What is the best course of action for a patient with persistent bacteremia due to enterococcus (sensitive to ampicillin, gentamicin, linezolid, and vancomycin) and methicillin-resistant Staphylococcus aureus (MRSA) cellulitis (sensitive to clindamycin, Bactrim, and vancomycin) who is currently on ampicillin and rocephin (ceftriaxone)?

Management of Persistent Enterococcal Bacteremia with Concurrent MRSA Cellulitis

For a patient with persistent enterococcal bacteremia and MRSA cellulitis, the optimal approach is to remove any intravascular catheter if present, switch from ampicillin-ceftriaxone to ampicillin-gentamicin combination therapy for the enterococcus, and add vancomycin for MRSA coverage.

Enterococcal Bacteremia Management

Addressing Persistent Bacteremia

1. Evaluate for endocarditis

   • Persistent enterococcal bacteremia (>72 hours despite appropriate therapy) warrants evaluation for endocarditis 1
   • Consider transesophageal echocardiography (TEE), especially if the patient has:
     • New murmur or embolic phenomena
     • Prolonged bacteremia despite appropriate therapy
     • Presence of prosthetic valve or other endovascular foreign bodies 1

2. Source control

   • Remove any intravascular catheter if present, as this is strongly recommended for persistent bacteremia 1
   • If long-term catheter must be retained, implement antibiotic lock therapy in addition to systemic antibiotics 1

3. Optimize antimicrobial therapy

   • Current regimen assessment: The combination of ampicillin and ceftriaxone is not optimal for persistent bacteremia
   • Recommended change: Switch to ampicillin plus gentamicin combination
     • Ampicillin is the drug of choice for ampicillin-susceptible enterococci (A-III) 1
     • Add gentamicin for synergistic activity against enterococci 1, 2
     • Dosing: Ampicillin 2g IV every 4 hours plus gentamicin 15 mg/kg/day IV in 2-3 divided doses 2

4. Alternative options if aminoglycoside cannot be used:

   • For aminoglycoside-resistant enterococci, ampicillin-ceftriaxone is reasonable (Class IIa; Level of Evidence B) 1, 2
   • Linezolid 600 mg IV/PO every 12 hours is an option for vancomycin-resistant enterococci 2, 3
   • Daptomycin 8-12 mg/kg IV daily is another alternative for resistant strains 2

MRSA Cellulitis Management

1. Optimal antibiotic selection

   • Vancomycin is the preferred agent for MRSA cellulitis with concurrent bacteremia
   • Although the isolate is sensitive to clindamycin and Bactrim, vancomycin is preferred when treating concurrent bacteremia

2. Alternative options:

   • Linezolid could be considered as it has activity against both MRSA and enterococci, but should not be used empirically when bacteremia is confirmed 1

Integrated Treatment Approach

1. Recommended regimen:

   • Ampicillin (for enterococcus) + gentamicin (for synergy against enterococcus) + vancomycin (for MRSA)
   • Discontinue ceftriaxone as it has limited activity against enterococci and MRSA

2. Duration of therapy:

   • For uncomplicated enterococcal bacteremia: 7-14 days 1
   • If endocarditis is confirmed: 4-6 weeks 1, 2
   • For MRSA cellulitis with bacteremia: minimum 14 days

3. Monitoring:

   • Follow-up blood cultures to confirm clearance of bacteremia
   • Weekly monitoring of renal function when using aminoglycosides 2
   • Target gentamicin levels: 1-hour concentration of ~3 μg/mL and trough <1 μg/mL 2

Important Considerations

• The combination of ampicillin and gentamicin has been shown to be more effective than monotherapy when treating enterococcal bloodstream infections 1
• If the patient has risk factors for endocarditis or persistent bacteremia despite 72 hours of appropriate therapy, consider TEE 1
• Ceftriaxone alone has poor activity against enterococci due to intrinsic resistance to cephalosporins 2
• Monitor for nephrotoxicity with aminoglycoside therapy, especially if combined with vancomycin

Pitfalls to Avoid

• Do not continue ceftriaxone for enterococcal infections as enterococci have intrinsic resistance to most cephalosporins
• Do not rely on ceftriaxone for MRSA coverage as it has poor activity against MRSA
• Avoid delaying removal of intravascular catheters in persistent bacteremia
• Do not miss the opportunity to evaluate for endocarditis in persistent enterococcal bacteremia