Neonatal Sepsis (NNS)

Dr Jerome Siyambu
- Bsc.HB, MBChB UNZA.

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Pathogenesis and Aetiology of Infections in the Neonate
• Infections are a frequent and important cause of
neonatal and infant morbidity and mortality
• Neonatal infections are unique:
1. Infectious agents can be transmitted from the
mother to the fetus or newborn infant by diverse
modes
2. Newborn infants are less capable of responding to
infection because of 1 or more immunologic
deficiencies
3. Coexisting conditions often complicate the diagnosis
and management of neonatal infections 2
Pathogenesis and Aetiology of Infections in the Neonate
4. The clinical manifestations of newborn infections vary
and include:
- Subclinical infection
- Mild to severe manifestations of focal or systemic
infection
- Congenital syndromes resulting from in utero infection
6. Variety of etiologic agents infect the newborn:
bacteria, viruses, fungi, protozoa
7. Immature, VLBW newborns have improved survival but
remain in the hospital for a long time in an environment
that puts them at continuous risk for acquired infections3
 What is Sepsis?
• Derived from Greek words:
- Sepo = rot
- Haima = blood

Hence, sepsis = rotten blood

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 Definitions

• Bacteraemia : transient presence of viable bacteria in

blood
- Septicaemia = Bacteraemia. Thus, septicaemia is NOT
sepsis

• Systemic inflammatory response syndrome (SIRS):

- Is the systemic inflammatory response to a variety of
severe clinical insults

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 Definitions

- In adults, the response is manifested by 2 or more of the

following:
1. Temperature: > 38⁰C or < 36⁰C
2. HR: > 90 bpm
3. RR > 20 b/m or PaCO2 < 4.3 kPa
4. White cell count:
a. > 12 x 10^9/L
b. < 4 x 10^9/L
c. > 10% immature forms

Check the diagnostic criteria in paediatrics on the next slide 6

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Know definitions of the following terms:

• Bacteraemia
• Sepsis
• Sepsis syndrome
• Severe sepsis
• Shock
• Septic shock
• Refractory shock
• Compensatory anti-inflammatory response syndrome
(CARS)
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• Sepsis = systemic inflammatory syndrome (SIRS)
to a localised primary site of infection (there must
be a documented infection)
• Sepsis syndrome = presence of either a positive
blood culture or clinical features of fever,
tachypnoea, tachycardia and suspected infection
• Severe sepsis = sepsis associated with organ
dysfunction, hypotension or hypoperfusion.
Hypoperfusion and perfusion abnormalities
include, but are not limited to, lactic acidosis,
oliguria or an acute alteration in mental state
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• Septic shock = severe sepsis with hypotension (know the
normal systolic values) in the absence of other causes for
hypotension and despite adequate fluid resuscitation
- Patients receiving inotropic or vasopressor agents may not
be hypotensive when perfusion abnormalities are
documented
• Refractory shock = shock unresponsive to conventional
therapy (IVFs and inotropic/vasoactive agents) within 1
hour
• Compensatory anti-inflammatory response syndrome
(CARS):
- Release of anti-inflammatory mediators which
downregulate the inflammatory response. If excessive, may10
lead to inappropriate immune hyporesponsiveness
Shock

• Shock is a syndrome that results from inadequate

oxygen delivery to meet metabolic demands
• Oxygen delivery (DO2 ) is less than Oxygen
Consumption (< VO2)
SUPPLY < DEMAND
Oxygen delivery < Oxygen Consumption
DO2 < VO2
• Deviation of blood to from non-vital organs e.g. skin,
GIT to vital organs e.g. brain, heart, kidneys occurs
• Untreated this leads to metabolic acidosis, organ
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dysfunction and death
Oxygen Delivery

 Oxygen delivery = Cardiac Output x Arterial

Oxygen Content
(DO2 = CO x CaO2)
 Cardiac Output = Heart Rate x Stroke Volume
(CO = HR x SV) Neonates depend on HR
(can’t increase SV)
– SV determined by preload, afterload and contractility
 Art Oxygen Content = Oxygen content of the
RBC + the oxygen dissolved in plasma
(CaO2 = Hb X SaO2 X 1.34 + (.003 X PaO2)
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 Types of Shock
1. Hypovolemic 3. Distributive
Hemorrhage Anaphylactic
Neurogenic
Fluid loss
Septic
Drugs

