Neonates are particularly susceptible to infection both in utero, around the time of delivery and post-natally. This article will focus mainly on early onset neonatal sepsis (EONS). Early onset neonatal sepsis (EONS) is defined as sepsis occurring within the first 48-72 hours of life.
NICE introduced a guideline for the identification, investigation and treatment of babies with risk factors and clinical indicators for EONS (1). The guideline covers preventing infection within 72 hours of birth in healthy babies, treating pregnant women whose baby is at risk, and caring for babies who have a suspected or confirmed infection. It aims to reduce delays in recognising and treating sick babies and prevent unnecessary use of antibiotics.
Implementation of NICE quality standards was intended to reduce mortality along with reducing admissions and length of stay.
From the Neonatal Infection Surveillance Network, the incidence of culture positive sepsis is 0.9/1000 live births and 9/1000 admissions in the UK (2). While EONS is rare, there is a significant risk of death from delayed treatment of EONS.
A recent study of 400,000 infants found that despite neonatal intensive care, the mortality rate from EONS is 16%. The most immature and low birth weight infants are at highest risk of death (3). 85% of babies with early onset sepsis will show signs within the first 24 hours of life (4).
The most frequent cause of severe neonatal infection is Group B Streptococcus (GBS). Data collected prospectively in the UK over 1 year for neonates who required a septic screen in the first 72 h of life indicated a combined rate of definite and probable early onset GBS infection of 3.6 per 1000 livebirths (5).
Mainly caused by ascending infection in the mother with chorioamnionitis, perinatally via direct contact in the birth canal and haematogenous spread. The main micro-organisms associated with EONS include; GBS, E- coli, Coagulase-negative Staphylococcus, H influenzae and Listeria monocytogenes (4).
GBS is a gram-positive coccus that is present in up to 25% of pregnant women’s genital tract and is the commonest cause of EONS. Infection is via direct contact. Early infection often presents with respiratory distress, pneumonia and septicaemia.
Later presentation (after 72 hours) usually presents with septicaemia and/or meningitis. There is controversy over how to prevent GBS infections in babies. In the UK, mothers that are found to be GBS positive around the time of delivery will receive intrapartum antibiotics to prevent transmission to baby. If chorioamnionitis is suspected in the mother then broad-spectrum antibiotics should be used that include GBS cover (1).
Risk Factors and Clinical Features
Current practice is based on the NICE guidance (1). Babies who have either one red flag risk factor/clinical indicator (see below), or babies who have 2 non-red flag risk factors/clinical indicators warrant investigation and treatment with antibiotics for suspected EONS.
In babies without red flags and only one risk factor or one clinical indicator, using clinical judgement, consider: whether it is safe to withhold antibiotics, and whether it is necessary to monitor the baby’s vital signs and clinical condition (if monitoring is required continue it for at least 12 hours – at 0, 1 and 2 hours and then 2-hourly for 10 hours).
RISK FACTORS FOR INFECTION
- Invasive group B streptococcal infection in a previous baby
- Maternal group B streptococcal colonisation, bacteriuria or infection in the current pregnancy
- Prelabour rupture of membranes
- Preterm birth following spontaneous labour (before 37 weeks’ gestation)
- Suspected or confirmed rupture of membranes for more than 18 hours in a preterm birth
- Intrapartum fever higher than 38°C, or confirmed or suspected chorioamnionitis
- Parenteral antibiotic treatment given to the woman for confirmed or suspected invasive bacterial infection (such as septicaemia) at any time during labour, or in the 24-hour periods before and after the birth [This does not refer to intrapartum antibiotic prophylaxis] (Red Flag)
- Suspected or confirmed infection in another baby in the case of a multiple pregnancy (Red Flag)
CLINICAL INDICATORS SUGGESTIVE OF INFECTION
- Altered behaviour or responsiveness
- Altered muscle tone (for example, floppiness)
- Feeding difficulties (for example, feed refusal)
- Feed intolerance, including vomiting, excessive gastric aspirates and abdominal distension
- Abnormal heart rate (bradycardia or tachycardia)
- Signs of respiratory distress
- Respiratory distress starting more than 4 hours after birth (Red Flag)
- Hypoxia (for example, central cyanosis or reduced oxygen saturation level)
- Jaundice within 24 hours of birth
- Signs of neonatal encephalopathy
- Seizures (Red Flag)
- Need for cardio–pulmonary resuscitation
- Need for mechanical ventilation in a preterm baby
- Need for mechanical ventilation in a term baby (Red Flag)
- Persistent fetal circulation (persistent pulmonary hypertension)
- Temperature abnormality (lower than 36°C or higher than 38°C) unexplained by environmental factors
- Signs of shock (Red Flag)
- Unexplained excessive bleeding, thrombocytopenia, or abnormal coagulation (International Normalised Ratio greater than 2.0)
- Oliguria persisting beyond 24 hours after birth
- Altered glucose homeostasis (hypoglycaemia or hyperglycaemia)
- Metabolic acidosis (base deficit of 10 mmol/litre or greater)
- Local signs of infection (for example, affecting the skin or eye)
Red flag signs suggestive of neonatal infection
- Systemic anatibiotics given to mother for suspected bacterial infection within 24 hr of birth
- Signs of shock
- Respiratory distress starting more then 4 hours after birth
- Need for mechanical ventilation in a a term baby
- Suspected or confirmed infection in a co-twin
- Transient Tachypnoea of the newborn (TTN); in term babies, causes tachypnoea and increased work of breathing
- Surfactant deficient lung disease / respiratory distress syndrome (RDS); especially in preterm infants can cause tachypnoea and increased work of breathing
- Meconium Aspiration; can cause the baby to be born in poor condition, with respiratory distress, and may require intubation. Meconium aspiration can cause a rise in CRP.
