Did the patient test too soon after starting Augmentin (amoxicillin/clavulanate) or is it likely that Enterococcus has been cleared, leaving only Klebsiella to be treated?

Testing Timing After Augmentin and Enterococcus Clearance

The patient likely tested too soon—one day of Augmentin is insufficient to clear Enterococcus, and the negative result more likely reflects sampling issues, bacterial suppression without eradication, or initial misidentification rather than true clearance. 1, 2

Why One Day is Too Soon

Enterococcal Bacteremia Clearance Timeline

• Enterococcal bloodstream infections typically require 72+ hours of appropriate antibiotic therapy before bacteremia clears, and persistent bacteremia beyond this timeframe is associated with increased mortality and warrants further investigation including transesophageal echocardiography 1
• The Infectious Diseases Society of America guidelines specifically define persistent enterococcal bacteremia as continuing >72 hours after initiating appropriate antibiotics, indicating that clearance within 24 hours would be highly unusual 1

Augmentin's Activity Against Enterococcus

• Amoxicillin-clavulanate (Augmentin) is effective against ampicillin-susceptible Enterococcus faecalis, with treatment durations of 4-6 weeks recommended for serious infections like endocarditis 2, 3
• For enterococcal infections, particularly those involving biofilms or deep-seated sources, extended therapy is required—not single-day exposure 2
• One case report documented successful treatment of relapsed E. faecalis prosthetic valve endocarditis with oral amoxicillin/clavulanate, but this required prolonged therapy, not 24 hours 3

Alternative Explanations for the Negative Enterococcus Result

Bacterial Suppression vs. Eradication

• Augmentin may suppress bacterial growth in culture without achieving true eradication, particularly after just one day of therapy 4
• The antibiotic effect on culture results can occur rapidly, but this represents inhibition of growth in the sample, not clearance from the patient 1

Sampling and Technical Issues

• NGS testing performed on samples collected shortly after antibiotic initiation may yield false-negative results due to bacterial DNA degradation or reduced bacterial load below detection thresholds 1
• A single negative culture or test does not confirm eradication, especially in the context of recent antibiotic exposure 1

Initial Polymicrobial vs. Monomicrobial Infection

• The initial identification of both Enterococcus and Klebsiella may have been accurate, with both organisms present 1
• Klebsiella species are often more resistant to amoxicillin-clavulanate than Enterococcus, particularly ESBL-producing strains, which could explain why only Klebsiella was detected on repeat testing 5, 6, 4

Clinical Implications and Recommended Approach

Assume Both Organisms Remain Present

• Treat for both Enterococcus and Klebsiella until you have confirmatory evidence of clearance with adequate treatment duration 1
• For Enterococcus: Continue ampicillin-based therapy (Augmentin) for appropriate duration based on infection source 1, 2
• For Klebsiella: Augmentin may be inadequate, especially if ESBL-producing; consider susceptibility testing and potential need for alternative agents 5, 6, 4

Repeat Testing Strategy

• Obtain repeat cultures/NGS testing at 72+ hours after initiating appropriate antibiotic therapy to assess true microbiological response 1
• If using blood cultures, obtain at least two sets from different sites to distinguish true bacteremia from contamination 1

Klebsiella-Specific Considerations

• ESBL-producing Klebsiella pneumoniae is increasingly common and typically resistant to amoxicillin-clavulanate at standard doses 5, 6, 4
• High-dose amoxicillin-clavulanate (2875 mg amoxicillin twice daily) has shown success in select cases of ESBL-producing Klebsiella UTIs, but this requires MIC ≤2 mg/mL 5, 4
• Resistance can develop during therapy, particularly with Klebsiella species showing higher AMC MICs (≥8 mg/mL), with therapeutic failure rates of 71.4% in such cases 4
• Carbapenems remain the primary treatment for ESBL-producing Klebsiella infections when oral alternatives fail 5, 6

Common Pitfalls to Avoid

• Do not assume Enterococcus clearance based on a single negative test after only 24 hours of antibiotic therapy 1
• Do not rely solely on Augmentin for ESBL-producing Klebsiella without susceptibility data and close monitoring 5, 6, 4
• Do not discontinue gram-positive coverage prematurely—if Enterococcus was initially identified, maintain appropriate therapy for the full recommended duration based on infection source 1, 2
• Recognize that Enterococcus faecium has higher ampicillin resistance rates (33.1%) than E. faecalis, which may influence treatment decisions 7