What is the appropriate treatment regimen for a patient with a catheter-related bloodstream infection due to Enterococcus faecalis and Enterobacter cloacae, considering the use of Ceftazidime?

Treatment of Catheter-Related Bloodstream Infection Due to Enterococcus faecalis and Enterobacter cloacae

Ceftazidime is inappropriate for treating Enterococcus faecalis in this polymicrobial catheter-related bloodstream infection, as cephalosporins have no activity against enterococci; you must use ampicillin (or vancomycin if resistant) for E. faecalis combined with a third- or fourth-generation cephalosporin like ceftazidime or cefepime specifically for the Enterobacter cloacae. 1

Immediate Catheter Management

Remove the catheter immediately given the polymicrobial nature of this infection involving both gram-positive (E. faecalis) and gram-negative (E. cloacae) organisms. 1, 2

• Short-term catheters infected with enterococci should always be removed 1, 2
• Polymicrobial infections, particularly those involving both enterococci and gram-negative bacilli, have higher failure rates with catheter retention 1
• For long-term catheters, removal is mandatory when there is sepsis, persistent bacteremia, or complicated infection 1, 2

Antimicrobial Regimen

For Enterococcus faecalis:

• Ampicillin is the drug of choice for ampicillin-susceptible E. faecalis 1, 2
• Use vancomycin only if the isolate is ampicillin-resistant 1, 2
• Consider combination therapy with ampicillin plus gentamicin if attempting catheter salvage (long-term catheter only), as this combination is significantly more effective than monotherapy when catheters remain in situ 1, 2, 3

For Enterobacter cloacae:

• Use ceftazidime (third-generation) or cefepime (fourth-generation cephalosporin) for empirical coverage of gram-negative bacilli including Enterobacter species 1
• Ceftazidime is specifically recommended for severely ill or immunocompromised patients with suspected catheter-related bloodstream infection involving enteric gram-negative bacilli 1
• Adjust therapy based on susceptibility results, as Enterobacter species can develop resistance to third-generation cephalosporins during therapy 1

Critical Pitfall to Avoid:

Never use ceftazidime alone or as monotherapy for this infection - it has zero activity against Enterococcus species. 4 The FDA label for ceftazidime lists activity against gram-negative bacteria (Enterobacter, E. coli, Klebsiella, Pseudomonas) and some gram-positive organisms (S. aureus, Streptococcus species), but enterococci are notably absent from this list. 4

Duration of Therapy

For Uncomplicated Infection (catheter removed, no metastatic complications):

• 10-14 days of antimicrobial therapy for both organisms 1, 2
• Ensure clinical stability and negative follow-up blood cultures before discontinuation 1, 2

For Complicated Infection:

• 4-6 weeks of therapy if there is persistent bacteremia after catheter removal, evidence of endocarditis, or septic thrombosis 1
• 6-8 weeks if osteomyelitis develops 1

Monitoring for Complications

Mandatory Assessments:

• Obtain follow-up blood cultures at 72 hours after initiating appropriate therapy to document clearance 1, 2, 5
• Perform transesophageal echocardiography (TEE) if: 1, 2
  • New cardiac murmur or embolic phenomena develop
  • Bacteremia or fever persists >72 hours despite appropriate antibiotics
  • Patient has prosthetic valve or other endovascular foreign bodies
  • Radiographic evidence of septic pulmonary emboli appears

High-Risk Features:

• Enterococcal bacteremia persisting >4 days is independently associated with increased mortality 1, 2
• The risk of endocarditis with enterococcal catheter-related bloodstream infection is relatively low (1.5%), but persistent bacteremia warrants TEE evaluation 1

Special Considerations for This Polymicrobial Infection

The combination of enterococci with gram-negative bacilli creates unique challenges:

• Both organisms form biofilms on catheter surfaces, making eradication without removal extremely difficult 6, 7
• Enterobacter species can develop resistance during therapy through inducible chromosomal AmpC β-lactamases 1
• Do not attempt catheter salvage with this polymicrobial combination - the success rate is unacceptably low 3, 8

If Catheter Salvage Were Attempted (Long-Term Catheter Only)

This approach has poor outcomes with polymicrobial infections, but if absolutely necessary due to lack of alternative vascular access:

• Antibiotic lock therapy must be added to systemic antibiotics 1, 2, 5
• Use combination therapy: ampicillin + gentamicin for E. faecalis plus ceftazidime for E. cloacae 1, 2, 3
• Remove catheter immediately if bacteremia persists >72 hours despite appropriate therapy 1, 2, 5
• Success rate with catheter retention for enterococcal infection is only 38% compared to 83% with removal 3

Resistance Considerations

• Check susceptibilities immediately and adjust therapy accordingly 1
• For vancomycin-resistant E. faecalis: use linezolid or daptomycin based on susceptibility 1, 2
• For extended-spectrum β-lactamase (ESBL)-producing Enterobacter: switch from ceftazidime to a carbapenem (meropenem or imipenem) 1
• If multidrug-resistant gram-negative pathogen is suspected, consider dual gram-negative coverage initially, then de-escalate based on culture results 1