Comparison of oral immediate-release (IR) and extended-release (ER) metronidazole bactericidal activity against Bacteroides spp. using an in vitro model of infection

We used an anaerobic infection model capable of simulating human serum phar macokinetic parameters (C-max, C-min, half-life, and AUG) to compare the ac tivity of oral immediate-release (IR) and extended-release (ER) MTZ formula tions. Four oral regimens of MTZ plus a control regimen were simulated in t he model: [i] (IR) 500 mg q8h, [ii] ER 750 mg q12h, [iii] ER 750 mg q24h, a nd [iv] ER 1500 mg q24h. Two clinical Bacteroides frugilis isolates (MICs 0 .5, 4.0 mu g/mL) and two non-fragilis Bacteroides isolates (MICs 0.5, 3 mu g/mL) were studied. All four oral MTZ regimens exhibited rapid, bactericida l activity (greater than or equal to 3-log(10) decrease from the starting i noculum) within 12 h against both fragilis and non-fragilis Bacteroides iso lates. Overall, no appreciable difference in the rate of bacteria killing w as noted among the four MTZ formulations against either B. fragilis isolate s (P = 0.907, 0.737) or non-fragilis isolates (P = 0.809, 0.768). We conclu de that ER MTZ dosed at 12 or 24-h intervals possesses equivalent bacterici dal activity to standard IR MTZ dosed every eight hours against susceptible Bacteroides spp. (C) 2000 Elsevier Science inc. All rights reserved.