Based on standard information from NICE, other British sites and miscellaneous sources.

1. MANAGEMENT OF
FEBRILE YOUNG
INFANTS (0-3 MONTHS)
Dr. Taher Y. Kagalwala
M.D. (Paed.), M.R.C.P.C.H.
Paediatric Registrar
Blackpool Victoria Hospital, Blackpool, Lancashire, UK

2. Why is this information
pertinent?
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 According to statistics, feverish illnesses in
infants and small children are the most
common indication for visits to a doctor in the
UK, with 20-40% of all illness episodes
marked by fever; additionally, it is the second
most important reason for admission to
hospitals. (NICE Guidance, CG160, May
2013)
 To date, there is no full-proof method of
identifying which infant does or does not have
a serious infection (blood, urine or brain).
Hence, clinical suspicion is very important.22-09-2016

3. Case 1- history and
examination
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 OB, a 11 day old female, presented to the A & E from
primary care with high fever of 39.2 C . The child
developed fever and irritability on the day of
presentation. However, she was feeding well and
there was no vomiting. She had passed urine more
often than usual since that morning.
 Child was stable but tachypneoic. Her HR was
200/min, with normal heart sounds and equally
palpable femorals on both sides. The temp was 39.2
C. Her CRT was <2 secs.
 She was sucking well and had BM 4.2 and her AF was
soft and non-pulsatile.
 Air entry was equal on both sides.

4. Case 1- Background,
investigations and evolution of the
case
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 Term baby with no positive history. No PROM and no
GBS. No risk factors for sepsis. She was discharged
on D1. Mom was treated at 33 wks gestation at home
for fever. No history of genital herpes or STDs.
 Two older sibs, 8 and 7 years old, both normal.
 Investigations: Na 139, K 5.4 Creat 34, Urea 2.2 AST
47, Bil 37, WCC 11.8, Hb 217 Plt 285
 CSF WBC 10 cells, all lymphocytes RBC < 1, CSF
glucose 2.9 and protein 0.78
 Culture has grown enterovirus.
 Child was started on Cefotaxime Amoxycillin and
Acyclovir
 Improved rapidly within 3 days and was discharged.

5. The Big Three
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 Urinary tract infections (5-9%)
 Bacteraemia (2%)
 Bacterial Meningitis (0.5%)
 The latter two are called “invasive bacterial
infections”.
 Under-diagnosis can be catastrophic.
 Over-diagnosis can also create major
problems such as unnecessary tests,
inappropriate antibiotic use, unnecessary
hospitalisation, and increased costs.
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6. History Taking
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 Maternal History - PROM, GBS, Fever,
Antibiotic use during labour, history of STDs
 Neonatal Course - Stay in nursery or NNU,
results of tests and cultures, treatment history
 Contact or exposure to infected family
members and care-takers
 Symptoms related to specific problems
 Behaviour, feeding and activity of the infant
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7. Traffic Light system for serious illnesses
in young children (NICE Guidance,
CG160) - 1/5
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Green - Low Risk Amber - Intermediate
Risk
Red - High Risk
Normal colour Pallor reported by
parent or carer
Pale/mottled/ashen/blue
Colour of Skin, Lips or Tongue

8. Traffic Light system for serious illnesses
in young children (NICE Guidance,
CG160) - 2/5
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Green - Low Risk Amber - Intermediate
Risk
Red - High Risk
•Responds normally to
social cues
•Content/smiles
•Stays awake or
awakens quickly
•Strong normal cry/not
crying
•Not responding
normally to social cues
•No smile
•Wakes only with
prolonged stimulation
•Decreased activity
•No response to social
cues Appears ill to a
healthcare professional
•Does not wake or if
roused does not stay
awake Weak, high-
pitched or continuous
cry
Activity

