What are the antibiotics of choice for gram-positive and gram-negative bacteremia?

Antibiotics of Choice for Bacteremia

Gram-Positive Bacteremia

Staphylococcus aureus (Methicillin-Susceptible)

For methicillin-susceptible S. aureus (MSSA) bacteremia, cefazolin or antistaphylococcal penicillins (nafcillin, oxacillin) are the drugs of choice and should replace empiric vancomycin immediately once susceptibility is confirmed. 1, 2

• Vancomycin should NOT be used for MSSA bacteremia as it is associated with 2-3 times higher risk of morbidity and mortality compared to β-lactam agents 3, 1
• Cefazolin is preferred for patients with non-anaphylactic penicillin allergy (90% can tolerate first-generation cephalosporins safely) 1
• Dosing: Nafcillin or oxacillin 2 g IV every 4-6 hours; cefazolin 2 g IV every 8 hours 1
• Duration: 14 days for uncomplicated bacteremia with catheter removal and negative transesophageal echocardiography (TEE); 4-6 weeks if endocarditis is present 1

Staphylococcus aureus (Methicillin-Resistant)

For MRSA bacteremia, vancomycin 15 mg/kg IV every 8-12 hours or daptomycin 6-8 mg/kg/day IV are first-line options, with daptomycin preferred for persistent bacteremia or when vancomycin MIC ≥1.5 mg/mL. 1, 2

• Vancomycin should be avoided when MIC ≥1.5 mg/mL or in patients with renal impairment 1
• Daptomycin demonstrated noninferiority to standard therapy (treatment success 44% vs 42%) and should be dosed at 6-8 mg/kg/day for bacteremia 2, 4
• Linezolid 600 mg IV every 12 hours is an alternative, with comparable effectiveness and safety to vancomycin or daptomycin 5, 1
• Ceftaroline, telavancin, tedizolid, and dalbavancin are additional options for MRSA coverage 1, 6
• Critical pitfall: Empiric combination of vancomycin PLUS a β-lactam (nafcillin, oxacillin, or cefazolin) should be considered for all staphylococcal bacteremia until susceptibility results return, as de-escalation from vancomycin to β-lactam after results still shows inferior outcomes compared to initial β-lactam therapy 3

Enterococcus Species

Ampicillin is the drug of choice for ampicillin-susceptible enterococci; vancomycin should be used if ampicillin-resistant. 1

• For vancomycin-resistant enterococci (VRE), use daptomycin 6 mg/kg after each dialysis session or linezolid 600 mg PO every 12 hours 1
• Duration: 7-14 days for uncomplicated catheter-related bloodstream infection (CRBSI) 1
• The role of combination therapy (cell wall-active agent plus aminoglycoside) remains unresolved for enterococcal CRBSI without endocarditis 1

Gram-Negative Bacteremia

Empiric Therapy for Suspected Gram-Negative Bacteremia

Empiric therapy must be based on local antibiogram patterns and risk factors for multidrug-resistant (MDR) organisms, with antipseudomonal β-lactams as the foundation. 1

• Monotherapy options (choose one): 1

  • Piperacillin-tazobactam 4.5 g IV every 6 hours (extended infusions appropriate) 1, 7
  • Cefepime 2 g IV every 8 hours 1
  • Ceftazidime 2 g IV every 8 hours 1
  • Meropenem 1 g IV every 8 hours 1
  • Imipenem 500 mg IV every 6 hours 1

• Double antipseudomonal coverage is indicated for patients with: 1

  • Prior IV antibiotic use within 90 days
  • Septic shock
  • Five or more days of hospitalization
  • Acute renal replacement therapy

• Second agent options (add to β-lactam above): 1

  • Ciprofloxacin 400 mg IV every 8 hours
  • Amikacin 15-20 mg/kg IV every 24 hours
  • Gentamicin 5-7 mg/kg IV every 24 hours
  • Tobramycin 5-7 mg/kg IV every 24 hours

Specific Gram-Negative Pathogens

For Pseudomonas aeruginosa bacteremia, combination therapy is recommended due to high frequency of resistance development on monotherapy. 1

• Combination therapy is more likely to provide appropriate initial coverage, though it may not prevent resistance emergence 1
• Duration: 10-14 days for uncomplicated bacteremia 1

For Acinetobacter species, carbapenems, sulbactam, colistin, or polymyxin are most active agents. 1

• No data support improved outcomes with combination regimens 1
• Colistin dosing: 5 mg/kg IV loading dose, then 2.5 mg × (1.5 × CrCl + 30) IV every 12 hours 1

For ESBL-producing Enterobacteriaceae, carbapenems are the drugs of choice; avoid third-generation cephalosporin monotherapy. 1

For other gram-negative bacilli (non-Pseudomonas), quinolones with or without rifampin may be preferred as they can be given orally and effectively eradicate bacteria from foreign bodies. 1

• Duration: 10-14 days for uncomplicated catheter-related bacteremia 1
• Catheter removal is strongly recommended for Burkholderia cepacia, Stenotrophomonas, Agrobacterium, and Acinetobacter baumannii, especially if bacteremia persists despite appropriate therapy 1

Critical Considerations

• Aminoglycosides as monotherapy were associated with lower clinical response rates on meta-analysis, though mortality was unchanged 1
• Polymyxins should be reserved for settings with high MDR prevalence and local expertise 1
• Aztreonam 2 g IV every 8 hours is acceptable when other options are unavailable 1
• For prolonged bacteremia after appropriate therapy and catheter removal, especially with underlying valvular disease, extend treatment to 4-6 weeks 1