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Neonatal Sepsis

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Neonatal sepsis is a life-threatening condition caused by systemic bacterial, viral or fungal infection within the first 28 days of life. It is classified as early-onset neonatal sepsis (occurring within the first 48-72 hours of life) or late-onset neonatal sepsis (occurring after the first 48-72 hours of life) to reflect the differing microbiology and to guide empirical management.1 Neonatal sepsis is a major cause of neonatal mortality and morbidity and has an incidence of 6.1 per 1000 live births and 48.8 per 1000 admissions to the neonatal unit in the UK.2 This article aims to give you an overview of the key points regarding this important neonatal condition.

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Aetiology and risk factors 1,2

Neonates are susceptible to infection as the newborn immune system is immature. This is especially true in preterm infants. Early-onset sepsis is caused by infection with organisms from the maternal genital tract, while late-onset sepsis is caused by organisms acquired through interaction with the home or hospital environment. The most common organisms and important risk factors are compared below (Table 1).

Table 1. Comparing risk factors and organisms for early and late-onset neonatal sepsis.

Β  Early-Onset Sepsis (< 48-72h) Late-Onset Sepsis (> 48-72h)
Risk factors


Low birth weight

Prolonged rupture of membranes (> 18 hours)

Maternal Group-B streptococcus (GBS) colonisation

Maternal infection during labour (e.g. chorioamnionitis)


Low birth weight

Invasive procedures (e.g. IV access or intubation)

Most common*

GBS (~40%)

E. coli (~20%)

Listeria monocytogenes



Coagulase-negative staphylococci (e.g. Staph. epidermidis) (~60%)

Staph. aureus (~6%)

E. coli (~6%)

Other Gram-negative organisms (e.g. Klebsiella, Enterobacter and Pseudomonas)

While neonatal sepsis is commonly associated with bacterial infection, viruses and fungi can cause sepsis too. These usually result in late-onset sepsis. The most common viruses are herpes simplex virus (HSV) and enteroviruses, and the most common fungus is Candida albicans.

*A global perspective: It is worth noting that, although the above table represents the commonest organisms in high-income countries such as the UK, Klebsiella species, E. coli and Staph. aureus are significant causes of early-onset neonatal sepsis in low and middle-income countries, while GBS is relatively uncommon.3 The preponderance of these Gram-negative organisms may relate to poor infection prevention and control practices around the time of delivery and are likely acquired from the environment, rather than vertically from the mother.

Clinical features

The clinical features of neonatal sepsis may be non-specific; therefore, it is important to consider this life-threatening condition among your list of differentials in any sick neonate.


A focussed history should be obtained from the obstetric team, the parents and/or the baby’s medical records. The aim of the history is to identify any risk factors for neonatal sepsis, as mentioned above.

Specific areas to cover are shown below.


  • Any fetal concerns during the pregnancy (e.g. growth problems or ultrasound scan abnormalities)?
  • Any maternal illness during pregnancy (particularly infections)?
  • Has the mum previously given birth to a baby who developed an invasive infection?

Labour and delivery:

  • What was the duration of membrane rupture?
  • Did the mum develop a fever during labour?
  • Were prophylactic antibiotics for GBS recommended and, if so, were they given?


  • What gestational age was the baby born at?
  • What was the baby’s birth weight?
  • What were the baby’s Apgar scores?
  • Were any abnormalities noticed during the baby check?

Since birth:

  • Have there been any feeding problems?
  • Has the baby passed urine and meconium?
  • Has the baby received any interventions?
  • Have the parents or nursing staffed noticed any of the clinical features of sepsis (mentioned below)?


Any sick neonate should undergo a thorough clinical examination (see our neonatal examination guide).

Clinical features of neonatal sepsis are shown below, categorised by body system.


  • Fever or temperature instability
  • Lethargy
  • Jaundice
  • Hypo- or hyperglycaemia


  • Apnoea
  • Respiratory distress
  • Cyanosis


  • Tachycardia or bradycardia
  • Hypotension
  • Poor perfusion and prolonged capillary refill


  • Poor feeding
  • Abdominal distention

Neurological (consider meningitis):

  • Irritability
  • Seizures
  • Bulging fontanelle (Figure 1)
Anterior fontanelle
Figure 1. Anatomy of the neonatal skull. Note the anterior fontanelle, which may appear β€œbulged” in cases of neonatal sepsis.8


Differential diagnoses

As the presentation of neonatal sepsis is generally non-specific, several other conditions have a similar presentation. Due to the difficulty of excluding sepsis clinically, antibiotics are usually still given whilst awaiting investigation results.

