Note from the National Guideline Clearinghouse (NGC): This guideline was developed by the National Collaborating Centre for Women's and Children's Health, (NCC-WCH) on behalf of the National Institute for Health and Clinical Excellence (NICE). See the "Availability of Companion Documents" field for the full version of this guidance.
This guideline should be read in conjunction with:
Unless otherwise indicated, all references to infection in the guideline recommendations refer to early-onset neonatal infection (that is, onset of infection within 72 hours of birth).
Terms Used in This Guideline
Peak gentamicin concentration: The level of gentamicin in the baby's bloodstream shortly after administration. The blood sample is usually taken about 1 hour after giving the drug. High peak concentrations of gentamicin are necessary to kill bacteria.
Therapeutic monitoring: A process of measuring the concentration of a drug in the bloodstream, to avoid excessive levels that might be associated with adverse effects or to ensure adequate levels for therapeutic effect.
Trough gentamicin concentration: The level of gentamicin in the baby's bloodstream shortly before a further dose is given. High trough gentamicin concentrations may be associated with an increased risk of adverse effects.
Information and Support
If clinical concerns about possible early-onset neonatal infection arise during pregnancy or in the first 72 hours after birth (for example, in relation to risk factors [see Table 1, below] or clinical indicators [see Table 2, below]):
- Tell the baby's parents and carers.
- Explain the reason for concern (including the nature of early-onset neonatal infection).
- Discuss the preferred options for management (for example, observation, investigations, or antibiotic treatment).
- Give the baby's parents and carers time to consider the information provided, and offer further opportunities for discussion if necessary.
If considering antibiotic treatment because of clinical concerns about possible early-onset neonatal infection, discuss:
- The rationale for the treatment
- The risks and benefits in the individual circumstances
- The observations and investigations that may be needed to guide clinical management (for example, when to stop treatment)
- The preferred antibiotic regimen and likely duration of treatment
- The impact, if any, on where the woman or her baby will be cared for
To maintain communication with a woman in labour whose baby is at increased risk of infection, healthcare professionals should involve the woman in any handover of care, either when additional expertise is brought in because of the risk of infection or during planned changes in staff. The handover should include an update about the presence of any infection. (This recommendation is adapted from the related recommendation in the section "Care throughout Labour" in NICE clinical guideline 55, Intrapartum care. )
Reassure parents and carers that they will be able to continue caring for, and holding, their baby according to their wishes unless the baby is too ill to allow this. If the severity of the baby's illness means they need to change the way they care for the baby, discuss this with them.
Reassure parents and carers that babies at increased risk of, or with, early-onset neonatal infection can usually continue to breastfeed, and that every effort will be made to facilitate this. If a baby is temporarily unable to breastfeed, support the mother to express breast milk if she wishes to do so.
If the woman had group B streptococcal colonisation in a previous pregnancy but without infection in the baby, reassure her that this will not affect the management of the birth in the current pregnancy.
Offer parents and carers contact details of organisations that provide parent support, befriending, counselling, information, and advocacy. They may signpost families to other sources of help. (This recommendation is adapted from the related recommendation in the section "Long-term Management" in NICE clinical guideline 102.)
If there have been any concerns about early-onset neonatal infection before a baby is discharged, advise the parents and carers verbally and in writing that they should seek medical advice (for example, from National Health Service [NHS] Direct, 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), or
- Is unusually floppy, or
- Has developed difficulties with feeding or with tolerating feeds, or
- Has an abnormal temperature unexplained by environmental factors (lower than 36°C or higher than 38°C), or
- Has rapid breathing, or
- Has a change in skin colour
When the baby is discharged from the hospital or midwifery-led unit (or in the immediate postnatal period in the case of babies born at home), inform the parents and carers and the baby's general practitioner (GP), verbally and in writing, if the baby is considered to be at increased risk of infection.
If a baby has been treated for suspected or confirmed early-onset neonatal infection:
- Inform the parents and carers about potential long-term effects of the baby's illness and likely patterns of recovery, and reassure them if no problems are anticipated.
- Take account of parents' and carers' concerns when providing information and planning follow-up.
When a baby who has had a group B streptococcal infection is discharged from hospital:
- Advise the woman that if she becomes pregnant again:
- There will be an increased risk of early-onset neonatal infection
- She should inform her maternity care team that a previous baby has had a group B streptococcal infection
- Antibiotics in labour will be recommended
- Inform the woman's GP in writing that there is a risk of:
- Recurrence of group B streptococcal infection in the baby, and
- Group B streptococcal infection in babies in future pregnancies
If the woman has had group B streptococcal colonisation in the pregnancy but without infection in the baby, inform her that if she becomes pregnant again, this will not affect the management of the birth in the next pregnancy.
