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[Antimicrobial therapy with nitroheterocyclic compounds, for example, metronidazole and nitrofurantoin].

Nitroheterocyclic compounds, such as metronidazole and nitrofurantoin, are widely used in medical practice for the treatment of infectious diseases. Indeed, they exhibit a strong antimicrobial effect, which is directed not only against several groups of bacteria but also against certain protozoa and even worms. The nitrogroup coupled onto a heterocyclic structure, for example an imidazole, a thiazole or a furan ring, represents the proper site of effect. A priori the nitrogroup is, however, inactive. It has to be activated by microbial nitroreductases after penetration into the microbial cell. Those microorganisms which possess an anaerobic metabolism exhibit marked nitroreductase activity. The intracellularly produced intermediate products attack the chromosomal DNA of the target cell. Consequently, diverse mutations may occur. Partially, these chromosomal damages can be compensated by an SOS repair mechanism, which is under the control of the uvrB, lexA and polA genes. SOS repair-deficient mutants are much more susceptible to nitrocompounds than repair-proficient strains. Principally, the genotoxic activity of nitrocontaining compounds can also be expressed in eukaryotic cells of human or animal origin. This virtual property does not, however, prohibit clinical use, since until now no evidence of increased cancer incidence has been observed after rational therapy with nitrocompounds.