9. Traffic Light system for serious illnesses
in young children (NICE Guidance,
CG160) - 3/5
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Green - Low Risk Amber - Intermediate
Risk
Red - High Risk
Normal with no distress
•Nasal flaring
•Tachypnoea
•Oxygen saturation
≤95% in air
•Crackles in the chest
•Grunting
•Tachypnoea: RR >60
breaths/minute
•Moderate or severe
chest indrawing
Respiratory

10. Traffic Light system for serious illnesses
in young children (NICE Guidance,
CG160) - 4/5
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Green - Low Risk Amber - Intermediate
Risk
Red - High Risk
•Normal skin and eyes
•Moist mucous
membranes
•Tachycardia: - >160
beats/minute,
•CRT ≥3 seconds
•Dry mucous
membranes
•Poor feeding in infants
•Reduced urine output
•Reduced skin turgor
Circulation and hydration

11. Traffic Light system for serious illnesses
in young children (NICE Guidance,
CG160) - 5/5
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Green - Low Risk Amber - Intermediate
Risk
Red - High Risk
•None of the amber or
red symptoms or signs
•Age 3–6 months,
•temperature ≥39°C
•Fever for ≥5 days
•Rigors
•Swelling of a limb or
joint
•Non-weight bearing
limb/not using an
extremity
•Age < 3 months or fever
more than or equal to 38
C
•Non-blanching rash
•Bulging fontanelle
•Neck stiffness
•Status epilepticus
•Focal seizures or
neurological signs.
Other

12. SBI (Serious Bacterial Infection)
score
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 This team of experts have recommended scoring based on
vital signs, consciousness level, dehydration level, presence
or absence of Hypoxia and a baseline risk assessment for
SBI which includes presence or absence of developmental
delay. Out of a maximum score of 18, SBI should be
considered if the score is 9 or more.
 In their study carried out at Queen’s Hospital in Nottingham
between September 2000 and March 2001, and then again
between September 2001 and March 2002, a total of 1951
infants and children were evaluated for SBI. Neonates and
children who needed emergency medicines and resuscitation
were excluded.
 They have advised that clinical scores should be assessed
with results of investigations to predict possibility of a serious
bacterial infection.
Ref: Brent, et al. Arch Dis Child 2011;96:361–367. doi:10.1136/adc.2010.183111

13. Physical Examination
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 Vital signs, especially the SpO2 levels; Tachypnoea (RR > 60/min) or
grunting are signs of serious infection; Tachycardia (HR > 160/min)
suggests high risk; Temperature > 38 C.
 Signs of toxicity - perfusion (CRT > 3 sec), activity, alertness, colour,
tone, irritability, lethargy, drowsy or limp, abnormal cry
 Signs of localising infection such as omphalitis, limb or joint
swelling, rash on skin or mucous membranes
 Soft signs of meningitis - look for abnormal breathing, dull or
glazed look, irritability, high-pitched cry, temperature instability,
excessive vomiting or decreased feeding, etc.
 Bulging fontanelles are always a sign of significance but usually
found in less than 20% of young infants with meningitis
 Look at ears, bones and other sites too.
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14. Investigations that help differentiate
between routine/serious vs. invasive
bacterial infections
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The most important tests are the WCC, CRP and PCT (procalcitonin)
(Note: Currently, NICE does not recommend PCT.)
Name of test Normal Mild to
moderate
infection or
SBI
Abnormal for
Invasive
bacterial
illness (IBI)
WCC ( X 10^9) 5-15 (Immature
neutrophils<
10% or ratio of
imm:mat < 0.2)
5-15 < 5 OR > 15
CRP (More
important to do
sequentially)
Less than 10
mg/L
10-40 mg/L More than 40
mg/L, often
above 100 mg/L
PCT (see NICE
Guidance
DG18)
Less than 0.5
ng/mL
0.5-2.0 ng/mL More than 2.0
ng/mL
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15. Additional tests
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 Urine examination (dipstick, culture if needed) (On microscopy:
Less than 10 WBC/HPF helps to rule out UTI) (however, up to 20%
of UTI can be missed if one relies only on dipstick - UpToDate)
 Blood culture (BAC-Tec)
 CSF examination (all neonates, and in 1-3 month olds, if unwell or
if WCC < 5 or > 15). This is mandated by NICE guidance) (Count of
less than 8 cells/cu.mm helps rule out meningitis)
 X-ray chest (only if respiratory symptoms and signs)
 Stool exam (more than 5 leukocytes/HPF) only in infants with
diarrhoea),and if positive, stool culture
 Remember: Tests should be interpreted along with clinical findings
and history of whether baby was immunised or/and given
antibiotics in the previous 24 hours
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16. This is important:
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To reiterate, in neonates, most scoring
systems and protocols are not full-proof
& a high degree of suspicion is needed.