For every baby about whom there has been a clinical concern regarding early-onset neonatal infection, formulate a post-discharge management plan, taking into account factors such as:
- The level of the initial clinical concern
- The presence of risk factors
- Parents' and carers' concerns
Risk Factors for Infection and Clinical Indicators of Possible Infection
Recognising Risk Factors and Clinical Indicators
Use Table 1 below to identify risk factors for early-onset neonatal infection and Table 2 below to identify clinical indicators of early-onset neonatal infection.
Use Tables 1 and 2, below to identify red flags (risk factors and clinical indicators that should prompt a high level of concern regarding early-onset neonatal infection).
Table 1. Risk factors for Early-onset Neonatal Infection, Including 'Red Flags'
|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)
|Suspected or confirmed infection in another baby in the case of a multiple pregnancy
Table 2. Clinical Indicators of Possible Early-onset Neonatal Infection (Observations and Events in the Baby), Including 'Red Flags'
|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
|Signs of neonatal encephalopathy
|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 (lower than 36°C or higher than 38°C) unexplained by environmental factors
|Signs of shock
|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)
Before the Birth
For women in labour identify and assess any risk factors for early-onset neonatal infection (see Table 1, above). Throughout labour monitor for the emergence of new risk factors, such as intrapartum fever higher than 38°C, or the development of chorioamnionitis.
Manage prelabour rupture of membranes at term according to the recommendations in NICE clinical guideline 55, Intrapartum care .
After the Birth
If there are any risk factors for early-onset neonatal infection (see Table 1, above) or if there are clinical indicators of possible early-onset neonatal infection (see Table 2, above) perform a careful clinical assessment without delay. Review the maternal and neonatal history and carry out a physical examination of the baby including an assessment of the vital signs.
Use the following framework based on risk factors and clinical indicators, including red flags (see Tables 1 and 2, above), to direct antibiotic management decisions:
- In babies with any red flags, or with two or more 'non-red flag' risk factors or clinical indicators (see Tables 1 and 2, above), perform investigations (see the related recommendations in the section "Investigations before Starting Antibiotics in the Baby," below) and start antibiotic treatment. Do not delay starting antibiotics pending the test results (see the related recommendations in the section "Antibiotics for Suspected Infection," below).
- 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)
In babies being monitored for possible infection:
- If clinical concern increases, consider performing necessary investigations (see the related recommendations in the section "Investigations before Starting Antibiotics in the Baby," below) and starting antibiotic treatment (see the related recommendations in the section "Antibiotics for Suspected Infection," below).
- If no further concerns arise during the period of observation reassure the family and, if the baby is to be discharged, give advice to the parents and carers (see the related recommendation in the section "Information and Support," above).
If a baby needs antibiotic treatment it should be given as soon as possible and always within 1 hour of the decision to treat.
Manage suspected bacterial meningitis according to the recommendations in NICE clinical guideline 102 (Bacterial meningitis and meningococcal septicaemia) unless the baby is already receiving care in a neonatal unit.
Manage suspected urinary tract infection according to the recommendations in NICE clinical guideline 54 Urinary tract infection in children .
Continue routine postnatal care (see Postnatal care , NICE clinical guideline 37) for babies without risk factors (see Table 1, above) or clinical indicators of possible infection (see Table 2, above).
If maternal colonisation with group B streptococcus is first identified after the birth but within the first 72 hours of life, ask the person directly involved in the baby's care (for example, a parent, carer or healthcare professional) whether they have any concerns, identify any other risk factors present, and look for clinical indicators of infection. Use this assessment to decide on clinical management (see the related recommendation in the section "Risk Factors for Infection and Clinical Indicators of Possible Infection," above).
Offer intrapartum antibiotic prophylaxis using intravenous benzylpenicillin to prevent early-onset neonatal infection for women who have had:
- A previous baby with an invasive group B streptococcal infection
- Group B streptococcal colonisation, bacteriuria, or infection in the current pregnancy
If the woman decides to take intrapartum antibiotic prophylaxis, give the first dose as soon as possible and continue prophylaxis until the birth of the baby.
Consider intrapartum antibiotic prophylaxis using intravenous benzylpenicillin to prevent early-onset neonatal infection for women in preterm labour if there is prelabour rupture of membranes of any duration.
Consider intrapartum antibiotic prophylaxis using intravenous benzylpenicillin to prevent early-onset neonatal infection for women in preterm labour if there is suspected or confirmed intrapartum rupture of membranes lasting more than 18 hours.
