Investigate The Safety Profile of Metronidazole, Exploring Potential Adverse Effects And Toxicity

Authors

  • K. Sarvesh
  • S. Navneet
  • A. Prasant
  • S. Vivek
  • V. Payal
  • K. Sanjeev
  • S. Peeush

DOI:

https://doi.org/10.63682/jns.v14i30S.6947

Keywords:

Metronidazole, antimicrobial therapy, anaerobic bacteria, parasites, pharmacology, resistance, adverse effects, neurotoxicity, hepatotoxicity, drug interactions

Abstract

This analysis takes an in-depth look at the safety profile of metronidazole, a popular antibiotic that works well against anaerobic bacteria and parasites. The development of medicine over time, starting with the discovery of azomycin, demonstrated its ability to treat diseases, particularly trichomoniasis and giardiasis. The way metronidazole works is that it forms a cytotoxic intermediate intracellularly that damages the bacterial DNA, thereby clearing the anaerobic infection. The pharmacology of metronidazole encompasses diverse formulations, rapid absorption, and extensive tissue penetration. While generally well-tolerated, metronidazole presents considerations for dosage, duration, and patient-specific factors to minimize toxicity risks. Despite its efficacy, rare instances of resistance and adverse effects, such as neurotoxicity and hepatotoxicity, warrant cautious use.

This review delves into metronidazole-induced complications, including neurotoxicity, encephalopathy, and pancreatitis. Risk mitigation and monitoring strategies are outlined, emphasizing patient assessments, dosage adjustments, and organ function monitoring. Specific considerations for pregnant individuals and potential cytogenetic effects are also discussed.

In conclusion, while metronidazole remains a cornerstone in antimicrobial therapy, its judicious use requires an understanding of therapeutic benefits and associated risks. The review provides insights into metronidazole's intricate pharmacology, toxicity factors, and strategies for optimizing patient safety during clinical use. Ongoing research and vigilant clinical practices are crucial for ensuring the sustained efficacy of metronidazole across diverse medical contexts

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Jolles GE. Origins and anti-infective activities of metronidazole. In: Finegold SM, Conference IM, eds. Metronidazole: Proceedings of the International Metronidazole Conference, Montreal, Quebec, Canada, May 26-28, 1976. Excerpta Med.; 1977.

Maeda K. A new antibiotic, azomycin. J Antibiot (Tokyo). 1953;6(4):182. CRID: 1572261551093773440; NII Article ID :10027192787.

Cosar C, Julou L. Activity of (Hydroxy-2'Ethyl)-1 Methyl-2 Nitro-5 Imidazole (8823, RP) in Experimental Trichomonas vaginalis Infections. Ann Inst Pasteur (Paris). 1959;96(2):238-41. CABI Record Number: 19592702329.

Edwards DI. Nitroimidazole drugs-action and resistance mechanisms I. Mechanism of action. Journal of Antimicrobial Chemotherapy. 1993 Jan 1;31(1):9-20. https://doi.org/10.1093/jac/31.1.9.

Edwards DI. Reduction of nitroimidazoles in vitro and DNA damage. Biochemical pharmacology. 1986 Jan 1;35(1):53-8. https://doi.org/10.1016/0006-2952(86)90554-X.

Tocher JH, Edwards DI. The interaction of reduced metronidazole with DNA bases and nucleosides. International Journal of Radiation Oncology* Biology* Physics. 1992 Jan 1;22(4):661-3. https://doi.org/10.1016/0360-3016(92)90498-7.

Muller M, Lindmark DG, McLaughlin J. Mode of action of metronidazole on anaerobic microorganisms. In: Finegold SM, ed. Metronidazole. Amsterdam: Excerpta Medica 1977:12-9. CABI Record Number: 19780848037

Farthing MJ. Giardiasis. Gastroenterology Clinics. 1996 Sep 1;25(3):493-515. DOI:https://doi.org/10.1016/S0889-8553(05)70260-0.

Lau AH, Lam NP, Piscitelli SC, Wilkes L, Danziger LH. Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives. Clinical pharmacokinetics. 1992;23(5):328-64. https://doi.org/10.2165/00003088-199223050-00002.

Goldstein EJ, Citron DM, Vreni Merriam C, Warren Y, Tyrrell KL. Comparative in vitro activities of ertapenem (MK-0826) against 1,001 anaerobes isolated from human intra-abdominal infections. Antimicrobial agents and chemotherapy. 2000 Sep 1;44(9):2389-94. DOI: https://doi.org/10.1128/aac.44.9.2389-2394.2000.

Freeman CD, Klutman NE, Lamp KC. Metronidazole: a therapeutic review and update. Drugs. 1997;54(5):679-708. https://doi.org/10.2165/00003495-199754050-00003.

Lau AH, Lam NP, Piscitelli SC, Wilkes L, Danziger LH. Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives. Clinical pharmacokinetics. 1992;23(5):328-64. https://doi.org/10.2165/00003088-199223050-00002.

