Can Augmentin (amoxicillin-clavulanate) and Flagyl (metronidazole) be used together to cover Bacteroides fragilis?

From the Guidelines

Augmentin (amoxicillin-clavulanate) and Flagyl (metronidazole) can be used together to cover Bacteroides fragilis infections, as recommended by the most recent guidelines 1. This combination is effective because metronidazole provides excellent coverage against anaerobic bacteria like B. fragilis, while Augmentin offers broader coverage against many gram-positive and some gram-negative organisms. For intra-abdominal infections involving B. fragilis, a typical regimen might include metronidazole 500 mg orally or IV every 8 hours along with Augmentin 875/125 mg orally every 12 hours, or 1.2 g IV every 6-8 hours, for 7-14 days depending on infection severity and clinical response. This combination works well because B. fragilis frequently produces beta-lactamase enzymes that can inactivate many beta-lactam antibiotics, but metronidazole's mechanism of action is not affected by these enzymes. Additionally, the clavulanic acid in Augmentin inhibits beta-lactamases, enhancing the effectiveness of the amoxicillin component. Some key points to consider when using this combination include:

• Monitoring for side effects, including diarrhea, nausea, and potential drug interactions
• Adjusting both medications for renal impairment if necessary
• Being aware of local resistance patterns and adjusting the treatment regimen accordingly, as suggested by the World Society of Emergency Surgery and the Surgical Infection Society and the Infectious Diseases Society of America guidelines 1. It's also important to note that the use of fluoroquinolones, such as ciprofloxacin or levofloxacin, may be considered as second options due to resistance and harm concerns, but the combination of Augmentin and Flagyl is generally preferred for its efficacy and limited resistance potential 1.

From the FDA Drug Label

INTRA‑ABDOMINAL INFECTIONS, including peritonitis, intra‑abdominal abscess, and liver abscess, caused by Bacteroides species including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B vulgatus)

Metronidazole has been shown to have in vitro and clinical activity against the following organisms: Anaerobic gram negative bacilli, including: Bacteroides species, including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B vulgatus)

The use of Augmentin and Flagyl together may be considered to cover Bacteroides fragilis, as Flagyl (metronidazole) has been shown to have clinical activity against Bacteroides fragilis. However, the decision to use these medications together should be based on the specific clinical scenario and susceptibility patterns of the organism.

• Key points:
  • Metronidazole is active against Bacteroides fragilis
  • Augmentin may be used in combination with metronidazole for certain infections, but the specific indication and susceptibility patterns should be considered 2, 2

From the Research

Bacteroides Fragilis Treatment

To determine if Augmentin (amoxicillin/clavulanic acid) and Flagyl (metronidazole) can be used together to cover Bacteroides fragilis, let's examine the available evidence:

• The study 3 suggests that metronidazole plus an aminoglycoside is a successful antimicrobial agent against B. fragilis.
• Another study 4 found metronidazole to be a safe and effective agent in the treatment of B. fragilis infections.
• Research 5 compared the efficacy of amoxycillin/clavulanic acid with other antibiotics, including metronidazole, in experimental mixed infections and found amoxycillin/clavulanic acid to be effective against B. fragilis.
• The susceptibility profiles of B. fragilis strains isolated from clinical specimens and human intestinal microbiota were determined in study 6, which found that the organisms were uniformly susceptible to metronidazole and had low resistance rates to amoxicillin-clavulanate.

Combination Therapy

Considering the evidence, using Augmentin and Flagyl together may be effective against B. fragilis:

• Study 5 demonstrated the efficacy of amoxycillin/clavulanic acid in experimental mixed infections, including those caused by B. fragilis.
• The uniform susceptibility of B. fragilis to metronidazole, as found in study 6, supports the use of Flagyl in combination with Augmentin.
• However, it is essential to note that the effectiveness of combination therapy may depend on various factors, including the specific strain of B. fragilis and the severity of the infection.

Antibiotic Susceptibility

The antibiotic susceptibility profiles of B. fragilis strains are crucial in determining the most effective treatment:

• Study 6 found that B. fragilis strains were uniformly susceptible to metronidazole and had low resistance rates to amoxicillin-clavulanate.
• Another study 7 highlighted the importance of using EUCAST methodology and breakpoints in susceptibility testing for amoxicillin/clavulanic acid in B. fragilis.
• The findings of study 3 suggest that piperacillin has a low rate of resistance among beta-lactam antibiotics, which may be useful in combination with other antibiotics.