DOI: 10.1111/tog.12085 2014;16:87–92
The Obstetrician & Gynaecologist
Review
http://onlinetog.org
Antibiotics for early-onset neonatal infection: a summary
of the NICE guideline 2012
Moira A Mugglestone BSc MSc PhD FCMI,a,* M Stephen Murphy BSc DCH MD FRCPI FRCPCH,b,c,d Cristina Visintin
e f g
PhD, David T Howe DM FRCOG FRCS(Ed), Mark A Turner BSc MBChB PhD MRCP(UK) MRCPCH DRCOG
a
Director, National Collaborating Centre for Women’s and Children’s Health, Royal College of Obstetricians and Gynaecologists, 27 Sussex Place,
Regent’s Park, London NW1 4RG, UK
b
Clinical Director for Children’s Health, National Collaborating Centre for Women’s and Children’s Health, Royal College of Obstetricians and
Gynaecologists, 27 Sussex Place, Regent’s Park, London NW1 4RG, UK
c
Senior Lecturer in Paediatrics and Child Health, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15
2TT, UK
d
Consultant Paediatric Gastroenterologist, Birmingham Children’s Hospital, NHS Foundation Trust, Birmingham B4 6NH, UK
e
Project Manager, National Collaborating Centre for Women’s and Children’s Health, Royal College of Obstetricians and Gynaecologists, 27 Sussex
Place, Regent’s Park, London NW1 4RG, UK
f
Consultant and Honorary Senior Lecturer in Feto-Maternal Medicine, Wessex Fetal Medicine Unit, Princess Anne Hospital, Coxford Road,
Southampton SO16 5YA, UK
g
Senior Lecturer in Neonatalogy and Consultant in Neonatology, Department of Women’s and Children’s Health, University of Liverpool and
Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, UK
*Correspondence: Moira A Mugglestone. Email:
Accepted on 13 January 2014
Key content Learning objectives
Early-onset neonatal infection (infection arising within 72 hours of To be aware of the risk factors for early-onset neonatal infection.
birth) is an important cause of morbidity and mortality and is To understand how IAP can reduce the risk of an early-onset
often caused by Streptococcus agalactiae (group B streptococcus neonatal infection.
[GBS]). To know which antibiotic to use for IAP of GBS.
Identifying and assessing risk factors for early-onset neonatal
Ethical issues
infection before and during labour and birth is integral to clinical
How should decisions about whether to administer IAP trade off
management.
the potential benefit to the baby of preventing an early-onset
Intrapartum antibiotic prophylaxis (IAP) to prevent early-onset
neonatal infection and potential harms to the woman, such as,
neonatal infection is effective when given to women with particular
allergic reactions and increased medicalisation of pregnancy?
risk factors, including maternal GBS colonisation. How should decisions about the choice of antibiotics used in
When IAP is given specifically to prevent early-onset neonatal
intrapartum prophylaxis take account of the risk of promoting
infection with GBS the National Institute for Health and Care
antibiotic resistance?
Excellence (NICE) recommends using benzylpenicillin.
Alternative antibiotic regimens are appropriate for women who are Keywords: cost effectiveness / early-onset neonatal infection / group
allergic to penicillin or where local microbiological surveillance B streptococcus / intrapartum antibiotic prophylaxis / preterm
data indicate antibiotic resistance. rupture of membranes
Please cite this paper as: Mugglestone MA, Murphy MS, Visintin C, Howe DT, Turner MA. Antibiotics for early-onset neonatal infection: a summary of the NICE
guideline 2012. The Obstetrician & Gynaecologist 2014;16:87–92.
early-onset neonatal infection before and during birth, and
Introduction
indications for intrapartum antibiotic prophylaxis (IAP) for
This review summarises evidence and guidance in the the prevention of early-onset neonatal infection with
guideline on antibiotics for the prevention and treatment of Streptococcus agalactiae (group B streptococcus [GBS]).
early-onset neonatal infection published by the National Several other guidelines published by NICE and the Royal
Institute for Heath and Care Excellence (NICE).1 The authors College of Obstetricians and Gynaecologists (RCOG) are
of this article highlight the aspects that are most relevant to relevant to this topic and are cited in the article
obstetricians, namely the identification of risk factors for where relevant.
