What is the treatment and duration of therapy for coagulase-negative staph (CoNS) infections?

Treatment and Duration of Therapy for Coagulase-Negative Staphylococcal Infections

For coagulase-negative staphylococcal (CoNS) infections, vancomycin remains the empiric antibiotic of choice, with treatment duration ranging from 5-7 days for catheter-removed infections to 10-14 days for catheter-retained infections, and up to 6 weeks for prosthetic valve endocarditis. 1

Initial Antibiotic Selection

• Start empiric therapy with vancomycin 30-60 mg/kg/day IV in 2-4 divided doses, targeting trough levels of 10-15 mg/L 1
• Once susceptibility results confirm oxacillin susceptibility, switch to a semisynthetic penicillin (nafcillin or oxacillin) as beta-lactams are superior to vancomycin when the organism is susceptible 1
• Vancomycin remains appropriate empiric therapy despite concerns about MIC creep, as recent data shows vancomycin MICs have actually decreased over time and clinical outcomes remain favorable 2, 3

Treatment Duration Based on Clinical Scenario

Catheter-Related Bloodstream Infections (Most Common CoNS Infection)

If catheter is removed:

• 5-7 days of systemic antibiotic therapy for uncomplicated infections 1
• Most patients have a benign clinical course with fever alone or exit site inflammation 1

If nontunneled catheter is retained:

• 10-14 days of systemic antibiotic therapy PLUS antibiotic lock therapy when intraluminal infection is suspected 1
• This approach is only appropriate for uncomplicated infections without persistent bacteremia 1

If tunneled catheter or implantable device is retained:

• 7 days of systemic therapy PLUS 14 days of antibiotic lock therapy 1
• Catheter retention should only be attempted in uncomplicated cases without septic thrombosis or metastatic infection 1

Indications for Mandatory Catheter Removal

Remove the catheter immediately if any of the following are present: 1

• Persistent fever after 72 hours of appropriate antibiotics
• Persistent positive blood cultures after 72 hours
• Septic thrombophlebitis
• Endocarditis
• Tunnel infection or port pocket infection
• Relapse of infection after antibiotic discontinuation

Endocarditis Due to CoNS

Native Valve Endocarditis

• Vancomycin 30 mg/kg/24h IV divided into 2 doses for 4-6 weeks 1
• Add gentamicin 3 mg/kg/24h IV for the first 3-5 days only 1
• Note: CoNS typically produce more protracted valve infections compared to S. aureus, except for S. lugdunensis which behaves more aggressively 1

Prosthetic Valve Endocarditis

• Vancomycin 30 mg/kg/24h IV divided into 2 doses for 6 weeks 1
• PLUS rifampin 900 mg/24h IV divided into 3 doses for 6-8 weeks 1
• PLUS gentamicin 3 mg/kg/24h IV for the first 2 weeks 1
• Rifampin is added after 3-5 days once bacteremia has cleared, based on its synergy against dormant bacteria within biofilm 1

Special Considerations for Oxacillin-Susceptible CoNS

• If susceptibility testing reveals oxacillin susceptibility, replace vancomycin with oxacillin (same dosing as for MSSA: 8-12 g/24h IV divided into 3-4 doses) 1
• This switch improves outcomes as beta-lactams are more effective than vancomycin for susceptible organisms 1

Pharmacodynamic Targets for Vancomycin

• For serious CoNS bloodstream infections, target an AUC24 ≥ 424 mg/L·h (when median MIC is 1 mg/L) or AUC24/MIC ≥ 373 4
• Trough-based monitoring should target 10-15 mg/L for most CoNS infections, though some experts recommend 15-20 mg/L for endocarditis (similar to S. aureus) 1
• Early treatment initiation within 24 hours is associated with the greatest chance of bacteriological cure 4

Common Pitfalls and Caveats

• Do not use combination therapy (vancomycin plus gentamicin or rifampin) for routine CoNS bacteremia—this is not recommended and increases toxicity without benefit 1
• Do not continue vancomycin if the organism is oxacillin-susceptible—excessive vancomycin use selects for vancomycin-resistant organisms 1
• Biofilm-embedded CoNS infections (such as those on prosthetic material) demonstrate inadequate bacterial killing even at high vancomycin exposures (AUC24/MIC of 260-354), and may require device removal or alternative therapy 4
• S. lugdunensis is always methicillin-susceptible and should be treated with cloxacillin, but it behaves more aggressively than other CoNS species 1
• Approximately 58-78% of CoNS isolates are oxacillin-resistant, making vancomycin appropriate empiric therapy while awaiting susceptibilities 2