What antibiotics are appropriate for empiric treatment of coagulase‑negative Staphylococcus infections?

Antibiotics for Coagulase-Negative Staphylococcus Infections

For empiric treatment of suspected coagulase-negative Staphylococcus (CoNS) infections, vancomycin is the first-line antibiotic, given that the majority of CoNS isolates are methicillin-resistant. 1

Key Clinical Context

Coagulase-negative staphylococci are weak pathogens that rarely cause rapid clinical deterioration, so there is usually no urgent need to initiate vancomycin empirically at the time of fever unless specific high-risk features are present. 2 A single positive blood culture for CoNS should generally be dismissed as a contaminant if subsequent cultures are negative. 2

Empiric Antibiotic Selection

When to Cover CoNS Empirically

Vancomycin should be added to the empiric regimen in the following specific circumstances: 2

• Hemodynamic instability or severe sepsis
• Clinically suspected serious catheter-related infection (chills, rigors with catheter infusion, cellulitis around catheter site)
• Positive blood culture for gram-positive cocci before final identification
• Skin or soft-tissue infection at any site
• Pneumonia documented radiographically

Dosing for Empiric Coverage

• Vancomycin: 30–60 mg/kg/day IV in 2–4 divided doses, targeting trough concentrations of 15–20 µg/mL for serious infections 1
• Alternative: Daptomycin 6 mg/kg IV once daily for MRSA coverage while awaiting culture results 1

Definitive Therapy After Susceptibility Results

Methicillin-Susceptible CoNS

Switch immediately to cefazolin or an anti-staphylococcal penicillin (nafcillin, oxacillin, flucloxacillin) once methicillin susceptibility is confirmed. 3, 4 Beta-lactam agents are superior to vancomycin for methicillin-susceptible organisms. 5

• Cefazolin is preferred over anti-staphylococcal penicillins due to comparable efficacy with better safety profile 1
• First-generation cephalosporins (cefazolin, cephalexin) are effective alternatives 3, 4

Methicillin-Resistant CoNS (Most Common)

Continue vancomycin as the treatment of choice for confirmed methicillin-resistant CoNS. 3, 4

• Vancomycin: 30–60 mg/kg/day IV (target trough 15–20 µg/mL) 1
• Alternative: Teicoplanin where available 3
• Alternative: Linezolid 600 mg IV/PO twice daily for serious infections 6, 7
• Alternative: Daptomycin 6 mg/kg IV once daily 6, 7

Catheter-Related CoNS Bloodstream Infection

Remove the implicated catheter and treat with vancomycin for 5–7 days for uncomplicated catheter-related infection. 1 True CoNS infection (versus contamination) is suggested by multiple positive blood cultures, quantitative catheter cultures ≥100 CFU/mL, or differential time to positivity >2 hours. 1

Treatment Duration

• Uncomplicated catheter-related CoNS bacteremia: 5–7 days after catheter removal 1
• Prosthetic device infection: Prolonged therapy (often weeks) with device removal generally required 3
• If vancomycin was added empirically but CoNS is not confirmed: Discontinue after 2–3 days if susceptible bacteria are not recovered 2

Special Populations

Neutropenic Patients with Cancer

Vancomycin is not a standard part of empirical therapy for fever and neutropenia, even though CoNS are the most common cause of bacteremia in this population. 2 CoNS rarely cause rapid deterioration in neutropenic patients, so empiric vancomycin can be safely withheld unless high-risk features are present. 2

Hospital-Acquired Infections

In settings where MRSA prevalence among S. aureus isolates is >20%, or when CoNS infection is suspected, empiric vancomycin coverage is warranted. 2 The 20% threshold balances effective initial therapy against risks of excessive antibiotic use. 2

Renal Dosing

For creatinine clearance <30 mL/min: Adjust vancomycin dosing based on serum levels; give daptomycin 6 mg/kg every 48 hours. 1

Critical Pitfalls to Avoid

• Do not continue vancomycin if methicillin-susceptible CoNS is confirmed—switch to beta-lactam therapy for superior outcomes 1, 5
• Do not treat a single positive blood culture for CoNS without confirming with repeat cultures—this is likely contamination 2
• Catheter removal alone is insufficient—systemic antibiotics remain required after device extraction 1
• Never use cefazolin for methicillin-resistant CoNS—it lacks activity against resistant strains 1
• Obtain follow-up blood cultures 2–4 days after therapy initiation to document clearance 1