Sepsis

Epidemiology & Risk Factors

• Definitions:
  • Sepsis: Life-threatening organ dysfunction caused by dysregulated host response to infection (SOFA score change ≥ 2).
  • Septic Shock: Sepsis + vasopressor requirement to maintain MAP ≥ 65 mmHg AND serum lactate > 2 mmol/L despite adequate IV fluid resuscitation.
• Most Common Primary Sources: Pneumonia (50%), UTI, intra-abdominal infections, skin/soft tissue, catheter-related bloodstream infections (CRBSI).
• Risk Factors: Age < 1 yr or > 65 yrs, immunosuppression (chemotherapy, HIV, chronic steroids, asplenia), indwelling invasive devices (CVC, Foley catheter), major trauma/burns, DM, CKD, cirrhosis.
• Common Pathogens:
  • Gram-positive: S. aureus, S. pneumoniae, Enterococcus.
  • Gram-negative: E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa.
  • Fungal: Candida spp. (ICU, prolonged broad-spectrum Abx, TPN).

Clinical features

• Systemic Manifestations:
  • Fever (> 38°C) or Hypothermia (< 36°C; worse prognosis). c
  • Tachycardia (HR > 90 bpm), Tachypnea (RR > 20/min or PaCO2 < 32 mmHg).
  • Altered Mental Status (confusion, lethargy, encephalopathy).
  • Skin: Early “warm shock” (flushed, warm extremities, bounding pulses) → Late “cold shock” (cool, mottled extremities, sluggish capillary refill).
• End-Organ Hypoperfusion Signs:
  • Oliguria (UO < 0.5 mL/kg/hr).
  • Hypotension (SBP < 90 mmHg or MAP < 65 mmHg).
  • Petechiae / Purpura (suggests DIC or Neisseria meningitidis).
• Source-Specific Symptoms: Cough/purulent sputum (pulmonary), dysuria/CVA tenderness (renal), peritoneal signs (intra-abdominal).

Neonatal sepsis

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Epidemiology & Risk Factors

• Early-Onset Sepsis (EOS): Onset <7 days (typically <72 hrs). Vertical transmission.
  • #1 Cause: Group B Streptococcus (GBS) (Streptococcus agalactiae).
  • #2 Cause: Escherichia coli (especially in preterm infants).
  • Other: Listeria monocytogenes.
  • Risk Factors: Maternal GBS colonization, Chorioamnionitis (maternal fever + leukocytosis, fetal tachycardia, purulent amniotic fluid), PROM >18 hrs, Preterm birth (<37 wks).
• Late-Onset Sepsis (LOS): Onset 7–28 days (or >72 hrs). Horizontal/nosocomial or community transmission.
  • #1 Cause: Coagulase-negative Staphylococci (CoNS) (e.g., S. epidermidis, secondary to indwelling lines).
  • Other: S. aureus, E. coli, Klebsiella, Pseudomonas, Candida spp.
  • Risk Factors: Low birth weight / Prematurity, indwelling central venous access (UVC/PICC), prolonged intubation, parenteral nutrition.

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Clinical features

• General/Systemic:
  • Temperature instability (Hypothermia [< 36.5°C] is classic and more common than fever [> 38.0°C] in preterm/early neonates). c
  • Lethargy, irritability, poor feeding/weak suck, hypotonia.
• Respiratory:
  • Tachypnea, grunting, intercostal retractions, nasal flaring, apnea.
• Cardiovascular:
  • Tachycardia or bradycardia, delayed CRT (> 3 sec), mottling, hypotension (late sign of shock).
• Gastrointestinal:
  • Abdominal distension, emesis (bilious or non-bilious), feed intolerance, hepatomegaly.
• Laboratory/Metabolic clues:
  • Hypoglycemia or hyperglycemia, unexplained metabolic acidosis.

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Differential Diagnostics

• Transient Tachypnea of the Newborn (TTN): Diff by rapid recovery (< 72h), fluid in interlobar fissures on CXR, non-toxic infant without temperature instability.
• Respiratory Distress Syndrome (RDS): Diff by premature infant with diffuse ground-glass appearance and air bronchograms on CXR; lacks systemic infectious signs.
• Congenital Heart Disease (Ductal-Dependent): Diff by severe cyanosis/shock upon ductus arteriosus closure (days 1-3), murmur, asymmetric pulses, failure to improve on 100% O2 hyperoxia test.
• Inborn Errors of Metabolism (IEM): Diff by symptom onset after protein/sugar feeds begin, severe metabolic acidosis with elevated plasma ammonia/ketones.
• Neonatal Abstinence Syndrome (NAS): Diff by maternal substance use history, high-pitched cry, tremors, diarrhea, hyperreflexia, normal inflammatory markers.

Management

1. Emergency Stabilization (ABCDEs):
   • Airway/Breathing: Supplemental O2, CPAP, or mechanical ventilation if apneic/respiratory distress.
   • Circulation: Fluid resuscitation (10–20 mL/kg Normal Saline bolus); start vasoactive agents (dopamine/epinephrine) if fluid-refractory shock.
2. Empiric Antibiotic Therapy (Initiate immediately after cultures):
   • Early-Onset Sepsis (<7 days):
     • Ampicillin (covers GBS, Listeria) + Gentamicin (covers Gram-negative bacilli including E. coli). c
     • Alternative: Ampicillin + Cefotaxime (avoid Ceftriaxone in neonates due to biliary sludging & risk of hyperbilirubinemia/kernicterus).
   • Late-Onset Sepsis (>7 days / Hospitalized):
     • Vancomycin (covers MRSA, CoNS) + Gentamicin or Cefotaxime (covers Gram-negatives).
     • Add Acyclovir if HSV suspected (maternal vesicles, seizures, CSF pleocytosis w/ RBCs, elevated LFTs).
3. Targeted Therapy:
   • Adjust Abx based on culture & sensitivity. Duration: 7–10 days for uncomplicated sepsis, 14 days for GBS, 21 days for Gram-negative meningitis.

Complications

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• Critical illness polyneuropathy (CIP)
  • Definition: axonal injury, particularly to the motor neurons, as a sequela of sepsis and multiple organ dysfunction
  • Clinical features
    • Predominantly distal, symmetrical, flaccid paralysis of the extremities with muscle atrophy; may affect the diaphragm
    • Absent or reduced reflexes
    • Dysesthesias in a glove-and-stocking distribution may be present
• Critical illness myopathy (CIM), which results in a decrease of muscle membrane excitability and loss of myosin with resultant atrophy of myofibers