What is the recommended treatment for a patient with a cervical spine hardware infection caused by Enterococcus (bacteria) sensitive to ampicillin (antibiotic)?

Treatment of Cervical Spine Hardware Infection with Ampicillin-Susceptible Enterococcus

For ampicillin-susceptible enterococcal cervical spine hardware infection, ampicillin monotherapy is insufficient—you should add ceftriaxone 2g IV every 12 hours to ampicillin 2g IV every 4-6 hours for synergistic bactericidal activity, treating for a minimum of 6 weeks. 1, 2

Rationale for Combination Therapy

The combination of ampicillin and ceftriaxone provides critical synergistic bactericidal activity that ampicillin monotherapy cannot achieve for serious enterococcal infections involving hardware and bone. 1, 2

• Hardware-associated infections require bactericidal therapy because biofilm formation on spinal instrumentation prevents adequate antibiotic penetration and immune cell access, making bacteriostatic therapy inadequate. 2, 3

• The American Heart Association explicitly states that ampicillin-ceftriaxone combination therapy is reasonable for enterococcal infections when aminoglycosides are contraindicated or when dealing with aminoglycoside-resistant strains (Class IIa, Level of Evidence B). 1

• A pilot study specifically examining orthopedic enterococcal infections (including 3 instrumented spine arthrodesis device infections) demonstrated 90% cure rates with ampicillin-ceftriaxone combination therapy, with most patients retaining their hardware. 2

Specific Dosing Regimen

Ampicillin 2g IV every 4 hours (12g/day total) PLUS ceftriaxone 2g IV every 12 hours (4g/day total) for 6 weeks minimum. 1, 2

• The higher ampicillin dose (12-16g/day) is necessary for adequate bone and biofilm penetration in hardware-associated infections. 2

• After completing IV therapy, consider transitioning to oral amoxicillin for extended suppressive therapy if hardware must be retained, though this decision requires infectious disease consultation. 2

Critical Considerations Before Starting Treatment

Obtain comprehensive susceptibility testing immediately, including:

• Ampicillin MIC determination (not just susceptible/resistant) 1
• High-level aminoglycoside resistance testing 1
• Ceftriaxone susceptibility confirmation 1
• Vancomycin susceptibility 1

Arrange infectious disease consultation—this is a Class I recommendation for managing enterococcal hardware infections. 4, 5, 6

Why Not Gentamicin Instead?

While gentamicin plus ampicillin is the traditional combination for enterococcal infections, ceftriaxone offers several advantages in this clinical scenario:

• Zero nephrotoxicity risk compared to 23% nephrotoxicity rate with ampicillin-gentamicin. 1

• No need for therapeutic drug monitoring of serum levels, simplifying management. 1

• Equally effective outcomes in large comparative studies (272 patients) showing no difference in mortality, relapse, or need for surgery between ampicillin-ceftriaxone and ampicillin-gentamicin. 1

• Effective against high-level aminoglycoside-resistant strains, which are increasingly common. 1

Important Caveats and Pitfalls

The synergy is less reliable for Enterococcus faecium compared to Enterococcus faecalis. 7

• Time-kill studies show synergy in 100% of E. faecalis but only 33% of ampicillin-susceptible E. faecium. 7
• If your isolate is E. faecium, consider alternative regimens such as high-dose daptomycin (10-12 mg/kg/day) plus ampicillin instead. 4, 5

Monitor for dual β-lactam hypersensitivity reactions. 1

• If allergic reaction occurs, you cannot determine which β-lactam is responsible, requiring discontinuation of both agents. 1
• Alternative regimen would be vancomycin plus gentamicin (if gentamicin-susceptible) or linezolid 600mg every 12 hours. 1

Hardware removal may still be necessary if: 1, 3

• Bacteremia persists >72 hours despite appropriate antibiotics
• Progressive neurologic deficits develop
• Spinal instability or progressive kyphosis occurs
• Abscess formation is present

Expected Clinical Timeline

• Initial symptom improvement within 5-7 days 4, 5
• More complete clinical response within 10-14 days 4, 5
• Obtain repeat blood cultures at 72 hours to document clearance 1
• Follow-up imaging at 4-6 weeks to assess bone healing 3

The minimum treatment duration is 6 weeks for hardware-associated spinal infections, regardless of symptom resolution, due to the difficulty of eradicating biofilm-associated bacteria. 1, 2, 3