Recommendations

Parents and carers have the right to be involved in planning and making decisions about their baby's health and care, and to be given information and support to enable them to do this, as set out in the NHS Constitution and summarised in NICE's information on making decisions about your care.

Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

Please note that the Royal College of Obstetricians and Gynaecologists has produced guidance on COVID-19 and pregnancy for all midwifery and obstetric services. The Royal College of Paediatrics and Child Health has published guidance on COVID-19 for neonatal services.

Throughout this guideline, unless otherwise specified, the term neonatal infection covers both early-onset and late-onset infections.

1.1 Information and support

Parents and carers of babies at increased risk of neonatal infection

1.1.2

If clinical concerns about possible neonatal infection arise at any point:

  • talk to the baby's parents and carers, explaining the reason for concern, and explain what neonatal infection is

  • discuss the options for management that may be best for their baby (for example, observation, investigations or antibiotic treatment)

  • do not delay treatment, but when possible give the baby's parents and carers time to think about the information they have been given and ask any questions they may have before making treatment decisions. [2021]

1.1.3

If giving antibiotics because of clinical concerns about possible early- or late-onset neonatal infection, discuss with parents and carers:

  • the reason for the treatment

  • the risks and benefits in relation to their baby's circumstances

  • the observations and investigations that might be needed to guide treatment (for example, to help decide when to stop treatment)

  • the preferred antibiotic regimen (including how it will be delivered) and likely duration of treatment

  • the impact, if any, on where the woman or her baby will be cared for. [2021]

1.1.4

To maintain communication with a woman in labour whose baby is at increased risk of early-onset neonatal infection:

  • 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

  • include an update in the handover about the presence of any infection.

    For more guidance, see the section on communication in the NICE guideline on intrapartum care. [2012]

1.1.5

For babies who are considered to be at increased risk of early-onset infection, inform their parents and GP about this verbally and in writing:

  • when the baby is discharged from the hospital or midwifery-led unit or

  • in the immediate postnatal period, if the baby was born at home. [2012]

1.1.6

Reassure parents and carers that babies who have or are at increased risk of neonatal infection can usually continue to breastfeed, and that every effort will be made to help with this. If a baby is temporarily unable to breastfeed, support the mother to express breast milk if she wishes to do so. [2012]

1.1.7

When a woman is identified as having group B streptococcal colonisation, bacteriuria or infection during her current pregnancy:

  • advise the woman that if she becomes pregnant again:

    • that her new baby will be at increased risk of early-onset group B streptococcal infection

    • she should inform her maternity care team that she has had a positive group B streptococcal infection test in a previous pregnancy

    • her maternity care team will offer her antibiotics in labour

  • inform the woman's GP in writing that there is a risk of group B streptococcal infection in babies in future pregnancies. [2012, amended 2021]

Parents and carers of babies treated for neonatal infection

1.1.8

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. [2012]

1.1.9

Offer parents and carers contact details of organisations that provide parent support, befriending, counselling, information and advocacy. [2012]

1.1.10

If a baby has been treated for suspected or confirmed neonatal infection:

  • advise 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. [2021]

1.1.11

When a baby who has had a group B streptococcal infection is discharged from hospital:

  • advise the woman that if she becomes pregnant again:

    • that her new baby will be at increased risk of early-onset group B streptococcal infection

    • she should inform her maternity care team that she has had a previous baby with a group B streptococcal infection

    • her maternity care team will offer her antibiotics in labour

  • inform the woman's GP in writing that there is a risk of:

    • group B streptococcal infection recurrence in the baby and

    • group B streptococcal infection in babies in future pregnancies. [2012]

Parents and carers of babies being treated for bacterial meningitis

1.1.12

Early in the management of confirmed bacterial meningitis, discuss the following with parents and carers:

  • what might happen during the course of the disease

  • the uncertainty about the initial prognosis, and when they can expect to know more

  • the risk of passing on the infection

  • whether close contacts need to take any preventative measures (for example, for meningococcal meningitis or Haemophilus influenzae type b). [2024]

1.1.13

Repeat information over time and check the parents and carers understand, as they may be distressed and unable to ask questions when their baby is first diagnosed. [2024]

1.1.14

Provide emotional and pastoral support for family members and carers during hospitalisation. [2024]

For a short explanation of why the committee made these recommendations and how they might affect practice, see the rationale and impact section on information and support after diagnosis.

Full details of the evidence and the committee's discussion are in evidence review J: information for confirmed bacterial meningitis and evidence review K: support for confirmed bacterial meningitis.

Parents and carers of all babies

1.1.15

Before any baby is transferred home from the hospital or midwifery-led unit (or in the immediate postnatal period in the case of babies born at home), advise parents and carers to seek urgent medical help (for example, from NHS 111, their GP, or an accident and emergency department) if they are concerned that their baby:

  • is showing abnormal behaviour (for example, inconsolable crying or listlessness) or

  • is unusually floppy or

  • has an abnormal temperature unexplained by environmental factors (lower than 36°C or higher than 38°C) or

  • has abnormal breathing (rapid breathing, difficulty in breathing or grunting) or

  • has a change in skin colour (for example, where the baby becomes very pale, blue/grey or dark yellow) or

  • has developed new difficulties with feeding.

