What is the plan of care and differential diagnosis for a patient presenting with severe sepsis?

Severe Sepsis: Differential Diagnosis and Plan of Care

Administer broad-spectrum IV antimicrobials within the first hour of recognition and initiate aggressive fluid resuscitation with at least 30 mL/kg crystalloid within the first 3 hours. 1

Differential Diagnosis

The differential for severe sepsis centers on identifying the source of infection and the causative organism:

Common Infection Sources (in order of frequency):

• Pulmonary: Pneumonia (community or hospital-acquired), empyema 2
• Abdominal: Peritonitis, cholangitis, appendicitis, diverticulitis, infected pancreatitis 2
• Urinary tract: Pyelonephritis, urosepsis 2
• Bloodstream: Catheter-related infections, endocarditis 2
• Skin/soft tissue: Cellulitis, necrotizing fasciitis, toxic shock syndrome 1
• Central nervous system: Meningitis, brain abscess 1

Causative Organisms to Consider:

• Gram-negative bacteria (most common): E. coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter 2
• Gram-positive bacteria: Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, Enterococcus 1, 2
• Fungal: Candida species (especially in immunocompromised, prolonged ICU stay, broad-spectrum antibiotic exposure) 1
• Viral: Influenza, COVID-19, HSV, CMV (in immunocompromised) 1
• Anaerobes: Consider with intra-abdominal or aspiration sources 1

Risk Factors Modifying Differential:

• Multidrug-resistant organisms: Recent hospitalization, ICU stay, recent antibiotics, nursing home residence 1
• Neutropenia: Broader fungal and bacterial considerations 1
• Immunosuppression: Opportunistic infections, atypical organisms 1

Immediate Plan of Care (First Hour)

1. Obtain Cultures BEFORE Antibiotics (but don't delay >45 minutes)

• At least 2 sets of blood cultures (aerobic and anaerobic bottles): one percutaneous, one through each vascular access device if present >48 hours 1, 3, 4
• Site-specific cultures: Urine, sputum, wound, CSF, or other body fluids as indicated 1
• Imaging to identify source: Chest X-ray, ultrasound, or CT as clinically appropriate (balance transport risk) 1

2. Laboratory Assessment

Essential Initial Labs:

• Complete blood count with differential: WBC >12,000/μL or <4,000/μL, or >10% bands 3
• Lactate level: Elevated >1 mmol/L indicates tissue hypoperfusion; guide resuscitation to normalize 1, 3
• Procalcitonin (PCT): Levels ≥1.5 ng/mL have 100% sensitivity for sepsis; rises within 4 hours, peaks at 6-8 hours 5
• C-reactive protein (CRP): Levels ≥50 mg/L have 98.5% sensitivity; rises 12-24 hours post-insult 5
• Comprehensive metabolic panel: Creatinine (≥0.5 mg/dL increase or >2.0 mg/dL indicates organ dysfunction), glucose (>140 mg/dL without diabetes) 3
• Liver function tests: Bilirubin >2 mg/dL indicates organ dysfunction 3
• Coagulation studies: INR >1.5, aPTT >60s, platelets <100,000/μL indicate coagulopathy 3
• Arterial blood gas: PaO₂/FiO₂ ratio, assess for metabolic acidosis 3

Biomarker Guidance:

• PCT is superior to CRP for sepsis diagnosis (AUC 0.85 vs 0.73) and correlates with severity and mortality 5
• Use PCT to guide de-escalation and discontinuation of antibiotics in patients without confirmed infection 1, 5

3. Antimicrobial Therapy (Within 1 Hour)

Empiric broad-spectrum coverage targeting all likely pathogens:

Standard Empiric Regimens:

• Community-acquired sepsis: Piperacillin-tazobactam OR ceftriaxone PLUS vancomycin (if MRSA risk) 1
• Hospital-acquired/healthcare-associated: Anti-pseudomonal beta-lactam (piperacillin-tazobactam, cefepime, or meropenem) PLUS vancomycin 1
• Neutropenic patients: Combination therapy with anti-pseudomonal beta-lactam PLUS aminoglycoside or fluoroquinolone 1
• Abdominal source: Add anaerobic coverage (metronidazole if not using piperacillin-tazobactam) 1
• Suspected toxic shock syndrome: Add clindamycin for toxin suppression 1

