Metronidazole: an antibiotic and antiprotozoal medication

Introduction

Metronidazole is a critical antibiotic primarily used for the treatment of anaerobic bacterial infections, protozoal infections, and microaerophilic bacterial infections. It demonstrates cytotoxicity towards facultative anaerobic microorganisms and is FDA-approved for certain anaerobic and protozoal infections, making it a mainstay in treating these conditions​^1, ​​²​.

Mechanism of Action

The mechanism of action of Metronidazole is distinct among antibiotics. It possesses a nitro group which, under reductive conditions within microbial cells, forms reactive nitro radicals. These radicals are responsible for causing DNA strand breakage and subsequently inhibit bacterial nucleic acid synthesis, leading to cell death.

Pharmacokinetics

• Absorption: Metronidazole is well absorbed when administered orally, with food not influencing its absorption.
• Distribution: It is extensively distributed in the body, penetrating all tissues and body fluids, including the central nervous system.
• Metabolism: Metronidazole undergoes hepatic metabolism, with its major component appearing in the plasma, along with lesser quantities of metabolites.
• Excretion: The drug and its metabolites are primarily excreted via the kidneys​³​.

Therapeutic Uses

1. Anaerobic Bacterial Infections: Core treatment for infections caused by Bacteroides, Fusobacteria, and Clostridia species.
2. Protozoal Infections: Used for trichomoniasis, amoebiasis, and giardiasis.
3. Microaerophilic Bacterial Infections: Exhibits cytotoxicity towards facultative anaerobic microorganisms.
4. Diverticulitis: Commonly used alongside Ciprofloxacin for treatment​⁴​.
5. Gynecologic Infections: Treats various infections of the vagina, stomach, liver, skin, joints, brain and spinal cord, lungs, heart, or bloodstream​⁵​.
6. Other Infections: Including oral and dental infections, bone and joint infections, endocarditis, septicemia, and respiratory tract infections.
7. Rosacea: Management of this chronic skin condition.
8. Crohn’s Disease: Treatment of Crohn’s disease.
9. Prophylaxis: Used as a prophylactic agent before surgical procedures.
10. Helicobacter pylori (H. pylori) Treatment: Few regimens have consistently achieved high eradication rates with limited data on antibiotic resistance rates​^6, ​​⁷​.

Recent Updates

1. Expanded Therapeutic Uses: From its initial application in 1959 for Trichomonas vaginalis infection, Metronidazole’s therapeutic use has broadened to treat a plethora of infections ranging from gynecologic to respiratory tract infections, and its use as a prophylactic agent before surgical interventions.
2. Concerns and Further Investigations: Associated concerns of neurotoxicity and genotoxicity warrant further studies to ascertain the secure use of Metronidazole and explore new usages for this drug​⁷​.

Adverse Effects

Common adverse effects include nausea, abdominal pain, and diarrhea. Serious adverse effects, although rare, include neurotoxicity, optic neuropathy, peripheral neuropathy, and encephalopathy. Controversial findings regarding its genotoxic effects observed in animal models versus humans have been reported​⁷​.

Resistance

Overuse or misuse of Metronidazole could foster the evolution of antibiotic resistance. Overprescribing, particularly, may lead to a surge in future antibiotic resistance to Metronidazole​⁸​.

Drug Interactions

Metronidazole has extensive drug interactions with 342 known interactions categorized into 12 major, 327 moderate, and 3 minor interactions. Notable drugs with major interactions with Metronidazole encompass:

1. Disulfiram: A medication for treating alcohol use disorder, it halts alcohol breakdown, rendering drinking unpleasant​⁹​.
2. Other frequently examined interactions encompass medications like Adderall (amphetamine/dextroamphetamine), Aspirin Low Strength (aspirin), Augmentin (amoxicillin/clavulanate), Cipro (ciprofloxacin), Lexapro (escitalopram), among others​¹⁰​.

Alcohol/Food Interactions: Metronidazole has two known alcohol/food interactions. Consuming alcohol or products containing propylene glycol during and for a minimum of three days post-therapy with Metronidazole can trigger a disulfiram-like reaction, exhibiting symptoms like abdominal cramps, nausea, vomiting, headaches, and flushing​^11, ​​¹⁰​.

Contraindications

Metronidazole is contraindicated under these scenarios:

1. Patients with documented hypersensitivity to the drug or its constituents.
2. First-trimester pregnancy.
3. Individuals in pregnancy or breastfeeding phases.
4. Those with liver ailments or undergoing dialysis.
5. Individuals unable to abstain from alcohol while on Metronidazole​^12, ​​⁸​.

Furthermore, specific disease interactions including colitis, blood dyscrasias, neurologic toxicity, dialysis, liver disease, sodium, and alcoholism require consideration when prescribing Metronidazole​¹⁰​.

Conclusion

Metronidazole remains a vital antibiotic, especially for anaerobic and protozoal infections. Its broad therapeutic applications, coupled with a well-tolerated profile, make it a valuable asset in the antimicrobial armamentarium. However, concerns regarding its neurotoxicity and genotoxicity necessitate further investigations to ensure its safe use and explore new therapeutic avenues.