Treatment of Citrobacter freundii and VRE Co-Infection
For a patient with both Citrobacter freundii and vancomycin-resistant Enterococcus faecium (VRE), tigecycline 100 mg IV loading dose followed by 50 mg IV every 12 hours is the optimal single agent, as it is FDA-approved for intra-abdominal infections caused by both organisms and achieves excellent peritoneal penetration. 1
Rationale for Tigecycline as First-Line
Tigecycline is specifically FDA-approved for complicated intra-abdominal infections caused by both Citrobacter freundii and vancomycin-resistant Enterococcus faecalis (with activity against E. faecium as well), making it uniquely suited for polymicrobial infections involving both pathogens. 1
The drug achieves high penetration into the peritoneal space, making it ideal for intra-abdominal infections where both organisms are commonly encountered together. 2
Treatment duration should be 5-14 days based on clinical response and severity of infection. 1
Critical Limitation of Tigecycline
Tigecycline must NOT be used if bacteremia is present or suspected, as it achieves poor serum concentrations due to large volume of distribution and is associated with treatment failures in bloodstream infections. 2, 3
If blood cultures are positive for either organism, alternative therapy is mandatory. 2
Alternative Regimen for Bacteremia or Severe Sepsis
If the patient has bacteremia, severe sepsis, or septic shock, use combination therapy:
For VRE Component:
Linezolid 600 mg IV every 12 hours is the preferred agent for VRE bacteremia, with microbiological cure rates of 86.4% and clinical cure rates of 81.4%. 2, 3, 4
High-dose daptomycin 10-12 mg/kg IV once daily is an alternative, particularly when combined with a β-lactam (ampicillin 2 g IV every 4-6 hours or meropenem), which reduces mortality by 77% when daptomycin MIC ≤2 mg/L. 2, 3
For Citrobacter freundii Component:
Ceftazidime-avibactam 2.5 g IV every 8 hours (infused over 3 hours) is recommended for carbapenem-resistant Enterobacterales including Citrobacter species. 5
If the Citrobacter isolate is carbapenem-susceptible, meropenem 2 g IV every 8 hours (extended infusion over 3 hours) can be used. 2
Site-Specific Considerations
Uncomplicated Urinary Tract Infection:
- Fosfomycin 3 g PO single dose is first-line for uncomplicated VRE cystitis. 2, 3
- Nitrofurantoin 100 mg PO every 6 hours for 5-7 days is an effective alternative. 2, 3
- High-dose ampicillin (18-30 g IV daily in divided doses) can overcome resistance due to high urinary concentrations, even against ampicillin-resistant strains. 2, 3
Complicated Intra-Abdominal Infection Without Bacteremia:
- Tigecycline monotherapy as described above is optimal. 2, 1
- Eravacycline 1 mg/kg IV every 12 hours is an alternative with 94% clinical cure rates in complicated intra-abdominal infections, including those caused by carbapenem-resistant Enterobacterales. 2
Monitoring Requirements
Monitor creatine kinase (CK) levels at baseline and twice weekly when using high-dose daptomycin to detect rhabdomyolysis early. 3
Monitor for serotonin syndrome symptoms every 4-6 hours during the first 72 hours of linezolid therapy, especially in patients on serotonergic medications (SSRIs, SNRIs, MAOIs). 3
Obtain repeat blood cultures 72 hours after initiating therapy; persistent bacteremia mandates investigation for endocarditis, undrained abscess, or device-related infection and extension of therapy to 4-6 weeks. 3
Common Pitfalls to Avoid
Do not use tigecycline for bacteremia—this is the most critical error, as treatment failure rates are unacceptably high due to inadequate serum levels. 2, 3
Do not use standard-dose daptomycin (6 mg/kg) for VRE bacteremia; doses of 10-12 mg/kg are required for optimal outcomes. 2, 3
Differentiate colonization from true infection before initiating anti-VRE therapy, as unnecessary treatment drives resistance. 2, 3
Remove central venous catheters or other potential sources of persistent infection, as device-related infections will not clear with antibiotics alone. 3