17. Case 2: Missing Diagnostic
Support
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 AT, 26 days old ex-33 weeker was discharged from the SCBU on
the 13th day after a non-complicated neonatal course.
 Brought for assessment for reduced feeds and lethargy with 2
vomits since the past 4 hours. Focus not found on history or
examination.
 Blood results showed WCC 11.6, Hb 121, Platelets 264, and CRP
13. Blood cultures sent. BM and biochemistry were normal.
 In view of clinical symptoms, child admitted and observed.
Antibiotics not started.
 On Day2, child had a bilious vomit and deteriorated further.
 Sepsis suspected and antibiotics initiated. CRP repeated, was 22.
 Blood cultures came back negative at 48 hours.
 Day 3, further clinical deterioration occurred and LP done, which
showed 422 leucocytes, 70% neutrophils.
What are the lessons from this case? (Discuss)

18. Sepsis 6 - (1/2) : When to suspect
sepsis
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 When to suspect sepsis?
Go for the following:
a) Core temperature < 36°C or > 38.5°C
b) Inappropriate tachycardia (ref. APLS for limits)
c) Altered circulation - CRT > 3 sec
d) Altered sensorium -irritable or sleepy, or floppy
infant
 Reduced threshold for infants below 3 months.
Ref: http://sepsistrust.org/wp-content/uploads/2015/08/Paediatric-
Sepsis-6-version-11_1.pdf

19. Sepsis 6 - (2/2) : What six steps
MUST be taken to reduce mortality
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 Give High flow oxygen
 Take bloods for cultures, biochemistry, lactate,
etc. and get a secure IV/IO line
 Give emperical broad-spectrum antibiotics as per
protocols
 Consider fluid resuscitation (20 ml/kg bolus, for
example) - prevent overloading by monitoring
basal lung fields for crepitations, checking for
hepatomegaly,etc.
 Involve seniors early
 Give inotropes early (use definitely if no
improvement with more than 40 ml/kg IV fluids.)

20. Treatment with empirical
antibiotics
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 This is indicated for the following cases, but always after
doing tests as previously described, whenever possible:
 Infants less than a month old (neonatal sepsis protocols)
 Infants 29-90 days old who are unwell or have WCC < 5
or > 15 X 10^9/mL
 Infants with reduced consciousness, seizures or
asymmetrical paralysis, where acyclovir should also be
started
 Infants with clear source or focus of infection on history,
who must be investigated and treated appropriately.
22-09-2016

21. Other important considerations in
Management - 1
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 Hospital observation of at least 2 hours in all 29-90 day
old infants with fever (in the CAU while awaiting results);
check if prior use of antipyretics is masking the fever.
 If signs of shock are present, bolus of crystalloids
(normal saline, usually 20 mL/kg) is a must
 Thorough checking for meningococcaemia is part of
the initial testing, and should be considered if there is
a purpuric or non-blanching rash
 Do not forget GBS and listeria in neonates. One should
distinguish between early onset (0-7 days) and late
onset (7-28 days) neonatal sepsis, as causes and
implications are different.
22-09-2016