Possible differential diagnoses for neonatal sepsis include:

  • Congenital infections* (e.g. TORCH): Toxoplasmosis, Other (e.g. syphilis, varicella-zoster, parvovirus B19, HIV), Rubella, Cytomegalovirus and Herpes simplex virus.
  • Respiratory distress syndrome (RDS)
  • Transient tachypnoea of the newborn (TTN)
  • Necrotising enterocolitis (NEC)
  • Congenital pneumonia
  • Congenital heart disease
  • Haemolytic disease of the newborn (HDN)
  • Metabolic diseases (e.g. galactosaemia)

*A note on terminology: β€˜congenital infection’ refers to an infection that is acquired by the fetus in utero (usually through the placenta), whereas β€˜neonatal infection’ refers to infection acquired during or after delivery.5

Investigations 4,6

Laboratory investigations

  • Full blood count (FBC) and CRP
  • Blood cultures
  • Lumbar puncture
  • Urine culture (β€˜in-out’ catheter or suprapubic aspiration)
  • Swabs of specific lesions (skin swabs of pustules, eye swabs for eye discharge etc.)


  • Chest X-ray (if respiratory signs present on examination)
  • Abdominal X-ray (if abdominal signs present on examination)

Other investigations

More recently, scoring systems have been developed in an attempt to predict the risk of neonatal sepsis, guide management and reduce unnecessary antibiotic exposure. Currently, the most commonly used is the Kaiser Permanente Neonatal Early-Onset Sepsis Calculator. This score combines maternal risk factors (such as maternal temperature, duration of rupture of membrane and maternal GBS status) with the clinical appearance of the baby to estimate the risk of early-onset sepsis at birth and provide a recommended management plan.

Management 4,6

Neonatal sepsis is a life-threatening emergency. As such, prompt empirical management with broad-spectrum antibiotics is warranted whilst awaiting investigation results. The exact choice of antibiotic therapy can get complicated and depends on the local sensitivities of the neonatal unit you are working in (always consult local guidelines and the BNFC). However, in the interest of simplicity, some common empirical therapy options are listed below.

Early-onset sepsis

  • Benzylpenicillin plus gentamicin (IV)
  • Add cefotaxime (IV) if there is microbiological evidence of Gram-negative infection

Late-onset sepsis

  • Flucloxacillin (or vancomycin) plus gentamicin (IV)

Specific situations

  • Give amoxicillin and cefotaxime (IV) if meningitis is suspected
  • Add metronidazole if NEC is suspected
  • Add an antifungal (e.g. amphotericin B) if fungal sepsis is suspected (high-risk baby with a negative blood culture)
  • Add aciclovir (IV) if HSV infection is suspected (e.g. vesicular rash, late-onset sepsis with respiratory disease or sepsis not responding to antibiotics)

The choice of antibiotics should be reviewed and rationalised once culture results become available. Even if cultures are negative, antibiotics are often continued as neonates can deteriorate quickly and the blood culture may be falsely negative due to a low bacterial load, an inadequate volume of blood in the sample, or previous antibiotic exposure in the mother or baby. If at 36 hours tests are negative for infection and the baby appears well, antibiotics can be stopped.

Prognosis and complications 7

Complications of neonatal sepsis:

  • Poor cognitive development
  • Visual or hearing deficits
  • Cerebral palsy
  • Bronchopulmonary dysplasia (BPD)
  • Death

Key points

  • Neonatal sepsis is caused by bacterial, viral or fungal infection.
  • It is classified as either early-onset (<48-72 hours) or late-onset (>48-72 hours) sepsis.
  • The presentation can be non-specific, so diagnosis requires a high index of suspicion.
  • Key investigations include a septic screen (blood, CSF and urine cultures, FBC and CRP) with further investigations for specific concerns.
  • Management involves empirical antibiotic therapy depending on the likely organisms, followed by targeted therapy once culture results are available.
  • Complications include neurological sequelae, BPD and death.


Dr Felicity Fitzgerald

Academic Clinical Lecturer and Senior Registrar in Paediatric Infectious Diseases


  1. Shane A.L. et al. Neonatal sepsis. 2017 Oct;390(10104):1770-80. Available from: [LINK].
  2. Cailes B. et al. Epidemiology of UK neonatal infections: the neonIN infection surveillance network. Arch Dis Child Fetal Neonatal Ed. 2018 Nov;103(6):F547-53. Available from: [LINK].
  3. Zaidi A.K.M. et al. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009 Jan;28(1 Suppl):S10-8. Available from: [LINK].
  4. National Institute for Health and Care Excellence (NICE). Neonatal infection (early onset): antibiotics for prevention and treatment (CG149) [Internet]. 2012 [cited 12 June 2020]. Available from: [LINK].
  5. Vergnano S. and Heath P.T. Fetal and neonatal infections. 2017 Nov;45(11):P715-22. Available from: [LINK].
  6. Greater Glasgow and Clyde Paediatric Guidelines. 2018. Antibiotic guidelines for the neonatal unit [Internet]. 2018 [cited 12 June 2020]. Available from: [LINK].
  7. Singh M. and Gray C.P. Neonatal sepsis [Internet]. 2019 [cited 12 June 2020]. Available from: [LINK].
  8. Xxjamesxx. Cranial sutures shown from the top of the head. Licence: [CC BY-SA 3.0]. Available from: [LINK].


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