What are the recommended antibiotics and treatment duration for a patient with Staphylococcus (Staph) aureus bacteremia?

Staphylococcus aureus Bacteremia: Antibiotic Selection and Treatment Duration

Immediate Antibiotic Selection

For methicillin-susceptible S. aureus (MSSA) bacteremia, use cefazolin or an antistaphylococcal penicillin (nafcillin/oxacillin); for methicillin-resistant S. aureus (MRSA), use vancomycin or daptomycin as first-line therapy. 1

Empirical Therapy (Before Susceptibilities Known)

• Start vancomycin 15-20 mg/kg IV every 8-12 hours OR daptomycin 6 mg/kg IV once daily, as both cover MRSA while awaiting culture results 2, 3, 1
• These agents demonstrated equivalent efficacy in phase 3 trials (treatment success 44% vs 42% for daptomycin vs standard care) 1

Definitive Therapy for MSSA

• Switch to cefazolin or antistaphylococcal penicillins (nafcillin, oxacillin, flucloxacillin) once MSSA is confirmed 4, 5, 1
• Beta-lactams are superior to vancomycin for MSSA and associated with lower recurrence rates 6
• First-generation cephalosporins are acceptable alternatives but have slightly lower antimicrobial activity than penicillinase-resistant penicillins 5

Definitive Therapy for MRSA

• Continue vancomycin with target trough levels of 15-20 mcg/mL for serious infections 6
• Daptomycin 6 mg/kg IV once daily is equally effective (some experts recommend 8-10 mg/kg for complicated cases) 2, 3
• Ceftobiprole demonstrated noninferiority to daptomycin (treatment success 70% vs 69%) 1

Treatment Duration Based on Complexity

Uncomplicated Bacteremia (Minimum 2 Weeks)

Treat for at least 14 days to prevent relapse, as shorter courses are associated with significantly higher relapse rates (7.9% vs 0%). 2, 7

Uncomplicated bacteremia requires ALL of the following criteria 2:

• Negative follow-up blood cultures at 2-4 days after initial positive cultures
• Defervescence within 72 hours of starting effective therapy
• No evidence of endocarditis on echocardiography
• No implanted prostheses
• No metastatic sites of infection identified

Complicated Bacteremia (4-6 Weeks)

• Treat for 4-6 weeks if ANY criterion for uncomplicated bacteremia is not met 2, 3
• Prolonged bacteremia (≥48 hours) carries a 90-day mortality risk of 39% and requires extended therapy 1
• Metastatic infection occurs in more than one-third of cases, including endocarditis (12%), septic arthritis (7%), vertebral osteomyelitis (4%), and abscess formation 1

Endocarditis (6 Weeks)

• Vancomycin or daptomycin 6 mg/kg IV once daily (consider 8-10 mg/kg for daptomycin) for 6 weeks 2, 3

Critical Management Steps Beyond Antibiotics

Mandatory Source Control

• Remove all infected intravascular catheters and implanted devices immediately 1
• Drain abscesses and perform surgical debridement of infected tissue—failure to do so leads to treatment failure regardless of antibiotic choice 3, 6

Required Diagnostic Workup

• Obtain follow-up blood cultures 2-4 days after initial positive cultures and as needed thereafter to document clearance 2, 3
• Perform transthoracic echocardiography on ALL patients with S. aureus bacteremia 2
• Perform transesophageal echocardiography (preferred over transthoracic) for patients with: persistent bacteremia, persistent fever beyond 72 hours, metastatic infection foci, or implantable cardiac devices 2, 1
• Obtain CT or MRI imaging based on symptoms suggesting metastatic infection (back pain, joint pain, abdominal pain, neurological changes) 1

What NOT to Do: Common Pitfalls

• Do NOT add gentamicin to vancomycin for uncomplicated bacteremia or native valve endocarditis—this is not recommended 2, 6
• Do NOT add rifampin to vancomycin for uncomplicated bacteremia or native valve endocarditis 2, 6
• Do NOT use daptomycin for S. aureus pneumonia, as it is inactivated by pulmonary surfactant 3
• Do NOT use vancomycin for MSSA when beta-lactams are available—beta-lactams are superior 6, 5
• Do NOT treat primary bacteremia with short-course therapy (<14 days), even if it appears uncomplicated, as it has poor prognosis 7
• Do NOT use beta-lactam antibiotics alone for MRSA—they are by definition resistant 3

Special Populations

Pediatric Dosing

• Vancomycin IV is recommended for children with MRSA bacteremia 2, 3
• Clindamycin 10-13 mg/kg IV every 6-8 hours can be used if clindamycin resistance is <10% and the patient is stable without ongoing bacteremia 2, 3
• Linezolid: 600 mg PO/IV twice daily for children >12 years; 10 mg/kg every 8 hours for children <12 years 2, 3