What is the initial treatment for a patient with an infection caused by Escherichia coli (E. coli) and Enterococcus faecalis?

Treatment of E. coli and Enterococcus faecalis Co-Infection

For polymicrobial infections involving E. coli and Enterococcus faecalis, initiate ampicillin 2 g IV every 4-6 hours plus gentamicin 1 mg/kg IV every 8 hours (or a third-generation cephalosporin or fluoroquinolone for E. coli coverage if ampicillin-resistant E. coli is suspected), as ampicillin provides optimal coverage for E. faecalis while the aminoglycoside or alternative gram-negative agent covers E. coli. 1, 2

Initial Empiric Approach

Identify the Infection Source and Severity

• For urinary tract infections: Ampicillin 2 g IV every 4-6 hours covers both E. faecalis and susceptible E. coli, as amoxicillin/ampicillin is FDA-approved for genitourinary infections caused by both organisms 2
• For intra-abdominal infections: Imipenem-cilastatin 500 mg IV every 6 hours provides comprehensive coverage for both E. coli and E. faecalis in polymicrobial infections 3
• For serious infections requiring bactericidal activity (endocarditis, bacteremia): Combine ampicillin 2 g IV every 4 hours with gentamicin for synergistic killing of E. faecalis, while ensuring gram-negative coverage 4, 1

Critical Species Differentiation

• E. faecalis retains ampicillin susceptibility in 97% of cases, making ampicillin the gold standard first-line agent 1
• Only 3% of E. faecalis strains are multidrug-resistant, and many vancomycin-resistant E. faecalis remain penicillin-susceptible 1
• Never assume E. faecium has the same susceptibility as E. faecalis—E. faecium has intrinsic penicillin resistance and requires different coverage 1

Specific Treatment Regimens by Clinical Scenario

Uncomplicated Infections (UTI, Simple Skin/Soft Tissue)

• Ampicillin 2 g IV every 4-6 hours for 7-14 days provides adequate coverage for both organisms in most cases 1, 2
• Alternative: Amoxicillin 500 mg PO every 8 hours if oral therapy is appropriate and susceptibilities confirm coverage 1
• For ampicillin-resistant E. coli, add a fluoroquinolone or third-generation cephalosporin while maintaining ampicillin for enterococcal coverage 5

Complicated Intra-Abdominal Infections

• Imipenem-cilastatin 500 mg IV every 6 hours covers both E. coli and E. faecalis in polymicrobial peritonitis 3, 6
• Alternative: Ampicillin-sulbactam or piperacillin-tazobactam provides dual coverage, though verify E. faecalis susceptibility 7
• Duration: 7-14 days based on source control and clinical response 1

Bacteremia or Endocarditis

• Ampicillin 2 g IV every 4 hours plus gentamicin 1 mg/kg IV every 8 hours for 4-6 weeks for native valve endocarditis 4, 1
• Gentamicin provides synergy against E. faecalis and covers E. coli; limit gentamicin to 2 weeks if renal function permits, then continue ampicillin alone 4
• For prosthetic valve involvement, extend treatment to minimum 6 weeks 4, 1
• Check for high-level aminoglycoside resistance in E. faecalis—if present, use ampicillin plus ceftriaxone 4 g/day IV as double β-lactam regimen 4, 1

Healthcare-Associated Infections with Risk Factors

• Patients with prolonged hospitalization, recent antibiotic use (especially cephalosporins or fluoroquinolones), or critically ill status require broader initial coverage 4, 8, 9
• Consider imipenem-cilastatin 500 mg IV every 6 hours or piperacillin-tazobactam 4.5 g IV every 6 hours for empiric coverage of resistant gram-negatives while maintaining enterococcal activity 3, 10
• De-escalate to ampicillin-based therapy once susceptibilities confirm coverage 10, 11

Critical Pitfalls to Avoid

Antibiotic Selection Errors

• Never use cephalosporins alone for enterococcal coverage—they have no intrinsic activity against enterococci despite potential synergy when combined with ampicillin 1
• Do not empirically prescribe vancomycin for E. faecalis—ampicillin is superior and vancomycin should be reserved for documented β-lactam allergy 1
• Avoid monotherapy with fluoroquinolones or cephalosporins in polymicrobial infections, as these lack enterococcal coverage 5

Aminoglycoside Considerations

• Test for high-level gentamicin resistance (≥500 μg/mL) in E. faecalis, as this eliminates synergy with cell wall-active agents 4
• Monitor renal function closely in elderly or debilitated patients receiving gentamicin, as nephrotoxicity may complicate 4-6 week courses 4
• Consider single daily dosing of gentamicin for improved tolerability, though data for enterococcal infections are conflicting 4

Source Control and Monitoring

• Verify the antibiogram and adjust therapy within 48-72 hours when culture and sensitivity results are available 1
• Remove infected catheters or devices—failure to achieve source control results in treatment failure regardless of antimicrobial choice 7
• For enterococcal bacteremia persisting >4 days, evaluate for endocarditis with transesophageal echocardiography 4

Duration of Therapy

• Uncomplicated infections: 7-14 days 1
• Complicated infections with adequate source control: 10-14 days 4
• Native valve endocarditis: 4-6 weeks (4 weeks if symptoms <3 months, 6 weeks if symptoms >3 months) 4, 1
• Prosthetic valve or prosthetic material: Minimum 6 weeks 4, 1

When to Consult Infectious Disease

• Always obtain infectious disease consultation for enterococcal endocarditis as standard of care 1
• Consider consultation for high-level aminoglycoside resistance, vancomycin resistance, or treatment failure after 48-72 hours of appropriate therapy 1