What are the diagnostic criteria and treatment for sepsis?

Diagnosing Sepsis

Sepsis is diagnosed by identifying life-threatening organ dysfunction (defined by an acute change in Sequential Organ Failure Assessment [SOFA] score ≥2 points) caused by a dysregulated host response to a documented or suspected infection. 1

Core Diagnostic Criteria

The diagnosis requires both components:

1. Evidence of Infection

• Obtain at least 2 sets of blood cultures (aerobic and anaerobic) before starting antibiotics if this causes no substantial delay (>45 minutes) in antimicrobial administration 1, 2
• Draw at least one set percutaneously and one through each vascular access device (unless inserted <48 hours ago) 1
• Blood cultures should be obtained immediately when fever, chills, hypothermia, leukocytosis, left-shift neutrophils, neutropenia, hypoalbuminemia, new renal failure, or hemodynamic compromise develops 3
• Use proper technique: clean skin twice with 70% isopropyl alcohol or iodine solution, obtain 20-60 mL total blood volume (10-30 mL per bottle), change needle before inoculation 3

2. Evidence of Organ Dysfunction

Systemic inflammatory response indicators (need multiple):

• Temperature: >38.3°C or <36°C 1
• Heart rate: >90 beats/minute or >2 SD above normal for age 1
• Respiratory rate: >20 breaths/minute 1
• Altered mental status 1
• White blood cell count: >12,000/μL or <4,000/μL, or >10% immature forms 1

Organ dysfunction markers (any present):

• Cardiovascular: SBP <90 mmHg, MAP <70 mmHg, or SBP decrease >40 mmHg 1
• Renal: Urine output <0.5 mL/kg/h for ≥2 hours despite adequate fluid resuscitation, or creatinine increase ≥0.5 mg/dL 1
• Respiratory: PaO₂/FiO₂ <300 1
• Hepatic: Total bilirubin >4 mg/dL 1
• Hematologic: Platelet count <100,000/μL, INR >1.5, or aPTT >60 seconds 1
• Metabolic: Lactate >1 mmol/L 1
• Perfusion: Decreased capillary refill, skin mottling, or peripheral cyanosis 1

Biomarker Testing

Procalcitonin (PCT)

• Rises within 4 hours of bacterial exposure, peaks at 6-8 hours 2
• PCT ≥1.5 ng/mL has 100% sensitivity and 72% specificity for sepsis in ICU patients 2
• Higher diagnostic accuracy than CRP (AUC 0.85 vs 0.73) 2
• Correlates with sepsis severity and predicts mortality 3, 2
• Most useful for antibiotic de-escalation decisions rather than initial diagnosis 4

C-Reactive Protein (CRP)

• Rises 12-24 hours after inflammatory insult, peaks at 48 hours 2
• CRP ≥50 mg/L has 98.5% sensitivity and 75% specificity for sepsis 3, 2
• Less specific than PCT but widely available 2

Lactate

• Elevated lactate >1 mmol/L indicates tissue hypoperfusion 1
• Serial lactate measurements guide resuscitation effectiveness 1, 4
• Lactate >2 mmol/L is part of septic shock definition 4

Critical caveat: No single biomarker can differentiate sepsis from other causes of systemic inflammatory response syndrome (SIRS); they must be integrated with clinical examination and directed diagnostics 3, 2

Imaging for Source Identification

Initial Imaging Based on Clinical Presentation

For respiratory symptoms (cough, dyspnea, chest pain):

• Start with chest radiography for rapid screening—sensitivity 58%, specificity 91% for pneumonia 3
• If chest X-ray is normal/equivocal but suspicion remains high, proceed immediately to CT chest with IV contrast—identifies infectious source in 72% of cases and changes management in 45% 3
• CT has 81.82% positive predictive value for identifying septic foci 3

For abdominal/pelvic symptoms:

• CT abdomen/pelvis with IV contrast is the primary modality—identifies source in 52.8% of cases 3
• Ultrasound is appropriate for childbearing-age women with suspected gynecologic or hepatobiliary sources 3
• Abdominal radiography rarely provides definitive diagnosis but may show pneumoperitoneum 3

Special situations:

• Urosepsis with suspected obstruction: CT without contrast can identify obstructing calculi 3
• Neutropenic patients with perianal symptoms: MRI pelvis with/without contrast detects abscesses in 88% of cases 3
• Sepsis of unknown origin after initial workup: FDG-PET/CT identifies source in 66% and changes management in 25% 3

Diagnostic Algorithm

1. Implement routine sepsis screening for all acutely ill, high-risk hospitalized patients 1, 2

2. When sepsis is suspected, immediately:

   • Obtain blood cultures (≥2 sets) before antibiotics 1, 2
   • Measure lactate level 1
   • Check complete blood count with differential, creatinine, bilirubin, coagulation studies 1
   • Consider PCT and CRP if available 2

3. Identify infection source with targeted imaging:

   • Chest X-ray for respiratory symptoms 3
   • CT with IV contrast if X-ray nondiagnostic or for abdominal/pelvic source 3

4. Assess organ dysfunction using clinical and laboratory parameters above 1

5. Initiate treatment within 1 hour of recognition—do not delay for imaging if source is clinically apparent 1, 2

Common Pitfalls

• Waiting for culture results before diagnosis: Sepsis is a clinical diagnosis; cultures confirm but should not delay treatment 1, 2
• Relying on single biomarker: PCT or CRP alone cannot rule in/out sepsis; use comprehensive clinical assessment 3, 2
• Delaying imaging >45 minutes: If imaging will delay antibiotics beyond 45 minutes, start antibiotics first 2
• Using WBC count in neutropenic patients: Cannot be used as diagnostic criterion in this population 1
• Ordering MRI in unstable patients: Most septic patients are too unstable for prolonged MRI; use CT instead 3
• Missing the diagnosis entirely: Maintain high index of suspicion in febrile patients with nonspecific symptoms—sepsis often mimics viral illness initially 5