Is Escherichia coli (E. coli) pneumonia susceptible to Augmentin (amoxicillin-clavulanate)?

E. coli Pneumonia Susceptibility to Augmentin

Augmentin (amoxicillin-clavulanate) has variable and often inadequate activity against E. coli pneumonia, and should not be used as empiric monotherapy for this infection. 1, 2

FDA-Approved Indications and Limitations

The FDA label for amoxicillin-clavulanate specifically lists lower respiratory tract infections caused by beta-lactamase-producing H. influenzae and M. catarrhalis, but does not include E. coli pneumonia as an approved indication. 2 The label explicitly states that skin/soft tissue infections and urinary tract infections caused by beta-lactamase-producing E. coli are approved indications, but respiratory tract infections due to E. coli are notably absent. 2

Guideline Recommendations for Enterobacteriaceae Pneumonia

For community-acquired pneumonia (CAP) caused by Enterobacteriaceae (including E. coli and Klebsiella species), Taiwan guidelines recommend ertapenem 1g once daily or ceftriaxone 1g once daily as preferred agents, based on multicenter randomized studies showing equivalence between these agents. 1 Amoxicillin-clavulanate is not mentioned as a recommended option for Enterobacteriaceae pneumonia in these guidelines. 1

The 2003 IDSA/ATS guidelines recommend amoxicillin-clavulanate only for empiric treatment of bacterial superinfection following influenza, where the target pathogens are S. pneumoniae, S. aureus, and H. influenzae—not E. coli. 1

Resistance Patterns and Clinical Implications

E. coli resistance to amoxicillin-clavulanate is substantial and increasing:

• In urinary tract infections, resistance rates to amoxicillin-clavulanate range from 33-56% in various studies. 3, 4
• A Swiss hospital study documented that only 54.9% of E. coli isolates were susceptible to amoxicillin-clavulanate in 1992-1993. 3
• A postoperative ICU study found significantly increased mortality, prolonged ventilation, and longer ICU stays in patients with amoxicillin-clavulanate-resistant E. coli peritonitis. 5
• The resistance mechanisms in E. coli include OXA-1 beta-lactamases, inhibitor-resistant TEM (IRT) enzymes, and chromosomal AmpC hyperproduction—all of which can confer resistance to amoxicillin-clavulanate. 6

Critical Clinical Pitfalls

Common mistakes to avoid:

• Never assume susceptibility based on UTI data alone—respiratory isolates may have different resistance patterns than urinary isolates. 2, 6
• Do not use amoxicillin-clavulanate for hospital-acquired or healthcare-associated pneumonia where E. coli is suspected, as resistance rates are even higher in these settings. 1, 5
• Always obtain cultures and susceptibility testing before considering amoxicillin-clavulanate for any suspected E. coli pneumonia. 2
• If E. coli pneumonia is documented, use definitive therapy based on susceptibility results—do not continue empiric amoxicillin-clavulanate without confirmation of susceptibility. 1, 2

Recommended Approach for E. coli Pneumonia

For empiric therapy when E. coli pneumonia is suspected:

• Use a third-generation cephalosporin (ceftriaxone 1-2g IV q12-24h or cefotaxime 1-2g IV q8h) or ertapenem 1g IV daily. 1
• Consider a respiratory fluoroquinolone (levofloxacin 750mg daily or moxifloxacin 400mg daily) as an alternative. 1

For definitive therapy after susceptibility results:

• If the isolate is susceptible to amoxicillin-clavulanate, it may be used, but narrow-spectrum alternatives like ceftriaxone are generally preferred for better tissue penetration and more predictable outcomes in pneumonia. 1
• If extended-spectrum beta-lactamase (ESBL) production is suspected or confirmed, use a carbapenem (ertapenem, meropenem, or imipenem). 1

The bottom line: While some E. coli strains may be susceptible to amoxicillin-clavulanate in vitro, this agent is not recommended for empiric or routine treatment of E. coli pneumonia due to inadequate respiratory tract data, high resistance rates, and availability of superior alternatives. 1, 2, 5