What is the recommended treatment for coagulase-negative staphylococcus (CoNS) infections?

Treatment of Coagulase-Negative Staphylococcus (CoNS) Infections

For CoNS infections, treatment depends critically on whether a prosthetic device is involved: vancomycin is the cornerstone of therapy for prosthetic valve endocarditis (requiring 6 weeks with rifampin and gentamicin), while native valve infections require vancomycin for 4-6 weeks, and single positive blood cultures often represent contamination rather than true infection. 1, 2

Initial Assessment and Clinical Significance

Before initiating treatment, determine if the CoNS represents true infection versus contamination:

• Single positive blood culture with CoNS likely represents contamination, especially if other cultures are negative 2
• True infection indicators include: multiple positive cultures, presence of prosthetic material (valves, joints, catheters), clinical signs of infection, and elevated inflammatory markers 3
• PCR detection of Staphylococcus species warrants empiric vancomycin while awaiting full susceptibility results 2

Treatment by Infection Type

Prosthetic Valve Endocarditis (PVE)

The recommended regimen is vancomycin 30 mg/kg/24h IV divided into 2 doses for ≥6 weeks, PLUS rifampin 900 mg/24h IV/PO in 3 divided doses for 6-8 weeks, PLUS gentamicin 3 mg/kg/24h IV in 2-3 divided doses for the first 2 weeks. 1

Key considerations for PVE:

• Vancomycin trough levels should be 10-20 μg/mL for serious infections 1, 4
• Rifampin should be added after 3-5 days of effective antibiotic therapy once bacteremia has cleared, due to antagonistic effects against planktonic bacteria but synergy against biofilm-embedded organisms 1
• If gentamicin resistance is present, substitute with a susceptible aminoglycoside or consider a fluoroquinolone if the isolate is susceptible 1
• Oxacillin-susceptible CoNS can be treated with oxacillin/nafcillin instead of vancomycin (12 g/24h IV in 6 divided doses), combined with rifampin and gentamicin using the same duration 1

Native Valve Endocarditis (NVE)

Vancomycin 30 mg/kg/24h IV divided into 2 doses for 4-6 weeks is recommended, with gentamicin 3 mg/kg/24h for the first 3-5 days only. 1

Important distinctions from PVE:

• Aminoglycosides are no longer recommended beyond 3-5 days in native valve infections due to increased renal toxicity without proven benefit 1
• Rifampin is NOT routinely added for native valve CoNS endocarditis 1
• Duration is shorter (4-6 weeks vs 6-8 weeks for PVE) 1

Prosthetic Joint Infections (PJI)

For staphylococcal PJI with retained hardware, use 2-6 weeks of IV vancomycin (15 mg/kg every 12h) combined with rifampin 300-450 mg PO twice daily, followed by rifampin plus an oral companion drug (ciprofloxacin or levofloxacin preferred) for a total of 3 months. 1

• Vancomycin trough targets may be lower (≥10 μg/mL) when rifampin or vancomycin-impregnated spacers are used, rather than the 15-20 μg/mL target for other serious infections 1
• Alternative oral companions to fluoroquinolones include cotrimoxazole, minocycline/doxycycline, or cephalexin if susceptibility, allergies, or intolerances preclude quinolone use 1

Catheter-Related Bloodstream Infections

Remove the infected catheter and treat with vancomycin for 5-7 days for uncomplicated infections, or 4-6 weeks if complicated by endocarditis or persistent bacteremia. 3

• Obtain blood cultures 2-4 days after initial positive cultures to document clearance of bacteremia 4
• Perform echocardiography if bacteremia persists beyond 72 hours or if there are signs of endocarditis 4, 2

Vancomycin Dosing and Monitoring

Standard vancomycin dosing is 15-20 mg/kg/dose IV every 8-12 hours (not exceeding 2g per dose), with target trough concentrations of 15-20 μg/mL for serious infections like endocarditis. 4, 5

Critical dosing considerations:

• For critically ill patients with normal renal function, doses of at least 1g IV every 8 hours are needed to achieve therapeutic troughs 5
• Recent evidence for CoNS bloodstream infections suggests an AUC₂₄ ≥424 mg/L·h or AUC₂₄/MIC ≥373 improves clinical outcomes 6
• Monitor vancomycin levels weekly and adjust based on renal function 1
• Peak levels should be 30-45 mg/mL when monitoring is performed 1 hour after infusion completion 1

Resistance Patterns and Alternative Agents

CoNS demonstrate high resistance to penicillin G, oxacillin, and erythromycin (>70%), medium resistance to tetracycline, clindamycin, and fluoroquinolones (30-70%), and low resistance to rifampin, gentamicin, and vancomycin (<30%). 7

Emerging concerns:

• Teicoplanin-non-susceptible strains are increasing (4.5% to 6.7%) and may harbor inducible vancomycin resistance 7
• Vancomycin MIC ≥1.5 mg/L is associated with higher mortality even when technically susceptible 1
• For biofilm-embedded CoNS infections, vancomycin may be inadequate even at AUC₂₄/MIC ratios of 260-354, and alternative therapy should be considered 6

Common Pitfalls to Avoid

• Do not treat single positive blood cultures for CoNS without additional evidence of true infection, as this likely represents contamination 2
• Do not continue empiric vancomycin if repeat cultures are negative for resistant gram-positive organisms 2
• Do not omit rifampin in prosthetic valve endocarditis, as it is essential for biofilm penetration 1
• Do not add rifampin immediately—wait 3-5 days until bacteremia clears to avoid antagonism 1
• Do not fail to obtain follow-up blood cultures to document clearance of bacteremia 4
• Do not use prolonged aminoglycosides in native valve endocarditis beyond 3-5 days due to nephrotoxicity 1
• Retest antibiotic susceptibilities on organisms recovered from surgical specimens or relapsed bacteremia, as resistance patterns can change during therapy 1

Special Populations

For pediatric patients, vancomycin dosing is 15 mg/kg/dose IV every 6 hours, not exceeding adult doses. 4

For penicillin-allergic patients with oxacillin-susceptible CoNS, first-generation cephalosporins or vancomycin may be substituted, though penicillin desensitization can be attempted in stable patients. 1, 2