What is the recommended treatment for a patient with 2 Staph (Staphylococcus) species in blood cultures?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: December 7, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Management of 2 Staphylococcus Species in Blood Cultures

Do not initiate treatment based solely on a single positive blood culture for coagulase-negative staphylococci (CoNS), as this typically represents contamination rather than true infection. 1

Initial Assessment and Culture Interpretation

The critical first step is determining whether you have true bacteremia versus contamination:

  • A single blood culture positive for CoNS should be dismissed as a contaminant if a second set of blood cultures drawn simultaneously is negative 1
  • If multiple blood cultures (≥2 separate draws) are positive for CoNS, this suggests true bacteremia requiring treatment 1
  • The presence of 2 different Staph species raises the possibility of either polymicrobial infection or mixed contamination—repeat blood cultures immediately to clarify 1

When to Treat CoNS Bacteremia

Treatment should be initiated for CoNS bacteremia only when multiple blood cultures are positive AND the patient meets specific clinical criteria: 1

  • Disease severity (hemodynamic instability, sepsis)
  • Immunosuppression status
  • Presence of indwelling central venous catheters or prosthetic devices
  • Antibacterial resistance pattern

In adults and children (excluding neonates), remove central and arterial lines if several blood cultures are positive for methicillin-resistant CoNS (MRCoNS) 1

Empirical Antibiotic Selection

If true bacteremia is confirmed and treatment is warranted, vancomycin 15-20 mg/kg IV every 8-12 hours is the first-line agent for empirical coverage of both methicillin-resistant S. aureus (MRSA) and CoNS 1, 2

Alternative IV Options if Vancomycin Cannot Be Used:

  • Daptomycin 6 mg/kg IV once daily (FDA-approved for S. aureus bacteremia; some experts recommend 8-10 mg/kg for complicated infections) 1, 3
  • Linezolid 600 mg IV twice daily (excellent alternative with proven efficacy) 1

Critical Pitfall to Avoid:

Never use vancomycin as definitive therapy if methicillin-susceptible S. aureus (MSSA) is identified—this is associated with 2-3 times higher mortality compared to beta-lactam therapy 4, 5

Definitive Therapy Based on Final Culture Results

If MSSA is Identified:

Immediately switch from vancomycin to a beta-lactam antibiotic: 4, 5

  • Nafcillin or oxacillin 2 g IV every 4 hours (preferred for serious infections) 6
  • Cefazolin 2 g IV every 8 hours (acceptable alternative) 4, 6

The empirical combination of vancomycin PLUS a beta-lactam (nafcillin, oxacillin, or cefazolin) from the outset may improve outcomes by ensuring adequate coverage regardless of methicillin susceptibility, though this increases cost and adverse event risk 5

If MRSA or MRCoNS is Confirmed:

Continue vancomycin with target trough levels of 15-20 mg/L to achieve AUC:MIC ratio ≥400 2

For MRSA with vancomycin MIC >1 mg/L, consider alternative therapy: 1

  • High-dose daptomycin 8-10 mg/kg IV once daily 1
  • Linezolid 600 mg IV twice daily 1

Treatment Duration

For uncomplicated bacteremia (no endocarditis, no prosthetic devices, negative repeat cultures at 2-4 days, defervescence within 72 hours, no metastatic infection): 1

  • Minimum 2 weeks of IV therapy

For complicated bacteremia (any of the above criteria not met): 1

  • 4-6 weeks of IV therapy depending on extent of infection

Essential Monitoring

Obtain repeat blood cultures 2-4 days after initial positive cultures and as needed thereafter to document clearance of bacteremia 1

Perform echocardiography (preferably transesophageal) for all adult patients with S. aureus bacteremia to evaluate for endocarditis 1

Conduct clinical assessment to identify and eliminate/debride the source of infection 1

Special Consideration for Neutropenic Patients

In neutropenic cancer patients, vancomycin is NOT part of standard empirical therapy for fever and neutropenia 1

Add vancomycin only if: 1

  • Hemodynamic instability or severe sepsis
  • Positive blood culture for gram-positive bacteria before final identification
  • Clinically suspected catheter-related infection
  • Known colonization with MRSA

Discontinue vancomycin after 2-3 days if susceptible bacteria are not recovered 1

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.