Neonatal sepsis is an infection that occurs in the first month of life. It can involve the bloodstream (sepsis), lungs (pneumonia), or brain (meningitis). Risk factors include preterm birth, rupture of membranes over 18 hours before delivery, and maternal infection. Symptoms may include poor feeding, temperature instability, respiratory distress, and lethargy. Diagnosis involves blood, CSF, and culture tests. Treatment requires antibiotics, respiratory support, and care of other organ systems until the infant recovers. Preventing infection in both mother and baby is important to reduce the risk of neonatal sepsis.

1. Neonatal Sepsis

2. Definition
‡ Neonatal sepsis is defined as a clinical syndrome
of bacteremia with systemic signs and symptoms
of infection in the first 4 weeks of life.
‡ When pathogenic bacteria gain access into the
blood stream, they may cause overwhelming
infection without much localization (septicemia)
or may get predominantly localized to the lung
(pneumonia) or the meninges (meningitis).

3. Classification
‡ Neonatal sepsis can be classified into two
sub-types depending upon whether the onset
of symptoms is before 72 hours of life (early
onset) or later (late onset).

4. Etiology
‡ The microorganisms most commonly associated with early-
onset infection include group B Streptococcus (GBS),
Escherichia coli , coagulase-negative Staphylococcus,
Haemophilus influenzae.
‡ Meningoencephalitis and neonatal sepsis syndrome can
also be caused by infection with adenovirus, enterovirus, or
coxsackievirus.
‡ Additionally, sexually transmitted diseases (eg, gonorrhea,
syphilis, herpes simplex virus [HSV], cytomegalovirus
[CMV], hepatitis, human immunodeficiency virus [HIV],
rubella, toxoplasmosis, Trichomonas vaginalis, Candida
species) have all been implicated in neonatal infection.

5. Early onset Sepsis
‡ Early-onset infections are caused by organisms prevalent in
the maternal genital tract or in the delivery area.
‡ The associated factors for early-onset sepsis include
± low birth weight,
± prolonged rupture of membranes,
± foul smelling liquor,
± multiple per vaginum examinations,
± maternal fever,
± difficult or prolonged labour
± aspiration of meconium.
‡ Early onset sepsis manifests frequently as pneumonia and
less commonly as septicemia or meningitis.

6. Late Onset Sepsis
‡ Late-onset septicemia is caused by the organisms thriving in the
external environment of the home or the hospital.
‡ The infection is often transmitted through the hands of the care-
providers.
‡ The associated factors of late-onset sepsis include:
± low birth weight,
± lack of breastfeeding,
± superficial infections (pyoderma, umbilical sepsis),
± aspiration of feeds,
± disruption of skin integrity with needle pricks
± use of intravenous fluids.
‡ These factors enhance the chances of entry of organisms into the
blood stream of the neonates whose immune defences are poor as
compared to older children and adults.

7. PathoPhysiology
‡ Numerous host factors predispose the
newborn infant to sepsis:
‡ It involves all levels of host defense, including
± cellular immunity,
± humoral immunity,
± barrier function.

8. Cellular immunity
‡ Is mainly divided into 4 main components:
‡ neonatal neutrophil or polymorphonuclear (PMN) cell:
± is vital for effective killing of bacteria
± is deficient in chemotaxis and killing capacity
± neutrophil reserves are easily depleted because of the diminished
response of the bone marrow, especially in the premature infant.
‡ Neonatal monocyte
± concentrations are at adult levels; however,
± macrophage chemotaxis is impaired and continues to exhibit
decreased function into early childhood.
± The absolute numbers of macrophages are decreased
± The chemotactic and bacteriocidal activity and the antigen
presentation by these cells are also not fully competent at birth.