Allen Jr LV, Erickson III MA. Stability of ketoconazole, metolazone, metronidazole, procainamide hydrochloride, and spironolactone in extemporaneously compounded oral liquids. American journal of health-system pharmacy. 1996 Sep 1;53(17):2073-8. https://doi.org/10.1093/ajhp/53.17.2073.

Sprandel KA, Schriever CA, Pendland SL, Quinn JP, Gotfried MH, Hackett S, Graham MB, Danziger LH, Rodvold KA. Pharmacokinetics and pharmacodynamics of intravenous levofloxacin at 750 milligrams and various doses of metronidazole in healthy adult subjects. Antimicrobial agents and chemotherapy. 2004 Dec;48(12):4597-605. DOI: https://doi.org/10.1128/aac.48.12.4597-4605.2004.

Plaisance KI, Quintiliani R, Nightingale CH. The pharmacokinetics of metronidazole and its metabolites in critically ill patients. Journal of Antimicrobial Chemotherapy. 1988 Feb 1;21(2):195-200. https://doi.org/10.1093/jac/21.2.195.

Somogyi A, Kong C, Sabto J, Gurr FW, Spicer WJ, McLean AJ. Disposition and removal of metronidazole in patients undergoing haemodialysis. European journal of clinical pharmacology. 1983;25(5):683-687. https://doi.org/10.1007/BF00542359.

Ralph ED, Clarke JT, Libke RD, Luthy RP, Kirby WM. Pharmacokinetics of metronidazole as determined by bioassay. Antimicrobial Agents and Chemotherapy. 1974 Dec;6(6):691-6. DOI: https://doi.org/10.1128/aac.6.6.691.

Ings RM, McFadzean JA, Ormerod WE. The fate of metronidazole and its implications in chemotherapy. Xenobiotica. 1975 Jan 1;5(4):223-35. https://doi.org/10.3109/00498257509052069

Placidi GF, Masuoka D, Alcaraz A, Taylor JA, Earle R. Distribution and metabolism of 14C-metronidazole in mice. Archives Internationales de Pharmacodynamie et de Therapie. 1970; 188:168-79. CABI Record Number: 19712203098.

Ralph ED, Clarke DA. Inactivation of metronidazole by anaerobic and aerobic bacteria. Antimicrobial Agents and Chemotherapy. 1978 Sep;14(3):377-83. DOI: https://doi.org/10.1128/aac.14.3.377.

Edwards DI ED, Thompson EJ, Tomusange J, Shanson D. Inactivation of metronidazole by aerobic organisms. J Antimicrob Chemother 1979; 5:315-6. DOI: 10.1093/jac/5.3.315

McCalla DR. Biological effects of nitrofurans. Journal of Antimicrobial Chemotherapy. 1977 Sep 1;3(5):517-20. https://doi.org/10.1093/jac/3.5.517

Lamp KC, Freeman CD, Klutman NE, Lacy MK. Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clinical pharmacokinetics. 1999 May; 36:353-73. PMID: 10384859 DOI: 10.2165/00003088-199936050-00004

Lala VG, Bobat B, Haagensen M, Kathan P, Mahomed A. Metronidazole-induced encephalopathy. SA Journal of Radiology. 2021;25(1). doi: 10.4102/sajr. v25i1.2016. PMID: 33824746; PMCID: PMC8008077.

Edwards DI. Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs. Sexually Transmitted Infections. 1980 Oct 1;56(5):285-90. PMID: 7000306; PMCID: PMC1045807. https://doi.org/10.1136/sti.56.5.285

Sørensen CG, Karlsson WK, Amin FM, Lindelof M. Metronidazole-induced encephalopathy: a systematic review. Journal of neurology. 2020 Jan; 267:1-3. DOIhttps://doi.org/10.1007/s00415-018-9147-6

Kuriyama A, Jackson JL, Doi A, Kamiya T. Metronidazole-induced central nervous system toxicity: a systematic review. Clinical neuropharmacology. 2011 Nov 1;34(6):241-7. DOI: 10.1097/WNF.0b013e3182334b35

Patel L, Batchala P, Almardawi R, Morales R, Raghavan P. Acute metronidazole-induced neurotoxicity: an update on MRI findings. Clinical Radiology. 2020 Mar 1;75(3):202-8. https://doi.org/10.1016/j.crad.2019.11.002

Appleby DH, Vogtland HD. Suspected metronidazole hepatotoxicity. Clinical pharmacy. 1983 Jul 1;2(4):373-4. PMID: 6883967.

Lam S, Bank S. Hepatotoxicity caused by metronidazole overdose. Annals of internal medicine. 1995 May 15;122(10):803. https://doi.org/10.7326/0003-4819-122-10-199505150-00023.

