Treatment for CRBSI with Different Cultures from Two Sites
When you have different organisms growing from two different blood culture sites in a patient with suspected CRBSI, you must first confirm whether this represents true CRBSI versus contamination or polymicrobial bacteremia from another source—obtain additional paired blood cultures (catheter hub and peripheral vein) before making treatment decisions. 1
Diagnostic Clarification Required
The presence of different organisms from two culture sites creates diagnostic uncertainty that must be resolved before proceeding with definitive treatment:
If one site shows coagulase-negative staphylococci and the other shows a different organism, obtain additional blood cultures from both the catheter hub and a peripheral vein to rule out contamination, as a single positive culture growing coagulase-negative staphylococci may represent contamination rather than true infection. 1
For definitive CRBSI diagnosis, you need the same organism growing from both a peripheral blood culture and either the catheter tip culture OR paired blood cultures meeting quantitative criteria (≥3-fold higher colony count from catheter) or differential time to positivity (≥2 hours earlier growth from catheter). 1, 2
Treatment Algorithm When Different Organisms Are Confirmed
Step 1: Initiate Empiric Broad-Spectrum Therapy Immediately
While awaiting clarification of the microbiology:
- Start vancomycin for gram-positive coverage (including MRSA) in healthcare settings with elevated MRSA prevalence. 1, 2
- Add gram-negative coverage with a fourth-generation cephalosporin, carbapenem, or β-lactam/β-lactamase inhibitor combination based on your local antibiogram. 2, 3
- Consider adding antifungal coverage (echinocandin or fluconazole) if the patient has risk factors: total parenteral nutrition, prolonged broad-spectrum antibiotics, hematologic malignancy, transplant recipient, femoral catheterization, or Candida colonization at multiple sites. 1
Step 2: Catheter Management Decision
Remove the catheter immediately if any of the following apply:
- Short-term catheters: Remove for CRBSI due to gram-negative bacilli, S. aureus, enterococci, fungi, or mycobacteria. 1, 3
- Long-term catheters: Remove for severe sepsis, suppurative thrombophlebitis, endocarditis, persistent bloodstream infection >72 hours despite appropriate therapy, or infections due to S. aureus, P. aeruginosa, fungi, or mycobacteria. 1, 2
- Any catheter type: Remove if there is purulence at the exit site, tunnel infection, or hemodynamic instability. 2, 3
Step 3: Obtain Follow-Up Cultures at 72 Hours
- Draw repeat blood cultures 72 hours after initiating appropriate antimicrobial therapy to document clearance of bacteremia. 1, 2, 3
- If cultures remain positive at 72 hours, remove the catheter (if not already removed) and extend therapy to 4-6 weeks, as this indicates complicated infection. 1, 2, 3
Pathogen-Specific Treatment Duration
Once you have clarified which organism(s) represent true CRBSI:
For Uncomplicated CRBSI (after catheter removal):
- Coagulase-negative staphylococci: 5-7 days (or 10-14 days per standard recommendation). 2
- S. aureus: Minimum 14 days. 2
- Enterococcus: 7-14 days. 2
- Gram-negative bacilli: 7-14 days (10-14 days for Klebsiella and similar organisms). 2, 3
- Candida species: 14 days after first negative blood culture. 2
For Complicated CRBSI:
- Persistent bacteremia/fungemia >72 hours after catheter removal: 4-6 weeks. 1, 2, 3
- Endocarditis or suppurative thrombophlebitis: 4-6 weeks. 1, 2
- Osteomyelitis: 4-6 weeks (pediatric) or 6-8 weeks (adults). 1
Critical Pitfalls to Avoid
- Do not assume polymicrobial CRBSI without confirming both organisms meet diagnostic criteria—one may represent contamination, especially if coagulase-negative staphylococci are involved. 1
- Do not delay catheter removal in short-term catheters with gram-negative bacilli or S. aureus, as mortality increases 5-fold when treated with antibiotics alone without removal. 1, 4
- Do not attempt catheter salvage for S. aureus, P. aeruginosa, or Candida species in any catheter type unless there are absolutely no alternative access sites. 1
- Always clean catheter hubs meticulously with alcohol, alcoholic chlorhexidine (>0.5%), or tincture of iodine before drawing blood cultures to minimize contamination. 1, 2