What are the most appropriate antibiotics for a patient with a Staphylococcus aureus (S. aureus) infection?

Most Appropriate Antibiotics for Staphylococcus aureus Infections

The choice of antibiotic for S. aureus depends critically on methicillin susceptibility and infection site: use cefazolin or nafcillin/oxacillin for methicillin-susceptible S. aureus (MSSA), and vancomycin or daptomycin for methicillin-resistant S. aureus (MRSA). 1, 2

Initial Approach: Determine Methicillin Susceptibility

• Obtain blood cultures and site-specific cultures before initiating antibiotics to guide definitive therapy based on susceptibility results 1, 2
• Start empirical therapy covering MRSA if the patient has risk factors including: intravascular devices, recent hospitalization, injection drug use, diabetes, previous MRSA infection, or severe systemic illness 1, 2
• De-escalate to MSSA-targeted therapy once susceptibilities confirm methicillin susceptibility to optimize outcomes and reduce resistance 2, 3

Skin and Soft Tissue Infections (SSTIs)

Simple Cutaneous Abscesses

• Incision and drainage is the primary treatment; antibiotics may not be necessary for simple abscesses 1
• Add antibiotics if: multiple infection sites, rapid progression with cellulitis, systemic illness signs, immunosuppression, extremes of age, difficult-to-drain locations (face, hand, genitalia), or failure of drainage alone 1

Outpatient Purulent SSTIs (with drainage/exudate)

Empirical MRSA coverage is recommended pending cultures 1:

• Clindamycin 300-450 mg PO three times daily (first-line if local resistance <10%) 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily 1
• Doxycycline 100 mg PO twice daily (avoid in children <8 years) 1, 4
• Linezolid 600 mg PO twice daily (reserve for severe cases or multiple drug intolerance) 1
• Duration: 5-10 days based on clinical response 1

Outpatient Nonpurulent Cellulitis

• Empirical therapy targeting β-hemolytic streptococci with a β-lactam (e.g., cephalexin) 1
• Add MRSA coverage only if: no response to β-lactam therapy or systemic toxicity present 1

Hospitalized Patients with Complicated SSTIs

Empirical IV therapy for MRSA should be initiated 1:

• Vancomycin 30-60 mg/kg/day IV divided every 6-12 hours (target trough 15-20 mcg/mL for serious infections) 1
• Daptomycin 4 mg/kg IV once daily 1, 5
• Linezolid 600 mg IV/PO twice daily 1
• Telavancin 10 mg/kg IV once daily 1
• Duration: 7-14 days with surgical debridement as needed 1

Bacteremia and Endocarditis

Uncomplicated Bacteremia (no endocarditis, no metastatic foci)

For MSSA 2, 3:

• Cefazolin 2 g IV every 8 hours (preferred over vancomycin for MSSA) 2
• Nafcillin or oxacillin 2 g IV every 4 hours 2, 3
• Duration: Minimum 2 weeks 1, 2

For MRSA 1, 2:

• Vancomycin 30-60 mg/kg/day IV divided every 6-12 hours (target trough 15-20 mcg/mL) 1
• Daptomycin 6 mg/kg IV once daily (preferred if vancomycin MIC >1 mg/L) 1, 5, 2
• Duration: Minimum 2 weeks 1, 2

Complicated Bacteremia (persistent fever, metastatic infection, or endocarditis)

For MSSA endocarditis 2, 3:

• Nafcillin or oxacillin 2 g IV every 4 hours for 4-6 weeks 2, 3
• Cefazolin 2 g IV every 8 hours for 4-6 weeks (alternative) 2

For MRSA endocarditis 1, 2:

• Vancomycin 30-60 mg/kg/day IV divided every 6-12 hours for 4-6 weeks 1
• Daptomycin 6-10 mg/kg IV once daily for 4-6 weeks (higher doses for endocarditis) 1, 5, 2
• Do NOT add gentamicin or rifampin to vancomycin for uncomplicated bacteremia (no proven benefit, increased toxicity) 1, 6

Prosthetic Valve Endocarditis

• Vancomycin 30-60 mg/kg/day IV + rifampin 300 mg PO every 8 hours for 6 weeks minimum 1
• Consider adding gentamicin 1 mg/kg IV every 8 hours for first 2 weeks only if valve retention planned 1

Pneumonia

For MRSA pneumonia 1, 3:

• Vancomycin 30-60 mg/kg/day IV divided every 6-12 hours (target trough 15-20 mcg/mL) 1
• Linezolid 600 mg IV/PO twice daily (may have superior lung penetration) 1, 3
• Duration: 7-21 days depending on severity and clinical response 1

Pediatric Considerations

Dosing Adjustments by Age

For SSTIs 1:

• Ages 12-17 years: Daptomycin 5 mg/kg IV once daily 1, 5
• Ages 7-11 years: Daptomycin 7 mg/kg IV once daily 1, 5
• Ages 2-6 years: Daptomycin 9 mg/kg IV once daily 1, 5
• Ages 1-<2 years: Daptomycin 10 mg/kg IV once daily 1, 5

For bacteremia 1, 5:

• Ages 12-17 years: Daptomycin 7 mg/kg IV once daily 1, 5
• Ages 7-11 years: Daptomycin 9 mg/kg IV once daily 1, 5
• Ages 1-6 years: Daptomycin 12 mg/kg IV once daily 1, 5

Important Pediatric Restrictions

• Never use tetracyclines (doxycycline, minocycline) in children <8 years of age 1, 4
• Administer daptomycin by 30-minute infusion in ages 7-17 years, and 60-minute infusion in ages 1-6 years (never as 2-minute push in pediatrics) 5
• Vancomycin 15 mg/kg/dose IV every 6 hours is recommended for hospitalized children with complicated SSTIs 1

Renal Impairment Dosing

For adults with CrCl <30 mL/min 1, 5:

• Vancomycin: Use standard dosing with close monitoring of trough levels and renal function 1
• Daptomycin: Reduce to every 48 hours dosing (4 mg/kg for SSTI, 6 mg/kg for bacteremia) 5
• Administer daptomycin after hemodialysis on dialysis days 5
• Doxycycline requires no dose adjustment in renal impairment (safe even with GFR 61 mL/min) 4

Critical Pitfalls to Avoid

• Never use rifampin as monotherapy or add it to vancomycin for simple SSTIs or uncomplicated bacteremia (rapid resistance development, no proven benefit) 1, 6
• Do not add gentamicin to vancomycin for uncomplicated bacteremia (increases nephrotoxicity without improving outcomes) 1, 6
• Always perform transesophageal echocardiography in patients with persistent bacteremia (≥48 hours), persistent fever, or implantable cardiac devices to rule out endocarditis 2, 7
• Switch from vancomycin to cefazolin or nafcillin immediately once MSSA is confirmed (β-lactams have superior efficacy for MSSA) 2, 3
• Do not use daptomycin for pneumonia (inactivated by pulmonary surfactant) 3
• Ensure adequate source control including removal of infected devices, drainage of abscesses, and surgical debridement—antibiotics alone are insufficient 1, 2