22. Other important considerations in
Management - 2
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 A third generation cephalosporin like cefotaxime or
ceftriaxone is adequate, but ampicillin or amoxicillin
must be added to cover for listeriosis and benzyl
penicillin for GBS.
 If meningococcaemia or meningococcal meningitis is
suspected, specialist consultation must be sought, and
treatment with benzyl penicillin considered.
 Fever should be treated with antipyretics. Tepid
sponging, bathing, etc. is not recommended.
 Clothing should neither be less nor more than what
the infant is comfortable with.
22-09-2016

23. Use of antipyretics
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 Either paracetamol or ibuprofen may be used.
Clinicians should be familiar with their doses,
safety margins and common side-effects. Refer to
BNFC in case of doubt
 Both agents should NOT be used at the same time.
 Alternate use of these two agents is now
considered rational in infants in whom one agent
used repeatedly is ineffective or crosses safety
margins
22-09-2016

24. Final Points
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 There is considerable ground left to be covered
and NICE recommends that more large-scale
studies be carried out to clear the gray areas; this
includes studies on the significance of the various
tests
 Eventually, it is up to the clinician to decide on the
exact course of treatment to be adopted, such as
the need for hospitalisation, the duration of
antibacterial therapy, what to do if the LP is dry or
traumatic, etc.
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25. Summary
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 Fever in young infants is a challenging clinical
problem which calls upon all the skills of the
clinician in identifying its source, measuring its
seriousness, evaluating it by investigations and
deciding the course of action.
 Several guidances are available, but none is full-
proof and clinician’s discretion is usually the way to
go in difficult cases.
22-09-2016

26. References
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 https://www.nice.org.uk/guidance/cg160
 http://nice.org.uk/guidance/ng51
 Putto, A, Ruuskanen, O., et.al. C Reactive Protein in the Evaluation of Febrile
Illness. Arch. of Dis. in Child., 1986, 61, 24-29
 http://sepsistrust.org/professional/educational-tools/
 http://www.survivingsepsis.org/Pages/default.aspx
 Strategies for the evaluation of fever in neonates and infants (less than three
months of age) (UpToDate)
 Evaluation and management of fever in the neonate and young infant (less
than three months of age) (UpToDate)
 Kuppermann N. and Mahajan P. Role of Serum Procalcitonin in Identifying
Young Febrile Infants with Invasive Bacterial Illness, Editorial. JAMA Pediatrics,
2015
 Simon, L., Gauvin, F., et.al. Serum Procalcitonin and C-Reactive Protein Levels
as Markers of Bacterial Infection: A Systematic Review and Meta-analysis.
Clinical Infectious Diseases 2004; 39:206–17
22-09-2016

27. Important NICE Guidelines
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 NICE has come out with new guidance in June
2016 on suspecting, diagnosing, triaging and
managing sepsis in all age groups. This guidance
has “out of the hospital” and “in the hospital”
algorithms for managing suspected or proven
cases of sepsis in infants, children, and adults.
 It also has risk stratification tables for deciding
what the risk level is in each scenario and how to
manage them
 Check out this link:
http://nice.org.uk/guidance/ng51
 Also check out the guidance on intravenous fluid
therapy (ng29) and the one on antimicrobial

28. Importance of Acute Phase Reactants in
Sepsis
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 A small discussion on acute phase reactants:
 In the 0-90 days age group, CRP is still the best bet, but
results do depend on gestational age, birth weight,
neonatal stress, PROM, maternal antibiotics and timing
of test. Thus, sequential testing and use of other
parameters and clinical condition are very important.
Blood cultures are still the gold standard.
 Among other markers, pro-calcitonin is very reliable, but
the time has come to look at other markers like IL1, IL8,
TNFɑ when resources are available. Still to come are
CD11b and CD64, which are nearly 100% sensitive and
specific and need only 0.05 ml blood.
 In general, clinical features, using more than one marker
and blood cultures will make the evidence base nearly
fool-proof.

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