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SYMPOSIUM: NEONATOLOGY

streptococcus infections presenting within 7 days of life, also


Neonatal sepsis as EONS
 Late onset sepsis (LONS) e occurring more than 72 h after
Oliver Walker birth e usually attributed to organisms acquired from hos-
Celyn B Kenny pital or community environment
The perinatal period is a particularly risky time for the fetus
Nitin Goel and newborn. Neonatal skin and mucous membranes are fragile
and immature neonates have an underdeveloped immune system
without the full complement of maternal antibodies.
Abstract The newborn’s journey from the uterus to the birth canal is
Neonatal sepsis is a cause of significant mortality and morbidity. It can potentially a source of infection and these risks are extended if
be early (less than 72 h) or late onset (more than 72 h age). Group B the baby is transferred to the neonatal unit environment. The
Streptococcus (GBS) is the leading cause of early onset neonatal newborn infant admitted to the neonatal unit is subjected to
sepsis (EONS). Risk factors include maternal sepsis, prolonged multiple invasive clinical procedures and their bowel flora is
rupture of membranes, chorioamnionitis and GBS colonization. Risk- adversely affected by antibiotics use and feeding practices.
based predictive models are used to identify and screen infants.
Late onset neonatal sepsis (LONS) is largely caused by gram positive
organisms. Risks for LONS include prematurity, low birth weight and
Early onset neonatal sepsis
common neonatal interventions and procedures. Signs and symptoms Epidemiology and causative organisms
of neonatal sepsis are often subtle leading to over and under treat- Culture-positive EONS has an incidence of around 0.5e0.9 per
ment. Standard investigations include blood cultures, full blood 1000 live births in infants 34 weeks gestation, representing
count, C Reactive Protein and lumbar puncture. Procalcitonin is about 1% of neonatal unit admissions. Incidence and mortality is
being investigated as a sensitive and specific biomarker of bacterae- higher in preterm and very low birth weight (VLBW) infants.
mia in aiding diagnosis and management. Physiological monitoring EONS presentation can vary, ranging from subtle early signs of
can be used to monitor the early signs of sepsis on the neonatal being unwell such as temperature instability and poor feeding to
unit and facilitate prompt intervention. EONS is treated with benzylpe- pneumonia or a fulminating septic illness. Main routes of trans-
nicillin and an aminoglycoside antibiotic, and most LONS can be mission are from the mother via trans-placental or ascending
managed with narrow spectrum antibiotics, in addition to supportive vaginal routes or via haematogenous spread in mothers with
management as required. Antibiotic duration is best determined by bacteraemia or viraemia.
culture results, biomarkers and clinical response to treatment. This In the UK and US, the leading organism causing EONS is
article will discuss the evidence for treatment of neonatal sepsis and Group B Streptococcus (GBS) (about 43%), followed by gram-
offers practical advice and guidance for a clinician faced with this negative isolates mainly Escherichia Coli (E.coli) (25e29%) and
important clinical dilemma. other gram positive organisms such as Streptococci and Staphy-
Keywords early onset sepsis; group B streptococcus; late onset lococcus aureus (S. aureus). Less frequently Haemophilus influ-
sepsis; neonatal sepsis enzae, Candida spp and Listeria monocytogenes can be isolated.
Listeria infection carries a significant mortality as meningitis and
has been associated with history of meconium stained liquor in
Introduction preterm births.
In the UK, GBS carriage rate in pregnant women is around 25
Neonatal sepsis is any form of infection that occurs within the e33%. Of the infants born to GBS colonized women 1e2% will
first 28 days of life. Sepsis is recognized as a leading cause of develop invasive disease. Mortality rate of GBS sepsis can be
mortality and morbidity in newborns and is responsible for one high up to 4e6%; with more than 10 times higher mortality in
third of neonatal deaths globally. Its incidence varies within preterm infants as compared to term infants.
healthcare settings and between neonatal units across the globe.
We can broadly classify neonatal sepsis as: Risk factors
 Early onset sepsis (EONS) e within 72 h of birth e acquired 
Intrapartum fever (more than 38 C), prolonged rupture of
before or soon after delivery and usually represent vertical membranes (PROM) more than 18 h, maternal GBS colonisation/
mother to infant transmission. Some clinicians class Group B bacteriuria and history of a previous infant with GBS are recog-
nized risk factors for EONS. Chorioamnionitis is the commonest
underlying reason for spontaneous preterm labour with maternal
Oliver Walker BSc PhD MBBS MRCPCH, Neonatal Grid Trainee, Neonatal UTI (most commonly E. Coli), being an important preceding risk
Unit, University Hospital of Wales, Cardiff, UK. Conflicts of interest: factor. Infection and mortality is inversely proportional to
none declared. gestation and birth weight.
Celyn B Kenny MBBCh, Paediatric Speciality Trainee, Neonatal Unit,
University Hospital of Wales, Cardiff, UK. Conflicts of interest: none Clinical presentation
declared. The National Institute for Health and Clinical Excellence (NICE)
Nitin Goel MBBS MD MRCPCH FRCPCH, Consultant Neonatologist, developed a guideline for management of EONS based on
Neonatal Unit, University Hospital of Wales, Cardiff, UK. Conflicts of maternal risk factors and infant clinical indicators. A baby with
interest: none declared. one ‘red flag’ indicator or risk factor, or two or more ‘non-red