    Give the advice both in person, and as written information and advice for them to take away. [2021]

Post-discharge planning for babies who have not been given antibiotics

1.1.16

When there has been a clinical concern about neonatal infection in a baby, make 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. [2012]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on information and support.

Full details of the evidence and the committee's discussion are in evidence review A: information and support.

1.2 Preventing early-onset neonatal infection before birth

Intrapartum antibiotics

1.2.1

Offer antibiotics during labour to women who:

  • are in pre-term labour or

  • have group B streptococcal colonisation, bacteriuria or infection during the current pregnancy or

  • have had group B streptococcal colonisation, bacteriuria or infection in a previous pregnancy, and have not had a negative test for group B streptococcus by enrichment culture or polymerase chain reaction (PCR) on a rectovaginal swab samples collected between 35 and 37 weeks' gestation or 3 to 5 weeks before the anticipated delivery date in the current pregnancy or

  • have had a previous baby with an invasive group B streptococcal infection or

  • have a clinical diagnosis of chorioamnionitis. [2021]

1.2.2

Use table 1 to decide which antibiotic to use when giving intrapartum antibiotics for neonatal infection.

Table 1 Intrapartum antibiotics

Allergies

Women without chorioamnionitis

Women with chorioamnionitis

No penicillin allergy

Use Benzylpenicillin.

Use Benzylpenicillin plus gentamicin plus metronidazole.

Penicillin allergy that is not severe

Use Cephalosporin with activity against group B streptococcus (for example, cefotaxime).

Use with caution.

In April 2021 this was an off-label use of cephalosporins. See NICE's information on prescribing medicines.

Use Cephalosporin with activity against group B streptococcus (for example, cefotaxime) plus metronidazole.

Use with caution.

In April 2021 this was an off-label use of cephalosporins. See NICE's information on prescribing medicines.

Severe penicillin allergy

Consider:

Vancomycin or

An alternative antibiotic that would be expected to be active against group B streptococcus based on either sensitivity testing performed on the woman's isolate or on local antibiotic susceptibility surveillance data.

In April 2021 this was an off-label use of vancomycin. See NICE's information on prescribing medicines.

Consider:

Vancomycin plus gentamicin plus metronidazole or

An alternative antibiotic to vancomycin that would be expected to be active against group B streptococcus based on either sensitivity testing performed on the woman's isolate or on local antibiotic susceptibility surveillance data plus gentamicin plus metronidazole.

In April 2021 this was an off-label use of vancomycin. See NICE's information on prescribing medicines.

1.2.3

If using intravenous gentamicin during labour, use once-daily dosing. [2021]

1.2.4

Give the first dose of antibiotics as soon as possible after labour starts (or as soon as infection is suspected, in the case of chorioamnionitis), and continue until the birth of the baby. [2021]

1.2.5

Be aware that therapeutic drug monitoring may be needed when using gentamicin or vancomycin during labour. [2021]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on intrapartum antibiotics.

Full details of the evidence and the committee's discussion are in evidence review B: intrapartum antibiotics.

Women with prolonged prelabour rupture of membranes who have group B streptococcal colonisation, bacteriuria or infection

1.2.6

Offer an immediate birth (by induction of labour or caesarean birth) to women who are between 34 and 37 weeks' gestation who:

  • have prolonged prelabour rupture of membranes and

  • have group B streptococcal colonisation, bacteriuria or infection at any time in their current pregnancy. [2021]

For a short explanation of why the committee made the 2021 recommendation and how it might affect practice, see the rationale and impact section on women with prolonged prelabour rupture of membranes.

Full details of the evidence and the committee's discussion are in evidence review C: timing of delivery.

1.3 Risk factors for and clinical indicators of possible early-onset neonatal infection

Before birth

1.3.1

For women in labour, identify and assess any risk factors for early-onset neonatal infection (see box 1). Throughout labour, monitor for any new risk factors. [2021]

Assessing and managing the risk of early-onset neonatal infection after birth

1.3.3

If there are any risk factors for early-onset neonatal infection (see box 1), or if there are clinical indicators of possible early-onset neonatal infection (see box 2):

  • perform an immediate clinical assessment

  • review the maternal and neonatal history

  • carry out a physical examination of the baby, including an assessment of vital signs. [2021]

1.3.4

If group B streptococcus is first identified in the mother within 72 hours after the baby's birth:

  • ask those directly involved in the baby's care (for example, a parent, carer, or healthcare professional) whether they have any concerns in relation to the clinical indicators listed in box 2and

  • identify any other risk factors present and

  • look for clinical indicators of infection.

    Use this assessment to decide on clinical management (see recommendation 1.3.5). [2021]

Box 1 Risk factors for early-onset neonatal infection, including 'red flags'

Red flag risk factor:

  • Suspected or confirmed infection in another baby in the case of a multiple pregnancy.

