Should we change the current antibiotic regimen of vancomycin (Vanco) and cefepime for a patient with a synovial aspirate positive for Methicillin-Susceptible Staphylococcus aureus (MSSA) and Pseudomonas, given that the MSSA is susceptible to vancomycin and oxacillin?

Switch to Oxacillin or Cefazolin for MSSA and Continue Cefepime for Pseudomonas

Yes, you should change the antibiotic regimen by de-escalating from vancomycin to oxacillin, nafcillin, or cefazolin for the MSSA component while continuing cefepime for Pseudomonas coverage. This targeted approach improves outcomes for MSSA infections while maintaining appropriate coverage for the polymicrobial infection.

Rationale for De-escalation from Vancomycin

• Vancomycin is inferior to beta-lactams for MSSA infections. Multiple studies demonstrate significantly worse outcomes when vancomycin is used to treat MSSA compared to antistaphylococcal penicillins or first-generation cephalosporins 1, 2.

• In hemodialysis patients with MSSA bacteremia, vancomycin use was independently associated with treatment failure (odds ratio 3.53) compared to cefazolin, with failure rates of 31.2% versus 13% 1.

• A propensity-matched cohort study found MSSA bacteremia-related mortality was 37% with vancomycin versus 18% with beta-lactam treatment, with vancomycin showing an adjusted odds ratio of 3.3 for mortality 2.

• The IDSA explicitly states that oxacillin, nafcillin, or cefazolin are preferred agents for treatment of proven MSSA due to superior outcomes 3, 4.

Optimal Regimen for Your Polymicrobial Infection

Recommended regimen: Oxacillin/nafcillin OR cefazolin PLUS cefepime

• Since you have both MSSA (in synovial fluid) and Pseudomonas, you need dual coverage 4.

• Cefazolin (2 g IV q8h) or an antistaphylococcal penicillin (oxacillin/nafcillin) should replace vancomycin for the MSSA component once susceptibilities confirm MSSA 4, 5.

• Continue cefepime for Pseudomonas coverage, as it provides appropriate antipseudomonal activity 4, 6.

• Cefepime alone does NOT provide optimal MSSA coverage compared to dedicated antistaphylococcal agents, despite having some activity against MSSA 3.

Clinical Decision Algorithm

Step 1: Confirm susceptibilities

• MSSA susceptible to oxacillin ✓
• Pseudomonas susceptibilities to cefepime (assumed covered based on current regimen)

Step 2: De-escalate MSSA coverage

• Discontinue vancomycin
• Start cefazolin 2 g IV q8h (preferred for ease of dosing) OR oxacillin/nafcillin 4, 1

Step 3: Maintain Pseudomonas coverage

• Continue cefepime at appropriate dosing (typically 2 g IV q8h) 4, 6

Step 4: Source control

• Ensure adequate drainage/debridement of the infected joint 5
• Remove any prosthetic material if present 5

Common Pitfalls to Avoid

• Do not continue vancomycin for MSSA "because it's working" – the data clearly show inferior outcomes compared to beta-lactams, even when vancomycin appears clinically effective 1, 2.

• Do not rely on cefepime alone for MSSA coverage – while cefepime has some MSSA activity, it is not a preferred agent and guidelines recommend dedicated antistaphylococcal therapy 3, 4.

• Do not use monotherapy – you have a polymicrobial infection requiring coverage of both pathogens 4.

• Ensure adequate source control – septic arthritis requires drainage, and failure to achieve source control is independently associated with treatment failure 1, 5.

Duration and Monitoring

• Duration depends on the site of infection: septic arthritis typically requires 3-4 weeks of IV antibiotics, with longer courses if osteomyelitis is present 5.

• Monitor clinical response including fever curve, inflammatory markers, and repeat imaging/aspiration as clinically indicated 5.

• Follow-up blood cultures should be obtained if bacteremia was present to document clearance 5.