Early onset sepsis in the neonate: prevention and treatment

Early Onset Sepsis (EoS) in the Neonate is defined as infection in the first 72 hours after birth, although, in practice, most of these infections present within the first 24h of life.  The organisms responsible for EoS in the neonate are predominantly those which may colonise the vagina or lower gastrointestinal tract in the mother.  Such colonisation is frequently asymptomatic however it may be associated with rupture of the membranes and preterm labour.  Less frequently these organisms may lead to chorioamnionitis which may in turn lead to sepsis in the mother or the neonate.

Causative organisms

• Group B Streptococcus (GBS)
• Gram negative bacteria (E. Coli, Enterobacter, Klebsiella)
• Staphylococci (Predominantly St. Aureus)
• Streptococci (other than GBS)
• Listeria

The commonest organism is GBS.  The incidence of early onset sepsis in the neonate due to GBS may be reduced by offering intrapartum antibiotic prophylaxis (IAP) to mothers who are at risk of transmitting this organism to their baby during the birth.  Those women who may benefit from IAP have been identified in two ways: firstly by screening for GBS carriage during the pregnancy and secondly by identifying clinical risk factors.  The most cost-effective method depends on local epidemiology including maternal GBS carriage rates and the incidence of neonatal sepsis in the population.  In the UK a risk-factor based approach is employed which is outlined in detail in the RCOG guideline “Group B Streptococcal Disease, Early-onset”  (Green-top Guideline No. 36  2017)

The following groups of women should be offered IAP with an intravenous antibiotic which is effective against group B Streptococcus.  This will be Benzylpenicillin or, for penicillin sensitive women, another antibiotic with activity against GBS should be used.  (This will usually be either Vancomycin, Teicoplanin, or Clindamycin dependent on local antibiotic policy)

• Women in whom colonisation with GBS has been identified in current or previous pregnancy
• Women with GBS bacteriuria in current or previous pregnancy
• Women with previous baby affected by early- or late-onset neonatal GBS disease
• Women in confirmed preterm labour < 37⁺⁰ weeks gestation

IAP should be given, where possible, at least 2 hours prior to delivery for optimum efficacy

Note: - Women with GBS in a previous pregnancy

Women with GBS detected in a previous pregnancy have a 50% risk of recurrent GBS carriage and should be offered routine IAP or the option of bacteriological testing in late pregnancy, followed by IAP if still positive.

If performed, bacteriological testing should be carried out at 35-37 weeks gestation or 3-5 weeks prior to the anticipated delivery date, i.e. 32-34 weeks gestation in multiple pregnancies. A single (Amies charcoal) swab should be taken from the lower vagina and anorectum. Healthcare professionals should indicate that the swab is being taken for GBS.

Potentially infected women who require antibiotics that also cover GBS

For the following women, antibiotic therapy should be determined by Obstetric guidelines for sepsis, but in addition must include specific GBS prophylaxis (as above).

• Where chorioamnionitis is suspected
• Who have a pyrexia during labour (> 38°C) or a temperature of ≥ 37.5°C on 2 separate occasions at least 2 hours apart or maternal sepsis with a temperature < 36°C
• For whom the sepsis 6 bundle is triggered

The NICE guideline shifts the emphasis away from offering treatment to babies whose mothers did not receive adequate intrapartum prophylaxis for GBS. 

Babies with ‘red flags’, multiple risk factors or abnormal clinical signs

In a number of high-risk situations referred to as "red flags", or where there are a number of lesser risk factors or clinical signs (see table 1 below), NICE recommends the prompt introduction of intravenous antibiotics. 

NB.  Antibiotics are recommended in this group even if adequate intrapartum prophylaxis has been given.

Babies with a single risk factor and no abnormal clinical signs

For infants without any "red flags", who have only a single risk factor for sepsis,  NICE recommends withholding antibiotics but closely monitoring the clinical condition of the infant over the first 24-36 hours.  

NICE further recommends that parents are involved in planning the care of their baby.  We will provide a parental information leaflet to explain the recommendations outlined above.  If parents remain concerned about the possibility of infection after having received this advice, they may opt to have the antibiotic therapy and/or the investigations offered to babies with multiple risk factors.   

Use the following framework based on risk factors and clinical indicators, including red flags, to direct antibiotic management advice:

Table 1 - Risk Factors and Clinical indicators

Red Flags	Risk Factors
	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 - (spontaneous ROM more than 24 hours before the onset of established labour  at term)
	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]
	Suspected or confirmed infection in another baby in the case of a multiple pregnancy

Red Flags	Clinical Indicators
	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
	Hypoxia (for example, central cyanosis or reduced oxygen saturation level)
	Jaundice within 24 hours of birth
	Apnoea
	Signs of neonatal encephalopathy
	Seizures
	Need for cardio–pulmonary resuscitation
	Need for mechanical ventilation in a preterm baby
	Need for mechanical ventilation in a term baby
	Persistent fetal circulation (persistent pulmonary hypertension)
	Temperature abnormality ( 36°C or  38°C) unexplained by environmental factors
	Signs of shock
	Unexplained excessive bleeding, thrombocytopenia, or abnormal coagulation
	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)

*  note that sleepiness, minor vomiting and early reluctance to feed are common symptoms in the normal neonate in the first day of life.  Clinical judgement must be used to determine whether these are more pronounced than usual for a baby of that gestation and age.

