Antimicrobial activity of metronidazole in anaerobic bacteria

Abstract

The antimicrobial activity of metronidazole was investigated in anaerobic bacteria by use of time-viability studies. This antimicrobial agent has a rapid onset of bactericidal activity under proper reducing conditions. The bactericidal rates were not affected by inoculum size or nutritional requirements, nor by inhibition of growth and protein synthesis by chloramphenicol. Using supernatant fractions of actively growing cultures of susceptible organisms, we observed a disappearance of metronidazole and a loss of biological activity, but there was no significant change in preparations from resistant bacteria. The decrease in drug concentration with susceptible cells occurred during the time that its bactericidal action was being exerted. Extracts from susceptible organisms rapidly reduced the concentration of metronidazole, confirming previous observations which suggest that the drug acts as a terminal electron acceptor. Radioisotope experiments with ['4C]metronidazole revealed that the compound was taken up by both resistant and susceptible bacteria, although there was a difference in rate and extent of accumulation. These studies demonstrate that mentronidazole's antimicrobial activity against anaerobic bacteria is bactericidal and independent of growth rate, and that it involves the uptake and metabolism of the compound.

The Antimicrobial Treatment of Periodontal Disease: Changing the Treatment Paradigm

“…The plaque samples could be sent to reference laboratories for cultural, immunological, or DNA probe analysis (Listgarten, 1992;Rams et al, 1992; Zambon, 1997 (Tally et al, 1978), and resistance to metronidazole in a clinical setting is extremely rare (Walker et al 1985;Garcia-Rodriguez et al, 1995). against anaerobes.…”

Nitroimidazoles Part 7. Synthesis and Anti-HIV Activity of New 4-Nitroimidazole Derivatives

“…1) [8]. Moreover, numerous examples of nitroimidazoles have been reported with a range of biological activities, including antibacterial agents [9 -12], potential radiosensitizers [13], anticancer agents [14] such as Dacarbazine R (DTIC) [15] and misonidazole [16], fungicides and/or antiprotozoal agents such as clotrinazole [1-(2-chlorotrityl)-1H-imidazole] [17], metronidazole (Flagyl) [18,19] and 2-styryl-5-nitroimidazoles [20,21].…”

Isolation and Properties of Metronidazole-resistant Mutants of Clostridium Perfringens

“…The exclusive activity of these compounds against anaerobes (Edwards, Dye and Carne, 1973;Tanowitz et al, 1975) is thought to be related to the unique ability of anaerobes to take up the drugs and rapidly metabolise them to reduced intermediate substances (Ings, McFadzean and Ormerod, 1974;Tally et al, 1978), which kill bacteria by interacting with DNA (LaRusso et al, 1977). The proposed site of metronidazole reduction is the pyruvate phosphoroclastic reaction (O'Brien and Morris, 1972;Edwards et al, 1973) in which ferredoxin serves as the terminal electron acceptor in the generation of acetate, H2, C02 and energy.…”