Special Considerations:

• Respiratory failure + shock with P. aeruginosa risk: Combination therapy with extended-spectrum beta-lactam PLUS aminoglycoside or fluoroquinolone 1, 4
• Pneumococcal bacteremia with shock: Beta-lactam PLUS macrolide 1, 4
• Fungal coverage: Add echinocandin if risk factors present (prolonged ICU stay, TPN, broad-spectrum antibiotics, immunosuppression) 1
• Avoid recently used antibiotics (within 3 months) 1

4. Fluid Resuscitation

• Initial bolus: 30 mL/kg IV crystalloid within first 3 hours for sepsis-induced hypoperfusion 1, 3, 4
• Crystalloids preferred (normal saline or lactated Ringer's); consider albumin if requiring substantial crystalloid 1
• Avoid hetastarch formulations 1
• Reassess frequently using dynamic variables (pulse pressure variation, stroke volume variation) over static variables (CVP) when available 1, 4
• Continue fluid challenges as long as hemodynamic improvement occurs without causing pulmonary edema 1

5. Hemodynamic Support

Vasopressor Therapy (if hypotension persists after fluid resuscitation):

• First-line: Norepinephrine to maintain MAP ≥65 mmHg 1, 3, 4
• Second-line: Epinephrine if additional agent needed 1
• Vasopressin (0.03 U/min) can be added to norepinephrine to raise MAP or decrease norepinephrine dose 1
• Avoid dopamine except in highly selected circumstances 1
• Add dobutamine if myocardial dysfunction with elevated filling pressures and low cardiac output, or ongoing hypoperfusion despite adequate volume and MAP 1

6. Source Control

• Identify anatomic source within 12 hours and intervene if feasible 1, 4
• Drain abscesses percutaneously when possible (less physiologic insult than surgery) 1
• Remove infected devices (catheters, prosthetics) promptly after establishing alternative access 1
• Surgical debridement for necrotizing infections 1
• Delay intervention for infected pancreatic necrosis until demarcation occurs 1

Ongoing Management (First 6-24 Hours)

Resuscitation Targets:

• MAP ≥65 mmHg 1, 3
• Lactate normalization (guide resuscitation to clear elevated lactate) 1, 3
• Urine output ≥0.5 mL/kg/h 3
• ScvO₂ ≥70% or SvO₂ normalization 1
• Capillary refill <2 seconds, warm extremities, normal mental status 1, 3

Antimicrobial Stewardship:

• Reassess daily for de-escalation once culture results available 1, 4
• Narrow to targeted therapy based on susceptibilities 1
• Discontinue combination therapy after 3-5 days 1
• Typical duration: 7-10 days; longer if slow response, undrained foci, S. aureus bacteremia, immunodeficiency 1
• Use PCT levels to guide discontinuation in patients without confirmed infection 1, 5, 4

Additional Monitoring:

• Serial lactate measurements every 2-4 hours until normalized 3
• Continuous hemodynamic monitoring 1
• Daily organ function assessment (renal, hepatic, respiratory, coagulation) 3
• Sepsis-Induced Coagulopathy (SIC) scoring to identify coagulation disorders early 5

Critical Pitfalls to Avoid

• Delaying antibiotics beyond 1 hour: Each hour delay increases mortality significantly 1, 4
• Inadequate initial fluid resuscitation: Must give full 30 mL/kg bolus in first 3 hours 1, 4
• Failing to obtain cultures before antibiotics: Obtain within 45 minutes or give antibiotics first 1, 3, 4
• Using narrow-spectrum empiric therapy: Must cover all likely pathogens initially 1
• Missing occult source requiring drainage: Actively search for and control source within 12 hours 1, 4
• Continuing broad-spectrum antibiotics unnecessarily: Daily reassessment for de-escalation is mandatory 1, 4
• Ignoring MDR risk factors: Recent hospitalization, antibiotics, or ICU stay require broader coverage 1