ª 2014 Royal College of Obstetricians and Gynaecologists 87
, Antibiotics for early-onset neonatal infection
monitor throughout labour for emergence of new risk
Early-onset neonatal infection
factors, such as intrapartum fever higher than 38°C, or
The NICE guideline,1 defines early-onset neonatal infection development of chorioamnionitis.
as infection occurring within 72 hours of birth. This
definition was agreed during the guideline scoping process
in the absence of a validated definition, although the
Box 1. Risk factors for early-onset neonatal infection
literature uses definitions ranging from infection within
48 hours to within 1 week of birth. When reviewing the Invasive group B streptococcal infection in a previous baby
literature, the guideline development group (GDG) Maternal group B streptococcal colonisation, bacteriuria or infection
considered all relevant information irrespective of study in the current pregnancy
authors’ definitions of early-onset infection. Prelabour rupture of membranes
Preterm birth following spontaneous labour (before 37 weeks of
A key factor in the management of early-onset neonatal gestation)
infection is an awareness of causative micro-organisms. Two Suspected or confirmed rupture of membranes for more than
UK population-based neonatal infection surveillance studies, 18 hours in a preterm birth
both of which defined early-onset neonatal infection as Intrapartum fever higher than 38°C, or confirmed or suspected
chorioamnionitis
infection with onset within 48 hours of birth, were published Parenteral antibiotic treatment given to the woman for confirmed or
during the development of the guideline.2,3 These studies suspected invasive bacterial infection (such as septicaemia) at any
showed that after exclusion of coagulase negative staphylocci time during labour, or in the 24-hour periods before or after the
birth. (This does not refer to intrapartum antibiotic prophylaxis.)
(CONS), which are usually considered to be blood sample
Suspected or confirmed infection in another baby in the case of a
contaminants soon after birth, the common organisms were multiple pregnancy
Gram-positive in about 75% of cases. These included GBS
(50% of cases), non-pyogenic streptococci and Staphylococcus
aureus. The most common Gram-negative organism was
Escherichia coli. Both GBS and E. coli were susceptible in nearly Intrapartum antibiotic prophylaxis
all cases to antibiotic regimens combining benzylpenicillin and
gentamicin, benzylpenicillin and amoxicillin, cefotaxime, or The GDG conducted a systematic review of evidence from
cefotaxime and amoxicillin. S.aureus isolates were resistant to randomised controlled trials (RCTs) evaluating the
benzylpenicillin and gentamicin in combination. effectiveness of antibiotic prophylaxis offered to pregnant
women at, or shortly before, the expected time of labour and
birth for the prevention of early-onset neonatal infection.
Risk factors for early-onset neonatal The term IAP was used to refer to such practice. Since the
infection NICE guideline on routine intrapartum care4 covers IAP for
prelabour rupture of membranes (PROM) at term, evidence
The GDG conducted a systematic review of studies evaluating relating to women with PROM was considered in the
putative maternal and fetal risk factors (individually or in systematic review only where the study population included
combination) as predictors of early-onset neonatal infection women with preterm PROM.
and their relevance in guiding clinical management before Thirty-seven articles reporting 34 RCTs and one
and after the birth. Eleven studies (all observational in non-comparative observational study were included in the
design) were included in the systematic review, investigating review. The GDG agreed that they would recommend IAP
risk assessment based on either single or a combination only where the purpose of the intervention was to prevent
of factors. early-onset neonatal infection with GBS. Population
None of the studies included in the systematic review screening (universal testing) for GBS, or testing in
demonstrated that single or combined features in the particular groups of women, was not the focus of the
maternal or fetal history would be useful for predicting GDG’s review because routine screening for GBS is not
which babies would develop an early-onset neonatal recommended in the NICE guideline for routine
infection. The GDG concluded that healthcare professionals antenatal care.5
should recognise the criteria listed in Box 1 as risk factors for
early-onset neonatal infection, although not all of these were
Women with group B streptococcal colonisation
sufficiently important individually to warrant intervention in