- Haemolytic Disease of the Newborn; can present with jaundice within the first 24 hours of life.
- Manage suspected bacterial meningitis according to the recommendations in Bacterial meningitis and meningococcal septicaemia (NICE clinical guideline 102)
- Manage suspected urinary tract infection according to the recommendations in Urinary tract infection in children (NICE clinical guideline 54).
Full blood count, C- Reactive Protein (CRP) and blood cultures are taken initially before commencing antibiotics. If there is any obvious source e.g. foul smelling urine, or an eye with purulent discharge, relevant swabs/cultures should be taken. The CRP is then repeated at 18-24 hours.
A lumbar puncture (LP) may be performed to obtain a cerebrospinal fluid sample (CFS) before starting antibiotics if it is thought safe to do so and there is a strong clinical suspicion of infection, or there are clinical symptoms or signs suggesting meningitis. If performing the LP would unduly delay starting antibiotics, perform it as soon as possible after starting antibiotics.
LP may also be considered if the first or repeat CRP is raised (>10mg/L), the blood culture is positive or the baby does not respond satisfactorily to antibiotics. Asymptomatic babies on postnatal ward/ transitional care unit with CRP ≤60mg/L do not require a routine LP but should be reviewed by a middle grade doctor.
Use intravenous benzylpenicillin with gentamicin as the first-choice antibiotic regimen for empirical treatment of suspected EONS unless microbiological surveillance data reveal local bacterial resistance patterns indicating a different antibiotic.
Consider stopping the antibiotics at 36 hours if:
- the blood culture is negative, and
- the initial clinical suspicion of infection was not strong, and
- the baby’s clinical condition is reassuring with no clinical indicators of possible infection, and
- the levels and trends of C-reactive protein concentration are reassuring.
If the blood cultures are positive, antibiotics are continued for 7-10 days and up to 14 days if CSF is also positive. Babies who have a rise in their CRP at 24 hours of life, but who have negative blood cultures may go on to receive 5 days of IV antibiotics.
Overall mortality rates in late preterm and term infants from sepsis is 2-4%, with the rate being higher in babies with low birth weight and those who are preterm. Neonates with EONS from E.Coli have mortality rates of 6-10%. Mortality rates for term babies with early onset GBS sepsis are around 2-3% (6).
|1.||National Institute for Health and Clinical Excellence. Antibiotics for early-onset neonatal infection. NICE clinical guideline CG149. http://www.guidance.nice.org.uk/cg149. July 2014|
|2.||Vergnano S, Menson E, Kennea N et al. Neonatal infections in England:the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011; 96: F9-F14|
|3.||Stroll B, Hansen N, Sanchez P et al. Early onset neonatal sepsis: the burden of group B streptococcal and E. Coli disease continues. Pediatrics 2011;127:817-826|
|4.||A L Anderson-BerryMedscape. Neonatal Sepsis. Medscape. http://emedicine.medscape.com/article/978352-overview#a5|
|5.||Luck S, Torny M, d’Agapeyeff K et al. Estimated early onset Group B streptococcal neonatal disease. Lancet 2003; 361:1953-4|
|6.||M S Edwards. Management and outcome of sepsis in term and late preterm infants. https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants?source=search_result&search=neonatal+sepsis&selectedTitle=2%7E94|