ROTSCHAFER JC, IBRAHIM KH, GUNDERSON BW, HOVDE LB; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. A-498.

University of Minnesota College of Pharmacy, Minneapolis, MN

BACKGROUND: Antibacterial activity of certain antibiotics may be influenced by the administration interval. By administering antibiotics in a pulsatile manner, target bacteria may be exposed to high concentrations of antibiotic at varying phases of their growth cycle. The objective of this investigation was to compare and contrast the activity of metronidazole dosed in pulses to standard three-times daily dosing in an anaerobic in-vitro pharmacodynamic model. METHODS: Using an in-vitro pharmacodynamic model in duplicate, two ATCC B. fragilis isolates (25285 & 23745, MIC = 1 mg/L for each organism) were exposed to metronidazole for 96 hours. The peristaltic pump was set to simulate human pharmacokinetics of metronidazole after 500 mg doses every 8 hours (C[max] = 12 mg/L, t[1/2] = 8 h), or after pulsatile dosing where pulses were given at time 0, 2, 4, and 6 h of each of the four 24 h cycles to achieve a change in metronidazole concentration in the model of 9 mg/L, again with a t[1/2] of 8 h. 100 microliter aliquots were removed from the chemostats at times 0, 2, 4, 6, 12 and 24 h of each 24 h cycle for bacterial enumeration. Time-kill curves were generated for each experiment and analyzed for bacteridical activity, evidenced by a 3-log[10] kill, and evidence of regrowth. RESULTS: In each of the conventional dosing and pulsatile experiments, metronidazole was bactericidal, and colony counts were reduce to undetectable levels within 10 hours. Regrowth occurred in only one of the conventional dosing experiments, but was not associated with changes in MIC. Regrowth did not occur in any of the pulsatile dosing experiments. Conclusion: Metronidazole was highly active against these susceptible strains of B. fragilis when given to simulate conventional dosing or pulsatile administration, as evidenced by rapid bactericidal activity and the prevention of regrowth.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Bacteroides fragilis
• Humans
• Metronidazole
• Microbial Sensitivity Tests
• Models, Biological

Other ID:

• GWAIDS0027602

UI: 102267226

From Meeting Abstracts