Neonatal sepsis
Neonatal sepsis occurs when a serious bacterial or viral infection in the blood affects babies within the first 28 days of life. Neonatal sepsis is categorised into early-onset (EOS, within 72 hours of birth) and late-onset (LOS, between 7-28 days of life) sepsis, with each category tending to have a distinct group of causes and common presentations. Neonatal sepsis account for 10% of all neonatal mortality and therefore must be promptly identified and managed to prevent significant consequences, as untreated, the mortality can be very high.
Epidemiology
Male:female incidence 1:1
Incidence of neonatal sepsis: 1-5 per 1000 live births
Term neonates: 1-2 per 1000 live births
Late pre-term infants: 5 per 1000 live births
Birth weight <2.5kg: 0.5 per 1000 live births
Black race is an independent risk factor for group B streptococcus-related sepsis
Causes
Neonatal infection is present in 8 per 1000 live births (note: this is the incidence of neonatal infection, not yet necessarily progressed to neonatal sepsis), and is the key factor which leads to subsequent life-threatening neonatal sepsis
The overall most common causes of neonatal sepsis are group B streptococcus (GBS) and Escherichia coli, accounting for approximately two thirds of neonatal sepsis cases
Early-onset sepsis in the UK is primarily caused by GBS infection (75%)
Infective causes in early-onset sepsis are usually due to transmission of pathogens from the mother to the neonate during delivery
Late-onset sepsis usually occurs via the transmission of pathogens from the environment post-delivery, this is normally from contacts such as the parents or healthcare workers
Infective causes are more commonly coagulase-negative staphylococcal species such as Staphylococcus epidermidis, Gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella and Enterobacter, and fungal species
Other less common causes include:
Staphylococcus aureus
Enterococcus
Listeria monocytogenes
Viruses including herpes simplex and enterovirus
Risk factors
Mother who has had a previous baby with GBS infection, who has current GBS colonisation from prenatal screening, current bacteruria, intrapartum temperature ≥38ºC, membrane rupture ≥18 hours, or current infection throughout pregnancy
Premature (<37 weeks): approximately 85% of neonatal sepsis cases are in premature neonates
Low birth weight (<2.5kg): approximately 80% are low birth weight
Evidence of maternal chorioamnionitis
Patients typically present with a subacute onset of:
Respiratory distress (85%)
Grunting
Nasal flaring
Use of accessory respiratory muscles
Tachypnoea
Tachycardia: common, but non-specific
Apnoea (40%)
Apparent change in mental status/lethargy
Jaundice (35%)
Seizures (35%): if cause of sepsis is meningitis
Poor/reduced feeding (30%)
Abdominal distention (20%)
Vomiting (25%)
Temperature: not usually a reliable sign as the temperature can vary from being raised, lowered or normal
Term infants are more likely to be febrile
Pre-term infants are more likely to be hypothermic
The clinical presentation can vary from very subtle signs of illness to clear septic shock
Frequently, the symptoms will be related to the source of infection (e.g. pneumonia + respiratory symptoms, meningitis + neurological symptoms)
Investigations:
Blood culture: this will usually establish the diagnosis, as the sensitivity for septicaemia is around 90%. Should usually obtain two blood cultures if possible to distinguish from contamination, however one culture is still sufficient depending on hospital protocol
Full blood examination: neonatal sepsis is often associated with abnormal neutrophil counts (both neutrophilia and neutropenia), however in neonates, parameters on full blood examination are usually not always useful for diagnosis, rather may help to exclude healthy neonates
C-reactive protein: not useful for diagnosis, but sequential assessment will help to guide management and patient progress with treatment. CRP will usually be raised, and a persistently normal level is likely to exclude neonatal sepsis
Blood gases: metabolic acidosis is particularly concerning for neonatal sepsis, particularly a base deficit of ≥10 mmol/L
Urine microscopy, culture and sensitivity: rarely positive in EOS, more useful in LOS. Will show signs of infection (e.g. raised leukocytes, positive culture, haematuria, proteinuria) if urinary tract infection is the source of sepsis
Lumbar puncture: particularly if there is concern of meningitis as the source of sepsis based on clinical features, however many hospitals will require lumbar puncture as part of a septic screen in any baby below the age of 28 days
Management
In neonatal sepsis, the most important part of management to improve outcomes is early identification and treatment
The NICE guidelines recommend use of intravenous benzylpenicillin with gentamicin as a first-line regimen for suspected or confirmed neonatal sepsis
The exception to this is if microbiological surveillance data reveal local bacterial resistance patterns, in which case an alternative antibiotic should be considered
CRP should be re-measured 18-24 hours after presentation in babies given antibiotics to monitor ongoing progress and guide duration of therapy
The evidence suggests that antibiotics can be ceased at 48 hours in neonates who have CRP of <10 mg/L and a negative blood culture at presentation and at 48 hours
In all other neonates, the duration of antibiotic treatment will depend on the ongoing investigations and clinical picture, this will involve specialist decision making. Normally, in neonates with culture-proven sepsis, duration will be approximately 10 days
Other important management factors to consider include:
Maintaining adequate oxygenation status
Maintaining normal fluid and electrolyte status: severely ill neonates may require volume and/or vasopressor support. Body weight needs to be measured daily for accurate assessment of fluid status
Prevention and/or management of hypoglycaemia
Prevention and/or management of metabolic acidosis