Offer benzylpenicillin as the first choice for intrapartum antibiotic prophylaxis. If the woman is allergic to penicillin, offer clindamycin unless individual group B streptococcus sensitivity results or local microbiological surveillance data indicate a different antibiotic.
Avoiding Routine Use of Antibiotics in the Baby
Do not routinely give antibiotic treatment to babies without risk factors for infection or clinical indicators or laboratory evidence of possible infection.
Investigations Before Starting Antibiotics in the Baby
When starting antibiotic treatment in babies with risk factors for infection or clinical indicators of possible infection, perform a blood culture before administering the first dose.
Measure the C-reactive protein concentration at presentation when starting antibiotic treatment in babies with risk factors for infection or clinical indicators of possible infection.
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.
Do not routinely perform urine microscopy or culture as part of the investigation for early-onset neonatal infection.
Do not perform skin swab microscopy or culture as part of the investigation for early-onset neonatal infection in the absence of clinical signs of a localised infection.
Be aware that, although minor conjunctivitis with encrusting of the eyelids is common and often benign, a purulent discharge may indicate the presence of a serious infection (for example, with chlamydia or gonococcus).
In babies with a purulent eye discharge take swab samples urgently for microbiological investigation, using methods that can detect chlamydia and gonococcus. Start systemic antibiotic treatment for possible gonococcal infection while awaiting the swab microbiology results.
In babies with clinical signs of umbilical infection, such as a purulent discharge or signs of periumbilical cellulitis (for example, redness, increased skin warmth, or swelling), perform a blood culture, take a swab sample for microscopy and culture, and start antibiotic treatment with intravenous flucloxacillin and gentamicin (see the related recommendation in the section "Antibiotics for Suspected Infection," below)*. If the microbiology results indicate that the infection is not due to a Gram-negative infection, stop the gentamicin.
Antibiotics for Suspected Infection
Use intravenous benzylpenicillin with gentamicin as the first-choice antibiotic regimen for empirical treatment of suspected infection unless microbiological surveillance data reveal local bacterial resistance patterns indicating a different antibiotic.
Give benzylpenicillin in a dosage of 25 mg/kg every 12 hours†. Consider shortening the dose interval to 8-hourly based on clinical judgement (for example, if the baby appears very ill).
Give gentamicin in a starting dosage of 5 mg/kg*.
If a second dose of gentamicin is to be given (see the related recommendation in the section "Duration of Antibiotic Treatment," below) it should usually be given 36 hours after the first dose. The interval may be shortened, based on clinical judgement, for example if:
- The baby appears very ill
- The blood culture shows a Gram-negative infection
Decide on subsequent gentamicin doses and intervals taking account of blood gentamicin concentrations (see the related recommendations in the section "Therapeutic Drug Monitoring for Gentamicin," below).
Record the times of:
- Gentamicin administration
- Sampling for therapeutic monitoring
Regularly reassess the clinical condition and results of investigations in babies receiving antibiotics. Consider whether to change the antibiotic regimen taking account of:
- The baby's clinical condition (for example, if there is no improvement)
- The results of microbiological investigations
- Expert microbiological advice, taking account of local surveillance data
If there is microbiological evidence of Gram-negative bacterial sepsis, add another antibiotic to the benzylpenicillin and gentamicin regimen that is active against Gram-negative bacteria (for example, cefotaxime). If Gram-negative infection is confirmed stop benzylpenicillin.
Duration of Antibiotic Treatment
Investigations during Antibiotic Treatment
In babies given antibiotics because of risk factors for infection or clinical indicators of possible infection, measure the C-reactive protein concentration 18–24 hours after presentation.
Consider performing a lumbar puncture to obtain a cerebrospinal fluid sample in a baby who did not have a lumbar puncture at presentation who is receiving antibiotics, if it is thought safe to do so and if the baby:
- Has a C-reactive protein concentration of 10 mg/litre or greater, or
- Has a positive blood culture, or
- Does not respond satisfactorily to antibiotic treatment
Decisions 36 Hours after Starting Antibiotic Treatment
In babies given antibiotics because of risk factors for infection or clinical indicators of possible infection, 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
Consider establishing hospital systems to provide blood culture results 36 hours after starting antibiotics to facilitate timely discontinuation of treatment and discharge from hospital.
Clinical microbiology or paediatric infectious disease advice should be available every day from healthcare professionals with specific experience in neonatal infection.