PAEDIATRICS AND CHILD HEALTH 29:6 263 Crown Copyright Ó 2019 Published by Elsevier Ltd. All rights reserved.
SYMPOSIUM: NEONATOLOGY

flag’ indicators should be assessed and screened for infection and Acute phase reactants: CRP is the most commonly available
treated with antibiotics promptly without delay. The presence of acute phase reactant. Its levels rise in response to IL-6 secretion
no red flags, but one ‘non-red flag’ qualifies for a period of close by macrophages and T-cells. Babies can have a negligible CRP
observation for 12e24 h. result at birth even with positive blood cultures, but 12e24 h
Clinical signs in the early stages of any infection may be subtle later the CRP may rise. Serial CRP measurements are used to
and non-specific and include: facilitate decision making regarding lumbar punctures (LP),
- Respiratory distress, tachypnoea or apnoea monitoring the progress of infection and determining duration of
-Lethargy or poor feeding antibiotic therapy.
-Temperature instability less than 36 or more than 37.8 CRP has limited sensitivity and a poor positive predictive
-Poor capillary refill time value, in the detection of EONS. An increase is seen non-
-Tachycardia, or bradycardia in more serious cases specifically with any inflammation, asphyxia, meconium aspi-
-Fulminant sepsis may present with respiratory failure, cyanosis ration and prolonged rupture of membranes.
and shock. Procalcitonin, a precursor for calcitonin and composed of 116
Given the clinical picture the differential diagnoses include amino acids, has been proposed as a more reliable biomarker for
pneumonia, generalized sepsis, meningitis, cardiac disease neonatal sepsis. Levels of procalcitonin are undetectable in healthy
and metabolic conditions. EONS may be clinically indistin- individuals thus demonstrating its high negative predictive value.
guishable from hypoxic ischaemic encephalopathy at delivery. In the face of bacterial sepsis, levels have been seen to rise
Sepsis is increasingly recognized as a risk factor for neonatal dramatically and may be more sensitive and specific in the differ-
encephalopathy. entiation between neonatal infection and inflammation compared
The Kaiser Permanente (KP) group in the US has developed a with CRP. A cut-off value of 2.4 ng/ml has high specificity and
different EONS screening and management algorithm to reduce sensitivity. A natural rise is seen in the first 24e36 h following
the unnecessary use of antibiotic in large number of healthy birth, so a higher cut off point is needed for this age group. There
newborns. This is available as a web-based application known as are reports in the USA, that the use of procalcitonin as a guide can
Sepsis Risk Calculator. This algorithm adopts the Bayesian model. reduce the duration of antibiotics used in EONS by up to 50%.
It starts with the population risk of EONS and modifies this by
applying the maternal risk factors and then infant’s objective Blood culture: blood cultures are the gold standard in diagnosing
clinical measures to specify an infant-specific final risk. Based on bacteraemia. Previous reports suggested positive yields of 15
this it then recommends the need for enhanced observations and/ e20%; however with modern culture bottles and inoculating
or antibiotics. This is already used widely in the USA with re- adequate volume of blood (minimum 1 ml) in a single paediatric
