What is the prognosis and management of neonatal sepsis?

Prognosis and Management of Neonatal Sepsis

Neonatal sepsis remains a major cause of mortality and morbidity worldwide, with mortality rates of 11-19% in high and middle-income countries, and significantly higher rates in low and lower-middle-income countries (LLMICs) where the incidence can be up to 40 times higher than in high-income countries. 1

Epidemiology and Mortality

• Neonatal sepsis accounts for approximately 22% of global annual neonatal deaths 1
• Approximately 1.3 million cases occur worldwide annually, resulting in 203,000 deaths per year 2
• Mortality is higher in preterm and low birth weight infants 2
• In LLMICs, Gram-negative bacteria cause about 60% of neonatal sepsis cases, with significant regional variations in pathogen distribution 1, 3

Classification and Pathophysiology

Neonatal sepsis is typically classified based on timing of onset:

1. Early-onset sepsis (EOS):

   • Occurs within 72 hours to 7 days of birth
   • Associated with organisms acquired peripartum from maternal genital tract
   • In LLMICs, predominantly caused by Gram-negative bacteria 1, 3

2. Late-onset sepsis (LOS):

   • Occurs after 72 hours or 7 days up to 28 days of life
   • Often associated with hospital-acquired pathogens
   • Risk factors include prematurity, low birth weight, invasive procedures, and prolonged hospital stay 3

Hemodynamic Response in Neonatal Sepsis

The hemodynamic response in neonatal sepsis differs significantly from adults:

• Term neonates: Often present with low cardiac output and high systemic vascular resistance (SVR) 1
• Premature infants: Hemodynamic response is less understood but often complicated by persistent pulmonary hypertension of the newborn (PPHN) 1
• Preterm VLBW infants: Limited data available, mostly from echocardiographic evaluations 1

Management Algorithm

1. Initial Resuscitation (First 5 minutes)

• Recognize decreased mental status and perfusion
• Begin high-flow oxygen
• Establish IV/IO access 1

2. Fluid Resuscitation (First 15 minutes)

• Push boluses of 20 mL/kg isotonic saline or colloid up to and over 60 mL/kg until perfusion improves
• Correct hypoglycemia and hypocalcemia
• Begin antibiotics unless rales or hepatomegaly develop 1

3. Antimicrobial Therapy

• First-line empiric therapy: Combination of ampicillin or penicillin plus an aminoglycoside (gentamicin) 4, 5

  • Important caveat: High resistance rates to first-line antibiotics have been documented in LLMICs, with ampicillin resistance in 90% of E. coli cases and gentamicin resistance in 42-70% of Gram-negative species 3

• Duration: 10-14 days for confirmed sepsis with minimal focal infection 5

• Antibiotic stewardship:

  • Reevaluate when culture results are available
  • Discontinue antibiotics at 48 hours if cultures are negative and clinical suspicion is low 6
  • Prolonged empirical treatment (≥5 days) in preterm infants is associated with higher risks of late-onset sepsis, necrotizing enterocolitis, and mortality 6

4. Hemodynamic Support for Refractory Shock

• For fluid-refractory shock, begin inotropes 1
• In term newborns with PPHN, inhaled nitric oxide is often effective (greatest effect at 20 ppm) 1
• For poor left ventricle function with normal blood pressure, consider adding nitrosovasodilators or type III phosphodiesterase inhibitors to epinephrine (0.05-0.3 μg/kg/min) 1
• For refractory hypotension, norepinephrine can be effective but maintain ScvO2 >70% 1
• Consider hydrocortisone therapy for adrenal insufficiency 1

5. Advanced Support for Refractory Cases

• ECMO should be considered in term newborns with refractory shock after excluding other causes
  • Current ECMO survival rate for newborn sepsis is 80% 1
• For inadequate urine output and 10% fluid overload despite diuretics, consider CRRT 1

Prognostic Factors

Several factors influence the prognosis of neonatal sepsis:

1. Timing of intervention: Early diagnosis and prompt intervention with aggressive fluid therapy and antibiotics significantly improve outcomes 1

2. Pathogen type: Gram-negative infections, particularly those with antimicrobial resistance, are associated with worse outcomes 1

3. Hemodynamic response: Attainment of cardiac index 3.3-6.0 L/min/m² and oxygen consumption >200 mL/min/m² is associated with improved survival 1

4. Birth weight and gestational age: Mortality is higher in preterm and low birth weight infants 2

5. Regional factors: Outcomes are significantly worse in LLMICs due to higher antimicrobial resistance rates and limited resources 1

Prevention Strategies

• Intrapartum antibiotic prophylaxis for GBS-positive mothers 3
• Strict infection control measures in neonatal units 3
• Appropriate hand hygiene and minimizing invasive procedures 3
• Antimicrobial stewardship programs to prevent emergence of resistant organisms 3

Emerging Challenges

• Antimicrobial resistance: High resistance rates to WHO-recommended first-line antimicrobials have been documented globally, particularly in LLMICs 1, 3
• Diagnostic challenges: Lack of optimal diagnostic tests and frequent presence of noninfectious conditions that resemble sepsis 7
• Treatment dilemmas: Balancing the risks of antibiotic overuse with the need for prompt treatment 8

The prognosis of neonatal sepsis has improved with advances in neonatal care, but significant challenges remain, particularly in resource-limited settings where antimicrobial resistance is a growing concern.