Other risk factors:

  • Invasive group B streptococcal infection in a previous baby or maternal group B streptococcal colonisation, bacteriuria or infection in the current pregnancy.

  • Pre-term birth following spontaneous labour before 37 weeks' gestation.

  • Confirmed rupture of membranes for more than 18 hours before a pre-term birth.

  • Confirmed prelabour rupture of membranes at term for more than 24 hours before the onset of labour.

  • Intrapartum fever higher than 38°C if there is suspected or confirmed bacterial infection.

  • Clinical diagnosis of chorioamnionitis.

Box 2 Clinical indicators of possible early-onset neonatal infection (observations and events in the baby), including 'red flags'

Red flag clinical indicators:

  • Apnoea (temporary stopping of breathing)

  • Seizures

  • Need for cardiopulmonary resuscitation

  • Need for mechanical ventilation

  • Signs of shock

Other 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 (including grunting, recession, tachypnoea)

  • Hypoxia (for example, central cyanosis or reduced oxygen saturation level)

  • Persistent pulmonary hypertension of newborns

  • Jaundice within 24 hours of birth

  • Signs of neonatal encephalopathy

  • Temperature abnormality (lower than 36°C or higher than 38°C) unexplained by environmental factors

  • Unexplained excessive bleeding, thrombocytopenia, or abnormal coagulation

  • Altered glucose homeostasis (hypoglycaemia or hyperglycaemia)

  • Metabolic acidosis (base deficit of 10 mmol/litre or greater)

1.3.5

Use the following framework, based on the risk factors in box 1 and the clinical indicators in box 2, to make antibiotic management decisions as directed:

Kaiser Permanente neonatal sepsis calculator

1.3.6

The Kaiser Permanente neonatal sepsis calculator can be used as an alternative to the framework outlined in recommendation 1.3.5 for babies born after 34+0 weeks of pregnancy who are being cared for in a neonatal unit, transitional care or postnatal ward. It should only be used if it is part of a prospective audit, which should record:

  • total number of babies assessed using the calculator

  • number of babies correctly identified by the calculator who develop a culture-confirmed neonatal infection

  • number of babies incorrectly identified by the calculator who do not develop a culture-confirmed neonatal infection

  • number of babies missed by the calculator who develop a culture-confirmed neonatal infection. [2021]

1.3.7

If using the Kaiser Permanente neonatal sepsis calculator (see recommendation 1.3.6) to assess the risk of early-onset neonatal infection, use the classification given by the calculator to direct management decisions. [2021]

Management for babies at increased risk of infection

1.3.9

If a baby needs antibiotic treatment, give this as soon as possible and always within 1 hour of the decision to treat. [2021]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on risk factors for and clinical indicators of possible early-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review D: maternal and neonatal risk factors.

1.4 Investigations before starting antibiotics in babies who may have early-onset infection

1.4.2

Measure baseline C-reactive protein concentration when starting antibiotic treatment in babies who may have early-onset neonatal infection. [2012]

1.4.3

Do not routinely perform urine microscopy or culture as part of the investigations for early-onset neonatal infection. [2012]

1.4.4

Do not perform skin swab microscopy or culture as part of the investigations for early-onset neonatal infection if there are no clinical signs of a localised infection. [2012]

Lumbar puncture

1.4.5

If it is safe to do so, perform a lumbar puncture to obtain a cerebrospinal fluid sample when:

  • there is a strong clinical suspicion of early-onset neonatal infection or

  • there are clinical symptoms or signs suggesting meningitis. [2012]

1.4.6

Treat and stabilise any of the following before performing a lumbar puncture:

  • unprotected airway

  • respiratory compromise

  • shock

  • uncontrolled seizures

  • bleeding risk. [2024]

1.4.7

Do not perform lumbar puncture if there is:

  • extensive or rapidly spreading purpura

  • infection at the lumbar puncture site

  • risk factors for an evolving space-occupying lesion

  • any of these symptoms or signs, which might indicate raised intracranial pressure:

    • new focal neurological features (including seizures or posturing)

    • abnormal pupillary reactions

    • a progressive and sustained or rapid fall in level of consciousness. [2024]

1.4.8

Measure blood glucose in babies immediately before lumbar puncture, so that the cerebrospinal fluid to blood glucose ratio can be calculated. [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on lumbar puncture.

Full details of the evidence and the committee's discussion are in evidence review L: investigating and diagnosing suspected bacterial meningitis with cerebrospinal fluid parameters.

