of Tartu University Clinics with a diagnosis of septic shock were studied. Patients receiving metronidazole treatment within 48 h before the study or with a BMI > 35 were excluded. Metronidazole muscle tissue concentration was assessed by a microdialysis technique. Based on the microdialysis data, similar kinetics were simulated in in vitro experiments using Bacillus fragilis strains with MIC(90)s of 0.125 mg/L (BF125) and 1.0 mg/L (BF1).
  
  
  RESULTS
  Metronidazole concentrations in plasma achieved a mean (s.d.) value of 11.4+/-2.0 mg/L at 30 min after administration of a single 500 mg intravenous dose, while in the muscle tissue, maximum concentrations of 8.2+/-4.5 mg/L were achieved at 140+/-92.3 min after the dose. When this metronidazole time course was simulated in vitro, the time to 99.9% kill ranged from 1.0 to 1.4 h for BF125 and from 1.8 to 3.5 h for BF1, while the eradication time ranged from 1.7 to 2.5 h and from 3.4 to 6.5 h, respectively. No regrowth was detected.
  
  
  CONCLUSIONS
  Pharmacokinetic-pharmacodynamic simulation of metronidazole interstitial concentrations shows a high efficacy of the drug in septic patients.
authors.affiliation: Anaesthesiology and Intensive Care Clinic, University of Tartu, 8 L. Puusepa Street, Tartu, Estonia. jyrika@kliinikum.ee
authors.forename: Juri
authors.initials: J
authors.lastname: Karjagin
authors.forename: Rein
authors.initials: R
authors.lastname: Pähkla
authors.forename: Tõnis
authors.initials: T
authors.lastname: Karki
authors.forename: Joel
authors.initials: J
authors.lastname: Starkopf
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001441:Bacteroides fragilis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D017551:Microdialysis; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*
chemical_list: D008795:Metronidazole