Empiric Antibiotics for Suspected Sepsis
Empiric antimicrobial therapy for suspected sepsis should be initiated as soon as possible and within one hour of recognition, using broad-spectrum antibiotics that cover all likely pathogens based on the suspected source, local resistance patterns, and patient risk factors. 1
Initial Assessment and Timing
- Immediate administration is critical: Each hour delay in antibiotic administration increases mortality in septic shock 1
- Obtain cultures before antibiotics: Draw at least two sets of blood cultures (aerobic and anaerobic) before starting antibiotics, but do not delay therapy more than 45 minutes to obtain cultures 1
Empiric Antibiotic Selection Algorithm
Step 1: Determine if Community-Acquired or Healthcare-Associated
Community-acquired sepsis:
- Standard risk: Single agent with narrower spectrum may be appropriate
- ESBL risk factors: Recent antibiotics (especially 3rd gen cephalosporins or fluoroquinolones) within 90 days or known ESBL colonization 1
Healthcare-associated sepsis (any of the following):
- Hospital-acquired (>48h after admission)
- Recent hospitalization within 90 days
- Residence in long-term care facility
- Recent invasive procedures or therapies 1
Step 2: Select Appropriate Regimen Based on Likely Source and Risk Factors
For Septic Shock:
- Recommended: Empiric combination therapy using at least two antibiotics of different classes 1
- Common regimens:
For Sepsis Without Shock:
- Recommended: Broad-spectrum monotherapy or targeted combination based on suspected source 1
- Common regimens:
Step 3: Consider Special Circumstances
- Neutropenic sepsis: Broad-spectrum β-lactam monotherapy recommended over combination therapy 1
- MDR risk factors: Consider combination therapy for suspected:
- Pseudomonas aeruginosa
- Acinetobacter species
- Other multidrug-resistant organisms 1
- Intra-abdominal sepsis: Add metronidazole if using agents with inadequate anaerobic coverage 1
- Suspected MRSA: Add vancomycin or other anti-MRSA agent if risk factors present 1
- Suspected fungal infection: Consider echinocandin if risk factors present (immunocompromised, prolonged ICU stay, total parenteral nutrition, recent major surgery) 1
Dosing Considerations
- Loading doses: Use maximum recommended doses initially, especially in critically ill patients 1
- Extended infusions: Consider for β-lactams to optimize time above MIC (T>MIC) 1, 3
- Renal/hepatic adjustments: Adjust maintenance doses based on organ function 2, 4
De-escalation and Duration
- De-escalation: Reassess antimicrobial regimen daily and narrow therapy once pathogen identification and sensitivities are established 1, 5
- Combination therapy duration: If used empirically, limit to 3-5 days and de-escalate to appropriate monotherapy 1
- Total duration: Typically 7-10 days for most infections 1
- Extended duration may be needed for:
- Slow clinical response
- Undrainable foci of infection
- S. aureus bacteremia
- Fungal/viral infections
- Immunodeficiencies including neutropenia 1
Common Pitfalls and Caveats
- Delayed administration: Every hour delay increases mortality - prioritize rapid administration within first hour 1
- Inadequate dosing: Underdosing in critically ill patients due to altered pharmacokinetics - use maximum doses initially 1
- Failure to de-escalate: Continuing broad-spectrum therapy unnecessarily increases resistance, toxicity, and costs 5
- Overlooking source control: Antibiotics alone may be insufficient without adequate source control 1
- Ignoring local resistance patterns: Local antibiograms should guide empiric choices 1
- Prolonged therapy without evidence of infection: Consider procalcitonin levels to guide discontinuation in patients without confirmed infection 1
By following this structured approach to empiric antibiotic selection in suspected sepsis, clinicians can optimize outcomes while minimizing adverse effects and antimicrobial resistance.