Late-Onset Neonatal Sepsis

Introduction

Sepsis is defined as ‘a life-threatening organ dysfunction caused by a dysregulated host response to infection’ (1). NICE defines late-onset neonatal sepsis (LONS) as sepsis in infants between 72 hours and 28 days corrected gestational age (2). Although the time element of the definition for LONS varies in the literature (3), for the purpose of this article, we will use the NICE definition.

Epidemiology

The NeonIN surveillance network found the incidence of LONS to be 3/1000 live births and 29/1000 neonatal admissions in 2010, however it should be noted that their definition of LONS was sepsis in infants above 48 hours of age (4).

Pathophysiology

Group B streptococci are a common cause of early and late onset neonatal sepsis. Other causative organisms to consider in late onset sepsis are (4):

• Coagulase-negative Staphylococci (most common cause)
• Enterobacteriaceae
• Staphylococcus aureus (including Methicillin resistant)
• Fungi (usually Candida albicans)

Gram-positive organisms (staphylococci) are usually introduced from the environment or the patient’s skin, whereas Gram-negative organisms are usually from the infant’s gut microbiome (5).

Risk Factors 

Risk factors for LONS include (2):

• Prematurity
• Mechanical ventilations
• History of surgery
• Presence of a central catheter
• Presence or concern of an infection in another baby when from a multiple birth.

Clinical Features

Clinical features are often non-specific, and are similar to those of early-onset sepsis (2):

Behaviour

• Parental concern for change in behaviour
• Reduced responsiveness

Respiratory

• Increased respiratory rate >60
• Signs of respiratory distress
• Grunting or apnoea

Circulation

• Tachycardia or bradycardia

Skin

• Mottled or ashen skin
• Non-blanching rash
• Cyanosis

Other

• Abdominal distension
• Temperature abnormality (lower than 36°C or higher than 38°C)
• Seizures
• Reduced feeding
• Bulging fontanelle

Differential Diagnosis

Differential diagnoses of late-onset neonatal sepsis include (6):

• Bowel obstruction

  • This can present as a failure to pass meconium (thick sticky dark-green stool), abdominal distension, reduced feeding, and bilious vomiting (7).

• Necrotizing enterocolitis (NEC)

  • This is a medical and surgical emergency, most commonly occurring in preterm infants. It commonly presents as reduced feeding, abdominal distension and decreased bowel sounds. The baby may also have signs of sepsis (8).

• Metabolic disease

  • A variety of metabolic diseases can present in the neonatal period. Clinical features include drowsiness, poor feeding, hypoglycaemia and seizures (9).

• Cardiac

  • Congenital cardiac disease may present with lethargy, difficulty breathing, or poor feeding, which can mimic symptoms of LONS.

Investigations

Ideally the following investigations should be performed prior to starting antibiotics, although they should not delay antibiotics being given within 1 hour of the decision to treat sepsis. These are (2):

• Blood culture
• CRP (useful to monitor serially to assess likelihood of infection and monitor response to treatment)
• Urine microscopy and culture (clean catch or catheter only)
• Lumbar puncture if safe to do so and there is a strong clinical suspicion of neonatal infection/meningitis

Management

The antibiotic regimes used to treat LONS vary depending upon the following factors due to their influence on the most likely bacterial cause:

1. If the baby has never been discharged home after birth, flucloxacillin and gentamicin are most commonly used.
2. If the baby was discharged home and then readmitted, ceftriaxone is recommended (caution must be taken if there is coexisting jaundice due to potential liver damage.)
3. If there are clinical signs of meningitis, IV amoxicillin and cefotaxime are most commonly used.

Local antibiotic guidelines should always be followed and cases discussed with the microbiology team regarding  culture findings. A CRP should be repeated 18-24 hours after starting antibiotics, and antibiotics should be continued for at least 48 hours (2).

Antibiotics may be stopped if all the following criteria are met:

• Initial clinical suspicion of infection was not strong
• Baby is clinically well with no signs of infection
• CRP level and trend are reassuring
• Blood culture is negative

If the blood culture is positive and there are no signs of meningitis, then antibiotics should be continued to complete a 7-day course (2).

• A shorter course can be considered if baby is well and no causative organism is identified/the causative organism is a common commensal such as coagulase negative staphylococcus. The decision to continue treatment with antibiotics should be reviewed every 24 hours.
• A prolonged course can be considered if baby has not yet fully recovered or if the causative organism/site of infection requires a prolonged course.

Complications

LONS is a major cause of death in newborns, especially in preterm infants or those who develop fungal sepsis (5). However, newborns who recover from sepsis alone generally do not go on to develop long-term complications.

Newborns who develop LONS secondary to meningitis however, can suffer from significant sequelae, including hearing loss, seizures and cognitive impairment (12).

References