What is the difference in antimicrobial coverage between Augmentin (amoxicillin-clavulanate) and amoxicillin?

From the Guidelines

Augmenting amoxicillin coverage with clavulanic acid is recommended for patients with acute bacterial sinusitis who are at high risk of beta-lactamase producing bacteria, such as those with recent antimicrobial use, attendance at child care, or age younger than 2 years. The addition of clavulanic acid to amoxicillin creates amoxicillin-clavulanate (Augmentin), which significantly broadens the antibiotic spectrum to include beta-lactamase producing bacteria, including Haemophilus influenzae and Moraxella catarrhalis 1. Typical adult dosing for Augmentin is 875mg/125mg twice daily or 500mg/125mg three times daily for 7-10 days, depending on the infection. For children, dosing is weight-based, usually 45mg/kg/day divided twice daily, with a maximum of 2 g per dose 1.

• The benefits of augmenting amoxicillin coverage include increased efficacy against beta-lactamase producing bacteria, which are commonly found in respiratory infections, sinusitis, otitis media, skin infections, and urinary tract infections.
• The harms of augmenting amoxicillin coverage include increased risk of gastrointestinal side effects, such as diarrhea, nausea, and rash, as well as potential for C. difficile infection.
• The American Academy of Pediatrics recommends amoxicillin-clavulanate as first-line empirical therapy for acute bacterial sinusitis in children, particularly for those with moderate to severe illness or risk factors for resistance 1.
• A recent guideline published by the Infectious Diseases Society of America also recommends amoxicillin-clavulanate as initial empirical antimicrobial therapy for acute bacterial sinusitis in children, due to the increasing prevalence of H influenzae as a cause of sinusitis since introduction of the pneumococcal conjugate vaccines and an increasing prevalence of β-lactamase production among these strains 1. In summary, augmenting amoxicillin coverage with clavulanic acid is a recommended approach for patients with acute bacterial sinusitis who are at high risk of beta-lactamase producing bacteria, and should be used judiciously when broader coverage is specifically indicated.

From the FDA Drug Label

Bacteriological eradication on therapy (day 4-6 visit) in the per protocol population is summarized in Table 5. Table 5. Bacteriologic Eradication Rates in the Per Protocol Population Pathogen Bacteriologic Eradication on Therapy n/N % 95% CI* All S. pneumoniae 121/123 98.4 (94.3,99.8) S. pneumoniae with penicillin MIC = 2 mcg/mL 19/19 100 (82. 4,100) S. pneumoniae with penicillin MIC = 4 mcg/mL 12/14 85.7 (57.2,98.2) H. influenzae 75/81 92.6 (84.6,97.2) M. catarrhalis 11/11 100 (71. 5,100)

The FDA drug label does not directly compare Augmentin (amoxicillin/clavulanate) to amoxicillin in terms of coverage. However, it provides information on the bacteriologic eradication rates of amoxicillin/clavulanate against various pathogens, including:

• S. pneumoniae: 98.4% eradication rate
• H. influenzae: 92.6% eradication rate
• M. catarrhalis: 100% eradication rate It is essential to note that the label does not provide a direct comparison to amoxicillin, and therefore, no conclusion can be drawn regarding the relative coverage of Augmentin vs amoxicillin 2.

From the Research

Amoxicillin Coverage

• Amoxicillin/clavulanate (Augmentin) is a broad-spectrum antibacterial that has been available for clinical use in a wide range of indications for over 20 years and is now used primarily in the treatment of community-acquired respiratory tract infections 3.
• The combination of amoxicillin and clavulanate provides a potent broad spectrum of antibacterial activity, coverage of beta-lactamase-producing pathogens, and a favorable pharmacokinetic/pharmacodynamic (PK/PD) profile 3.
• Amoxicillin/clavulanate has a well-known safety and tolerance profile, and its efficacy has been demonstrated in various studies, including the treatment of acute otitis media, community-acquired pneumonia, and acute exacerbations of chronic bronchitis 3, 4, 5, 6.

Augmentin vs Amoxicillin

• Augmentin (amoxicillin/clavulanate) is an effective treatment for pediatric acute otitis media, and its twice-daily formulation has been shown to be equivalent to the three-times-daily formulation in terms of efficacy 4.
• The use of Augmentin has been compared to other antibiotics, such as ceftriaxone and cefuroxime, in the treatment of community-acquired pneumonia, and no statistically significant differences were found in the evolution of patients treated with these antibiotics 7, 5.
• A study comparing cefixime versus amoxicillin-clavulanate following ceftriaxone therapy of pneumonia found that both treatments were effective, with similar clinical response rates 6.

Resistance and Efficacy

• The emergence of S. pneumoniae strains with elevated penicillin MICs has been observed in certain defined geographical areas, which may affect the efficacy of amoxicillin/clavulanate 3.
• However, the development of new high-dose amoxicillin/clavulanate formulations, such as Augmentin XR and Augmentin ES-600, has been designed to meet the need to treat drug-resistant S. pneumoniae 3.
• The efficacy of amoxicillin/clavulanate has been demonstrated in various studies, and it continues to be an important agent in the treatment of community-acquired respiratory tract infections 3, 4, 5, 6.