Cerebrospinal fluid investigations in babies with suspected bacterial meningitis
1.4.9

Perform the following cerebrospinal fluid investigations in babies with suspected bacterial meningitis:

  • red and white cell count and cell type (including differential white cell count)

  • total protein

  • glucose concentration (to calculate cerebrospinal fluid to blood glucose ratio)

  • microscopy for bacteria (using gram stain)

  • microbiological culture and sensitivities

  • PCR for relevant pathogens. [2024]

1.4.10

Store the remaining cerebrospinal fluid in case more tests are needed. [2024]

1.4.11

Ensure that cerebrospinal fluid, cell counts, total protein and glucose concentrations are available within 4 hours of lumbar puncture. [2024]

1.4.12

When interpreting the results of cerebrospinal fluid investigations, take into account:

  • red cells in the sample, which may suggest blood contamination or a different diagnosis

  • whether earlier antibiotics may have reduced the diagnostic reliability of these investigations. [2024]

1.4.13

Interpret cerebrospinal fluid results using standard age-appropriate threshold values (taking into account factors such as gestational age, chronological age, birth weight, and earlier antibiotic use or suspected immunodeficiency). [2024]

1.4.14

Interpret cerebrospinal fluid results in babies alongside the clinical presentation and maternal history. [2024]

1.4.15

If cerebrospinal fluid results are abnormal, consider alternative viral, mycobacterial, fungal or non-infectious causes as well as bacterial meningitis. [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on cerebrospinal fluid investigations in babies with suspected bacterial meningitis.

Full details of the evidence and the committee's discussion are in evidence review L: investigating and diagnosing suspected bacterial meningitis with cerebrospinal fluid parameters.

Advice for site-specific infections

1.4.16

Be aware that, although minor conjunctivitis with encrusted eyelids is common and often benign, a purulent discharge may indicate a serious infection (for example, with chlamydia or gonococcus). [2012]

1.4.17

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 waiting for the swab microbiology results. [2012]

1.4.18

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 and

  • take a swab sample for microscopy and culture and

  • start antibiotic treatment with intravenous flucloxacillin and gentamicin (see recommendations 1.5.3 and 1.5.4).

    If the microbiology results show that the infection is not caused by a Gram-negative bacterium, stop the gentamicin. [2012]

1.5 Antibiotics for suspected early-onset infection

1.5.1

Use intravenous benzylpenicillin with gentamicin as the first-choice antibiotic regimen for empirical treatment of suspected early-onset infection, unless microbiological surveillance data show local bacterial resistance patterns that indicate the need for a different antibiotic. [2012]

1.5.2

Give benzylpenicillin in a dosage of 25 mg/kg every 12 hours. Consider shortening the dose interval to every 8 hours, based on clinical judgement (for example, if the baby appears very ill). [2012]

1.5.3

Give gentamicin in a starting dose of 5 mg/kg (see recommendation 1.5.4). [2012]

1.5.4

When prescribing gentamicin, be aware that:

  • the summary of product characteristics recommends a dosage of 4 to 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.

    In 2021, a dosage of 5 mg/kg every 36 hours is an off-label use of gentamicin. See NICE's information on prescribing medicines. [2012]

1.5.5

If a second dose of gentamicin is given (see recommendation 1.6.3) this should usually be 36 hours after the first dose. Use a shorter interval if clinical judgement suggests this is needed, for example, if:

  • the baby appears very ill

  • the blood culture shows a Gram-negative infection. [2012]

1.5.8

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, including local surveillance data. [2012]

1.5.9

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. [2012]

1.6 Duration of antibiotic treatment for early-onset neonatal infection

Investigations during antibiotic treatment for early-onset neonatal infection

1.6.1

In babies given antibiotics because of risk factors for infection or clinical indicators of possible early-onset infection, measure the C-reactive protein concentration 18 to 24 hours after presentation. [2012]

1.6.2

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 positive blood culture (other than coagulase negative staphylococcus) or

  • the baby does not respond satisfactorily to antibiotic treatment, or

  • there is a strong clinical suspicion of infection or

  • there are clinical symptoms or signs suggesting meningitis. [2012, amended 2021]

Decisions 36 hours after starting antibiotic treatment

1.6.3

In babies given antibiotics because of risk factors for early-onset 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. [2012]

1.6.4

Consider establishing hospital systems to provide blood culture results 36 hours after starting antibiotics, to allow timely stopping of treatment and discharge from hospital. [2012]

1.6.5

Healthcare professionals with specific experience in neonatal infection should be available every day to give clinical microbiology or paediatric infectious disease advice. [2012]

Treatment duration for early-onset neonatal infection without meningitis

1.6.6

Give antibiotic treatment for 7 days for babies with a positive blood culture, and for babies with a negative blood culture if sepsis has been strongly suspected. Consider continuing antibiotic treatment for more than 7 days if:

  • the baby has not yet fully recovered or

  • this is advisable because of the pathogen identified on blood culture (seek expert microbiological advice if necessary). [2012]

1.6.7

If continuing antibiotics for longer than 36 hours despite negative blood cultures, review the baby at least once every 24 hours. Consider at each review whether it is appropriate to stop antibiotic treatment, taking account of:

  • the level of initial clinical suspicion of infection and

  • the baby's clinical progress and current condition and

  • the levels and trends of C-reactive protein concentration. [2012]

1.7 Antibiotic-impregnated intravascular catheters for reducing the risk of late-onset neonatal infection

1.7.1

Do not use rifampicin-miconazole-impregnated catheters for newborn babies. [2021]

For a short explanation of why the committee made the 2021 recommendation and how it might affect practice, see the rationale and impact section on antibiotic-impregnated intravascular catheters for reducing the risk of late-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review F: intravascular catheters.

