Ampicillin-Resistant E. coli and Augmentin Susceptibility
Ampicillin-resistant E. coli may still be susceptible to amoxicillin-clavulanate (Augmentin), but this is not guaranteed and depends on the specific resistance mechanism present.
Understanding the Resistance Mechanisms
The key issue is that E. coli resistance to ampicillin can occur through multiple mechanisms, and clavulanic acid (the beta-lactamase inhibitor in Augmentin) only overcomes some of them:
When Augmentin May Work
- Beta-lactamase-mediated resistance: If ampicillin resistance is due to plasmid-mediated beta-lactamases that are susceptible to clavulanic acid inhibition, the organism will likely be susceptible to amoxicillin-clavulanate 1.
- Studies show that among ampicillin-resistant E. coli urinary isolates, approximately 37.5-82.9% remain susceptible to amoxicillin-clavulanate when tested by appropriate methods 2, 3.
When Augmentin Will NOT Work
- ESBL production: Extended-spectrum beta-lactamases are increasingly common in nosocomial E. coli isolates and confer resistance to amoxicillin-clavulanate 4.
- AmpC hyperexpression: While the AmpC enzyme of E. coli is not typically inducible, it can occasionally be hyperexpressed, leading to resistance to amoxicillin-clavulanate 4.
- Intrinsic mechanisms: Porin changes or efflux pumps that don't involve beta-lactamases will not be overcome by clavulanic acid 4.
Critical Clinical Implications
You cannot assume susceptibility to Augmentin based solely on ampicillin resistance—susceptibility testing is essential 5, 2.
Testing Discrepancies to Be Aware Of
- There are significant methodological differences between testing systems that can lead to discordant results 5, 2, 6.
- Studies show that 86.9% of ampicillin-resistant E. coli tested susceptible to amoxicillin-clavulanate by MicroScan, but only 39.4% by Kirby-Bauer disk diffusion 5.
- The FDA label specifies that beta-lactamase-negative, ampicillin-resistant strains must be considered resistant to amoxicillin-clavulanic acid 7.
Empiric Treatment Considerations
Given the high global resistance rates:
- Amoxicillin alone should never be used empirically for E. coli infections, with median resistance of 75% globally 8.
- Amoxicillin-clavulanate maintains higher susceptibility rates than amoxicillin alone and is recommended as a first-choice agent for uncomplicated lower UTIs 8.
- For serious infections or when ESBL production is suspected, carbapenems remain the most reliable option as ESBL-producing strains remain susceptible to carbapenems 4.
Practical Algorithm
- If ampicillin resistance is documented: Order specific susceptibility testing for amoxicillin-clavulanate before using it therapeutically 5, 2.
- If ESBL risk factors present (recent hospitalization, healthcare exposure, prior antibiotic use): Avoid amoxicillin-clavulanate and use a carbapenem 4.
- For empiric therapy of uncomplicated UTI: Amoxicillin-clavulanate is acceptable as first-line, but nitrofurantoin or fosfomycin may have more predictable activity 4, 8.
- For nosocomial isolates: Expect higher rates of amoxicillin-clavulanate resistance (up to 50% of ampicillin-resistant strains) 3.