For babies with ' red flags' OR a strong clinical suspicion of sepsis. 
NB – follow this guidance whether or not Intrapartum Prophylaxis has been given

These babies will be managed initially on the neonatal unit and treated according to the antibiotic guideline.

• Prescribe Benzylpenicillin and Gentamicin
• Consider Cefotaxime if there is evidence of meningitis

NB – If there is strong evidence, or proof, of Early Onset Sepsis (EOS) the paediatric team should inform their Obstetric colleagues.  This may help guide maternal therapy if the mother is also unwell.

For babies with two or more risk factors or clinical indicators but without a strong clinical suspicion of sepsis

NB – follow this guidance whether or not Intrapartum Prophylaxis has been given

These babies may be managed on the postnatal wards after their initial investigations. 

• Prescribe Benzylpenicillin 50 mg/kg BD
• Prescribe and administer a single dose of Gentamicin
  
  If both CRP tests (0hrs & 18-24h) are normal AND blood cultures have no growth by 24 - 36h then no further Gentamicin should be given and the Benzylpenicillin should be discontinued.
  
  If either CRP is raised OR a positive blood culture is reported then Gentamicin should be prescribed on an ongoing basis commencing alongside the 3rd/4th Benzylpenicillin dose

For babies with a single 'non-red flag' risk factor or clinical indicator and no clinical evidence of sepsis.

For these infants we would recommend the following:

• Withholding antibiotics and observing the baby for 18-24 hours.

Parents should be informed about the risk factor which has prompted this recommendation.  The parents should be told that the clinical examination has not identified any current signs or symptoms of active infection and that we will continue to monitor these clinical signs throughout the first day of life.  (Most babies who develop EOS will become unwell in the first 12-24h). 

We recommend that all such infants are observed for this period irrespective of whether intrapartum prophylaxis was given or not.

A parental leaflet will be provided which will explain this recommendation and to provide information about the signs and symptoms of infection in a baby.

If the parents are uncomfortable with the decision not to perform any additional investigations, or treat with antibiotics, then this should be taken into account when planning the baby's care.  At the discretion of the medical staff the baby could be managed in the same way as babies with multiple risk factors or clinical concerns as outlined above.

For those babies identified as requiring investigation the following tests should be requested.

Baseline

Babies receiving antibiotic therapy

• FBC and differential
• CRP
• Blood culture

Selected babies

• Lumbar Puncture Perform a lumbar puncture to obtain a cerebrospinal fluid sample 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 lumbar puncture would unduly delay starting antibiotics, perform it  as soon as possible after starting antibiotics.

• Swabs - Routine swabs are not required but should be taken if the baby has:
• A purulent eye discharge. Swabs should be taken using methods that can detect Chlamydia and Gonococcus.
• Clinical signs of umbilical infection, such as a purulent discharge or signs of periumbilical cellulitis. Swabs should be sent for microbiology.

18-24 hours

   Babies receiving antibiotic therapy

• CRP

If antibiotic therapy continuing

• FBC
• U&E
• LFT

Subsequent investigations

Only babies requiring ongoing antibiotic therapy require additional investigations

• CRP - at appropriate intervals to monitor response to treatment
• Gentamicin levels before 3rd dose

*It is important to ensure that the local microbiology department regularly monitors blood cultures for growth during the incubation period.  This will ensure that the lack of a positive culture report in the period between 24-36h truly indicates a lack of microbial growth.

Decisions regarding investigation and treatment

Babies with a strong clinical suspicion of sepsis must receive appropriate treatment promptly to reduce the mortality and morbidity associated with early onset sepsis.  Parents should be fully informed regarding their baby's condition and the treatment required.  However, this counselling should not delay appropriate therapy.

Where a baby has only 'non-red flag' risk factors, or clinical indicators, we will recommend withholding antibiotics and keeping the baby under close observation for 24 hours.  If the parents are uncomfortable with this recommendation the clinician may, at discretion, manage the baby in the same fashion as an infant with multiple risk factors or clinical signs.

Advice regarding babies who become unwell after discharge

If there have been any concerns about early-onset neonatal infection before a baby is discharged, whether or not the baby received treatment, advise the parents and carers verbally and in writing that they should seek medical advice (for example, from NHS 24, their general practice, or an accident and emergency department) if they are concerned that the baby:

• Is showing abnormal behaviour (for example, inconsolable crying or listlessness),
• Is unusually floppy,
• Has developed difficulties with feeding or with tolerating feeds
• Has an abnormal temperature unexplained by environmental factors (lower than 36°C or higher than 38°C
• Has rapid breathing,
• Has a change in skin colour.