1.8 Risk factors for and clinical indicators of possible late-onset neonatal infection

1.8.1

When assessing or reviewing a baby:

  • Check for, the possible clinical indicators of late-onset neonatal infection shown in table 2.

  • take into account that prematurity, mechanical ventilation, history of surgery and presence of a central catheter are associated with greater risk of late-onset neonatal infection.

  • Think about infection in the other babies when one baby from a multiple birth has infection. [2021]

1.8.2

Seek early advice from a paediatrician when late-onset infection is suspected in non-inpatient settings. [2021]

1.8.3

Refer to the NICE guidelines on fever in under 5s and suspected sepsis when assessing babies for late-onset neonatal infection who have been admitted to the hospital from home. [2021]

Be aware that some pulse oximeters can underestimate or overestimate oxygen saturation levels, especially if the saturation level is borderline. Overestimation has been reported in people with dark skin. See also the NHS England Patient Safety Alert on the risk of harm from inappropriate placement of pulse oximeter probes.

Table 2 Clinical indicators of possible late-onset neonatal infection (observations and events in the baby)

Category

Indicators

Behaviour

Parent or care-giver concern for change in behaviour

Appears ill to a healthcare professional

Does not wake, or if roused does not stay awake

Weak high-pitched or continuous cry

Respiratory

Raised respiratory rate: 60 breaths per minute or more

Grunting

Apnoea

Oxygen saturation of less than 90% in air or increased oxygen requirement over baseline

Circulation and hydration

Persistent tachycardia: heart rate 160 beats per minute or more

Persistent bradycardia: heart rate less than 100 beats per minute

Skin

Mottled or ashen appearance

Cyanosis of skin, lips or tongue

Non-blanching rash of skin

Other

Temperature 38°C or more unexplained by environmental factors

Temperature less than 36°C unexplained by environmental factors

Alterations in feeding pattern

Abdominal distension

Seizures

Bulging fontanelle

This table has been adapted from the high-risk criteria in table 1 of the NICE guideline on suspected sepsis.

Timing of antibiotics for late-onset neonatal infection

1.8.4

If a baby needs antibiotic treatment, give this as soon as possible and always within 1 hour of the decision to treat. [2021]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on risk factors for and clinical indicators of possible late-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review E: risk factors for late-onset neonatal infection.

1.9 Investigations before starting antibiotics in babies who may have late-onset infection

1.9.2

Measure baseline C-reactive protein concentration when starting antibiotic treatment in babies who may have late-onset neonatal infection. Use this together with later readings to assess the likelihood of infection and response to treatment. [2021]

1.9.3

Do not routinely perform urine microscopy or culture as part of the investigations for late-onset neonatal infection for babies in neonatal units. [2021]

1.9.5

Do not perform skin swab microscopy or culture as part of the investigations for late-onset neonatal infection if there are no clinical signs of a localised infection. [2021]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on investigations for late-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review G: investigations before starting treatment.

Lumbar puncture

1.9.6

If it is safe to do so, perform a lumbar puncture to obtain a cerebrospinal fluid sample when:

  • there is a strong clinical suspicion of neonatal infection or

  • there are clinical symptoms or signs suggesting meningitis. [2021]

For a short explanation of why the committee made the 2021 recommendation and how it might affect practice, see the rationale and impact section on investigations for late-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review G: investigations before starting treatment.

1.9.7

Treat and stabilise any of the following before performing a lumbar puncture:

  • unprotected airway

  • respiratory compromise

  • shock

  • uncontrolled seizures

  • bleeding risk. [2024]

1.9.8

Do not perform lumbar puncture if there is:

  • extensive or rapidly spreading purpura

  • infection at the lumbar puncture site

  • risk factors for an evolving space-occupying lesion

  • any of these symptoms or signs, which might indicate raised intracranial pressure:

    • new focal neurological features (including seizures or posturing)

    • abnormal pupillary reactions

    • a progressive and sustained or rapid fall in level of consciousness. [2024]

1.9.9

Measure blood glucose in babies immediately before lumbar puncture, so that the cerebrospinal fluid to blood glucose ratio can be calculated. [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on lumbar puncture.

Full details of the evidence and the committee's discussion are in evidence review L: investigating and diagnosing suspected bacterial meningitis with cerebrospinal fluid parameters.

