Metronidazole (Flagyl) versus Vancomycin (Vancocin)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Metronidazole advantages over Vancomycin

  • No nephrotoxicity and ototoxicity.
  • Very high oral bioavailability.
  • Unlike vancomycin, metronidazole is active against gram-negative anaerobes.
  • The cost of metronidazole therapy for C. difficile infection is significantly lower than that of vancomycin therapy.

Vancomycin advantages over Metronidazole

  • Low potential for drug interactions.
  • There is no cross-resistance between vancomycin and other antibiotics.
  • Vancomycin is effective against most resistant gram-positive bacterial infections.


Metronidazole Vancomycin
Brand names
Flagyl® Vancocin®
Drug class
Nitroimidazole antibiotic Glycopeptide antibiotic
Dose formulations
• Oral
• Topical
• Intravaginal
• Intravenous
• Oral
• Intravenous
Antimicrobial spectrum
Anaerobic bacteria
• Microaerophilic bacteria
• Certain protozoa
• The antibacterial activity is mainly restricted to Gram positive bacteria
FDA-approved indications
Anaerobic infections:
• Intra-abdominal infections
• Bone and joint infections
• Skin and skin structure Infections
• Gynecologic infections
• Meningitis
• Pneumonia
• Endocarditis
• Surgical prophylaxis
• Trichomoniasis
• Amebiasis
• Bacteremia
• Endocarditis
• Meningitis
• Other serious or severe infections caused by Gram-positive pathogens (especially those caused by methicillin-resistant staphylococci) and in patients hypersensitive to β-lactam antibiotics

• Enterocolitis caused by Staphylococcus aureus
• Antibiotic-associated pseudomembranous due to C. difficile
"Off-label" uses
C. difficile colitis
• Crohn's disease
• Surgical prophylaxis
• Posttraumatic and postoperative endophthalmitis (inflammation of the intraocular cavities)
Mechanism of action
• Metronidazole is bactericidal, inhibits bacterial DNA synthesis and causes DNA degradation. • Vancomycin is slowly bactericidal and works by inhibition of cell-wall biosynthesis in dividing bacteria. It also affects RNA synthesis.
• 8 hours • 4 to 6 hours
Oral bioavailability
• ~100%, well absorbed • <10%
• Vancomycin is poorly absorbed after oral administration.
Metabolism, Elimination
• Metronidazole is metabolised by cytochrome P-450 enzymes, and forms five major metabolites, which have antimicrobial activity.
• The primary route of elimination is urine (60-80% of the dose), feces 6-15%.
• Vancomycin is not metabolized to any significant extent.
• More than 80% of a vancomycin dose is eliminated unchanged in the urine.
• Renal dysfunction slows excretion of vancomycin.
• Hypersensitivity to nitroimidazole antibiotics
• First trimester of pregnancy
• Hypersensitivity to vancomycin
• Reported cases of convulsive seizures and peripheral neuropathy (numbness, paresthesia) • Nephrotoxicity (renal impairment, increased blood creatinine levels)
• Ototoxicity (vertigo, tinnitus may present)
Side effects
• Nausea
• Vomiting
• Metallic taste
• Nausea
• Abdominal pain
• Hypokalemia
Drug interactions
• Metronidazole may potentiate the anticoagulant effect of warfarin and other coumarin anticoagulants. • Gentamicin, loop diuretics may increase the potential for nephrotoxicity and ototoxicity.

Metronidazole vs Vancomycin for Clostridium difficile-associated diarrhea

One of the most serious cases of antibiotic-associated diarrhea is infection with Clostridium difficile, a gram-positive bacteria. C. difficile is the major cause of pseudomembranous colitis. Early diagnosis and prompt treatment are very important in cases of C. difficile diarrhea.

Currently vancomycin is one of two FDA-licensed drugs for the treatment of C.difficile colitis.

Metronidazole and vancomycin are equally effective for mild Clostridium difficile-associated diarrhea (CDAD), but vancomycin is superior for treating severe CDAD1, 2. There is evidence that treatment with vancomycin can significantly reduce the risk of death occurring within 30 days in patients with severe Clostridium difficile infection3.

Metronidazole is currently recommended as a first-line choice for mild-to-moderate infection5. Metronidazole cure rate is about 90%. Important benefit of metronidazole is very low cost. It is estimated that oral vancomycin costs $71-143 per day compared with metronidazole, which costs only $2 per day3.

Metronidazole dosage:
500 mg orally 3-4 times daily for 10 to 14 days.

Metronidazole, unlike vancomycin, is absorbed in upper intestine, and is usually not detected in feces in healthy people.

Vancomycin dosage:
125 to 500 mg orally 4 times daily for 10 to 14 days.
Vancomycin should not be used intravenously to treat colitis or diarrhea because sufficient drug concentration in the colon is not achieved after parenteral rote.

Vancomycin is an ideal medication for C. difficile–associated diarrhea. It is not absorbed, not metabolized, and as a result, achieves high intraluminal concentrations in the colon.

However, vancomycin is not recommend as an initial choice because of higher cost and emergence of vancomycin-resistant enterococci. It should be noted that both vancomycin and metronidazole when used to treat CDAD can promote emergence of vancomycin-resistant enterococci6.

Vancomycin is used for:

  • Severe C. difficile infection
  • Pregnant women
  • Cases of metronidazole failure or intolerance


Comparative clinical trials

In the prospective observational study among the patients with mild CDAD, treatment with metronidazole or vancomycin resulted in clinical cure in 90% and 98% of the patients. However, in severe CDAD clinical cure was 76% in metronidazole group and 97% in vancomycin group.

Results from 2 randomized, controlled trials of vancomycin, metronidazole, or tolevamer for Clostridium difficile Infection (CDI) 2 Metronidazole Vancomycin
Clinical success 72.7% 81.1%
Clinical success in patients with severe CDI 66.3% 78.5%

Note: Combination therapy of metronidazole and vancomycin is not superior to monotherapy because it is associated with an increased risk of side effects4.

Further reading


  • 1. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007 Aug 1;45(3):302-7. PubMed
  • 2. Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014 Aug 1;59(3):345-54. PubMed
  • 3. Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients With Clostridium difficile Infection. JAMA Intern Med. 2017 Feb 6. PubMed
  • 4. Li R, Lu L, Lin Y, et al. Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis. PLoS One. 2015 Oct 7;10(10):e0137252 PubMed
  • 5. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS.Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478-98; PubMed
  • 6. Al-Nassir WN, Sethi AK, Li Y et al. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob Agents Chemother 2008;52:2403–2406

Published: February 03, 2018
Last updated: February 03, 2018


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