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.