2. Cardiogenic 4. Obstructive
Pneumothorax
Myocardial dysfunction
Cardiac tamponade
Dysrrhythmia
Aortic dissection
Congenital heart disease

5. Dissociative
Heat, Carbon monoxide, Cyanide13
Endocrine
 Neonatal Sepsis
• Sepsis occurring within the first 4 weeks (28 days) of life
• Divided into two:
a. Early onset: within the 1st 72 hrs (3 days)
- Typically within the first 48 hours (2 days)
- Majority (85%) present within 24 hours of birth
b. Late onset: after the 72 hrs (3 days)

Nelson Textbook of Paediatrics, 18th Edition:

- Early onset: within 1st wk
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- Late onset: after 1st wk

• Integrity of the barrier to infection is
provided by:
• Placenta
• Low pathogenicity of colonizing
organisms (normal flora)
• Relative competence of the baby’s
defense system

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 Types of exposure to microbes
• Trans-placental
• Certain organisms have inherent ability to penetrate
placental barrier
• Ascending from vagina and cervix
• Risk increases if there is early rupture of membranes
• Intra-partum
• Neonatal infection may be caused by opportunistic
pathogens colonizing vaginal tract
• Post-natal
• Environmental with people being main source.
Hospital acquired infection most likely to be
antibiotic resistant
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Aetiology of Early Onset Neonatal Sepsis

- Is most rapid in premature neonates with a

tendency to have nonspecific signs and symptoms
- Is associated with acquisition of microorganisms
from the mother
- Routes:
Trans-placental infection
Intra-partum
Ascending infection
- Is caused by organisms that colonize the mother's
GUT
- Acquisition of the microbe is by passage through a
colonized birth canal at delivery 17
Aetiology of Early Onset Neonatal Sepsis

• The microorganisms most commonly associated with early-

onset infection include:
1. group B Streptococcus (GBS)
2. Escherichia coli
3. Haemophilus influenzae type B (Hib)
4. Listeria monocytogenes
• Pneumonia is more common in early-onset sepsis
• Meningitis and bacteremia are more common in late-
onset sepsis
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Aetiology of Late Onset Neonatal Sepsis

• Is acquired from the environment e.g. caregivers or

urinary or vascular devices
• Organisms include:
1. Coagulase-negative staphylococci
2. Staphylococcus aureus
3. E. coli
4. Klebsiella
5. Pseudomonas
6. Enterobacter
7. Candida
8. GBS
9. Anaerobes 19
Risk factors for Early Onset Neonatal
Sepsis
• Maternal colonisation • Low birth weight (LBW)
with GBS • Assisted vaginal delivery
• Premature rupture of • Maternal UTI
membranes (PROM) • Maternal pyrexia above
• Preterm prelabour 38 ⁰C
rupture of membranes • Poor maternal
(pPROM) nutrition/antenatal care
• Chorioamnionitis • Low socioeconomic status
• Prematurity • Maternal substance abuse
• Birth asphyxia
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Risk factors for Late Onset Neonatal Sepsis
• Prematurity
• Central venous catheterisation (duration >10 days)
• GIT pathology e.g. necrotising enterocolitis (NEC)

• An awareness of the many risk factors associated with

neonatal sepsis prepares the clinician for early
identification and effective treatment

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Prevention
• General
• Breastfeeding from outset, little contact with many
people

• Unit design
• Sufficient space between cots
• Good ventilation
• Ability to isolate

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 Prevention

• Equipment
• Ideally, individual stethoscopes, suction units
• Shared equipment should be cleaned after each
use, preferably should have disposable
attachments
• Avoid humidified incubators (haven for
pseudomonas); if using humidified incubators
(to maintain temp of small babies), drain
humidifier daily and refill with sterile distilled
water
• Ventilators: encourage disposable circuits 23
(expensive) that can be changed weekly
Prevention

• Control admissions
• Invasive procedures
• Keep sterile
• Hand-washing
• Advised before touching any baby and between
babies (more effective than gowning and masking)

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 Clinical Presentation
- Is non-specific
• Hyperthermia (> 38⁰C) • CVS:
- Tachycardia
- Bradycardia
• Hypothermia (< 35.5⁰C) - Poor perfusion (CRT > 2 secs)
- Cyanosis
• Respiratory: - Pallor
- Apnoea
• Hematological:
- Dyspnoea (RR > 60 b/m)
- Splenomegaly
- Grunting - Petechiae
- Nasal flaring - Purpura 25
Clinical Presentation