Cerebrospinal fluid investigations in babies with suspected bacterial meningitis
1.9.10

Perform the following cerebrospinal fluid investigations in babies with suspected bacterial meningitis:

  • red and white cell count and cell type (including differential white cell count)

  • total protein

  • glucose concentration (to calculate cerebrospinal fluid to blood glucose ratio)

  • microscopy for bacteria (using gram stain)

  • microbiological culture and sensitivities

  • PCR for relevant pathogens. [2024]

1.9.11

Store the remaining cerebrospinal fluid in case more tests are needed. [2024]

1.9.12

Ensure that cerebrospinal fluid, cell counts, total protein and glucose concentrations are available within 4 hours of lumbar puncture. [2024]

1.9.13

When interpreting the results of cerebrospinal fluid investigations, take into account:

  • red cells in the sample, which may suggest blood contamination or a different diagnosis

  • whether earlier antibiotics may have reduced the diagnostic reliability of these investigations. [2024]

1.9.14

Interpret cerebrospinal fluid results using standard age-appropriate threshold values (taking into account factors such as gestational age, chronologic age, birth weight, and earlier antibiotic use or suspected immunodeficiency). [2024]

1.9.15

Interpret cerebrospinal fluid results in babies alongside the clinical presentation and maternal history. [2024]

1.9.16

If cerebrospinal fluid results are abnormal, consider alternative viral, mycobacterial, fungal or non-infectious causes as well as bacterial meningitis. [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on cerebrospinal fluid investigations in babies with suspected bacterial meningitis.

Full details of the evidence and the committee's discussion are in evidence review L: investigating and diagnosing suspected bacterial meningitis with cerebrospinal fluid parameters.

1.10 Antibiotics for late-onset neonatal infection

Choice of antibiotics

1.10.1

For babies with suspected late-onset neonatal infection who are already in a neonatal unit:

  • give a combination of narrow-spectrum antibiotics (such as intravenous flucloxacillin plus gentamicin) as first-line treatment

  • use local antibiotic susceptibility and resistance data (or national data if local data are inadequate) when deciding which antibiotics to use

  • give antibiotics that are effective against both Gram-negative and Gram-positive bacteria

  • if necrotising enterocolitis is suspected, also include an antibiotic that is active against anaerobic bacteria (such as metronidazole). [2021]

1.11 Duration of antibiotic treatment for late-onset neonatal infection

Investigations during antibiotic treatment for late-onset neonatal infection

1.11.1

In babies given antibiotics because of risk factors for infection or clinical indicators of possible late-onset neonatal infection, measure the C‑reactive protein concentration 18 to 24 hours after starting antibiotics. [2021]

1.11.2

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 positive blood culture (other than coagulase negative staphylococcus) or

  • the baby does not respond satisfactorily to antibiotic treatment, or

  • there is a strong clinical suspicion of infection or

  • there are clinical symptoms or signs suggesting meningitis. [2021]

Decisions 48 hours after starting antibiotic treatment

1.11.3

For babies given antibiotics because of suspected late-onset infection, consider stopping the antibiotics at 48 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. [2021]

1.11.4

Healthcare professionals with specific experience in neonatal infection should be available every day to give clinical microbiology or paediatric infectious disease advice. [2021]

Treatment duration for late-onset neonatal infection without meningitis

1.11.5

Give antibiotic treatment for 7 days for babies with a positive blood culture. Consider continuing antibiotic treatment for more than 7 days if:

  • the baby has not yet fully recovered or

  • longer treatment is needed because of the pathogen identified on blood culture (for example, Gram-negative bacteria or Staphylococcus aureus; seek expert microbiological advice if necessary) or

  • longer treatment is needed because of the site of the infection (such as intra-abdominal co-pathology, necrotising enterocolitis, osteomyelitis or infection of a central venous catheter). [2021]

1.11.6

Use a shorter treatment duration than 7 days when the baby makes a prompt recovery, and either no pathogen is identified or the pathogen identified is a common commensal (for example, coagulase negative staphylococcus). [2021]

1.11.7

If continuing antibiotics for longer than 48 hours for suspected late‑onset neonatal infection despite negative blood culture, review the baby at least once every 24 hours. At each review, decide whether to stop antibiotics, taking account of:

  • the level of initial clinical suspicion of infection and

  • the baby's clinical progress and current condition and

  • the levels and trends of C-reactive protein. [2021]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on antibiotics for late-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review H: antibiotics.

1.12 Antifungals to prevent fungal infection during antibiotic treatment for late-onset neonatal infection

1.12.1

Give prophylactic oral nystatin to babies treated with antibiotics for suspected late-onset neonatal bacterial infection if they:

  • have a birthweight of up to 1,500 g or

  • were born at less than 30 weeks' gestation. [2021]

    If oral administration of nystatin is not possible, give intravenous fluconazole. In April 2021, this was an off-label use of fluconazole. See NICE's information on prescribing medicines and use clinical judgement to determine the dosage. [2021]

For a short explanation of why the committee made the 2021 recommendations and how they might affect practice, see the rationale and impact section on antifungals to prevent fungal infection during antibiotic treatment for late-onset neonatal infection.

Full details of the evidence and the committee's discussion are in evidence review I: antifungals.

