management of febrile young infants (0 3 months

MANAGEMENT OF FEBRILE YOUNG INFANTS (0-3 MONTHS)

Dr. Taher Y. Kagalwala M.D. (Paed.), M.R.C.P.C.H.

Paediatric RegistrarBlackpool Victoria Hospital, Blackpool, Lancashire, UK

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Why is this information pertinent?

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.


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Case 1- history and examination 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.


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Case 1- Background, investigations and evolution of the case 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.


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The Big Three 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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History Taking 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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Traffic Light system for serious illnesses in young children (NICE Guidance, CG160) - 1/5

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


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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


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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

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drtaherkagalwala/paeds


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


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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


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SBI (Serious Bacterial Infection) score

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

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Physical Examination


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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Investigations that help differentiate between routine/serious vs. invasive bacterial infectionsThe 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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Additional tests


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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This is important:


To reiterate, in neonates, most scoring systems and protocols are not full-

proof & a high degree of suspicion is

needed.


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Case 2: Missing Diagnostic Support 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)

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Sepsis 6 - (1/2) : When to suspect sepsis


When to suspect sepsis? Go for the following: a) Core temperature < 36°C or > 38.5°Cb) Inappropriate tachycardia (ref. APLS for limits)c) Altered circulation - CRT > 3 secd) 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


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Sepsis 6 - (2/2) : What six steps MUST be taken to

reduce mortality 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.)


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Treatment with empirical antibiotics

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.


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Other important considerations in Management - 1 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.


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Other important considerations in Management - 2

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.


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Use of antipyretics 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


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Final Points 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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Summary


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.


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References 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

https://www.nice.org.uk/guidance/cg160


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Important NICE Guidelines 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 stewardship (ng15).

http://nice.org.uk/guidance/ng51


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Importance of Acute Phase Reactants in Sepsis 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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management of febrile young infants (0 3 months

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