What are the antibiotics of choice for sepsis?

Antibiotics of Choice for Sepsis

For patients with sepsis or septic shock, we recommend immediate administration of broad-spectrum empiric antimicrobial therapy within one hour of recognition to cover all likely pathogens based on the suspected source of infection, patient factors, and local resistance patterns. 1

Initial Empiric Antimicrobial Selection

General Principles:

• Administer IV antimicrobials within one hour of sepsis recognition 1
• Use broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens 1
• Consider patient factors, infection site, local pathogen prevalence, and resistance patterns 1

Recommended Empiric Regimens:

For Septic Shock:

• Combination therapy recommended (using at least two antibiotics of different classes) aimed at the most likely pathogens 1
• Common combination options include:
  • Broad-spectrum β-lactam plus either an aminoglycoside or fluoroquinolone for suspected Pseudomonas aeruginosa 1, 2
  • β-lactam plus macrolide for suspected Streptococcus pneumoniae bacteremia 1

Specific Antimicrobial Options:

• Broad-spectrum β-lactams (first-line options):
  • Carbapenems (meropenem, imipenem/cilastatin, doripenem) 1, 2
  • Extended-spectrum penicillin/β-lactamase inhibitor combinations (piperacillin/tazobactam) 1, 2
  • Fourth-generation cephalosporins (cefepime) 2
• Additional coverage based on suspected pathogens:
  • Vancomycin or other MRSA-active agent if MRSA is suspected 1
  • Aminoglycosides (e.g., gentamicin) for gram-negative coverage, particularly Pseudomonas 3, 2
  • Antifungals if fungal infection is suspected (echinocandins preferred for severe illness) 1

De-escalation and Duration

• De-escalate antimicrobial therapy within the first few days based on clinical improvement and culture results 1
• Discontinue combination therapy within 3-5 days 1
• Typical treatment duration is 7-10 days for most infections 1
• Longer courses may be needed for:
  • Slow clinical response
  • Undrainable infection foci
  • S. aureus bacteremia
  • Fungal or viral infections
  • Immunocompromised patients including neutropenia 1
• Shorter courses may be appropriate for patients with rapid resolution after source control 1
• Perform daily assessment for de-escalation opportunities 1

Special Considerations

• For neutropenic sepsis, combination empiric therapy is suggested, but routine combination therapy for ongoing treatment is not recommended 1
• For difficult-to-treat, multidrug-resistant pathogens (e.g., Acinetobacter, Pseudomonas), combination therapy may be beneficial 1, 2
• Optimize dosing strategies based on pharmacokinetic/pharmacodynamic principles, especially in critically ill patients 1, 4
• Consider loading doses regardless of organ dysfunction to rapidly achieve therapeutic levels 4, 5
• Extended or continuous infusion of β-lactams may help achieve therapeutic levels in critically ill patients 4, 5

Common Pitfalls to Avoid

• Delaying antimicrobial administration - each hour delay increases mortality risk by approximately 8% 6
• Using inadequate spectrum coverage for likely pathogens 1, 7
• Failing to consider local resistance patterns 2, 4
• Not adjusting dosing for altered pharmacokinetics in critically ill patients 4, 5
• Prolonged broad-spectrum or combination therapy without de-escalation 1
• Not obtaining appropriate cultures before starting antimicrobials (if doing so doesn't delay therapy) 1