9. Cellular immunity
‡ T cells
± Found in early gestation and incrase till 6months of life
± Cell are immature
± Do not proliferate as readily as adult T cells
± The cytotoxic function of the T celss are only 50% of the adult T
cell
± Important factor is that new borns are lacking of memory T cells
‡ Natural Killer Cells
± Found in sma;; numbers
± Functionally immature as they produce very low levels of
interferon Gamma upon primary stimulation compared to adult
NK cells

10. Humoral immunity
‡ fetuses has some preformed immunoglobulin present,
primarily acquired through nonspecific placental
transfer from the mother
‡ Ability of the neonate to generate Ig in response to
antigenic stimulation is intact but response is initially
decreased and rapidly rises with increasing postnatal
age.
‡ The neonate is also capable of synthesizing
immunoglobulin M (IgM) in utero at 10 weeks'
gestation; however, IgM levels are generally low at
birth, unless the infant was exposed to an infectious
agent during the pregnancy

11. Humoral immunity
‡ Most of the IgG is acquired from the mother during
late gestation
‡ The neonate may receive immunoglobulin A (IgA) from
breastfeeding but does not secrete IgA until 2-5 weeks
after birth.
‡ Complement protein production can be detected as
early as 6 weeks' gestation; however, the concentration
of the various components of the complement system
widely varies among individual neonates.
‡ Mature complement activity is not reached until
infants are aged 6-10 months.

12. Barrier function
‡ Phisical an chemical barriers are present in
infants but are immature
‡ In premature infants, skin and mucous
membranes are easily broken down
‡ Invasive procedures cause an increased risk of
contracting an infection especially in those
who are clinically ill and are in the hospital.

13. Clinical features
‡ The manifestations of neonatal septicemia are often vague and
therefore demand a high index of suspicion for early diagnosis.
‡ The most common and characteristic manifestation is an alteration
in the established feeding behavior in late onset sepsis and
respiratory distress in early onset sepsis.
‡ Hypothermia is a common manifestation of sepsis, whilst fever is
infrequent.
‡ Diarrhea, vomiting and abdominal distension may occur.
‡ Episodes of apneic spells or gasping may be the only manifestation
of septicemia.
‡ In sick neonates, the skin may become tight giving a hide-bound
feel (sclerema) and the perfusion becomes poor (capillary refill time
of over 3 seconds).

14. Clinical Features in localized sepsis
‡ The additional features of pneumonia or meningitis may be present
‡ The evidence of pneumonia includes
± tachypnea,
± chest retractions,
± grunting,
± early cyanosis
± apneic spells
± Cough is unusual.
‡ Meningitis is often silent, the clinical picture being dominated by
manifestations of associated septicemia.
‡ However, the appearance of excessive or high-pitched crying, fever,
seizures, blank look, neck retraction or bulging anterior fontanel are
highly suggestive of meningitis.

15. WHO study published in 2003
‡ identified nine clinical features which predict severe
bacterial illness in young infants
1. Feeding ability reduced
2. No spontaneous movement
3. Temperature >38 C
4. Prolonged capillary refill time
5. Lower chest wall in drawing
6. Resp rate > 60/minute
7. Grunting
8. Cyanosis
9. H/o of convulsions

16. Investigations
‡ The CSF findings in infectious neonatal meningitis are an elevated WBC count
(predominately PMNs), an elevated protein level, a decreased CSF glucose
concentration, and positive culture results.
‡ An absolute neutrophil count of < 1800 per cmm is an indicator of infection.
‡ Immature neutrophils (Band cells + myelocytes + metamyelocytes) to total
neutrophils ratio (l/T) > 0.20
‡ Platelet count of less than 100,000 per cmm
‡ C-reactive protein (CRP) which has a high degree of sensitivity for neonatal sepsis
‡ A practical positive "sepsis screen" takes into account two or more positive tests as
given below:
1. Leukopenia (TLC <5000/cmm)
2. Neutropenia (ANC <1800/cmm)
3. Immature neutrophil to total neutrophil (I/T) ratio (> 0.2)
4. Micro ESR (> 15mm 1st hour)
5. CRP +ve

17. Treatment
‡ No investigation is required as a prerequisite to
start treatment in a clinically obvious case.
‡ Supportive care and antibiotics are two equally
important components of the treatment.
‡ It should be realized that antibiotics take at least
12 to 24 hours to show any effect and it is the
supportive care that makes the difference
between life and death early in the hospital
course.

