What is the recommended empiric treatment for sepsis?

Empiric Treatment for Sepsis

Immediate broad-spectrum antibiotic therapy must be initiated within one hour of recognizing sepsis to significantly reduce mortality. 1

Initial Assessment and Antibiotic Selection

First-line Empiric Therapy Options:

• Monotherapy options for moderate risk patients:

  • Meropenem
  • Imipenem/cilastatin
  • Piperacillin/tazobactam
  • Ceftazidime 1

• For high-risk patients, use combination therapy:

  • Antipseudomonal beta-lactam plus aminoglycoside 1
  • Consider adding vancomycin if:
    • Suspected catheter-related infection
    • Known MRSA colonization
    • Skin/soft tissue infection
    • Hemodynamic instability 1

Different-class combination therapy (DCCT) with antimicrobials having different mechanisms of action has been shown to reduce mortality compared to monotherapy or same-class combinations (34% vs 40% mortality) 2.

Timing is Critical:

• Each hour delay in antimicrobial administration is associated with a 7.6% decrease in survival 1
• The risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started 3

Source-Specific Recommendations

Pathogen	Recommended Antibiotic Therapy
E. coli	Third-generation cephalosporins or piperacillin/tazobactam [1]
S. aureus	Vancomycin (4-6 weeks duration) [1]
Candida species	Amphotericin B or fluconazole (for susceptible strains) [1]
Carbapenem-resistant Klebsiella	Ceftolozane/tazobactam, ceftazidime/avibactam, or meropenem-vaborbactam [1]

For intra-abdominal infections or other situations where anaerobes are significant pathogens, ensure anaerobic coverage 3.

Source Control and Supportive Care

Source Control:

• Ensure adequate source control within 12 hours 1
• Remove infected catheters or devices 1

Fluid Resuscitation:

• Initial resuscitation: 30mL/kg crystalloid for hypotension or lactate ≥4mmol/L 1
• Target parameters:
  • Mean arterial pressure ≥65 mmHg
  • Central venous pressure 8-12 mmHg
  • Urinary output ≥0.5 ml/kg/h
  • Central venous oxygen saturation ≥70% 1

Vasopressors:

• If hypotension persists despite adequate fluid resuscitation, start norepinephrine (0.1-1.3 μg/kg/min) 1
• Do not increase mean arterial pressure >85 mmHg with vasopressors 1

Blood Product Administration:

• Transfuse RBCs only when hemoglobin <7.0 g/dL (target 7.0-9.0 g/dL) after tissue hypoperfusion resolution 1
• Administer platelets prophylactically when:
  • Counts <10,000/mm³ without bleeding
  • Counts <20,000/mm³ with significant bleeding risk 1

Corticosteroids:

• Do not administer corticosteroids for sepsis in the absence of shock 1

Duration and De-escalation of Therapy

• Standard duration: 7-10 days for most serious infections 1
• Consider shorter courses (5-7 days) with rapid clinical resolution and adequate source control 1
• Prolonged antibiotic courses (>10 days) increase risk of secondary superinfections (Candida, Enterococcus, Enterobacteria, Staphylococcus) 1
• De-escalate therapy as soon as possible based on culture results and clinical improvement 1
• Daily reassessment of clinical response and monitoring for adverse effects is essential 1
• Consider procalcitonin levels to guide duration of therapy 1

Common Pitfalls to Avoid

1. Delayed antibiotic administration - Must be given within one hour of recognizing sepsis
2. Inadequate source control - Ensure removal of infected devices/catheters
3. Inappropriate antibiotic selection - Consider local resistance patterns
4. Failure to de-escalate - Narrow therapy once culture results are available
5. Prolonged antibiotic courses - Increases risk of superinfections
6. Inadequate fluid resuscitation - Critical for tissue perfusion
7. Overuse of corticosteroids - Not recommended in sepsis without shock

The personalized medicine approach using biomarkers to guide therapy is an emerging strategy that may further improve outcomes 4, but immediate broad-spectrum antibiotic administration remains the cornerstone of sepsis management.