DESCRIPTION

• Sepsis is a clinical syndrome resulting from a dysregulated systemic inflammatory response to infection.
  • The host response evolves with early proinflammatory reactions directed at eliminating pathogens responsible for tissue damage and subsequent anti-inflammatory responses implicated in increased susceptibility to secondary infection.
  • Many septic patients die secondary to inflammatory response to infection, despite successful removal of the inciting pathogen.
• The definition of pediatric sepsis is currently in a state of evolution.
  • Attempts have been made to revise 2005 pediatric sepsis definitions based on Sepsis-3 revised adult criteria, but the work is still pending.
  • The definitions help to distinguish sepsis from uncomplicated infection that does not lead to organ dysfunction, a poor course, or death.
  • Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Septic shock is a subset of sepsis, which involves circulatory and cellular/metabolic dysfunction.
• Organ dysfunction is based on an increase in the Sequential Organ Failure Assessment (SOFA) of 2 points or more. SOFA score is a 24-point measure of organ dysfunction that uses six organ systems (renal, cardiovascular, pulmonary, hepatic, neurologic, hematologic), where 0 to 4 points are assigned per organ system.

EPIDEMIOLOGY

• Incidence of sepsis depends on severity of chronic morbid conditions, geographic location, and illness severity.
• Respiratory infection and bloodstream infections are found in almost two-thirds of cases of severe sepsis worldwide.
• Overall mortality is estimated at 8%.

ETIOLOGY

Sepsis can be caused by bacterial, viral, fungal, parasitic, and rickettsial infections.

• Pathogens vary with age, host immune status, setting (community or hospital), and presence of indwelling vascular catheter:
  • Neonates
    • Group B Streptococcus
    • Escherichia coli
    • Staphylococcus aureus
    • Coagulase-negative Staphylococcus (hospitalized premature infants)
    • Listeria monocytogenes
    • Enterococcus spp.
    • Herpes simplex virus (HSV)
    • Enterovirus
  • Respiratory pathogens
    • S. pneumoniae
    • H. influenzae
    • S. aureus
    • Streptococcus pyogenes
  • IV-line sepsis
    • Coagulase-negative Staphylococcus
    • Klebsiella spp.
    • Enterobacter spp.
    • Serratia spp.
  • Urosepsis
    • Enterobacteriaceae
  • Meningitis
    • S. pneumoniae
    • H influenzae
    • N. meningitidis
  • Intraabdominal source
    • Enterobacteriaceae
    • Bacteroides fragilis and other anaerobes
    • Enterococci
  • Culture-negative sepsis
    • Patient presents with clinical features of sepsis without evidence of positive blood culture. It is a host response to bacterial components or the result of antibiotic treatment prior to obtaining bacterial cultures.
  • Viruses
    • Influenza, parainfluenza, adenovirus, respiratory syncytial virus, and human metapneumovirus, SARS-CoV-2
    • Viral infections can present as bacterial sepsis in specific populations such as immunocompromised patients (Epstein-Barr virus, cytomegalovirus, adenovirus) and neonates (HSV, enterovirus, adenovirus infection).
  • COVID-19 (multisystem inflammatory syndrome in children [MIS-C])
    • In the recent era with emergence of COVID-19 infection, MIS-C can manifest similar to septic shock.
  • Fungi
    • Frequently seen in patients with indwelling vascular catheters, neutropenia, and prolonged usage of broad-spectrum antibiotics

RISK FACTORS

Sepsis may occur in previously healthy children, but children with chronic medical conditions and immunosuppression that render them vulnerable to invasive infections, are at increased risk, including:

• Prematurity
• Chronic medical conditions (cerebral palsy, uncorrected congenital heart disease, short gut syndrome)
• Immunosuppressive conditions (neutropenia, primary or acquired immunodeficiency, malignancy, patients receiving chemotherapy, organ transplant recipients, chronic use of high-dose systemic corticosteroids, severe malnutrition, hyposplenism)
• Indwelling central venous catheters or other invasive devices (e.g., urinary catheter)
• Serious injuries (extensive burns, multiple trauma)
• Unimmunized/underimmunized children

GENERAL PREVENTION

• Routine vaccination for Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae
• Vaccination against Neisseria meningitidis for high-risk patients (e.g., asplenia, complement deficiency)
• Antibiotic prophylaxis for household or day care exposure to confirmed cases of Hib or N. meningitidis, as per guidelines.
• Antibiotic prophylaxis for children with asplenia
• Prompt evaluation of fever in immunosuppressed and asplenic patients
• Aseptic technique for insertion and care of vascular catheters and minimizing duration of use