ported reductions of antibiotic use by as much as 50%. culture bottle, the yields can be much higher. Utmost aseptic
With bacteria such as GBS and E. coli there can be rapid precautions should be taken while obtaining the blood sample
progression from mild symptoms to death in less than 24 h; for culture, to avoid contaminant organisms. Cultures can be
possibly as a consequence of brisk systemic inflammatory negative even in the face of signs and symptoms of infection.
response through cytokine release. A high index of suspicion for Time to positivity (TTP) for most blood cultures is 36e48 h.
GBS infection is required in any term baby with respiratory
distress or in preterm infants who has more severe respiratory Lumbar puncture: early onset meningitis is extremely uncom-
distress than anticipated. Radiologically RDS and GBS lung mon (0.01e0.02/1000 live births). In EONS, LP should not be a
infection may be indistinct. In severe cases, persistent pulmonary routine investigation; however a high CRP, clinical symptoms
hypertension of the newborn, hypotension, metabolic acidosis, suggesting meningitis or a positive blood culture, can be in-
tachycardia and poor peripheral perfusion may develop and are dications to consider LP. There is debate over the usefulness of a
poor prognostic features. specific CRP cut off value in undertaking a lumbar puncture in
EONS. CSF values indicative of neonatal meningitis are also not
Evaluation and investigations in EONS well established, especially as obtaining a non-bloodstained tap
A neonate with signs and symptoms of sepsis requires prompt can be technically challenging in a neonate and results are
assessment, identification of risk factors and initiation of anti- affected by delays in analysis. In most studies, the normal CSF
biotic therapy. Negative tests should not preclude sepsis. How- white cell count in healthy, uninfected preterm or term neonates
ever, if positive, they can be useful in supporting diagnosis and is less than 10 cells/mm3, with more than 95% having counts of
as guidance in determining length of therapy. fewer than 20 cells/mm3. However, the levels are age and
gestation dependent, with the higher cell counts recorded during
Blood gas: this is clinically very relevant as it may reveal a mixed the first week. In a blood stained tap there has been no proven
respiratory or metabolic acidosis. diagnostic benefit in comparing the ratio of CSF WBC count and
red blood cells with that of peripheral blood sample. CSF protein
White cell counts: white blood cell (WBC) counts, differential, levels are usually, but not always, elevated in neonates with
absolute neutrophil counts, and the ratio of immature to total meningitis. CSF glucose level (normally 70e80% of serum level)
neutrophils (I/T ratio) in the blood are widely used as screening usually drops significantly with bacterial meningitis but, may
tests for neonatal sepsis. Unfortunately, none of these tests have remain normal as well.
good positive predictive value. The values of WBC are age-
dependent, and should be used in clinical context along with Urine: obtaining uncontaminated urine specimens in babies is
the natural rise and fall in the first few hours and days of life. challenging but important. A suprapubic aspiration of urine

