What is the initial approach to treating suspected or confirmed Staphylococcus (Staph) aureus infections?

Initial Treatment of Staphylococcus aureus Infections

For suspected or confirmed S. aureus infections, initiate empiric therapy with vancomycin or an anti-MRSA agent in hospitalized patients or those with severe disease, then narrow to beta-lactams (nafcillin, oxacillin, or cefazolin) once methicillin-susceptible S. aureus (MSSA) is confirmed. 1, 2, 3, 4

Empiric Therapy Selection

For Hospitalized or Severe Infections

• Start vancomycin 15-20 mg/kg IV every 8-12 hours as first-line empiric therapy when MRSA prevalence is significant or resistance status is unknown 1, 2, 3
• Vancomycin is indicated for serious or severe infections caused by suspected methicillin-resistant (β-lactam-resistant) staphylococci and is effective for staphylococcal endocarditis, septicemia, bone infections, lower respiratory tract infections, and skin/soft tissue infections 3
• Linezolid 600 mg IV twice daily is an equally effective alternative to vancomycin for MRSA coverage 2, 5
• Daptomycin is another option, with phase 3 trials demonstrating noninferiority to standard care (treatment success 44% vs 42%) and ceftobiprole showing noninferiority to daptomycin (70% vs 69% treatment success) 4

For Outpatient Skin and Soft Tissue Infections

• For purulent infections (abscesses, furuncles), incision and drainage is the primary treatment—antibiotics are adjunctive 6, 5
• Clindamycin 600 mg PO three times daily is first-line oral therapy if local resistance rates are <10%, as it covers both MRSA and streptococci as monotherapy 2, 5
• Trimethoprim-sulfamethoxazole (TMP-SMX) is an excellent alternative for MRSA coverage but requires addition of a beta-lactam (amoxicillin) for streptococcal coverage in non-purulent cellulitis 6, 5
• Doxycycline or minocycline are effective alternatives, also requiring beta-lactam addition for streptococcal coverage 5

Definitive Therapy Based on Susceptibility

For Methicillin-Susceptible S. aureus (MSSA)

• Switch to cefazolin or antistaphylococcal penicillins (nafcillin, oxacillin) once MSSA is confirmed 1, 7, 4
• Beta-lactams are the mainstay of treatment for MSSA infections and should replace vancomycin to avoid unnecessary broad-spectrum coverage 8, 7

For Methicillin-Resistant S. aureus (MRSA)

• Continue vancomycin, daptomycin, or ceftobiprole for confirmed MRSA 7, 4
• For community-acquired MRSA with susceptibility data, oral options include clindamycin, TMP-SMX, or doxycycline based on local resistance patterns 6, 5, 8

Critical Clinical Decisions

When to Use Antibiotics for Skin Infections

Antibiotics are indicated when there is: 5

• Severe or extensive disease involving multiple sites
• Rapid progression with associated cellulitis
• Signs of systemic illness (fever, tachycardia, hypotension)
• Immunosuppression or comorbidities (diabetes, HIV)
• Extremes of age
• Difficult-to-drain locations (face, hand, genitalia)
• Lack of response to drainage alone

Duration of Therapy

• Uncomplicated skin/soft tissue infections: 5-10 days based on clinical response 6, 5
• Uncomplicated bacteremia without complications: 10-14 days for pathogens other than coagulase-negative staphylococci 1
• Complicated infections with endocarditis or septic thrombosis: 4-6 weeks 1
• Osteomyelitis: 6-8 weeks 1
• Respiratory infections: 7-14 days individualized based on clinical response 2

Essential Diagnostic Steps

• Obtain cultures (blood, tracheal secretions, wound) before starting antibiotics to confirm S. aureus and determine antimicrobial susceptibility 2, 3
• All patients with S. aureus bacteremia require transthoracic echocardiography; transesophageal echocardiography should be performed in high-risk patients with persistent bacteremia, persistent fever, metastatic infection foci, or implantable cardiac devices 4
• Assess clinical response within 48-72 hours of initiating therapy 2

Source Control Requirements

Source control is critical and may include: 4

• Removal of infected intravascular or implanted devices
• Drainage of abscesses
• Surgical debridement of infected tissue

Common Pitfalls to Avoid

• Do not rely on clinical or epidemiological risk factors to distinguish MRSA from MSSA—a prospective study of 180 adults with community-acquired S. aureus found that even patients lacking the three strongest MRSA risk factors still had a 7% probability of MRSA in low-prevalence populations 9
• Do not use TMP-SMX as monotherapy for cellulitis due to potential group A Streptococcus involvement, which may have intrinsic resistance 6
• Do not continue vancomycin once MSSA is confirmed—switch to beta-lactams to avoid unnecessary broad-spectrum coverage 1, 2
• Do not use clindamycin if local resistance rates are ≥10% or unknown 2, 5
• Do not use tetracyclines in children <8 years of age 2
• Do not fail to obtain appropriate cultures before initiating antibiotics, as this leads to inadequate treatment 2, 10

Special Populations

Pediatric Dosing

• Vancomycin: standard pediatric dosing for empiric MRSA coverage 2
• Clindamycin: 10-13 mg/kg/dose IV every 6-8 hours if local resistance <10% 2
• Linezolid: 600 mg PO/IV twice daily for children >12 years; 10 mg/kg/dose PO/IV every 8 hours for children <12 years 2

Penicillin-Allergic Patients

• Vancomycin is indicated for penicillin-allergic patients who cannot receive beta-lactams 3