1.13 Avoiding routine use of antibiotics in babies

1.13.1

Do not routinely give antibiotic treatment to babies without risk factors for infection or clinical indicators or laboratory evidence of possible infection. [2012]

1.14 Early- and late-onset meningitis (babies in neonatal units)

1.14.1

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. [2012, amended 2021]

1.14.2

If a baby is in a neonatal unit and meningitis is shown (by either cerebrospinal fluid Gram stain or culture) to be caused by Gram-negative infection, stop amoxicillin and treat with cefotaxime alone. [2012, amended 2021]

1.14.3

If a baby is in a neonatal unit and meningitis is shown (by cerebrospinal fluid Gram stain) to be caused by a Gram-positive bacterium:

  • continue treatment with intravenous amoxicillin and cefotaxime while waiting for the cerebrospinal fluid culture result and

  • seek expert microbiological advice. [2012, amended 2021]

1.14.4

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, with:

1.14.5

If the blood culture or cerebrospinal fluid culture is positive for listeria, consider stopping cefotaxime and treating with amoxicillin and gentamicin. [2012, amended 2021]

1.14.6

If the cerebrospinal fluid culture identifies a Gram-positive bacterium other than group B streptococcus or listeria, seek expert microbiological advice on management. [2012, amended 2021]

For a short explanation of why the committee amended the 2012 recommendations and how they might affect practice, see the rationale and impact section on early- and late-onset meningitis.

Fluid restriction

1.14.7

Do not routinely restrict fluid intake to below routine maintenance needs in babies with bacterial meningitis. [2024]

1.14.8

Give maintenance fluids orally or by enteral tube, if tolerated. [2024]

For more guidance on fluid therapy, see the NICE guideline on intravenous fluid therapy in children and young people.

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on fluid restriction for confirmed bacterial meningitis.

Full details of the evidence and the committee's discussion are in evidence review M: fluid restriction in bacterial meningitis.

Assessing for immunodeficiency and recurrence risk in babies with bacterial meningitis

1.14.9

Refer babies with pneumococcal meningitis to a paediatric immunology and infectious disease specialist to assess for primary immunodeficiency. [2024]

1.14.10

For babies with bacterial meningitis, examine their back and scalp for signs of a sinus tract. [2024]

1.14.11

For babies with bacterial meningitis, take a history of:

  • head trauma, surgery or cerebrospinal fluid leak

  • immunisations

  • medicines, including drugs that suppress the immune system (such as complement inhibitors). [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on assessing for immunodeficiency and recurrence risk in babies with bacterial meningitis.

Full details of the evidence and the committee's discussion are in evidence review N: factors associated with recurrent bacterial meningitis.

Discharge after antibiotic treatment

1.14.12

After antibiotic treatment, consider prompt discharge of the baby from hospital, with support for the parents and carers and a point of contact for advice. [2012]

Preparing for hospital discharge

Identifying and managing complications
1.14.13

Identify follow-up needs for babies who have had bacterial meningitis, taking into account potential cognitive, neurological, developmental, hearing, psychosocial, education, and renal complications. [2024]

Cognitive, neurological and developmental complications
1.14.14

Refer babies for community neurodevelopmental follow-up. [2024]

1.14.15

For babies who are taking anti-epileptic drugs, refer for a medicines review 3 months after hospital discharge, with a clinician with an interest in epilepsy, an epilepsy specialist nurse, or a neurologist. [2024]

Audiological assessment
1.14.16

Offer an audiological assessment within 4 weeks of the baby being well enough for testing (and preferably before discharge). [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on identifying and managing complications.

Full details of the evidence and the committee's discussion are in evidence review O: long-term complications and follow-up for bacterial meningitis.

Psychosocial support

1.14.17

Consider referral to psychosocial support for family members and carers of babies who have had bacterial meningitis. [2024]

For a short explanation of why the committee made the 2024 recommendation and how it might affect practice, see the rationale and impact section on planning for care after hospital discharge.

Full details of the evidence and the committee's discussion are in evidence review Q: support for confirmed bacterial meningitis.

Care after hospital discharge

First review
1.14.18

For babies who have had bacterial meningitis, arrange for a review with a neonatologist or paediatrician at 4 to 6 weeks after discharge from hospital. As part of this review, cover:

  • the results of their audiological assessment, and whether cochlear implants are needed

  • damage to bones and joints

  • skin complications (including scarring from necrosis)

  • psychosocial problems (if relevant, see the NICE guideline on post-traumatic stress disorder)

  • neurological and developmental problems, in liaison with community child development services. [2024]

1.14.19

Arrange a review with a neonatologist or paediatrician for 1 year after discharge. At this review, assess for possible late-onset neurodevelopmental, sensory and psychosocial complications. [2024]

1.14.20

Healthcare professionals (such as school nurses, health visitors and GPs) with responsibility for monitoring the health and wellbeing of babies should be alert for late-onset complications of bacterial meningitis. [2024]

1.14.21

Be aware that late-onset complications may not be apparent until transition points (such as starting nursery or school). [2024]

1.14.22

Community child development services should follow up and assess the risk of long-term neurodevelopmental complications for at least 2 years after discharge. [2024]

1.14.23

If a neurodevelopmental deficit is identified, refer to the appropriate services (for example, neurodisability services) and agree with them who will be responsible for follow-up, to ensure that nobody misses out on care. [2024]

1.14.24

Advise parents and carers to get advice from their GP if their child develops possible neurodevelopmental complications more than 2 years after discharge. [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on care after hospital discharge.