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SYMPOSIUM: NEONATOLOGY

(SPA) or fresh catheter specimen urine or a clean catch sample in ototoxicity and sensorineural hearing loss. There are two
following thorough skin cleansing is required. Urine cultures are different mechanisms associated with gentamicin toxicity e a
of greater importance in LONS. high trough gentamicin concentration damaging the sensory cells
and genetically determined ototoxicity. 1:500 individuals carry a
Other sites: surface cultures are of limited value. Colonization in mitochondrial DNA mutation linked with permanent profound
the absence of suspicious clinical signs does not warrant anti- hearing loss from aminoglycosides even when drug levels are
biotic treatment. However this can be useful if disseminated within the therapeutic range.
Herpes is suspected. Antibiotics, particularly those with broad-spectrum activity,
alter the natural microflora of the infant, in particular gut flora.
Radiology: chest radiograph (CXR) should be considered in a This can result in a rise of antibiotic resistance among the normal
baby undergoing EONS screening as pneumonia may be present commensals and the emergence of other resistant pathogens.
with limited clinical signs. Over the past three decades in the developed world, there have
been reports of substantial increases in the incidence of allergic
Treatment of EONS and autoimmune diseases in young children. These have shown
Supportive care: prompt treatment of suspected sepsis is association with altered microbiome secondary to peripartum
important as delay in recognizing and treating can result in antibiotic exposure.
serious morbidity or death. Supportive management may include
non-invasive respiratory support with nasal cannula oxygen, Prevention of EONS
nasal CPAP or heated humidified high-flow nasal cannula The maternal to fetal transmission can be decreased by identi-
(HFNC) oxygen therapy. Mechanical ventilation may be required fying GBS carriage in late pregnancy along with early recognition
in non-responding cases or with severe respiratory acidosis. and adequate treatment of chorioamnionitis. Vertical trans-
IV fluids and feeding via nasogastric tube may be required in mission can be prevented through the administration of intra-
babies with significant respiratory distress. Blood glucose should partum antibiotic prophylaxis using penicillin or cefazolin/
be monitored and abnormalities corrected promptly. Severe clindamycin. Treatment is more effective if commenced at least 4
cases with shock and hypotension should be promptly managed hours prior to delivery. At-risk women can be identified by e
through volume support with crystalloids and inotropic support. universal bacteriological screening (at 35e37 wks) or using a
risk-based approach. Despite concerns over emerging resistance,
Antibiotic treatment: if the decision to treat has been made, GBS in most countries remains susceptible to penicillin. In the
antibiotics should be administered within the first hour. Ben- UK routine screening is not currently recommended.
zylpenicillin with an aminoglycoside such as gentamicin is If, for clinical reasons, bacteriological swabs need to be taken
standard first line treatment in the UK. This provides narrow this should include a combined low vaginal and rectal swab.
spectrum coverage for typical EONS pathogens. Cephalospo- Detection of GBS on high vaginal swab and non-selective media is
rins do not provide better efficacy in terms of common patho- associated with increased risk of transmission to the neonate.
gens and may have an adverse effect on the infant’s Women with GBS bacteriuria or with history of a previous baby
microbiome. If S. aureus is suspected, flucloxacillin should with neonatal GBS disease should be considered for prophylactic
replace benzylpenicillin. If Listeria is suspected or identified, antibiotics. Antibiotics are not recommended for babies born to
amoxicillin should substitute benzylpenicillin. Once culture mothers with GBS carriage who undergo elective section without
results are available antibiotic regimen should be rationalized preceding labour or rupture of membranes. A Bayesian approach to
and targeted appropriately. directed therapy (like KP sepsis risk calculator) is helpful. Women
Antibiotic therapy should be commenced promptly in sus- with risk factors such as intrapartum pyrexia, prematurity, PROM,
pected infection and they should be stopped as soon as sepsis is should have lower threshold for consideration of antibiotics.
excluded. In general the following all apply:
 With suspected infection but asymptomatic baby, CRP not Late onset neonatal sepsis
rising and cultures negative at 36e48 h e antibiotics should Epidemiology and causative organisms
discontinued. Incidence of LONS is approximately 8/1000 live births, and af-
 Antibiotics started on high clinical suspicion of infection, yet fects about 7% of neonatal unit admissions. It is usually the
negative cultures and an elevated CRP e a longer course result of nosocomially acquired organisms. Mortality is higher
(usually 5 days) may be warranted. with fungal and gram negative infections and in more preterm,
 If pneumonia is evident on CXR, but negative blood cultures lower birthweight infants. The majority of LONS occurs in pre-
e a 5-day course may be appropriate. mature and VLBW babies with incidence ranging between 16 and
 If blood cultures positive and CSF cultures negative e treat 30% and approaching 50% in extremely low birth weight
for a minimum of 10 days in gram positive and 14 days in (ELBW) babies. Of all LONS, gram positive organisms comprise
gram negative organisms. 70%, gram negative 25% and fungi about 5%.
 With positive CSF cultures, and/or a clinical diagnosis of Coagulase negative Staphylococci (CoNS) accounts for
meningitis e treatment may be required for at least 21 days, approximately half of all LONS. Presence of central lines is
depending on the organism isolated. an important risk factor for CoNS. Other major isolates are
S. aureus, E. coli, Enterococcus, Klebsiella and Enterobacteriaceae.
Potential hazards of antibiotics: gentamicin has a narrow Meningitis is more frequently a feature of LONS than EONS.
therapeutic window and persistent high serum levels may result S. aureus sepsis or meningitis has a high mortality (up to 25%).