18. Supportive care
‡ The purpose of supportive care is to:
± normalize the temperature,
± stabilize the cardiopulmonary status,
± correct hypoglycemia and
± prevent bleeding tendency

19. Supportive care of a septic neonate
1. Provide warmth, ensure consistently normal temperature
2. Start intravenous line.
3. Infuse normal saline 10 ml/kg over 5-10 minutes, if perfusion is poor as
evidenced by capillary refill time (CRT) of more than 3 seconds. Repeat the
same dose 1-2 times over the next 30-45 minutes, if perfusion continues
to be poor.
4. Infuse glucose (10 percent) 2 ml/kg stat.
5. Inject Vitamin K 1 mg intramuscularly.
6. Start oxygen by hood or mask, if cyanosed or grunting.
7. Provide gentle physical stimulation, if apneic.
8. Provide bag and mask ventilation with oxygen if breathing is inadequate.
9. Avoid enteral feed if very sick, give maintenance fluids intravenously
10. Consider use of dopamine if perfusion is persistently poor.
11. Consider exchange transfusion if there is sclerema.

20. Treatment
‡ Antibiotic therapy should cover the common causative bacteria,
namely, Escherichia coli, Staphylococcus aureus and Klebsiella
pneumoniae.
‡ A combination of ampicillin and gentamicin is recommended for
treatment of sepsis and pneumonia.
‡ In cases of suspected meningitis, cefotaxime should be used along
with an aminoglycoside.
‡ On confirmation of sensitivity pattern, appropriate antibiotics are
used singly or in combination.
‡ In a baby in whom the antibiotics were started on low suspicion,
these may be stopped after 3 days, if baby is clinically well
‡ if a baby appears ill even though the cultures are negative,
antibiotic therapy should be continued for 7 to 10 days .

21. Superficial infections
‡ Superficial infections can be treated with local
application of antimicrobial agents.
‡ Pustules can be punctured with sterile needles and
cleaned with spirit or betadine.
‡ Purulent conjunctivitis can be treated with neosporin
or chloramphenicol ophthalmic drops.
‡ Oral thrush responds to local application of
clotrimazole or nystatin (200,000 units per ml) and
hygienic precautions.
‡ Superficial infections must be adequately managed; if
neglected they can lead to sepsis or even an epidemic.

22. Prevention of infections
‡ A good antenatal care goes a long way in decreasing
the incidence, morbidity and mortality from neonatal
sepsis.
‡ All mothers should be immunized against tetanus.
‡ All types of infections should be diagnosed early and
treated vigorously in pregnant mothers.
‡ Babies should be fed early and exclusively with
expressed breast milk (or breastfed) without any
prelacteal feeds.
‡ Cord should be kept clean and dry. Unnecessary
interventions should be avoided.

23. Hand washing
‡ This is the simplest and the most effective
method for control of infection in the hospital.
‡ All persons taking care of the baby should strictly
follow hand washing policies before touching any
baby.
‡ The sleeves should be rolled above the elbows.
‡ Rings, watches and jewellery should be removed.
‡ Hand should be washed with a thorough scrub
for 2 minutes before starting to see patients and
washed again for 20 second in between patients.

24. Prevention of infection in hospital
‡ The nursery environment should be clean and dry with
24 hour water supply and electricity.
‡ The nursery temperature should be maintained
between 30+2°C.
‡ All procedures should be performed after wearing
mask and gloves.
‡ Unnecessary invasive interventions such as needle
pricks and setting up of intravenous lines should be
kept to the barest minimum.
‡ Every baby must have separate thermometer and
stethoscope( if possible) and all barrier nursing
measures must be followed.

25. Congenital Pneumonia

26. Defination
‡ Pneumonia is an inflammatory pulmonary
process that may originate in the lung or be a
focal complication of a contiguous or systemic
inflammatory process within the first 24 ʹ 48
hours of life.

27. Pathogenesis
‡ In neonatal pneumonia, pulmonary and extrapulmonary injuries are
caused directly and indirectly by invading microorganisms or foreign
material and by poorly targeted or inappropriate responses by the
host defense system that may damage healthy host tissues as badly
or worse than the invading agent.
‡ Direct injury by the invading agent usually results from synthesis
and secretion of microbial enzymes, proteins, toxic lipids, and toxins
that disrupt host cell membranes, metabolic machinery, and the
extracellular matrix that usually inhibits microbial migration.7,8
‡ Indirect injury is mediated by structural or secreted molecules
which may alter local vasomotor tone and integrity, change the
characteristics of the tissue perfusate, and generally interfere with
the delivery of oxygen and nutrients and removal of waste products
from local tissues.

