Empiric MRSA Coverage for High-Risk Adults
For adults at high risk, empiric MRSA coverage is recommended and should be initiated with either vancomycin (15 mg/kg IV q8-12h, targeting trough 15-20 mg/mL) or linezolid (600 mg IV q12h), based on specific risk factors and clinical context. 1
Risk Stratification: When to Cover MRSA Empirically
Hospital-Acquired and Ventilator-Associated Pneumonia
Empiric MRSA coverage is indicated if ANY of the following are present: 1
- Prior intravenous antibiotic use within 90 days (strongest predictor) 1
- Hospitalization in a unit where ≥20% of S. aureus isolates are methicillin-resistant (or prevalence unknown) 1
- High risk of mortality: need for ventilatory support due to pneumonia or septic shock 1
- For VAP specifically: septic shock at time of VAP, ARDS preceding VAP, ≥5 days of hospitalization prior to VAP, or acute renal replacement therapy prior to VAP onset 1
Community-Acquired Pneumonia Requiring ICU Admission
Empiric MRSA coverage is recommended for severe CAP defined by: 1
Important caveat: One retrospective study of 621 ICU CAP patients found no mortality benefit from empiric MRSA therapy, suggesting this recommendation may lead to overtreatment in settings with low MRSA prevalence. 2 However, the IDSA guideline recommendation takes precedence for patient safety in severe illness. 1
Skin and Soft Tissue Infections
For emergency department presentations with purulent skin infections: 3
- MRSA prevalence in U.S. emergency departments ranges from 15-74%, with an overall prevalence of 59% 3
- When antimicrobial therapy is indicated, obtain cultures and consider empiric MRSA coverage 3
Risk scoring for SSTI can guide empiric therapy: 4
- MRSA risk score ≥1 point warrants consideration of empiric coverage 4
- Risk factors (points assigned): prior MRSA infection/colonization (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, IV drug use, HIV/AIDS, diabetes with obesity (1 point each) 4
- A score of 0 has >90% negative predictive value when MRSA prevalence is ≤30%, allowing safe avoidance of empiric MRSA coverage in low-risk patients 4
Recommended Empiric Regimens
First-Line Agents for MRSA Coverage
When empiric MRSA coverage is indicated, use: 1
- Vancomycin 15 mg/kg IV q8-12h (consider loading dose of 25-30 mg/kg for severe illness), targeting trough 15-20 mg/mL 1
- OR Linezolid 600 mg IV q12h 1
For pneumonia specifically, linezolid may be preferred due to superior lung penetration compared to vancomycin, though both are acceptable first-line options. 1, 5
Combination Therapy Considerations
For HAP/VAP with high mortality risk or recent IV antibiotic use within 90 days: 1
- Add two antipseudomonal agents from different classes (avoid two β-lactams) 1
- MRSA coverage (vancomycin or linezolid) PLUS one agent from column B (piperacillin-tazobactam, cefepime, ceftazidime, imipenem, or meropenem) PLUS one from column C (fluoroquinolone, aminoglycoside, or polymyxin) 1
Critical De-escalation Strategy
Discontinue empiric MRSA coverage if: 1
Switch to targeted MSSA therapy (oxacillin, nafcillin, or cefazolin) once MSSA is confirmed to reduce risk of C. difficile infection, antibiotic resistance, and adverse effects. 6
Common Pitfalls to Avoid
- Do not continue broad empiric MRSA coverage indefinitely without culture data – this increases toxicity and resistance without improving outcomes 6
- Do not rely solely on institutional antibiograms – individual patient risk factors (especially prior IV antibiotics within 90 days) are more predictive than surveillance percentages alone 4
- Do not use clindamycin empirically if local MRSA resistance is ≥10% 1
- In low-acuity outpatient SSTI without risk factors, empiric MRSA coverage may not be necessary if MRSA risk score is 0 and local prevalence is low 4
- Recognize that 57% of patients with MRSA SSTI in emergency departments receive discordant antibiotic therapy – obtain cultures when feasible to guide therapy 3