What is the management of gram-negative sepsis?

Management of Gram-Negative Sepsis

Gram-negative sepsis requires immediate administration of broad-spectrum antibiotics within one hour of recognition, along with aggressive fluid resuscitation and source control within 12 hours to reduce mortality. 1

Initial Assessment and Diagnosis

• Obtain at least 2 sets of blood cultures before starting antimicrobial therapy if no significant delay will occur (one percutaneously and one through each vascular access device unless inserted <48 hours prior) 2
• Perform appropriate imaging studies promptly to identify the source of infection 2
• Consider using procalcitonin levels to guide antibiotic therapy decisions, particularly when evaluating the need to discontinue empiric antibiotics 2

Immediate Management

Antimicrobial Therapy

• Administer effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis 1, 2
• Select empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens (including bacterial and potentially fungal or viral coverage) 1
• Consider patient risk factors for multidrug-resistant organisms (MDROs) when selecting initial therapy, including:
  • Prior infection or colonization with Gram-negative MDROs
  • Antibiotic therapy in the past 90 days
  • Poor functional status
  • Hospitalization for more than 2 days in the past 90 days
  • Occurrence five or more days after admission to an acute hospital
  • Receiving hemodialysis
  • Immunosuppression 1

Recommended Antimicrobial Regimens

• For patients without risk factors for MDROs, consider piperacillin-tazobactam or cefepime as appropriate first-line options 3, 4
• For patients with risk factors for MDROs, consider carbapenems or newer agents such as ceftazidime-avibactam, ceftolozane-tazobactam, or meropenem-vaborbactam 1, 5
• If MRSA is a concern, add daptomycin or another appropriate agent for Gram-positive coverage 6
• If vascular access is limited, prioritize antibiotics that can be administered as a bolus or rapid infusion (many β-lactams) 1
• Consider intraosseous access for rapid administration of antimicrobials if vascular access cannot be quickly established 1

Hemodynamic Support

• Initiate aggressive fluid resuscitation simultaneously with antimicrobial therapy 7
• Administer vasopressors if fluid resuscitation fails to restore adequate perfusion pressure 7
• Monitor capillary refill time as a guide for resuscitation adequacy 5

Source Control

• Rapidly identify and address the anatomical source of infection within 12 hours of diagnosis when feasible 2
• Remove potentially infected intravascular access devices promptly after establishing alternative access 2

Ongoing Management

Antimicrobial Stewardship

• Reassess antimicrobial therapy daily for potential de-escalation based on culture results 1, 2
• Narrow empiric antimicrobial therapy once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted 1
• Typical duration of therapy is 7-10 days; longer courses may be needed for patients with slow clinical response or undrainable foci of infection 2

Monitoring and Prevention of Complications

• Monitor for superinfection, particularly in patients receiving prolonged antimicrobial therapy 6
• Encourage early mobilization once the patient is stable to prevent complications of prolonged bed rest 1
• Actively wean invasive support as soon as the patient shows improvement 1

Special Considerations

Antimicrobial Resistance

• The prevalence of MDR Gram-negative bacteria is increasing, particularly in healthcare settings 1, 5
• Local antimicrobial resistance patterns should guide empiric therapy choices 1
• Consider region-specific empirical antibiotic regimens based on local epidemiology 1

Common Pitfalls to Avoid

• Delaying antimicrobial therapy beyond one hour of recognition of sepsis or septic shock significantly increases mortality 1
• Using inadequate antimicrobial coverage for likely pathogens based on patient risk factors and local resistance patterns 1
• Failing to reassess and de-escalate antimicrobial therapy once culture results are available 1, 2
• Neglecting source control, which is essential for successful treatment 2
• Overuse of broad-spectrum antibiotics when narrower spectrum options would be effective based on culture results 1