What is the difference between sepsis, Systemic Inflammatory Response Syndrome (SIRS), and infection?

Understanding the Differences Between Sepsis, SIRS, and Infection

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, SIRS is simply a nonspecific inflammatory response pattern that can occur with or without infection, and infection is the presence of microorganisms causing tissue invasion—these are three distinct entities that should not be conflated. 1

Current Definitions (Sepsis-3 Framework)

Sepsis

Sepsis requires two components: confirmed or suspected infection PLUS organ dysfunction (defined as an increase in SOFA score ≥2 points). 2, 1 This definition represents a fundamental shift from older frameworks that relied heavily on inflammatory markers. The organ dysfunction must be life-threatening, with associated in-hospital mortality >10%. 1

• Clinically identified using qSOFA criteria (≥2 of: respiratory rate ≥22/min, altered mental status with GCS ≤13, systolic BP ≤100 mmHg) for rapid bedside assessment outside the ICU 1
• The pathophysiology involves dysregulated inflammatory response leading to tissue injury, microcirculatory dysfunction, and organ failure 2
• The term "severe sepsis" is now obsolete and should not be used 2, 1

SIRS (Systemic Inflammatory Response Syndrome)

SIRS is a nonspecific physiologic response pattern that can be triggered by infection, trauma, burns, pancreatitis, or any major physiologic stress—it is NOT synonymous with sepsis. 2, 1

• Defined by ≥2 of: temperature >38°C or <36°C, heart rate >90 bpm, respiratory rate >20/min or PaCO2 <32 mmHg, WBC >12,000/mm³ or <4,000/mm³ or >10% bands 1
• SIRS criteria are no longer part of the sepsis definition per Sepsis-3 guidelines 1
• SIRS can occur without any infection present (e.g., severe pancreatitis, extensive burns, major surgery) 2
• Approximately 12% of patients with infection and organ failure do not meet SIRS criteria, yet have similar mortality to SIRS-positive patients 3

Infection

Infection is the invasion and multiplication of microorganisms in body tissues, which may or may not trigger SIRS or progress to sepsis. 1

• Over 90% of sepsis cases are bacterial (Gram-positive and Gram-negative equally), with fungi (particularly Candida) causing a significant minority 1
• Infection can be localized (e.g., cellulitis, uncomplicated UTI) without systemic manifestations 2
• Microbiological confirmation via blood cultures is essential but should not delay treatment 2

Critical Clinical Distinctions

The Hierarchy of Severity

1. Infection alone: Microorganisms present, may have local symptoms, no organ dysfunction
2. Infection + SIRS: Systemic inflammatory response to infection, but no organ dysfunction (this is NOT sepsis by current definitions) 1
3. Sepsis: Infection + organ dysfunction (SOFA ≥2) 2, 1
4. Septic shock: Sepsis + persistent hypotension requiring vasopressors (MAP ≥65 mmHg) + lactate >2 mmol/L despite adequate fluid resuscitation 2, 1

Common Pitfalls to Avoid

Do not diagnose sepsis based on SIRS criteria alone—this outdated approach misses 12% of patients with true sepsis and falsely labels many patients with noninfectious inflammatory conditions. 3

Do not withhold antimicrobials in suspected sepsis while waiting for SIRS criteria to be met—organ dysfunction can develop rapidly, and mortality increases with each hour of delayed antibiotics. 2

Do not assume all SIRS represents infection—in the first 48 hours post-operatively or after major trauma, SIRS commonly results from surgical stress and cardiopulmonary bypass rather than infection. 2 During this period, proven infection (positive cultures) should be required before diagnosing sepsis. 2

Do not continue antibiotics for prolonged periods in patients with SIRS from noninfectious causes (severe pancreatitis, burns)—this increases antimicrobial resistance without improving outcomes. 2

Practical Clinical Application

When evaluating a patient with suspected sepsis:

• Look for source of infection: Focused examination of surgical wounds, vascular access sites, pressure areas, sinuses; check for purulent urine, diarrhea (C. difficile), fundoscopic signs of candidal endophthalmitis 2
• Assess for organ dysfunction: Use SOFA score components (respiratory, cardiovascular, hepatic, coagulation, renal, neurologic) rather than SIRS criteria 1
• Obtain blood cultures immediately when fever, chills, hypothermia, hemodynamic compromise, or new organ dysfunction develops—ideally before antibiotics but do not delay treatment 2
• Measure procalcitonin and CRP for diagnostic support (PCT ≥1.5 ng/mL has 100% sensitivity, 72% specificity for sepsis; CRP ≥50 mg/L has 98.5% sensitivity, 75% specificity), but these cannot differentiate infection from other SIRS causes alone 2

Special populations requiring modified interpretation:

• Elderly patients may present with attenuated inflammatory responses and fewer peritoneal signs despite severe intra-abdominal sepsis 2, 1
• HIV-positive patients have increased sepsis susceptibility due to pre-existing immune activation and exhaustion, even on antiretroviral therapy 2, 1
• Neutropenic patients cannot mount typical SIRS responses; fever alone may be the only sign of life-threatening infection 2