Treatment of Complicated Staphylococcus Epidermidis Infection with Fosfomycin Sensitivity
For a complicated Staphylococcus epidermidis infection with documented fosfomycin sensitivity, use fosfomycin in combination with rifampin as the primary treatment regimen, following the successful approach demonstrated in prosthetic joint infections.
Treatment Approach
Primary Recommendation: Combination Therapy
Fosfomycin plus rifampin is the recommended combination for complicated S. epidermidis infections with fosfomycin sensitivity 1. This combination has demonstrated clinical success in treating methicillin-resistant S. epidermidis prosthetic infections 1.
- Fosfomycin administration: Continuous infusion via elastomeric pump (8 grams per day) provides stable drug levels and can be managed through outpatient parenteral antimicrobial therapy 1
- Rifampin: Oral administration at standard dosing (300 mg every 8 hours for adults) 2
- Duration: 4-6 weeks for complicated infections, depending on source control and clinical response 1
Alternative Combination Options
If fosfomycin-rifampin is not feasible, consider these evidence-based alternatives:
Fosfomycin plus vancomycin demonstrates additive or indifferent effects against S. epidermidis strains, with the added benefit of vancomycin nephroprotection when combined with fosfomycin 3. This combination was successfully used for 2 months in treating multidrug-resistant S. epidermidis meningitis without apparent toxicity 4.
Fosfomycin plus linezolid shows synergistic activity in vitro against resistant staphylococcal strains, though this data primarily derives from S. aureus studies 5.
Source Control Requirements
Surgical intervention is essential for complicated infections 2. This includes:
- Debridement of infected tissue 2
- Removal or replacement of prosthetic material if present 1
- Drainage of abscesses 2
Monitoring Parameters
Obtain follow-up cultures 2-4 days after initiating therapy to document clearance of infection 2, 6.
- Monitor creatine kinase if using daptomycin alternatives 7
- Assess clinical response including defervescence within 72 hours 2
- Evaluate for metastatic sites of infection 2
Important Caveats
Fosfomycin should never be used as monotherapy for complicated S. epidermidis infections due to rapid resistance development 3, 4. The combination approach is critical for treatment success.
Vancomycin intermediate susceptibility (S. epidermidis with vancomycin MIC ≥8 µg/mL) may require alternative agents such as daptomycin or linezolid if fosfomycin combinations fail 7.
For prosthetic joint infections, a two-stage revision procedure coupled with prolonged antimicrobial therapy (4-6 months total) achieves optimal outcomes 1.
When Fosfomycin is Not Available
If fosfomycin is unavailable despite documented sensitivity, follow standard complicated skin and soft tissue infection guidelines:
- Vancomycin 30-60 mg/kg/day IV in divided doses 2
- Daptomycin 4-6 mg/kg/dose IV once daily for skin infections, 6-10 mg/kg for bacteremia 2
- Linezolid 600 mg IV/PO every 12 hours 2
These agents have established efficacy against coagulase-negative staphylococci including S. epidermidis 2, 8.