Metronidazole for Bacterial Vaginosis

Medical uses

Metronidazole is classified as a nitroimidazole antiprotozoal and antibacterial agent used to treat protozoal infections and anaerobic bacterial infections, including1:

• Amebiasis
• Trichomoniasis (caused by Trichomonas vaginalis)
• Skin and skin structure infections
• CNS infections
• Intra-abdominal infections (as part of combination regimen)
• Antibiotic-associated pseudomembranous colitis (AAPC)
• Bacterial vaginosis (BV)

The most common side effects are gastrointestinal, particularly nausea reported by about 12% of patients, headache, vomiting, diarrhea, metallic taste, and abdominal discomfort.

Efficacy for Bacterial vaginosis

Bacterial Vaginosis (non-specific vaginitis or Gardnerella vaginitis) is the most common cause of abnormal vaginal discharge, characterized by vaginal malodor and increased white discharge. BV results from the replacement of the normal vaginal flora (Lactobacillus spp.) with a mixture of potentially pathogenic bacteria, including Gardnerella, Mobiluncus, Mycoplasma hominis, Prevotella, and Atopobium vaginae.

BV is often associated with pelvic inflammatory disease and can also lead to anaerobic bacterial infection of the endometrium and salpinge. Bacterial vaginosis early in pregnancy significantly increases the risk of preterm delivery. Bacterial present in BV may produce substances that favor survival of Chlamydia trachomatis.

Metronidazole is the preferred antibiotic for the treatment of BV. The cure rate ranges from 75 to 84 percent4. However, Atopobium vaginae is resistant to metronidazole, and is associated with recurrent bacterial vaginosis after treatment with metronidazole.

Oral metronidazole eradicates BV-associated bacteria better than vaginal formulation3. However, metronidazole vaginal gel is a reasonable choice for women experiencing side effects of oral metronidazole2.

Recurrent Bacterial Vaginosis
Treatment failure occurs rather commonly possibly due to an inability of the body to restore a normal Lactobacillus-dominated vaginal flora after antibiotic therapy. Abstinence or protected sex, and refraining from douching increase the chances of successful treatment5.

Dosage for Bacterial vaginosis

Oral: 500 mg twice daily for seven days.

Vaginal: Metronidazole vaginal gel (0.75%) twice daily for 5 days. One full applicator (approximately 37.5 mg metronidazole) is applied intravaginally in the morning and in the evening. Treatment with metronidazole gel is moderately effective for bacterial vaginosis.

Recurrent BV: In case of more than three episodes of bacterial vaginosis during past 12 months vaginal metronidazole gel may be used to prevent relapses. The regimen is twice weekly for 4-6 months7-8.

Regimens for pregnant women: Metronidazole is an acceptable therapy for BV during pregnancy8. However, some clinicians are hesitant to prescribe metronidazole in pregnant women because there are not enough studies confirming its safety. According to CDC Guidelines8 Clindamycin (300 mg twice a day for 7 days) is an alternative to metronidazole for the treatment of BV.

Benefits

• Low cost.
• Both oral and topical formulations of metronidazole are approved for the treatment of BV.
• Highly active against virtually all anaerobes (with exception of actinomyces, Propionibacterium acnes, and Lactobacillus spp.)

Concerns

• Frequently causes metallic taste and gastrointestinal upset.
• Alcohol interaction. Drinking alcohol while taking metronidazole can cause severe nausea, vomiting, flushing and rapid heart rate. A disulfiram-like reaction may occur if alcohol is ingested within 7 days of use.
• Possible carcinogenic potential. High doses of metronidazole are carcinogenic to animals. The drug has shown to have tumorigenic activity in mice and rats, the most prominent being pulmonary lesions in the mouse. Unnecessary use of metronidazole should be avoided.

Pharmacological characteristics

• Elimination half-life: 8 h in healthy adults, and the hydroxy-metabolite half-life is 15 h.
• Metabolism: metabolized in the liver with the formation of metabolites (2–hydroxymethyl, acid metabolite, glucuronide conjugation)
• Excretion: Main route of elimination is by kidney but it is also secreted in bile and breast milk. 77% is recovered from urine and 14% from stool.

Mechanism of action

Metronidazole is an anti-pathogen with selective toxicity to microaerophilic, anaerobic, and anoxic or hypoxic cells. It enters bacterial or protozoal cell and inhibits DNA synthesis, resulting in cell death.

However the mechanisms by which topical preparation works in reducing inflammatory lesions of rosacea are unknown. Possible mechanisms of action include antibacterial and/or anti-inflammatory effects.

Reviews & Discussions

• Metronidazole ratings for giardiasis, diverticulitis, tooth abscess in the Askapatient database
• Flagyl reviews, ratings by patients on DrugLib.com
• Metronidazole user reviews for bacterial vaginitis on Drugs.com

References

• 1. Metronidazole Prescribing Information (PDF format)
• 2. Ransom SB, McComish JF, Greenberg R, Tolford DA. Oral metronidazole vs. Metrogel Vaginal for treating bacterial vaginosis. Cost-effectiveness evaluation. J Reprod Med. 1999 Apr;44(4):359-62.
• 3. Mitchell CM, Hitti JE, Agnew KJ, Fredricks DN. Comparison of oral and vaginal metronidazole for treatment of bacterial vaginosis in pregnancy: impact on fastidious bacteria. BMC Infect Dis. 2009 Jun 10;9:89. PubMed
• 4. Ferris DG , Litaker MS, Woodward L, Mathis D, Hendrich J. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract. 1995 Nov;41(5):443-9. PubMed
• 5. Schwebke JR, Desmond RA. A randomized trial of the duration of therapy with metronidazole for treatment of symptomatic bacterial vaginosis. Clin Infect Dis. 2007 Jan 15;44(2):213-9. PubMed
• 7. Sobel JD, Ferris D, Schwebke J, et al. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol 2006;194:1283–9.
• 8. 2015 STD Treatment Guidelines: Bacterial Vaginosis. CDC

By HealthyStock Research Group, October 2009
Medical resources reviewed: August 2018