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

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Antibacterial Agents That Cause DNA Damage in Obligate Anaerobic Organisms, Page 1 of 2

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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.

Citation: Mascaretti O. 2003. Antibacterial Agents That Cause DNA Damage in Obligate Anaerobic Organisms, p 311-314. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch24
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Figures

Image of Figure 24.1
Figure 24.1

Chemical structures of metronidazole and tinidazole.

Citation: Mascaretti O. 2003. Antibacterial Agents That Cause DNA Damage in Obligate Anaerobic Organisms, p 311-314. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch24
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Image of Figure 24.2
Figure 24.2

Proposed mechanism for the reduction of 5-nitroimidazoles. Reprinted from D. I. Edwards, J. Antimicrob. Chemother. 31:9–20, 1993, with permission from the publisher.

Citation: Mascaretti O. 2003. Antibacterial Agents That Cause DNA Damage in Obligate Anaerobic Organisms, p 311-314. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch24
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References

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1. Edwards, D. J., 1987. Nitroimidazoles, p. 404415. In F. O’Grady,, H. L. Lambert,, R. G. Finch,, and D. Greenwood (ed.), Antibiotics and Chemotherapy, 7th ed. Churchill Livingstone, Ltd., Edinburgh, United Kingdom.
2. Reese, R. E.,, R. F. Betts,, and B. Gumustop. 2000. Handbook of Antibiotics. 3rd ed., p. 521526. Lippincott Williams & Wilkins, Philadelphia, Pa.
3. Scholar, E. M.,, and W. B. Pratt. 2000. The Antimicrobial Drugs, 2nd ed., p. 422429. Oxford University Press, Oxford, United Kingdom.
4. Edwards, D. I. 1993. Nitroimidazole drugs—action and resistance mechanisms I. Mechanism of action. J. Antimicrob. Chemother. 31:920.
5. Samuelson, J. 1999. Why metronidazole is active against both bacteria and parasites. Antimicrob. Agents Chemother. 43:15331541.
6. Debets-Ossenkopp, I. J.,, R. G. Pot,, D. J. van Westerloo,, A. Goodwin,, C. M. J. E. Vandenbroucke-Grauls,, D. E. Berg,, P. S. Hoffman,, and J. G. Kusters. 1999. Insertion of mini-IS605 and deletion of adjacent sequences in the nitroreductase (rdxA) gene cause metronidazole resistance in Helicobacter pylori NCTC11637. Antimicrob. Agents Chemother. 43:26572662.
7. Edwards, D. I. 1993. Nitroimidazole drugs—action and resistance mechanisms. II. Mechanism of resistance. J. Antimicrob. Chemother. 31:201210.
8. Haggoud, A.,, G. Reysset,, H. Azeddoug,, and M. Sebald. 1996. Nucleotide sequence analysis of two 5-nitroimidazole resistance determinants from Bacteroides strains and of a new insertion sequence upstream of the two genes. Antimicrob. Agents Chemother. 38:10471051.
9. Kwon, D. H.,, F. A. K. El-Zaatari,, M. Kato,, M. S. Osato,, R. Reddy,, Y. Yamaoka,, and D. Y. Graham. 2000. Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori. Antimicrob. Agents Chemother. 44:21332142.
10. Narcisi, E. M.,, and W. E. Secor. 1996. In vitro effect of tinidazole and furazolidinone on metronidazole-resistant Trichomonas vaginalis. Antimicrob. Agents Chemother. 40:11211125.
11. Upcroft, P.,, and J. A. Upcroft. 2001. Drug targets and mechanism of resistance in the anaerobic protozoa. Clin. Microbiol. Rev. 14:150164.
12. Dollery, C. 1999. Therapeutic Drugs. 2nd ed., vol. 2, p. M146M151. Churchill Livingstone, Ltd., Edinburgh, United Kingdom.
13. Kucers, A.,, S. Crowe,, M. L. Grayson,, and J. Hoy. 1997. The Use of Antibiotics, 5th ed., p. 936964. Butterworth-Heinemann, Oxford, United Kingdom.
14. Petrin, D.,, K. Delgaty,, R. Bhatt,, and G. Garber. 1998. Clinical and microbiological aspects of Trichomonas vaginalis. Clin. Microbiol. Rev. 11:300317.
15. Gardner, T. B.,, and D. R. Hill. 2001. Treatment of giardiasis. Clin. Microbiol. Rev. 14:114128.
16. Murdoch, D. A. 1998. Gram-positive anaerobic cocci. Clin. Microbiol. Rev. 11:61120.

Tables

Generic image for table
Table 24.1

Generic and common trade names of metronidazole, the preparations available, and manufacturers in the United States

Citation: Mascaretti O. 2003. Antibacterial Agents That Cause DNA Damage in Obligate Anaerobic Organisms, p 311-314. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch24

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