Five RCTs considered intrapartum antibiotics in women with
the form of IAP (see below). The GDG further recommended
GBS colonisation (Table 1). Having considered the evidence,
that, for women in labour, healthcare professionals should:
the GDG’s view was that women with GBS colonisation
identify and assess any risk factors for early-onset (including women in preterm labour) should be offered IAP
neonatal infection, with benzylpenicillin because:
88 ª 2014 Royal College of Obstetricians and Gynaecologists
The Obstetrician & Gynaecologist
Review
http://onlinetog.org
Antibiotics for early-onset neonatal infection: a summary
of the NICE guideline 2012
Moira A Mugglestone BSc MSc PhD FCMI,a,* M Stephen Murphy BSc DCH MD FRCPI FRCPCH,b,c,d Cristina Visintin
e f g
PhD, David T Howe DM FRCOG FRCS(Ed), Mark A Turner BSc MBChB PhD MRCP(UK) MRCPCH DRCOG
a
Director, National Collaborating Centre for Women’s and Children’s Health, Royal College of Obstetricians and Gynaecologists, 27 Sussex Place,
Regent’s Park, London NW1 4RG, UK
b
Clinical Director for Children’s Health, National Collaborating Centre for Women’s and Children’s Health, Royal College of Obstetricians and
Gynaecologists, 27 Sussex Place, Regent’s Park, London NW1 4RG, UK
c
Senior Lecturer in Paediatrics and Child Health, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15
2TT, UK
d
Consultant Paediatric Gastroenterologist, Birmingham Children’s Hospital, NHS Foundation Trust, Birmingham B4 6NH, UK
e
Project Manager, National Collaborating Centre for Women’s and Children’s Health, Royal College of Obstetricians and Gynaecologists, 27 Sussex
Place, Regent’s Park, London NW1 4RG, UK
f
Consultant and Honorary Senior Lecturer in Feto-Maternal Medicine, Wessex Fetal Medicine Unit, Princess Anne Hospital, Coxford Road,
Southampton SO16 5YA, UK
g
Senior Lecturer in Neonatalogy and Consultant in Neonatology, Department of Women’s and Children’s Health, University of Liverpool and
Liverpool Women’s Hospital, Crown Street, Liverpool L8 7SS, UK
*Correspondence: Moira A Mugglestone. Email:
Accepted on 13 January 2014
Key content Learning objectives
Early-onset neonatal infection (infection arising within 72 hours of To be aware of the risk factors for early-onset neonatal infection.
birth) is an important cause of morbidity and mortality and is To understand how IAP can reduce the risk of an early-onset
often caused by Streptococcus agalactiae (group B streptococcus neonatal infection.
[GBS]). To know which antibiotic to use for IAP of GBS.
Identifying and assessing risk factors for early-onset neonatal
Ethical issues
infection before and during labour and birth is integral to clinical
How should decisions about whether to administer IAP trade off
management.
the potential benefit to the baby of preventing an early-onset
Intrapartum antibiotic prophylaxis (IAP) to prevent early-onset
neonatal infection and potential harms to the woman, such as,
neonatal infection is effective when given to women with particular
allergic reactions and increased medicalisation of pregnancy?
risk factors, including maternal GBS colonisation. How should decisions about the choice of antibiotics used in
When IAP is given specifically to prevent early-onset neonatal
intrapartum prophylaxis take account of the risk of promoting
infection with GBS the National Institute for Health and Care
antibiotic resistance?
Excellence (NICE) recommends using benzylpenicillin.
Alternative antibiotic regimens are appropriate for women who are Keywords: cost effectiveness / early-onset neonatal infection / group
allergic to penicillin or where local microbiological surveillance B streptococcus / intrapartum antibiotic prophylaxis / preterm
data indicate antibiotic resistance. rupture of membranes
Please cite this paper as: Mugglestone MA, Murphy MS, Visintin C, Howe DT, Turner MA. Antibiotics for early-onset neonatal infection: a summary of the NICE
guideline 2012. The Obstetrician & Gynaecologist 2014;16:87–92.
early-onset neonatal infection before and during birth, and
Introduction
indications for intrapartum antibiotic prophylaxis (IAP) for
This review summarises evidence and guidance in the the prevention of early-onset neonatal infection with
guideline on antibiotics for the prevention and treatment of Streptococcus agalactiae (group B streptococcus [GBS]).
early-onset neonatal infection published by the National Several other guidelines published by NICE and the Royal
Institute for Heath and Care Excellence (NICE).1 The authors College of Obstetricians and Gynaecologists (RCOG) are
of this article highlight the aspects that are most relevant to relevant to this topic and are cited in the article
obstetricians, namely the identification of risk factors for where relevant.
