Chapter 24 : Antibacterial Agents That Cause DNA Damage in Obligate Anaerobic Organisms

Abstract:

This chapter focuses on metronidazole that has become an extremely important antibacterial agent, especially in the treatment of anaerobic bacterial infections. It causes bacterial DNA damage regardless of the growth phase of the organism and is rapidly bactericidal. The observation that metronidazole relieved acute ulcerative gingivitis in a patient being treated for trichomonal vaginitis led to studies, culminating in 1962, of its use in anaerobic bacterial infections. Subsequently, it was confirmed that metronidazole was useful for the treatment of Vincent's stomatitis and that it inhibited Fusobacterium necrophorum. According to published data, the selective activity of 5-nitroimidazoles (metronidazole and tinidazole) against anaerobic organisms is due to the preferential reduction of the 5-nitro group by obligate anaerobes but not by aerobes. Understanding of the antimicrobial resistance to metronidazole is based on studies with anaerobic microorganisms such as Bacteroides, Trichomonas, and Clostridium spp. Although resistance rates of Trichomonas vaginalis are low, treatment failures due to resistance are significant. The MIC of metronidazole for T. vaginalis causing refractory vaginitis is frequently three to eight times the MIC for susceptible strains.