What is the recommended treatment for Staph (Staphylococcus) bacteremia?

Treatment of Staphylococcus aureus Bacteremia

For methicillin-susceptible S. aureus (MSSA) bacteremia, use cefazolin or an antistaphylococcal penicillin (nafcillin/oxacillin), NOT vancomycin, as beta-lactams are superior in preventing bacteriologic failure and relapse. 1, 2 For methicillin-resistant S. aureus (MRSA), use vancomycin or daptomycin as first-line therapy. 3, 4, 2

Initial Empirical Treatment

• Start empirical therapy with vancomycin or daptomycin while awaiting susceptibility results, as these agents cover MRSA. 3, 2
• Vancomycin dosing: 30-60 mg/kg/day IV in 2-4 divided doses (target trough 15-20 mcg/mL for serious infections). 3
• Daptomycin dosing: 6 mg/kg IV once daily for bacteremia (some experts recommend 8-10 mg/kg for complicated cases). 4, 5

Definitive Antibiotic Selection Based on Susceptibility

For MSSA:

• Switch immediately to cefazolin or nafcillin/oxacillin once susceptibilities confirm methicillin-susceptibility. 1, 2
• Nafcillin is superior to vancomycin for MSSA, with significantly lower rates of bacteriologic failure and relapse. 1
• Vancomycin should NOT be used for MSSA when beta-lactams are available. 1

For MRSA:

• Continue vancomycin (30-60 mg/kg/day) or daptomycin (6 mg/kg for uncomplicated, up to 10 mg/kg for complicated bacteremia). 3, 4, 5
• For persistent MRSA bacteremia or concern for antibiotic failure, consider combination therapy with daptomycin plus ceftaroline. 3

Minimum Required Evaluation

Every patient with S. aureus bacteremia requires: 3

• Thorough history focusing on: injection drug use, presence of indwelling catheters/lines, prosthetic devices (cardiac devices, joint prostheses, vascular grafts), recent surgical procedures, diabetes, and symptoms suggesting metastatic infection (back pain, joint pain, neurologic changes). 3, 2

• Physical examination targeting: skin for abscesses or cellulitis, joints for effusion/warmth, spine for tenderness, cardiac auscultation for new murmurs, and neurologic assessment. 3

• Infectious diseases consultation - this improves outcomes. 3

• Follow-up blood cultures at 2-4 days after initiating therapy to document clearance. 3, 4, 6

• Echocardiography - at minimum transthoracic echocardiography (TTE) for all patients. 3, 4, 2

Echocardiography Strategy

• Obtain TTE in all patients with S. aureus bacteremia. 3, 2

• Proceed directly to transesophageal echocardiography (TEE) in high-risk patients: 3

  • Prosthetic heart valves or cardiac implantable electronic devices (CIEDs)
  • History of injection drug use or prior endocarditis
  • Persistent bacteremia >48 hours despite appropriate therapy
  • Persistent fever >72 hours
  • Clinical signs of metastatic infection
  • New cardiac murmur

• TEE has superior sensitivity (vs. TTE: 32-82%) for detecting vegetations, intracardiac abscesses, and prosthetic valve involvement. 3

Risk Stratification and Duration of Therapy

Low-Risk (Uncomplicated) SAB - Treat for 14 days: 3, 6

Criteria that must ALL be met:

• No predisposing host factors (no prosthetic devices, no injection drug use)
• Negative TTE
• Blood cultures clear within 48 hours
• Defervescence within 72 hours of therapy initiation
• Hospital-acquired (catheter-related) bacteremia
• No clinical signs of metastatic infection

Critical caveat: Even for uncomplicated SAB, treatment duration <14 days is associated with significantly increased relapse rates (7.9% vs. 0%). 6 The ongoing SAB7 trial is evaluating whether 7 days may be noninferior to 14 days, but current evidence supports at least 14 days. 3

High-Risk (Complicated) SAB - Treat for 4-6 weeks: 3, 4

Any of the following:

• Endocarditis (6 weeks required)
• Osteomyelitis or vertebral involvement (6-8 weeks)
• Prosthetic device infection
• Persistent bacteremia >48 hours
• Metastatic foci of infection (septic emboli, abscesses, septic arthritis)
• Delayed antibiotic initiation
• Primary bacteremia (no identifiable source) - even without other complications, consider longer therapy due to poor prognosis. 6

Indeterminate-Risk SAB:

• Does not meet criteria for low-risk or high-risk
• Perform additional imaging based on clinical features (CT, MRI, or PET/CT) to identify occult metastatic foci
• Treat for 4-6 weeks if metastatic infection cannot be excluded. 3

Source Control - Mandatory Component

Source control is critical and must be addressed immediately: 2

• Remove all removable infected intravascular catheters and devices immediately. 3, 1
• Failure to remove infected devices is a common cause of multiple relapses. 1
• Drain all identified abscesses (cutaneous, visceral, epidural). 3, 4
• Debride infected tissues surgically when indicated. 4
• For prosthetic joint infections: early-onset (<30 days) may allow retention with debridement plus rifampin-based therapy; late-onset requires device removal. 4
• For CIEDs with bacteremia: extraction is typically required, with timing of reimplantation guided by blood culture clearance (beware "skip phenomenon" of intermittently negative cultures). 3

Monitoring for Persistent Bacteremia

• Obtain repeat blood cultures at 2-4 days after starting therapy. 3, 4, 6
• Each additional day of positive blood cultures significantly increases mortality. 3
• Persistent bacteremia (≥48 hours) is associated with 39% 90-day mortality and mandates: 2
  • Reassessment of source control
  • TEE to evaluate for endocarditis
  • Additional imaging for metastatic foci
  • Consider combination therapy (daptomycin + ceftaroline for MRSA)
  • Extended treatment duration (4-6 weeks minimum)

Renal Dosing Adjustments

For adults with creatinine clearance <30 mL/min: 5

• Vancomycin: dose based on levels (target trough 15-20 mcg/mL)
• Daptomycin: 4 mg/kg every 48 hours (for skin/soft tissue) or 6 mg/kg every 48 hours (for bacteremia)
• Administer daptomycin after hemodialysis on dialysis days

Pediatric dosing has not been established for renal impairment. 5

Common Pitfalls to Avoid

• Never continue vancomycin for MSSA when beta-lactams are available - this is associated with higher failure rates. 1
• Never use short-course therapy (<14 days) even for "uncomplicated" bacteremia - relapse rates are significantly higher. 6
• Never skip follow-up blood cultures - persistent bacteremia dramatically worsens prognosis and changes management. 3
• Never skip echocardiography - endocarditis is diagnosed in approximately 12% of SAB cases and requires 6 weeks of therapy. 3, 4, 2
• Never fail to remove infected catheters/devices - this is the most common cause of treatment failure and relapse. 1
• Never use rifampin as monotherapy - resistance develops rapidly; only use in combination for specific indications (prosthetic valve endocarditis, prosthetic joint infections). 4
• Never assume primary bacteremia is "low-risk" - even without identified complications, primary bacteremia has poor prognosis and should receive longer therapy. 6