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SYMPOSIUM: NEONATOLOGY

Candida spp (most commonly C albicans and C parapsilosis) Other sites: routine swabbing of sites such as the umbilicus,
account for almost all fungal infections e they are relatively groin, ear, nose, throat, pharynx and rectum are informative
infrequent in the UK even in ELBW infants. Invasive Candidiasis about colonization. Tracheal aspirates are of value if taken
is associated with high mortality and increased risk of adverse immediately after placement of ETT; in several day old ET tubes,
neurodevelopmental outcome in survivors. Use of prophylactic the evaluation of sepsis is difficult and represents more of
Fluconazole in first 6 weeks of life significantly reduces the risk colonization.
of invasive fungal infection in VLBW and ELBW infants.
Radiology: chest radiograph (CXR) should be considered in a
Risk factors for LONS baby with clinical signs of respiratory distress. An abdominal
Factors predisposing to nosocomial infection and LONS include radiograph (AXR) may be helpful in the differentiation between
being premature, VLBW/ELBW, intensive care, lack of enteral septic ileus and NEC.
feeding, not receiving maternal breast milk, breakage of natural
barriers, invasive procedures, having an indwelling catheter, Haematological investigations:
receiving parenteral nutrition (PN) via central lines, prolonged Neutrophil count e contrary to older children and adults,
mechanical ventilation, H2 receptor antagonists (e.g. ranitidine), white cell count does not accurately predict neonatal sepsis.
and exposure to antenatal antibiotics. Babies who had gut sur- Serial values may be more useful. Infection may result in neu-
gery or gut related problems are at significant risk. Prolonged use tropenia or neutrophilia (<5  109/l or >20  109/l respec-
of antibiotics is associated with increased antibiotic resistance tively). Mortality rates are high in neonates who fail to mount a
and increased rates of necrotising enterocolitis (NEC) and death neutrophil response to infection or whose neutrophil supply
in ELBW infants. Broad spectrum antibiotics (especially third becomes exhausted by severe infection. I/T ratio may be useful
generation cephalosporins) are an important risk factor for in diagnosing and monitoring infection. The maximum normal
fungal infections. value is 0.16 during the first 24 h of age, 0.14 by 48 h, 0.13 by 60
h till 5 days of age and 0.12 until the end of the first month. I/T
Clinical presentation ratio of more than 0.2 is a useful marker of infection. Another
Clinical signs in the early stages of any infection may be subtle feature suggesting infection is the presence of toxic granulation
and non-specific. These include: in the neutrophils.
-Worsening respiratory distress, increasing desaturations and Platelet count e thrombocytopenia is a common feature of
oxygen requirements, and apnoea generalized infection and NEC.
-Lethargy, quiet state CRP e serial measurements of CRP are recommended to
-Feed intolerance facilitate decisions regarding LP, duration of antibiotic therapy
-Temperature instability and in monitoring the progress of infection. Persistently elevated
-Prolonged capillary refill time CRP during antibiotic therapy suggests ongoing infection or
-Hyperglycaemia inflammation.
-Lactic acidosis Polymerase chain reaction (PCR) e PCR has very high
-Cyanosis and shock sensitivity and specificity and can provide more rapid diagnosis
Progression from mild symptoms to death can occur in less of bacteraemia and viraemia. Currently it is used for targeted
than 24 h with gram negative bacteria such as E. coli and Kleb- diagnosis for e.g. in suspected Herpes infection.
siella. Bowel sounds may be relatively silent as functional ileus
due to generalized sepsis. A high pitched cry, abnormal move- Physiological monitoring: recent studies show that monitoring
ments, back-arching, and tense fontanelle, are late features of of physiological data is a promising non-invasive method to
neonatal meningitis. In evaluation for LONS, the limbs and joints predict sepsis before clinical/biochemical signs appear. The
should be examined for signs of osteomyelitis and septic arthritis. greatest advancement is in the monitoring of Heart Rate Char-
acteristics index (HRCi or HeRO). It has been introduced into
Evaluation and investigations in LONS neonatal practice following a large randomized controlled trial in
A neonate with suspected LONS requires prompt evaluation and the US in VLBW infants.
if required, initiation of antibiotic therapy. Progression can be In the healthy state there is beat-to-beat variability and
rapid. If tests are positive, they can be useful in guiding treatment numerous small accelerations (sympathetic) and decelerations
and determining the length of therapy. Careful evaluation as well (parasympathetic). Reduced variability and transient de-
as a complete examination, including skin and catheter insertion celerations in heart rate, mediated by the autonomic nervous
sites, should be performed. system, can occur hours to days before clinical suspicion of
Investigations are similar to those in EONS with some further sepsis is evident. HRCi or HeRO monitoring records heart rate
considerations: intervals in data sets of 20e25 min duration. Results are pre-
sented as the “fold increased risk” a baby will deteriorate from
Lumbar puncture: a lumbar puncture (LP) should be performed sepsis in the next 6e24 h (Figure 1). For example, a score of 1 is
as part of the sepsis screen in LONS. Infants with overt localized low risk, more than 2 is a 2-fold higher chance and more than 3 is
infection can be exempted, e.g. pneumonia, NEC, and babies who 3-fold and so on. The values are updated hourly and presented as
are critically ill and would not be able to tolerate the procedure. a graphical trend over 5 days.
Thrombocytopenia is a relative contraindication to LP; if essential HRC or HeRO monitoring cannot determine the exact time of
a platelet transfusion should be given to cover the procedure. sepsis onset and other conditions including severe IVH, chronic

