Microbiology Definition of Sepsis
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with infection being a sine qua non (essential component) of sepsis. 1, 2
Causative Microorganisms
- More than 90% of sepsis cases are caused by bacteria, with Gram-negative and Gram-positive organisms occurring with approximately equal frequency 2
- Common bacterial pathogens include Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes 3
- Fungi, particularly Candida species, are responsible for a significant minority of cases 2, 3
- Viruses can cause sepsis in vulnerable patients (e.g., neonates, infants, and immunocompromised individuals), though viral sepsis is less commonly diagnosed 4
Pathophysiological Mechanisms
- Sepsis involves the recognition of pathogen-associated molecular patterns (PAMPs) by the host immune system, triggering inflammatory signaling pathways 2
- The dysregulated host response leads to profound circulatory, cellular, and metabolic abnormalities 5
- Microcirculatory dysfunction causes tissue hypoperfusion, leading to organ dysfunction 5
- Cellular and metabolic abnormalities include altered cellular metabolism resulting in lactate accumulation 5
- The inflammatory response depends on both the causative pathogen and host factors (genetic characteristics and co-existing illnesses) 1
Clinical Identification and Diagnosis
- Organ dysfunction can be clinically identified by an increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points 1
- Quick SOFA (qSOFA) criteria for rapid identification outside ICU settings include:
- Respiratory rate ≥22 breaths/min
- Altered mental status (Glasgow Coma Scale score ≤13)
- Systolic blood pressure ≤100 mmHg 1
- Microbiological diagnosis is essential for effective antimicrobial therapy, with blood cultures being the cornerstone of diagnosis 2
- Distinguishing colonization from infection is a key challenge in interpreting microbiological findings 2
Septic Shock Definition
- Septic shock is defined as a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities 1, 5
- Clinically identified by:
- Vasopressor requirement to maintain mean arterial pressure ≥65 mmHg
- Serum lactate level >2 mmol/L (>18 mg/dL) despite adequate volume resuscitation 5
Evolution of Sepsis Definitions
- Previous definitions (pre-2016) focused heavily on inflammation and used Systemic Inflammatory Response Syndrome (SIRS) criteria 1
- SIRS was defined as at least two of:
- Temperature >38°C or <36°C
- Heart rate >90 beats/minute
- Respiratory rate >20 breaths/minute or PaCO2 <32 mmHg
- White blood cell count >12,000/mm³ or <4,000/mm³, or >10% immature forms 2
- Current definition (Sepsis-3) emphasizes organ dysfunction rather than inflammatory response alone 2
Clinical Implications and Pitfalls
- Early recognition is crucial for improving outcomes 1, 6
- Failing to recognize perfusion abnormalities despite normal blood pressure in patients receiving vasopressors is a common pitfall 5
- Not measuring lactate levels, which are essential for diagnosis according to current definitions, is a significant oversight 5
- Confusing septic shock with other forms of distributive shock can lead to inappropriate management 5
- Special consideration needed for immunocompromised and elderly patients who may present with attenuated inflammatory responses 1
Diagnostic Challenges
- Up to 42% of sepsis presentations are culture negative, suggesting possible non-bacterial causes 4
- Prior antibiotic therapy may lead to negative cultures despite ongoing infection 2
- Correctly identifying unfamiliar organisms and determining the significance of mixed culture results present additional challenges 2
- Interpreting the importance of organisms normally of low virulence requires clinical correlation 2
Understanding the microbiology of sepsis is essential for appropriate antimicrobial therapy, which significantly impacts patient survival compared to inadequate or inappropriate treatment 2.