28. Risk Factors
‡ Unexplained preterm labor
‡ Rupture of membranes before the onset of labor
‡ Membrane rupture more than 18 hours before delivery
‡ Maternal fever (>38°C/100.4°F)
‡ Uterine tenderness
‡ Foul-smelling amniotic fluid
‡ Infection of the maternal genitourinary tract
‡ Previous infant with neonatal infection
‡ Nonreassuring fetal well-being test results
‡ Fetal tachycardia
‡ Meconium in the amniotic fluid
‡ Recurrent maternal urinary tract infection
‡ Gestational history of illness consistent with an organism known to have
transplacental pathogenic potential

29. Clinical signs & symptoms
‡ may be pulmonary or systemic
‡ Pulmonary:
‡ Persistent tachypnea (respiratory rate >60/min)
‡ Expiratory grunting may occur.
‡ Accessory respiratory muscle recruitment, such as nasal flaring and retractions at subcostal,
intercostal, or suprasternal sites, may occur.
‡ Airway secretions may vary substantially in quality and quantity.
‡ If aspiration of meconium, blood, or other proinflammatory fluid is suspected, other colors and
textures reflective of the aspirated material may be seen.
‡ Rales, rhonchi, and cough are all observed much less frequently in infants with pneumonia than in
older individuals.
‡ Cyanosis of central tissues, such as the trunk, implies a deoxyhemoglobin concentration of
approximately 5 g/dL or more and is consistent with severe derangement of gas exchange from
severe pulmonary dysfunction as in pneumonia,
‡ Infants may have external staining or discoloration of skin, hair, and nails with meconium, blood, or
other materials when they are present in the amniotic fluid.
‡ Increased respiratory support requirements such as increased inhaled oxygen concentration,
positive pressure ventilation, or continuous positive airway pressure are commonly required before
recovery begins.
‡ Infants with pneumonia may manifest asymmetry of breath sounds and chest excursions, which
suggest air leak or emphysematous changes secondary to partial airway obstruction.

30. Systemic findings
‡ Similar to signs and symptoms seen in sepsis or
other severe infectionsTemperature instability
± Skin rash
± Jaundice at birth
± Tachycardia
± Glucose intolerance
± Abdominal distention
± Hypoperfusion
± Oliguria

31. Laboratory Studies
‡ Aspiration Culture
‡ Blood culture
‡ Culture of specimens from lumbar puncture
‡ Urine culture
‡ Imaging Studies
± Radiography
± Ultrasonography
‡ Ultrasonography is particularly useful for identifying
and localizing fluid in the pleural and pericardial spaces.

32. Treatment
‡ Antimicrobial therapy
± initial empiric therapy consists of ampicillin and either gentamicin or
cefotaxime
± Drainage of a restrictive or infected effusion or empyema may enhance
clearance of the infection and improves lung mechanics.
‡ Respiratory support
± Criteria for institution and weaning of supplemental oxygen and mechanical
support are similar to those for other neonatal respiratory diseases.
‡ Hemodynamic support
± Delivery of adequate amounts of glucose and maintenance of
thermoregulation, electrolyte balance, and other elements of neonatal
supportive care are also essential aspects of clinical care.
‡ Nutritional support:
± Attempts at enteral feeding often are withheld in favor of parenteral
nutritional support until respiratory and hemodynamic status is sufficiently
stable.

33. Complications
‡ Restrictive pleural effusion
‡ Infected pleural effusion
‡ Empyema
‡ Systemic infection with metastatic foci
‡ Pulmonary Hypertension, Persistent-newborn
‡ Air leak syndrome, including pneumothorax, pneumomediastinum,
pneumopericardium, and pulmonary interstitial emphysema
‡ Airway injury
‡ Obstructive airway secretions
‡ Hypoperfusion
‡ Chronic lung disease
‡ Hypoxic-ischemic and cytokine-mediated end-organ injury