What antibiotics are recommended for the treatment of sepsis?

Antibiotic Treatment for Sepsis

Broad-spectrum intravenous antimicrobials must be administered within one hour of sepsis recognition, with combination therapy recommended for septic shock targeting all likely pathogens based on suspected infection source. 1

Initial Antimicrobial Management

Timing and Administration

• Administer IV antimicrobials within the first hour of sepsis or septic shock recognition (strong recommendation) 1
• Obtain appropriate cultures before starting antibiotics, but do not delay antimicrobial therapy 1
• Always collect at least two sets of blood cultures (aerobic and anaerobic) 1

Empiric Antibiotic Selection

1. For sepsis without shock:

   • Broad-spectrum monotherapy covering likely pathogens based on suspected infection source 1
   • Examples include extended-spectrum β-lactams (piperacillin-tazobactam, cefepime, meropenem)

2. For septic shock:

   • Combination therapy using at least two antibiotics of different classes 1
   • For Pseudomonas risk: Extended-spectrum β-lactam (e.g., piperacillin-tazobactam) plus either an aminoglycoside or fluoroquinolone 1
   • For suspected pneumococcal bacteremia: β-lactam plus macrolide 1
   • For nosocomial pneumonia: Piperacillin-tazobactam 4.5g every 6 hours plus an aminoglycoside 2

3. Special considerations:

   • For MDR pathogens: Broaden coverage based on local resistance patterns 3
   • For suspected fungal infection: Add appropriate antifungal therapy 1
   • For suspected viral etiology: Initiate antiviral therapy as early as possible 1

Optimization of Antimicrobial Therapy

Dosing Strategies

• Use optimized dosing based on pharmacokinetic/pharmacodynamic principles 1
• Consider extended or continuous infusions of β-lactams in critically ill patients 3
• Adjust dosing in renal impairment (creatinine clearance ≤40 mL/min) 2
• Use appropriate loading doses regardless of organ dysfunction 3

De-escalation and Duration

• Reassess antimicrobial regimen daily for potential de-escalation 1
• De-escalate combination therapy within 3-5 days based on clinical improvement and culture results 1
• Standard duration: 7-10 days for most serious infections 1
• Consider longer courses for:
  • Slow clinical response
  • Undrainable infection foci
  • S. aureus bacteremia
  • Fungal/viral infections
  • Immunodeficiencies including neutropenia 1
• Consider shorter courses with rapid clinical resolution following effective source control 1

Common Pitfalls and Caveats

• Delay in administration: Each hour delay in appropriate antimicrobial administration increases mortality by approximately 8% 4
• Inadequate spectrum: Failure to cover all likely pathogens increases mortality
• Excessive duration: Prolonged antimicrobial therapy promotes resistance and adverse effects
• Failure to de-escalate: Continue broad-spectrum therapy unnecessarily
• Inappropriate discontinuation: Do not stop antimicrobials if infection remains the likely cause of shock 1
• Nephrotoxicity risk: Monitor renal function in critically ill patients receiving piperacillin-tazobactam, as it has been identified as an independent risk factor for renal failure 2
• Drug interactions: Piperacillin-tazobactam can significantly reduce tobramycin concentrations in hemodialysis patients 2

Special Populations

• Neutropenic patients: Current guidelines recommend against routine combination therapy for neutropenic sepsis/bacteremia (strong recommendation) 1
• Pediatric patients: Dosing should be weight-based and adjusted for age 2
• Renal impairment: Dose adjustment required based on creatinine clearance 2

Remember that early, appropriate antimicrobial therapy is one of the most critical interventions for improving survival in sepsis and septic shock 4. The initial empiric regimen should be broad enough to cover all likely pathogens, with subsequent de-escalation guided by culture results and clinical response.