What is the approach to managing a patient presenting with sepsis?

Approach to Sepsis Management

Administer IV broad-spectrum antibiotics within 1 hour of recognizing sepsis or septic shock, simultaneously initiating aggressive fluid resuscitation with at least 30 mL/kg crystalloids within the first 3 hours. 1

Immediate Recognition and Initial Assessment (First Hour)

Time is critical—each hour delay in antibiotic administration increases mortality by a measurable amount. 1

Risk Stratification

• Use NEWS2 score ≥7 to identify high-risk patients requiring immediate intervention 2
• Perform focused assessment to identify infection source through history and physical examination, looking specifically for: 2
  • Respiratory symptoms (pneumonia source) 1
  • Urinary symptoms (urinary tract source) 1
  • Abdominal pain/peritonitis (intra-abdominal source) 1
  • Skin/soft tissue infections 1
  • Indwelling devices (central lines, urinary catheters) 3

Obtain Cultures Before Antibiotics (But Don't Delay Treatment)

• Draw at least 2 sets of blood cultures (aerobic and anaerobic bottles)—one percutaneously and one through each vascular access device if present >48 hours 1
• If obtaining cultures delays antibiotic administration, give antibiotics first 1

Initial Resuscitation Bundle (First 3 Hours)

Fluid Resuscitation

• Administer at least 30 mL/kg IV crystalloids within first 3 hours for sepsis-induced hypoperfusion 2, 3
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) over normal saline when possible 3
• Continue fluid challenges (250-500 mL boluses) as long as hemodynamic parameters improve 3
• Consider albumin addition when patients require substantial crystalloid volumes 3
• Never use hydroxyethyl starches—associated with renal injury and coagulopathy 3

Antimicrobial Therapy (Within 1 Hour)

• Initiate empiric broad-spectrum IV antibiotics covering all likely pathogens (bacterial, and consider fungal/viral if indicated) 1
• Select antibiotics based on: 1
  • Suspected infection source 1
  • Local antibiotic resistance patterns 1
  • Recent antibiotic exposure (avoid agents used in previous 3 months) 1
  • Healthcare-associated infection risk factors 2
  • Immunosuppression status 1

Combination Therapy Considerations

• For septic shock: Use combination therapy with ≥2 antibiotics from different classes targeting most likely pathogens 1, 3
• For Pseudomonas aeruginosa with respiratory failure/shock: Combine extended-spectrum β-lactam with aminoglycoside or fluoroquinolone 1
• For pneumococcal septic shock: Combine β-lactam with macrolide 1
• Do NOT routinely use combination therapy for neutropenic sepsis/bacteremia 1

Empiric Antifungal Therapy

• Initiate echinocandin (caspofungin 70 mg load then 50 mg daily, micafungin 100 mg daily, or anidulafungin 200 mg load then 100 mg daily) immediately if: 4
  • Septic shock with suspected invasive candidiasis 4
  • Post-operative or community-acquired peritonitis with septic shock 4
  • Multiple risk factors: recent broad-spectrum antibiotics, multiple Candida colonization sites, central lines, TPN, immunosuppression 4

Vasopressor Support

• If hypotension persists despite initial fluid resuscitation, start vasopressors immediately 3
• Target mean arterial pressure (MAP) ≥65 mmHg 1, 3
• Norepinephrine is first-line vasopressor; dopamine or epinephrine are alternatives 2, 3
• Peripheral vasopressor administration is safe initially while obtaining central access 3

Monitoring Targets for Adequate Resuscitation

• Assess tissue perfusion markers: 2, 3
  • Capillary refill time <3 seconds 2, 3
  • Warm extremities (no mottling) 2, 3
  • Urine output >0.5 mL/kg/hour 2, 3
  • Lactate normalization (remeasure if initially elevated ≥4 mmol/L) 1, 3
• In persistent shock despite fluid resuscitation, consider measuring CVP (target ≥8 mmHg) and ScvO2 (target ≥70%) 1

Source Control (Within 12 Hours)

• Identify anatomic infection source rapidly through imaging (CT, ultrasound) 1, 2, 3
• Implement source control interventions within 12 hours when possible: 4, 3
  • Drain abscesses or infected fluid collections 2, 3
  • Debride necrotic tissue 2, 3
  • Remove infected devices (central lines, urinary catheters) after establishing alternative access 3
• Balance transport risks against diagnostic benefits—use bedside ultrasound when feasible 1

Ongoing Management (Days 1-10)

Daily Antimicrobial Reassessment

• Reassess antibiotic regimen daily for de-escalation once culture results available 1, 3
• Narrow to pathogen-directed therapy based on susceptibilities 1
• Discontinue combination therapy within first few days once clinical improvement evident 1, 3
• Optimize dosing using pharmacokinetic/pharmacodynamic principles: 1
  • Use loading doses regardless of organ dysfunction 5, 6
  • Consider extended or continuous infusion of β-lactams 5, 6
  • Adjust subsequent doses for renal/hepatic dysfunction 5, 6
  • Consider therapeutic drug monitoring when available 5, 6

Antifungal De-escalation

• Discontinue empiric antifungals at day 5 if no fungal infection confirmed 4
• If candidemia confirmed, continue for 2 weeks after blood culture clearance and symptom resolution 4
• For intra-abdominal candidiasis, treat for 2-3 weeks due to high recurrence rates 4

Duration of Therapy

• Typical duration: 7-10 days for most serious infections 1, 3
• Longer courses (>10 days) warranted for: 1
  • Slow clinical response 1, 3
  • Undrainable infection foci 1, 3
  • Staphylococcus aureus bacteremia 1
  • Fungal or viral infections 1
  • Neutropenia or immunodeficiency 1

Adjunctive Therapies

• Consider hydrocortisone or prednisolone if requiring escalating vasopressor doses 3
• Apply oxygen to maintain saturation >90% 2
• Position patient semi-recumbent (head of bed 30-45°) if mechanically ventilated 2

Critical Pitfalls to Avoid

• Never delay antibiotics beyond 1 hour—mortality increases significantly with each hour delay 1, 3
• Never use hydroxyethyl starches for resuscitation 3
• Never continue broad-spectrum antibiotics without daily reassessment for de-escalation 1, 3
• Never leave septic patients unmonitored—ensure continuous observation 2
• Never delay source control interventions when surgically correctable source identified 4, 3
• Never use antibiotics for confirmed noninfectious inflammatory states (severe pancreatitis, burns without infection) 1
• Never continue combination therapy beyond 3-5 days without clear indication 1, 3