Therapeutic uses of metronidazole and its side effects Original paper

What was reviewed?

This review examined the therapeutic applications and toxicological profile of metronidazole, an antibiotic widely prescribed for protozoal and anaerobic bacterial infections. The authors gathered data from original research, clinical trials, and previously published reviews to provide an updated synthesis of metronidazole’s uses across clinical and non-clinical contexts. They explored its mechanisms of action, therapeutic range, routes of administration, and associated adverse effects—especially neurotoxicity and genotoxicity. Although its widespread use underscores its clinical value, the review highlighted important gaps in understanding long-term and off-target consequences.

Who was reviewed?

The review compiled findings from diverse human clinical populations treated with metronidazole for various conditions, including trichomoniasis, amebiasis, giardiasis, Helicobacter pylori infections, Clostridioides difficile colitis, bacterial vaginosis, rosacea, and Crohn’s disease. It also referenced preclinical models, particularly animal studies and in vitro assays, to discuss metronidazole’s pharmacodynamics and potential mutagenic or carcinogenic effects. The inclusion of both clinical and experimental data offers a multifaceted view of the antibiotic’s effectiveness and limitations.

What were the most important findings?

The review confirmed that metronidazole remains one of the most effective antibiotics against anaerobic and microaerophilic organisms, including Bacteroides fragilis, Clostridium difficile, Entamoeba histolytica, and Giardia lamblia. Clinicians have prescribed it successfully in combination therapies for H. pylori eradication and surgical prophylaxis, and its topical forms have shown consistent efficacy in managing dermatological conditions like rosacea. Importantly for microbiome-oriented clinicians, metronidazole’s targeted anaerobic activity significantly impacts key microbial taxa in the gut and vaginal microbiomes. The review touched on the potential collateral dysbiosis from prolonged or repeated metronidazole exposure, though it did not quantify microbial shifts in terms of genus-level loss or gain.

On the safety front, the review noted that while short-term use causes mostly mild side effects like nausea or diarrhea, longer-term or high-dose exposure can induce neurotoxicity, including optic and peripheral neuropathies and encephalopathy. Mechanistic studies propose that free radicals or metabolite binding to RNA may underlie nerve damage. The review also synthesized findings on metronidazole’s genotoxic potential, which remains controversial. It induces DNA strand breaks and chromosomal aberrations in animal models, though human data remain inconclusive.

What are the implications of this review?

This review affirms metronidazole’s broad-spectrum clinical utility while encouraging a more cautious and microbiome-aware approach to its prescription. As one of the most commonly used antibiotics for anaerobic infections, metronidazole plays a crucial role in both outpatient and hospital settings. However, its impact on microbiome composition, particularly among anaerobic gut bacteria, deserves greater clinical attention. For microbiome-based therapeutic strategies, understanding how metronidazole alters microbial ecology could help mitigate risks of dysbiosis or secondary infection. Moreover, the review emphasized the need for further controlled human studies to resolve uncertainties around its genotoxicity and neurotoxicity. The pharmacokinetic advantage of oral formulations also supports a less invasive, more accessible treatment model, particularly for surgical prophylaxis or community-acquired infections.