How should I interpret a blood culture that grows two different bacterial organisms?

Interpreting Blood Cultures with Two Different Bacterial Organisms

When a blood culture grows two different bacterial organisms, this most likely represents true polymicrobial bacteremia requiring treatment of both pathogens, though contamination of one organism must be carefully excluded based on the number of positive bottles, organism identity, and clinical context.

Algorithmic Approach to Interpretation

Step 1: Assess the Number of Positive Blood Culture Bottles

The single most important factor in distinguishing true infection from contamination is how many bottles in your blood culture set grew each organism 1:

• Multiple bottles positive for the same organism → Strongly suggests true pathogen (not contamination)
• Only one bottle positive → May represent contamination, especially for skin flora
• Both organisms growing in multiple bottles → Highly likely true polymicrobial bacteremia

Step 2: Identify the Specific Organisms

Certain bacteria have vastly different probabilities of being true pathogens versus contaminants 1, 2:

High-probability pathogens (almost always treat, even if only 1 bottle positive):

• Staphylococcus aureus 3
• Escherichia coli and other Enterobacterales 3
• Pseudomonas species 3
• Candida species 3

Organisms requiring careful interpretation (often contaminants if only 1 bottle positive):

• Coagulase-negative staphylococci (CoNS): Only 3.5% chance of true infection with 1 positive bottle, but 78.9% with 3 bottles and 100% with ≥4 bottles 3
• Corynebacterium species 1
• Bacillus species (except B. anthracis) 1
• Cutibacterium acnes 4

Step 3: Apply Species-Specific Rules for Polymicrobial Cultures

If BOTH organisms are high-probability pathogens (e.g., S. aureus + E. coli):

• Treat both organisms regardless of bottle count
• This represents true polymicrobial bacteremia

If ONE organism is a high-probability pathogen and ONE is typical skin flora:

• Treat the pathogen definitively
• For the skin flora organism, apply the bottle-count rule:
  • CoNS in ≥2 bottles → likely true co-pathogen 3
  • CoNS in only 1 bottle → likely contaminant (98% negative predictive value for true infection) 5

If BOTH organisms are typical skin flora (e.g., two different CoNS species):

• Requires ≥3-4 bottles positive to confidently diagnose true infection 3
• Consider catheter-related infection if cultures drawn through vascular devices 1, 2

Step 4: Evaluate Clinical Context

Critical supporting evidence for true polymicrobial infection:

• Intra-abdominal source (peritonitis, abscess) - commonly polymicrobial
• Severe sepsis/septic shock at presentation 1
• Presence of intravascular devices (catheters) 1, 2
• Immunocompromised state
• Signs of local infection at catheter insertion site 1

Evidence suggesting contamination:

• Only one bottle positive for skin flora organism 1
• Blood drawn through catheters (higher contamination risk) 2
• Discordant results (one organism from catheter, different from peripheral) 1
• Growth detected after 48 hours (contaminants typically grow later than pathogens) 6

Common Pitfalls to Avoid

1. Don't dismiss polymicrobial bacteremia as contamination reflexively - Recent evidence shows that slow-growing anaerobes and certain organisms are genuinely underdetected in polymicrobial infections 7. True polymicrobial bacteremia occurs and carries worse outcomes.

2. Don't rely on a single blood culture set - Guidelines emphasize drawing 3-4 blood culture sets from separate sites within 24 hours specifically to distinguish pathogens from contaminants 1. If you only have one set, interpretation is much more difficult.

3. Beware of growth rate differences - Fast-growing organisms (like E. coli) can mask slower-growing organisms (like S. aureus) in polymicrobial infections. Research shows S. aureus was not detected when co-cultured with E. coli at ratios up to 25:1 8.

4. Consider catheter-related infection - Recovery of staphylococci, Corynebacterium jeikeium, Bacillus species, or Candida in multiple cultures strongly suggests intravascular device infection 1.

Practical Decision Framework

Treat both organisms if:

• ≥2 bottles positive for each organism, OR
• Either organism is S. aureus, E. coli, Pseudomonas, or Candida, OR
• Patient has severe sepsis/shock with clinical source consistent with polymicrobial infection

Treat only the more virulent organism and observe if:

• Only 1 bottle positive for typical skin flora (CoNS, diphtheroids)
• The skin flora organism is discordant (grows from catheter but not peripheral)
• Clinical picture doesn't support the second organism

Repeat blood cultures immediately if:

• Interpretation is unclear
• Only one culture set was obtained initially
• Need to establish whether skin flora represents true co-infection

The key principle: clinical judgment combined with the number of positive bottles and organism identity determines significance 1. When in doubt, err on the side of treating both organisms in critically ill patients, as polymicrobial bacteremia carries high mortality.