Is amoxicillin effective against Escherichia coli (E coli) infections?

Amoxicillin Coverage of E. coli

Amoxicillin alone should NOT be used for empiric treatment of E. coli infections due to unacceptably high resistance rates, with a median of 75% of E. coli urinary isolates resistant to amoxicillin globally. 1

Key Resistance Data

The WHO Expert Committee removed amoxicillin from recommended treatment options for urinary tract infections in 2021 after reviewing global surveillance data showing:

• Median 75% resistance among E. coli urinary isolates (range 45-100% across 22 countries) 1
• This high resistance rate has led multiple international guidelines to discourage empiric amoxicillin use for UTIs 1

FDA-Approved Indication vs. Clinical Reality

While the FDA label indicates amoxicillin is approved for E. coli genitourinary tract infections, this applies ONLY to β-lactamase-negative isolates 2. The critical caveat is:

• Most E. coli strains now produce β-lactamases (particularly TEM-1 and CTX-M enzymes), rendering amoxicillin ineffective 3, 4
• The FDA indication assumes susceptibility testing confirms the isolate is β-lactamase-negative—this is not the case for empiric therapy 2

When Amoxicillin MAY Cover E. coli

Amoxicillin can only be considered if:

• Culture and susceptibility testing confirms the specific E. coli isolate is amoxicillin-susceptible 2
• Rapid diagnostic testing (such as PCR detecting absence of blaTEM and blaCTX-M genes) confirms amoxicillin susceptibility within 3 hours 5
• The patient has documented infection with a β-lactamase-negative strain 2

Recommended Alternatives

For empiric treatment of E. coli infections, use:

For uncomplicated lower UTIs:

• Amoxicillin-clavulanate (first-choice) 1
• Nitrofurantoin 1
• Trimethoprim-sulfamethoxazole 1

For pyelonephritis (mild-moderate):

• Ciprofloxacin (if local resistance <10%) 1
• Ceftriaxone or cefotaxime 1

Clinical Implications

The addition of clavulanate (a β-lactamase inhibitor) to amoxicillin restores activity against most E. coli strains:

• Amoxicillin-clavulanate maintains high susceptibility rates among E. coli urinary isolates 1
• The inhibitor overcomes TEM-1 β-lactamase production, the most common resistance mechanism 3, 4

Critical pitfall: Using amoxicillin empirically for suspected E. coli infections risks treatment failure in 75% of cases and promotes further resistance development 1, 6. Amoxicillin prescribing is associated with increased ciprofloxacin resistance among E. coli (RR 1.09) 6.