• CNS:
• GIT:
- Irritability
- Poor feeding
- Lethargy
- Jaundice
- Tremors
- Abdominal distension
- Seizures
- Vomiting
- Full fontanelle
- Diarrhea
- Hypotonia
- Hepatomegaly
- High pitched cry

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 Differentials
• CCF
• Respiratory distress syndrome (RDS)
• Hypoglycemia
• Hemolytic disease of the newborn
• Aspiration pneumonia
• Metabolic acidosis
• Transient tachypnea of the newborn (TTNB)
• Tracheo-oesopageal fistula (TOF)
• Birth asphyxia
• Neonatal convulsions
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 Investigations

1. Sepsis screen
• Blood/CSF/urine/stool for MCS
Helpful;
• FBC/DC: Hb, Platelet count, immature band ratio > 0.2
• Acute phase reactants: CRP, ESR.
• Others: CXR
2. Surface swabs: typically suggests possible exposure but
may not point to offending pathogen
3. Maternal HVS
4. Immunological studies
• Antigen detection
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• Antibody detection (more valuable in viral infections)
 Investigations
In case of meningitis:

5. Head ultrasonogram:
a. Ventriculitis
b. Abnormal parenchymal echogenicities
c. Extracellular fluid
d. Chronic changes

6. CT scan:
e. Obstructive hydrocephalus
f. Cerebral infarctions
g. Abscesses
h. Atrophy 29
 Investigations

• Interpretation of Lab Results

WBC/ESR:
Normal range at birth: 10,000-30,000 cells/mm3 (may vary with
gestational age)
- Leukopenia: < 5000/mm3 is significant and a strong indicator of
sepsis
- ESR > 15mm/hr is indicative of neonatal sepsis (though sensitivity is
low)
CSF:
- Normal WBC in newborn: average of 6/mm3
- Range: 0-20/mm3
- CSF protein:
1. Term: 0.4-0.8 g/L 30
2. Preterm: can be as high as 1.2 g/L
 Investigations
• Neutropenia may be observed with:
- Maternal hypertension
- Severe perinatal asphyxia
- Periventricular or intraventricular hemorrhage
• Neutrophil ratios (neutrophil immature band ratio, NIBR)
have been more useful in diagnosing neonatal sepsis
• The maximum acceptable immature to total neutrophils
for excluding sepsis in the 1st day is 0.16 (> 0.2 indicates
infection)

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Treatment
Types of medical interventions:

• Antibiotics – main intervention

• Others (no substantial clinical trials have shown that

these treatments are beneficial):
- Granulocyte transfusion
- IV immune globulin (IVIG) replacement
- FFP
- Exchange transfusion
- Use of recombinant cytokines
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 Antibiotic Treatment
• Knowledge of prevalent organisms and antibiotic
susceptibility is very important
• Take specimens and start antibiotics
• May need to change according susceptibility results
• Duration:
- Blood stream infections: 7-10 or 5-7 days after clinical
response
- Meningitis: 14-21 days (gram positive = 2wks, gram
negative = 3wks) after a negative repeat LP

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 Antibiotic Treatment
• Benzyl penicilin:
- 100,000 i.u /kg/24 hrs in divided doses
- 200,000 i.u/kg/24 hrs in meningitis
• Gentamycin:
- 5mg/kg/24hrs in divided doses
- 7.5mg/kg/24 hrs in meningitis
• Cefotaxime: 50mg/kg/day increased to 200mg/kg/day in 2-4 divided
doses parenterally
• Ciprofloxacin: 5-10mg/kg in two divided doses
• Others:
- Cloxacillin (50 mg/kg BD, 100 mg/kg in meningitis) in suspected Staph
aureus
- Fluconazole: 6mg/kg/24hr OD if fungal
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 • KCH Antibiotics:
1st line
Xpen and Gentamycin are generally first line, alternative
- Early onset NNS: cefotaxime
- Late onset NNS: cefotaxime/cloxacillin
2nd line
- Ciprofloxacin
3rd line
- Imipenem/Cilastatin

• There is an increasing resistance to traditional first line

antibiotics: Xpen and gentamycin 35
Supportive Treatment
• Remember the ABCs (now CABs)
• Maintain nutrition
• Depends on general condition
• N/G tube
• Developed countries ( parenteral nutrition)
• Ensure:
- Normoglycemia
- Hydration
- Good perfusion
- Monitor renal and liver function
- Monitor bilirubin levels if jaundiced
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The End!

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