What is the treatment for sepsis?

Sepsis Treatment

Initiate intravenous broad-spectrum antibiotics within one hour of recognizing sepsis or septic shock, as each hour of delay increases mortality by 7.6%. 1

Immediate Antimicrobial Therapy

Timing is Critical

• Administer IV antimicrobials within 60 minutes of sepsis recognition - this is a strong recommendation that directly impacts survival. 1
• Each hour of delay in antimicrobial administration over the first 6 hours is associated with a 7.6% decrease in survival. 1

Blood Cultures Before Antibiotics (But Never Delay)

• Obtain at least two sets of blood cultures (aerobic and anaerobic) before starting antimicrobials - one drawn percutaneously and one through each vascular access device if present. 1
• However, never delay antibiotic administration beyond one hour to obtain cultures - if obtaining cultures will cause any delay, start antibiotics immediately. 1, 2
• Blood cultures detect bacteremia in only 30% of febrile neutropenia cases, so negative cultures should never alter initial empirical therapy. 1, 2

First-Line Antibiotic Selection

Broad-Spectrum Monotherapy Options

Choose one of the following antipseudomonal beta-lactams as initial empirical therapy: 1

• Meropenem (preferred for ESBL-producing organisms)
• Imipenem/cilastatin
• Piperacillin-tazobactam
• Ceftazidime (alternative option)

The 2017 Surviving Sepsis Campaign guidelines emphasize empiric broad-spectrum therapy covering all likely pathogens including bacterial and potentially fungal or viral coverage. 1 Recent research from 2023 suggests meropenem may have lower mortality rates compared to piperacillin-tazobactam in critically ill patients with septic shock, though both are acceptable first-line agents. 3

When to Add Combination Therapy

Add an aminoglycoside (gentamicin or amikacin) ONLY in these specific situations: 1, 2

• Septic shock with hemodynamic instability
• Suspected or documented multidrug-resistant gram-negative pathogens (Pseudomonas, Acinetobacter)
• Severe infections with respiratory failure and septic shock from Pseudomonas aeruginosa

Important caveat: The 2017 Surviving Sepsis Campaign guidelines recommend AGAINST routine combination therapy for most serious infections, as aminoglycosides increase renal toxicity without improving efficacy in standard cases. 1, 2 This represents an evolution from earlier 2011 guidelines that were more permissive of combination therapy. 1

Additional Coverage Considerations

Add vancomycin or another glycopeptide if: 1, 2

• Central venous catheter-related infection suspected
• Severe mucositis present (especially in head/neck cancer patients)
• Known MRSA colonization or high local MRSA prevalence
• Hemodynamic instability with suspected gram-positive source

Add antifungal therapy (echinocandin preferred) if: 2

• Fever persists beyond 96-120 hours despite appropriate antibacterial therapy
• Profound neutropenia expected to last >7 days
• Prior fungal infection or heavy antifungal prophylaxis

Hemodynamic Resuscitation

Fluid Resuscitation Goals

Initiate aggressive fluid resuscitation immediately, targeting: 1, 4

• Mean arterial pressure (MAP) ≥65 mmHg
• Central venous pressure 8-12 mmHg
• Urinary output ≥0.5 mL/kg/hour
• Central venous oxygen saturation ≥70%

Use crystalloids preferentially over colloids - meta-analyses show colloids increase risk of renal failure and mortality. 1 Specifically avoid human albumin, as it provides no survival benefit even in hypoalbuminemia. 1

Vasopressor Support

If MAP ≥65 mmHg cannot be achieved with fluids alone, initiate norepinephrine at 0.1-1.3 µg/kg/min as the first-line vasopressor. 1, 4 Do not escalate MAP targets above 85 mmHg, as higher targets do not improve outcomes. 1

Source Control

Identify and control the anatomic source of infection within 12 hours of diagnosis when feasible. 1

• Use the least physiologically invasive intervention (e.g., percutaneous drainage over surgical drainage when possible). 1
• Remove intravascular access devices promptly if they are a possible source, after establishing alternative access. 1
• For infected pancreatic necrosis, delay definitive intervention until adequate demarcation of viable/nonviable tissue occurs. 1

Antimicrobial De-escalation and Duration

Daily Reassessment

Reassess antimicrobial therapy daily for potential de-escalation once pathogen identification and sensitivities are available. 1

Combination Therapy Duration

If combination therapy was initiated for septic shock, discontinue the second agent within the first few days in response to clinical improvement or evidence of infection resolution. 1

Total Treatment Duration

7-10 days is adequate for most serious infections associated with sepsis. 1

Longer courses (>10 days) are appropriate for: 1

• Slow clinical response
• Undrainable foci of infection
• Staphylococcus aureus bacteremia
• Fungal or viral infections
• Immunologic deficiencies including neutropenia

Shorter courses may be appropriate for: 1

• Rapid clinical resolution after effective source control
• Uncomplicated urinary or intra-abdominal sepsis with adequate source control

Procalcitonin-Guided Therapy

Procalcitonin levels can support shortening antimicrobial duration or discontinuing empiric antibiotics in patients who initially appeared septic but have limited clinical evidence of infection. 1

Critical Pitfalls to Avoid

• Never delay antibiotics beyond one hour for any reason - not for cultures, imaging, or specialist consultation. 1, 2
• Avoid routine aminoglycoside combinations in standard sepsis without shock, as they increase nephrotoxicity without survival benefit. 1, 2
• Do not use colloids or albumin preferentially - crystalloids are safer and equally effective. 1
• Do not continue broad-spectrum antibiotics indefinitely - daily reassessment and de-escalation reduce resistance and toxicity. 1
• Do not target MAP >85 mmHg with high-dose vasopressors - this does not improve outcomes and may cause harm. 1

Special Populations

Neutropenic Patients

The 2017 Surviving Sepsis Campaign guidelines recommend AGAINST routine combination therapy for neutropenic sepsis/bacteremia, though multidrug therapy to broaden coverage is not precluded. 1 This contrasts with earlier 2011 guidelines that recommended combination therapy for neutropenic severe sepsis. 1 In practice, many centers still use combination therapy for neutropenic septic shock given the high mortality risk. 1, 2

Renal Impairment

Adjust piperacillin-tazobactam and other renally cleared antibiotics for creatinine clearance ≤40 mL/min. 5 Consider therapeutic drug monitoring for beta-lactams in critically ill patients to ensure adequate levels. 6