Early-onset Neonatal Infection without Meningitis
The usual duration of antibiotic treatment for babies with a positive blood culture, and for those with a negative blood culture but in whom there has been strong suspicion of sepsis, should be 7 days. Consider continuing antibiotic treatment for more than 7 days if:
- The baby has not yet fully recovered, or
- This is advisable, based on the pathogen identified on blood culture (seek expert microbiological advice if necessary)
If continuing antibiotics for longer than 36 hours despite negative blood cultures, review the baby at least once every 24 hours. On each occasion, using clinical judgement, consider whether it is appropriate to stop antibiotic treatment, taking account of:
- The level of initial clinical suspicion of infection
- The baby's clinical progress and current condition, and
- The levels and trends of C-reactive protein concentration
Meningitis (Babies in Neonatal Units)
If a baby is in a neonatal unit and meningitis is suspected but the causative pathogen is unknown (for example, because the cerebrospinal fluid Gram stain is uninformative), treat with intravenous amoxicillin and cefotaxime.
If a baby is in a neonatal unit and meningitis is shown to be due to Gram-negative infection either by cerebrospinal fluid Gram stain or culture, stop amoxicillin and treat with cefotaxime alone.
If a baby is in a neonatal unit and meningitis is shown by cerebrospinal fluid Gram stain to be due to a Gram-positive infection, continue treatment with intravenous amoxicillin and cefotaxime while awaiting the cerebrospinal fluid culture result and seek expert microbiological advice.
If the cerebrospinal fluid culture is positive for group B streptococcus consider changing the antibiotic treatment to:
- Benzylpenicillin 50 mg/kg every 12 hours†, normally for at least 14 days, and
- Gentamicin in a starting dosage of 5 mg/kg every 36 hours*, with subsequent doses and intervals adjusted if necessary based on clinical judgement (see the related recommendation in the section "Antibiotics for Suspected Infection," above) and blood gentamicin concentrations (see the related in the section "Therapeutic Drug Monitoring for Gentamicin," below); gentamicin treatment should continue for 5 days.
If the blood culture or cerebrospinal fluid culture is positive for listeria consider stopping cefotaxime and treating with amoxicillin and gentamicin.
If the cerebrospinal fluid culture identifies a Gram-positive bacterium other than group B streptococcus or listeria seek expert microbiological advice on management.
Discharge after Antibiotic Treatment
On completing antibiotic treatment, consider prompt discharge of the baby from hospital, with support for the parents and carers and a point of contact for advice.
Therapeutic Drug Monitoring for Gentamicin
If a second dose of gentamicin is to be given (see the related recommendation in the section "Antibiotics for Suspected Infection," above) measure the trough blood gentamicin concentration immediately before giving the second dose. Consider the trough concentration before giving a third dose of gentamicin.
Hospital services should make blood gentamicin concentrations available to healthcare professionals in time to inform the next dosage decision (for example, within 30 hours of sampling).
Consider repeating the measurement of trough concentrations immediately before every third dose of gentamicin, or more frequently if necessary (for example, if there has been concern about previous trough concentrations or renal function).
Adjust the gentamicin dose interval, aiming to achieve trough concentrations of less than 2 mg/litre. If the course of gentamicin lasts more than three doses a trough concentration of less than 1 mg/litre is advised.
If an intended trough concentration measurement is not available, do not withhold the next dose of gentamicin unless there is evidence of renal dysfunction (for example, an elevated serum urea or creatinine concentration, or anuria).
Consider measuring peak blood gentamicin concentrations in selected babies such as in those with:
- Macrosomia (birthweight more than 4.5 kg)
- An unsatisfactory response to treatment
- Proven Gram-negative infection
Measure peak concentrations 1 hour after starting the gentamicin infusion.
If a baby has a Gram-negative or staphylococcal infection, consider increasing the dose of gentamicin if the peak concentration is less than 8 mg/litre.
Using clinical judgement, consider completing a course of intravenous antibiotics outside of hospital (for example, at home or through visits to a midwifery-led unit) in babies who are well without ongoing concerns if there is adequate local support.
When deciding on the appropriate care setting for a baby, take into account the baby's clinical needs and the competencies necessary to ensure safe and effective care (for example, the insertion and care of intravenous cannulas).
* Gentamicin is licensed for use in newborn babies. The summary of product characteristics recommends a dosage of 4–7 mg/kg/day administered in a single dose. The evidence reviewed for the guideline supports a starting dosage of 5 mg/kg every 36 hours administered in a single dose.
† Benzylpenicillin is licensed for use in newborn babies. The summary of product characteristics recommends a dosage of 50 mg/kg/day in two divided doses in babies under 1 week of age. In babies aged 1–4 weeks the dosage should be increased to 75 mg/kg/day in three divided doses, as recommended in the summary of product characteristics.