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Neonatal Sepsis

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Overview

Neonatal sepsis describes an infection of the bloodstream in neonates in the first 28 days of life. It can be divided into two different types based on onset as they have differing causes:

  • Early-onset sepsis (EOS) – sepsis occurring within the first 72 hours of life
  • Late-onset sepsis (LOS) – sepsis occurring after the first 72 hours of life

The NICE guidelines use 72 hours as the cutoff, however, some sources use 7 days as the cutoff.

Neonatal sepsis presents with non-specific signs and has high morbidity and mortality, therefore, always keep a high degree of suspicion and a low threshold for diagnosis and treatment.

Epidemiology

  • Neonatal sepsis is the most common cause of neonatal death in hospital
  • Neonatal infection is present in up to 8 in 1,000 live births and sepsis occurs in up to around 4 in 1,000 live births
  • Black people are at a higher risk of group B Streptococcus-related sepsis

Causes

Early-onset sepsis

Early-onset sepsis (EOS) is caused by the transmission of pathogens from the female reproductive tract to the newborn. Causes include:

  • Group B Streptococcus (Streptococcus agalactiae) – the most common cause of neonatal sepsis in the UK
  • Escherichia coli – the second most common cause
  • Listeria monocytogenes – rare but has a high tendency to infect pregnant people

Late-onset sepsis

Late-onset sepsis (LOS) is caused by the transmission of pathogens from the surrounding environment after delivery, such as from healthcare workers or contacts such as parents. Common causes include:

  • Staphylococcus epidermidis
  • Pseudomonas aeruginosa
  • In some cases, it can also be the same organisms responsible for EOS
  • Listeria monocytogenes – rare but has a high tendency to infect pregnant people

Group B Streptococcus

Group B Streptococcus (GBS, Streptococcus agalactiae) is present in the bowel flora of up to 40% of adults. This is known as colonisation and people who are colonised are ‘carriers’ of GBS. GBS carrier rates vary in different racial groups and are highest in people of black African ethnicity.

Universal screening for GBS is not routinely performed and a maternal request is not an indication for screening.

The Royal College of Obstetricians guidelines

Some people are offered intrapartum antibiotic prophylaxis (IAP) with benzylpenicillin if certain criteria apply to them:

  • If GBS detected in a previous pregnancy:
    • Offer IAP or testing in late pregnancy (at 35-37 weeks or 3-5 weeks before delivery date) and offer IAP is GBS is present
  • Also IAP to all people with:
    • A previous baby with early- or late-onset GBS infection
    • Preterm labour, regardless of GBS status
    • Pyrexia during labour (>38ºC)

Risk Factors

Early-onset sepsis

  • Current group B Streptococcus colonisation – usually identified via:
    • Screening urine antenatally for asymptomatic bacteriuria
    • Identification in a previous pregnancy
    • Infection throughout pregnancy, fever ≥38ºC during delivery
    • Prolonged rupture of membranes
    • Evidence of or confirmed chorioamnionitis
  • Prematurity – the majority of cases of neonatal sepsis are in premature babies
  • Low birth weight (<2.5 kg) – also found in the majority of cases of neonatal sepsis

Late-onset sepsis

  • Indwelling foreign bodies and/or breached skin integrity (e.g. central venous catheter, endotracheal tubes, parenteral nutrition)

Presentation

Overview

The features of neonatal sepsis are non-specific, therefore a low threshold for treatment should be kept:

  • Respiratory distress – one of the most common features:
    • This includes tachypnoea, grunting, nasal flaring, and chest recessions
  • Red flag indicators:
    • Apnoea
    • Seizures – if the cause is meningitis
    • Signs of shock – hypotension, tachycardia, reduced urine output, prolonged capillary refill time, mottled/ashen skin, cyanosis
    • Requiring resuscitation
    • Requiring mechanical ventilation
    • Presumed sepsis in another baby in a multiple pregnancy
  • Jaundice
  • Altered behaviour/responsiveness – lethargy, drowsiness, apathy
  • Feeding difficulties – such as refusing feeds
  • Vomiting
  • Hypoglycaemia
  • Hypoxia
  • Bradycardia
  • Temperature abnormalities:
    • Not usually reliable as this can be <36°C or >38°C

Investigations

Overview

  • Blood cultures – ideally before antibiotics are given but do not delay treatment:
    • If possible, two cultures should be taken to distinguish from contamination
  • Full blood count (FBC):
    • May show neutrophilia or neutropenia
  • C-reactive protein (CRP):
    • Not for diagnosis but measured as a baseline and used to monitor the response to treatment
    • Usually elevated
  • Blood gases:
    • May show metabolic acidosis which suggests severe sepsis, especially if there is a large base deficit (10 mmol/L or greater)
  • Lumbar puncture – if safe to do so and neonatal sepsis is strongly suspected or meningitis is possible:
    • Many places perform a lumbar puncture as part of a septic screen in all babies under 28 days of age
    • Severe sepsis is a contraindication to lumbar punctures, however, they can be performed after the patient is stabilised

Management

Overview

Always consult an experienced paediatrician and follow local policies. In general, do not wait for test results before starting antibiotics.

  • If there is one risk factor or clinical feature that is not a red flag, use clinical judgement and consider monitoring
  • If there is a single red flag, start antibiotics
  • If there are two or more risk factors or clinical factors, start antibiotics

Treatment of neonatal sepsis

  • 1st-line: IV benzylpenicillin and gentamicin unless local guidelines state otherwise
  • Measure CRP at 18-24 hours post-presentation to monitor response to antibiotics
  • Consider stopping antibiotic treatment at 36 hours if all of the following apply:
    • Blood culture negative and
    • Initial clinical suspicion of infection was not strong and
    • Clinical condition is reassuring and there are no clinical indicators of infection and
    • CRP levels and trends are reassuring
  • In all other neonates, the duration of treatment varies depending on ongoing investigations. Babies are reviewed at least once every 24 hours including monitoring their progress and clinical condition and the levels and trends of CRP.

Complications

Patient Advice

Patients should contact their midwife, or GP, or go to the emergency department if their baby has any of the following features:

  • Fever of 38°C or above
  • Rapid breathing, difficulty breathing, features of respiratory distress
  • Poor feeding, little interest in feeding, feed refusal, persistent vomiting
  • Changes in skin colour – pale or jaundice
  • Lethargy, floppiness, not waking for feeds, listless
  • Changes in behaviour such as inconsolable crying

Prognosis

  • Premature babies have higher mortality rates than term babies
  • Early diagnosis and treatment are associated with reduced mortality rates

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