What is the empiric treatment for sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

Empiric treatment for sepsis should begin immediately after obtaining blood cultures, with broad-spectrum antibiotics that cover likely pathogens based on the suspected source of infection. For most adults with community-acquired sepsis, a reasonable initial regimen includes a combination of vancomycin (15-20 mg/kg IV every 8-12 hours) plus either piperacillin-tazobactam (4.5g IV every 6-8 hours) or a carbapenem like meropenem (1g IV every 8 hours) 1.

Key Considerations

• The choice of empiric antimicrobial regimen should be based on local epidemiology, individual patient risk factors for difficult-to-treat pathogens, clinical severity of infection, and infection source 1.
• In healthcare-associated sepsis, coverage for resistant organisms may require addition of an antipseudomonal agent like cefepime (2g IV every 8 hours) 1.
• Fluid resuscitation with crystalloids (30 ml/kg within the first 3 hours) and vasopressors (norepinephrine as first-line) for persistent hypotension are essential components of treatment 1.
• Source control through procedures like abscess drainage or removal of infected devices should be pursued when applicable 1.
• Antibiotics should be reassessed within 48-72 hours based on culture results and clinical response, with de-escalation to narrower therapy when possible 1.
• The duration of antibiotic therapy typically ranges from 7 to 10 days, but may be longer in patients with a slow clinical response, undrainable foci of infection, or certain types of infections such as those caused by Staphylococcus aureus or fungal pathogens 1.

De-escalation and Stewardship

• De-escalation of antibiotic therapy is recommended once the susceptibility profile of the pathogen is known, and the patient's clinical response has been assessed 1.
• The use of biomarkers such as procalcitonin can assist in the decision to discontinue empiric antibiotics in patients who initially appeared septic but have no subsequent evidence of infection 1. This aggressive initial approach is necessary because each hour of delay in appropriate antibiotic administration increases mortality by approximately 7-8% in septic shock patients, while the broad coverage addresses the uncertainty of the causative organism during the critical early treatment period 1.

From the Research

Sepsis Empiric Treatment

• Sepsis is a common consequence of infection, associated with a mortality rate >25% 2
• The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection, and urinary tract infection 2
• Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens 2
• Immediate, empiric, broad-spectrum therapy is necessary to reduce mortality in patients with severe sepsis and/or shock 2

Antibiotic Treatment

• Meropenem and piperacillin-tazobactam are commonly used antibiotics for sepsis treatment 3, 4
• A study comparing meropenem and piperacillin-tazobactam found no significant difference in ICU stay, but meropenem had a lower mortality rate on ventilator-free days, vasopressor-free days, and hospital-free days 3
• The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial aims to compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis 4

Combination Therapy

• The combination of piperacillin-tazobactam and vancomycin may be synergistic against methicillin-resistant Staphylococcus aureus (MRSA) 5
• However, the combination of vancomycin and piperacillin/tazobactam may increase the risk of acute kidney injury compared to other broad-spectrum antibiotic combinations 6
• Clinicians should be vigilant when employing this regimen, and consider alternative combinations such as vancomycin with cefepime or meropenem 6