Full details of the evidence and the committee's discussion are in evidence review O: long-term complications and follow-up for bacterial meningitis and evidence review Q: support for confirmed bacterial meningitis.

Recurrent bacterial meningitis

Risk factors
1.14.25

Risk factors for recurrent bacterial meningitis are:

  • primary or secondary immunodeficiency, including:

    • HIV

    • congenital complement deficiency or acquired inhibition

    • reduced or absent spleen function

    • hypogammaglobulinaemia

  • communication between the cerebrospinal fluid and external surface, for example, caused by:

    • prior trauma or surgery

    • a congenital anomaly. [2024]

Management
1.14.26

For babies who have had a recurrent episode of bacterial meningitis:

  • review with a paediatric immunology and infectious disease specialist and

  • agree which tests, investigations, vaccines and other interventions are needed to prevent re-occurrence. [2024]

1.14.27

Examine the baby's back and scalp for signs of a sinus tract. [2024]

1.14.28

Get specialist radiological advice on investigations for a cerebrospinal fluid leak. [2024]

1.14.29

Take an immunisation and medicine history, including for drugs that suppress the immune system (such as complement inhibitors). [2024]

1.14.30

In babies with recurrent meningitis with unconfirmed bacterial cause, consider other causes and get advice from an infection specialist. [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on recurrent bacterial meningitis.

Full details of the evidence and the committee's discussion are in evidence review N: factors associated with recurrent bacterial meningitis.

1.15 Therapeutic drug monitoring for babies receiving gentamicin

Trough concentrations

1.15.1

If giving a second dose of gentamicin, measure the trough blood gentamicin concentration immediately before giving the second dose. Take the trough concentrations into account before giving the third dose of gentamicin. [2012]

1.15.2

Repeat the measurement of trough concentrations immediately before every subsequent third dose of gentamicin, or more frequently if necessary (for example, if there has been concern about previous trough concentrations or renal function). [2012]

1.15.3

Hospital services should make blood gentamicin concentrations available to healthcare professionals in time to inform the next dosage decision. [2012]

1.15.4

Adjust the gentamicin dose interval, aiming to achieve trough concentrations of less than 2 mg/litre. If the course of gentamicin lasts for more than 3 doses, aim for a trough concentration of less than 1 mg/litre. [2012]

1.15.5

Do not withhold a dose of gentamicin because of delays in getting a trough concentration measurement, unless there is evidence of impaired renal function (for example, an elevated serum urea or creatinine concentration, or anuria). [2012]

Peak concentrations

1.15.6

Consider measuring peak blood gentamicin concentrations in selected babies, such as in those with:

  • oedema

  • macrosomia (birthweight more than 4.5 kg)

  • an unsatisfactory response to treatment

  • proven Gram-negative infection. [2012]

1.15.7

When measuring peak blood gentamicin concentrations, take the measurement 1 hour after starting gentamicin. [2012]

1.15.8

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. [2012]

1.16 Care setting

1.16.1

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 and for whom there are no ongoing concerns if there is adequate local support. [2012]

1.16.2

When deciding on the appropriate care setting for a baby, take into account the baby's clinical needs and the competencies needed to ensure safe and effective care (for example, the insertion and care of intravenous cannulas). [2012]

1.17 Planning for care after discharge

1.17.1

For babies who have had an infection, tell their GP (and health visitor if relevant), and explain any follow-up plans. [2024]

1.17.2

Tell the parents and carers who their main point of contact will be after discharge. [2024]

1.17.3

Document the follow-up plan for managing complications in the discharge summary. [2024]

1.17.4

The hospital team should coordinate with the following professionals for care after discharge:

  • tertiary and primary care and other specialists

  • allied professionals and community teams that will be involved in follow-up (for example, audiology and speech and language therapy departments). [2024]

For a short explanation of why the committee made the 2024 recommendations and how they might affect practice, see the rationale and impact section on planning for care after hospital discharge.

Full details of the evidence and the committee's discussion are in evidence review O: long-term complications and follow-up for bacterial meningitis, evidence review P: information for confirmed bacterial meningitis and evidence review Q: support for confirmed bacterial meningitis.

Terms used in this guideline

This section defines terms that have been used in a particular way for this guideline. For other definitions see the NICE glossary and the Think Local, Act Personal Care and Support Jargon Buster.

Early-onset neonatal infection

Neonatal infection less than 72 hours after birth.

Late-onset neonatal infection

Neonatal infection 72 hours or more after birth.

Peak blood 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.

Severe penicillin allergy

A history of allergy to penicillin with effects that are clearly likely to be allergic in nature such as anaphylaxis, respiratory distress, angioedema or urticaria.

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 blood 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.

  • National Institute for Health and Care Excellence (NICE)