ª 2014 Royal College of Obstetricians and Gynaecologists 87
, Antibiotics for early-onset neonatal infection
monitor throughout labour for emergence of new risk
Early-onset neonatal infection
factors, such as intrapartum fever higher than 38°C, or
The NICE guideline,1 defines early-onset neonatal infection development of chorioamnionitis.
as infection occurring within 72 hours of birth. This
definition was agreed during the guideline scoping process
in the absence of a validated definition, although the
Box 1. Risk factors for early-onset neonatal infection
literature uses definitions ranging from infection within
48 hours to within 1 week of birth. When reviewing the Invasive group B streptococcal infection in a previous baby
literature, the guideline development group (GDG) Maternal group B streptococcal colonisation, bacteriuria or infection
considered all relevant information irrespective of study in the current pregnancy
authors’ definitions of early-onset infection. Prelabour rupture of membranes
Preterm birth following spontaneous labour (before 37 weeks of
A key factor in the management of early-onset neonatal gestation)
infection is an awareness of causative micro-organisms. Two Suspected or confirmed rupture of membranes for more than
UK population-based neonatal infection surveillance studies, 18 hours in a preterm birth
both of which defined early-onset neonatal infection as Intrapartum fever higher than 38°C, or confirmed or suspected
chorioamnionitis
infection with onset within 48 hours of birth, were published Parenteral antibiotic treatment given to the woman for confirmed or
during the development of the guideline.2,3 These studies suspected invasive bacterial infection (such as septicaemia) at any
showed that after exclusion of coagulase negative staphylocci time during labour, or in the 24-hour periods before or after the
birth. (This does not refer to intrapartum antibiotic prophylaxis.)
(CONS), which are usually considered to be blood sample
Suspected or confirmed infection in another baby in the case of a
contaminants soon after birth, the common organisms were multiple pregnancy
Gram-positive in about 75% of cases. These included GBS
(50% of cases), non-pyogenic streptococci and Staphylococcus
aureus. The most common Gram-negative organism was
Escherichia coli. Both GBS and E. coli were susceptible in nearly Intrapartum antibiotic prophylaxis
all cases to antibiotic regimens combining benzylpenicillin and
gentamicin, benzylpenicillin and amoxicillin, cefotaxime, or The GDG conducted a systematic review of evidence from
cefotaxime and amoxicillin. S.aureus isolates were resistant to randomised controlled trials (RCTs) evaluating the
benzylpenicillin and gentamicin in combination. effectiveness of antibiotic prophylaxis offered to pregnant
women at, or shortly before, the expected time of labour and
birth for the prevention of early-onset neonatal infection.
Risk factors for early-onset neonatal The term IAP was used to refer to such practice. Since the
infection NICE guideline on routine intrapartum care4 covers IAP for
prelabour rupture of membranes (PROM) at term, evidence
The GDG conducted a systematic review of studies evaluating relating to women with PROM was considered in the
putative maternal and fetal risk factors (individually or in systematic review only where the study population included
combination) as predictors of early-onset neonatal infection women with preterm PROM.
and their relevance in guiding clinical management before Thirty-seven articles reporting 34 RCTs and one
and after the birth. Eleven studies (all observational in non-comparative observational study were included in the
design) were included in the systematic review, investigating review. The GDG agreed that they would recommend IAP
risk assessment based on either single or a combination only where the purpose of the intervention was to prevent
of factors. early-onset neonatal infection with GBS. Population
None of the studies included in the systematic review screening (universal testing) for GBS, or testing in
demonstrated that single or combined features in the particular groups of women, was not the focus of the
maternal or fetal history would be useful for predicting GDG’s review because routine screening for GBS is not
which babies would develop an early-onset neonatal recommended in the NICE guideline for routine
infection. The GDG concluded that healthcare professionals antenatal care.5
should recognise the criteria listed in Box 1 as risk factors for
early-onset neonatal infection, although not all of these were
Women with group B streptococcal colonisation
sufficiently important individually to warrant intervention in
Five RCTs considered intrapartum antibiotics in women with
the form of IAP (see below). The GDG further recommended
GBS colonisation (Table 1). Having considered the evidence,
that, for women in labour, healthcare professionals should:
the GDG’s view was that women with GBS colonisation
identify and assess any risk factors for early-onset (including women in preterm labour) should be offered IAP
neonatal infection, with benzylpenicillin because:
88 ª 2014 Royal College of Obstetricians and Gynaecologists