Hunaut T, Boulagnon-Rombi C, Thorn H, Doco-Fenzy M, Thiéfin G. Hepatotoxicity of metronidazole in Cockayne syndrome: a clinical report. European Journal of Medical Genetics. 2022 Jan 1;65(1):104388. DOI: 10.1016/j.ejmg.2021.104388. Epub 2021 Nov 9. PMID: 34768013.

Elgassim MA, Saied AS, Mustafa MA, Abdelrahman A, AlJaufi I, Salem W, Elgassim MA. A Rare Case of Metronidazole Overdose Causing Ventricular Fibrillation. Cureus. 2022 May 4;14(5). DOI: 10.7759/cureus.24728. PMID: 35676987; PMCID: PMC9166500.

Bradley WG, Karlsson IJ, Rassol CG. Metronidazole neuropathy. British medical journal. 1977 Sep 9;3(2)(6087):610-11. doi: 10.1136/bmj.2.6087.610

Evans J, Levesque D, Knowles K, Longshore R, Plummer S. Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases. Journal of veterinary internal medicine. 2003 May;17(3):304-10. https://doi.org/10.1111/j.1939-1676.2003.tb02452.x.

Ahmed A, Loes DJ, Bressler EL. Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy. Neurology. 1995 Mar;45(3):588-9. https://doi.org/10.1212/WNL.45.3.588.

Onder H. A case of MRI negative metronidazole-induced encephalopathy and recovery of electroencephalography at follow-up. Journal of Neurology Research. 2016 Sep 7;6(4):81-4. doi: http://dx.doi.org/10.14740/jnr386w.

Hobbs K, Stern-Nezer S, Buckwalter MS, Fischbein N, Finley Caulfield A. Metronidazole-induced encephalopathy: not always a reversible situation. Neurocritical care. 2015 Jun; 22:429-36. https://doi.org/10.1007/s12028-014-0102-9.

Kazy Z, Puhó E, Czeizel AE. Teratogenic potential of vaginal metronidazole treatment during pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2005 Dec 1;123(2):174-8. https://doi.org/10.1016/j.ejogrb.2005.03.016.

Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, Poston L. General obstetrics: A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: The PREMET Study. BJOG: An International Journal of Obstetrics & Gynaecology. 2006 Jan;113(1):65-74. https://doi.org/10.1111/j.1471-0528.2005.00788.x

Burtin P, Taddio A, Ariburnu O, Einarson TR, Koren G. Safety of metronidazole in pregnancy: a meta-analysis. American journal of obstetrics and gynecology. 1995 Feb 1;172(2):525-9. https://doi.org/10.1016/0002-9378(95)90567-7.

Grover JK, Vats V, Srinivas M, Das SN, Jha P, Gupta DK, Mitra DK. Effect of metronidazole on spermatogenesis and FSH, LH and testosterone levels of pre-pubertal rats. Indian J. Exp. Biol. 2001; 39: 1152–60.DOI: http://nopr.niscpr.res.in/handle/123456789/17523

Patanelli DJ. Suppression of fertility in the male. Handbook of physiology. 1975; 5:245-58.

McClain RM, Downing JC, Edgcomb JE. Effect of metronidazole on fertility and testicular function in male rats. Toxicological Sciences. 1989 Apr 1;12(3):386-96. https://doi.org/10.1093/toxsci/12.3.386

El‐Nahas AF, El‐Ashmawy IM. Reproductive and cytogenetic toxicity of metronidazole in male mice. Basic & clinical pharmacology & toxicology. 2004 May;94(5):226-31. https://doi.org/10.1111/j.1742-7843.2004.pto940505.

Urtasun RC, Rabin HR, Partington J. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously. Surgery. 1983 Jan 1;93(1):145-8. DOI: https://doi.org/10.5555/uri:pii:003960608390291X

Jain KK, Jain KK. Basics of personalized medicine. Textbook of Personalized Medicine. 2009:1-27. https://doi.org/10.1007/978-1-4419-0769-1_4.

Lee HC, Kim YE, Ma HI. Metronidazole-Induced Craniocervical Myoclonus with Reversible Bilateral Dentate Nucleus Lesions. J Mov Disord. 2017 Jan;10(1):67-68. doi: 10.14802/jmd.16021. Epub 2017 Jan 18. PMID: 28122422; PMCID: PMC5288659. doi: 10.14802/jmd.16021

Gelderman AH, Bartgis IL, Keister DB, Diamond LS. A comparison of genome sizes and thermal-denaturation-derived base composition of DNAs from several members of Entamoeba (histolytica group). J Parasitol. 1971 Aug;57(4):912–916. https://doi.org/10.2307/3277827

Downloads

Published

2025-06-02

How to Cite

1.
Sarvesh K, Navneet S, Prasant A, Vivek S, Payal V, Sanjeev K, Peeush S. Investigate The Safety Profile of Metronidazole, Exploring Potential Adverse Effects And Toxicity. J Neonatal Surg [Internet]. 2025Jun.2 [cited 2025Sep.20];14(30S):263-7. Available from: https://www.jneonatalsurg.com/index.php/jns/article/view/6947