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.