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SYMPOSIUM: NEONATOLOGY

Figure 1 HeRO/HRC monitoring showing risk score (top) and heart rate trace at any given point (bottom) over time. The current risk score is clearly
displayed (orange).

lung disease, surgery, acute respiratory decompensation and Amphotericin (a polyene), fluconazole (a triazole) and mica-
medications (steroids, muscle relaxants and anticholinergics) can fungin (an echinocandin only active against Aspergillus and
elevate HeRO. However in these cases a relative change in an Candida spp) are used to treat neonatal invasive fungal infection.
infant’s usual baseline can be used to detect sepsis.
Monitoring response to therapy: if the baby remains unwell,
Treatment of LONS there are persisting abnormal laboratory markers or ongoing pos-
There is no consensus on the best antibiotic regimens for neo- itive blood cultures, further investigations should be undertaken.
nates. Each antibiotic has its own benefits and side effects. In Consideration should also be given to optimizing antibiotic doses,
general, narrow spectrum antibiotics should be used wherever changing antibiotic regimens or removing indwelling catheters.
possible, and only used when significant infection is likely.
Supportive treatment should include central line removal if Length of treatment: while antibiotic therapy should be
high suspicion of line sepsis, escalation in respiratory support as commenced promptly for suspected infection, they should be
required and monitoring and stabilisation of blood glucose. stopped as soon as sepsis has been excluded. In general the
Enteral feeds may be withheld, if there are concerns about following apply:
abdominal sepsis. Intravenous fluids with fluid boluses or iono-  If suspected infection, the baby is asymptomatic, and nega-
tropic support are used in shock and hypotension. tive cultures at 36e48 h e antibiotics should be stopped.
 Antibiotics started on high clinical suspicion of infection, yet
Antibiotic treatment: the majority of the leading causes of negative cultures and an elevated CRP e a longer course
LONS, other than CoNS, can be treated by antibiotic regimen (usually 5 days) may be warranted.
such as flucloxacillin and gentamicin. Vancomycin and teico-  If blood cultures positive and CSF cultures negative e treat
planin are the antibiotics of choice for CoNS infections in pres- for a minimum of 10 days in gram positive and longer for
ence of central lines, but their excessive use has been associated gram negative organisms.
with the development of vancomycin resistant enterococcal in-  If S. aureus is isolated, treatment should be for at least 14
fections and resistant gram-negative infections. Flucloxacillin is days, as it can seed other tissues.
the best antibiotic to treat Methicillin Sensitive S. aureus (MSSA).  With positive CSF cultures, and/or a clinical diagnosis of
Gentamicin will treat most gram-negative bacteria, some of meningitis e treatment may be required for at least 21 days,
which e.g. Pseudomonas sp., give rise to significant mortality. depending on the organism isolated.
A cephalosporin given either alone or in combination with  Osteomyelitis, endocarditis and deep abscesses which are
amoxicillin may not adequately cover a number of Enterobac- not surgically drained, may require several weeks of anti-
teriaceae. If there is inadequate clinical improvement or dete- biotic therapy.
rioration, repeat cultures should be taken and antibiotic The length of treatment course may require extension in those
therapy changed according to the local guidelines and in dis- with slow clinical and microbiological resolution, and requires
cussion with microbiologists. Vancomycin with gentamicin specialist input.
provides good gram-negative and gram-positive cover but
potentially has additive renal toxicity. For b-lactamase Potential hazards of antibiotics: all antibiotics, particularly
eproducing organisms (Serratia, Citrobacter, and Entero- broad-spectrum antibiotics, alter the natural microflora of the
bacter), or other difficult to treat organisms, the use of a car- patient, particularly in the gut. This may result in an increase in
bapenem (e.g. meropenem), which is inherently resistant to antibiotic resistance among normal commensals or the emer-
beta-lactamases may be considered. gence of other pathogens.

