What are the empiric antibiotics for sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

For empiric treatment of sepsis, immediately administer a combination of broad-spectrum antibiotics intravenously, such as vancomycin 15-20 mg/kg IV every 8-12 hours (max 2g per dose) plus piperacillin-tazobactam 4.5g IV every 6 hours, to cover all likely pathogens, including bacterial and potentially fungal or viral coverage, as recommended by the Surviving Sepsis Campaign guidelines 1.

Key Considerations

• The choice of empiric antimicrobial therapy depends on complex issues related to the patient’s history, clinical status, and local epidemiologic factors, including the nature of the clinical syndrome/site of infection 1.
• The initial selection of antimicrobial therapy must be broad enough to cover all likely pathogens, including gram-positive and gram-negative organisms, and potential drug-resistant bacteria 1.
• Consider adding a supplemental gram-negative agent to the empiric regimen for critically ill septic patients at high risk of infection with multidrug-resistant pathogens, such as Pseudomonas or Acinetobacter 1.
• Vancomycin, teicoplanin, or another anti-MRSA agent can be used when risk factors for MRSA exist, and a macrolide or fluoroquinolone can be added for suspected Legionella species 1.

Empiric Regimen

• Start with vancomycin 15-20 mg/kg IV every 8-12 hours (max 2g per dose) plus piperacillin-tazobactam 4.5g IV every 6 hours.
• If pseudomonas is suspected or the patient is critically ill, add cefepime 2g IV every 8 hours.
• In cases of suspected MRSA or if the patient is hemodynamically unstable, include vancomycin in the regimen.

Duration and Adjustment

• Administer the first dose within one hour of recognizing sepsis.
• Continue this empiric regimen for 3-5 days, then narrow therapy based on culture results and clinical response.
• Alongside antibiotics, initiate fluid resuscitation with 30 mL/kg of crystalloid within the first 3 hours.

Rationale

• Early, appropriate antibiotic administration is crucial in reducing mortality in sepsis, hence the emphasis on rapid initiation and broad coverage 1.
• The combination targets both gram-positive and gram-negative organisms, including potential drug-resistant bacteria, while cultures are pending.

From the Research

Empiric Antibiotics for Sepsis

The selection of empiric antibiotics for sepsis is based on a combination of patient factors, predicted infecting organism(s), and local microbial resistance patterns 2. The initial drugs should have activity against typical gram-positive and gram-negative causative micro-organisms. Some key points to consider when selecting empiric antibiotics for sepsis include:

• The risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started 2
• Anaerobic coverage should be provided for intra-abdominal infections or others where anaerobes are significant pathogens 2
• Empiric antifungal or antiviral therapy may be warranted 2
• For patients with healthcare-associated infections, resistant micro-organisms will further complicate the choice of empiric antimicrobials 2

Combination Antibiotic Therapy

Combination antibiotic therapy directed against Gram-negative bacteria has been associated with improved outcomes in patients with severe sepsis and septic shock 3. The use of combination therapy, such as a beta-lactam plus an aminoglycoside or fluoroquinolone, can increase the likelihood of appropriate initial therapy and reduce the risk of hospital mortality 3. However, combination antibiotic therapy is not routinely required, and the use of certain combinations, such as vancomycin and piperacillin/tazobactam, can increase the risk of acute kidney injury 4.

Key Principles of Antibiotic Use in Sepsis

Some key principles of antibiotic use in sepsis include:

• Early administration of broad-spectrum antimicrobials within the first hour of diagnosis 2, 5
• Optimizing antibiotic use to ensure successful outcomes and reduce adverse effects and drug resistance 5
• Considering all likely pathogens involved to provide appropriate antibiotic coverage 5
• Investigating the previous risk of multidrug-resistant (MDR) pathogens 5
• Using individualized dosing and adjusting for pharmacokinetics (PK)/pharmacodynamics (PD) and renal/liver dysfunction 5
• Reevaluating the duration and appropriateness of treatment at regular intervals 5
• De-escalation and shortened courses of antimicrobials should be considered for most patients, except in some justified circumstances 5