title: Comparison of oral immediate-release (IR) and extended-release (ER) metronidazole bactericidal activity against Bacteroides spp. using an in vitro model of infection.
abstract: We used an anaerobic infection model capable of simulating human serum pharmacokinetic parameters (C(max), C(min), half-life, and AUC) to compare the activity of oral immediate-release (IR) and extended-release (ER) MTZ formulations. Four oral regimens of MTZ plus a control regimen were simulated in the model: [i] (IR) 500 mg q8h, [ii] ER 750 mg q12h, [iii] ER 750 mg q24h, and [iv] ER 1500 mg q24h. Two clinical Bacteroides fragilis isolates (MICs 0.5, 4.0 microg/mL) and two non-fragilis Bacteroides isolates (MICs 0.5, 3 microg/mL) were studied. All four oral MTZ regimens exhibited rapid, bactericidal activity (> or =3-log(10) decrease from the starting inoculum) within 12 h against both fragilis and non-fragilis Bacteroides isolates. Overall, no appreciable difference in the rate of bacteria killing was noted among the four MTZ formulations against either B. fragilis isolates (P = 0.907, 0.737) or non-fragilis isolates (P = 0.809, 0.768). We conclude that ER MTZ dosed at 12 or 24-h intervals possesses equivalent bactericidal activity to standard IR MTZ dosed every eight hours against susceptible Bacteroides spp.
authors.affiliation: University of Iowa College of Pharmacy, Iowa City, IA 52242-1112, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Lewis
authors.forename: M E
authors.initials: ME
authors.lastname: Klepser
authors.forename: E J
authors.initials: EJ
authors.lastname: Ernst
authors.forename: M A
authors.initials: MA
authors.lastname: Snabes
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000284:Administration, Oral; D001439:Bacteroides / Q000187:drug effects*; D001441:Bacteroides fragilis / Q000187:drug effects*; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D006801:Humans; D008795:Metronidazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological
chemical_list: D003692:Delayed-Action Preparations; D004304:Dosage Forms; D008795:Metronidazole