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SYMPOSIUM: NEONATOLOGY

Prevention of infection Cailes B, Kortsalioudaki C, Buttery J, et al. Epidemiology of UK


neonatal infections: the neonIN infection surveillance network. Arch
Infection control strategies include hand hygiene and washing
Dis Child Fetal Neonatal Ed 2018 Nov; 103: F547e53.
techniques, barrier precautions, minimal handling and the
Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments.
implementation of care bundles for processes such as line
Arch Dis Child Fetal Neonatal Ed 2015; 100: F257e63.
insertion.
Fairchild KD, Schelonka RL, Kaufman DA, et al. Septicemia mortality
Antibiotic stewardship programs have been shown to reduce
reduction in neonates in a heart rate characteristics monitoring trial.
infection rates and inappropriate antibiotic use. Reports of
Pediatr Res 2013 Nov; 74: 570e5.
vancomycin-resistant enterococcus, beta lactamaseeproducing
Kuzniewicz MW, Puopolo KM, Fischer A, et al. A quantitative, risk-
organisms (E coli, Klebsiella, Enterobacter), and highly resistant
based approach to the management of neonatal early-onset
Acinetobacter, Burkholderia, and Serratia are increasing in the
sepsis. JAMA Pediatr 2017 Apr 1; 171: 365e71.
neonatal population. A reminder that antibiotics must always be
Mukhopadhyay S, Puopolo KM. Risk assessment in neonatal early
used judiciously.
onset sepsis. Semin Perinatol 2012 Dec; 36: 408e15.
The earlier enteral feeds are commenced the lower the risk of
Puopolo KM, Draper D, Wi S, et al. Estimating the probability of
nosocomial infections. Breast milk has been shown to protect
neonatal early-onset infection on the basis of maternal risk factors.
babies from late onset infection. Introducing 0.5 ml/kg of “tro-
Pediatrics 2011 Nov; 128: e1155e63.
phic” breast milk in the first hours of life, in VLBW, will facilitate
Santos RP, Tristram D. A practical guide to the diagnosis, treatment,
gut colonisation with normal bacteria (lactobacilli and bifido-
and prevention of neonatal infections. Pediatr Clin North Am 2015
bacteria). Breast milk also contains secretory antibodies, immune
Apr; 62: 491e508.
cells, lactoferrin and prebiotics which can stimulate beneficial
Shane AL, Sanchez PJ, Stoll BJ. Neonatal sepsis. Lancet, 2017 oct 14;
gut flora. Such bacteria are critical for the development of the
390.
immune system, of mucosal barrier function, gut motility and
digestive functions.

Long term risks of neonatal sepsis Practice points


Survivors of neonatal sepsis are more likely to have poor growth,
C Early onset neonatal sepsis occurs within the first 72 h of
develop cerebral palsy, to have lower scores on neuro-
life whereas late onset neonatal sepsis occurs after this
developmental scales and to have visual impairment. Multiple
time; with different causative organisms and approach to
episodes, invasive candidiasis and NEC are all associated with
management.
increased risk of neurodevelopmental impairment. A C Accurate identification of risk factors and clinical signs are
key to successful management.
FURTHER READING C Algorithms using background risk, maternal risk factors in
Bedford Russell AR, Kumar R. Early onset neonatal sepsis: diagnostic combination with the infant’s clinical picture, have the po-
dilemmas and practical management. Arch Dis Child Fetal Neonatal tential to decrease antibiotic usage.
Ed 2015 Jul; 100: F350e4. C CRP and white cell counts have poor predictive value.
Bion J, Richardson A, Hibbert P, et al. ‘Matching Michigan’: a 2-year Procalcitonin and physiological monitoring tools have the
stepped interventional programme to minimise central venous potential for early detection of neonatal sepsis.
catheter-blood stream infections in intensive care units in England. C Survivors of neonatal sepsis are at risk of poor growth and
BMJ Qual Saf 2013; 22: 110e23. a poor neurodevelopmental outcome.

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