Neonatal sepsis refers to systemic bacterial infections in newborns. Early-onset sepsis occurs within 72 hours of birth and is usually caused by maternal genital tract organisms. Late-onset sepsis occurs after 72 hours and is often caused by environmental organisms acquired in the hospital or home. Treatment involves supportive care and empiric antibiotics targeting common causes like E. coli, S. aureus, and Klebsiella spp. Prompt treatment is important but overuse of antibiotics risks emerging resistance, so diagnosis is confirmed using blood cultures and sepsis screening tests when possible. Outcomes depend on the infant's health and prompt, appropriate treatment.

1. E R I C M D 4
Neonatal Sepsis

2. Systemic Infections When pathogenic organisms
gain access into the blood
stream, they may cause an overwhelming infection
without much localization (septicemia), or may get
predominantly localized to the lung (pneumonia) or
the
meninges (meningitis). Systemic bacterial infections
are
known by the generic term neonatal sepsis (NNS),
which
incorporates septicemia, pneumonia and meningitis.

3. Etiology
Escherichia coli, Staphylococcus aureus and
Klebsiella sp. are
the predominant organisms. Organisms like
Acinetobacter,
Pseudomonas and coagulase negative staphylococci
are also
important pathogens in hospital acquired infections.

4. Early Versus Late Sepsis
Early-onset sepsis (EOS) (less than 72 hr) infections are
caused by organisms prevalent in the maternal genital
tract or in the delivery area. The predisposing factors
include LBW, prolonged rupture of membranes, foul
smelling liquor, multiple per vaginal examinations,
maternal fever, difficult or prolonged labor and aspiration
of meconiurn. EOS frequently manifests as pneumonia and
less commonly as septicemia or meningitis.

5. Late-onset sepsis (LOS) (72 hr or later) infections are
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 presentation is that of septicemia, pneumonia or
meningitis. The predisposing factors include LBW, lack
of breastfeeding, poor cord care, superficial infections
(pyoderma, umbilical sepsis), aspiration of feeds and
disruption of skin integrity with needle pricks and use of
intravenous fluids.

7. Clinical Features
NNS often manifests with vague and ill-defined symptoms
and, therefore, requires high index of suspicion for early
diagnosis. An early but non-specific manifestation is
alteration in the established feeding behavior. The baby,
who had been active and sucking normally, refuses to suck
and becomes lethargic, or unresponsive. Poor cry,
hypothermia, abdominal distension, vomiting and apneic
spells are other common manifestations. Diarrhea is
uncommon.

8. Fast breathing, chest retractions and grunt
indicate pneumonia. Most cases of meningitis do not have
any distinct clinical picture per se, making it mandatory to
suspect meningitis in all cases suspected of sepsis. Though
the presence of excessive or high-pitched crying, fever,
seizures, blank look, neck retraction or bulging anterior
fontanel are suggestive of meningitis. Shock, bleeding,
sclerema and renal failure are indicators of overwhelming
sepsis.

9. Diagnosis of sepsis is fraught with poor specificity. A
host of conditions like hypothermia, hyperthermia,
hypoglycemia,
hypoxia, late metabolic acidosis, congestive
heart failure and even simple conditions like nasal block
may mimic sepsis. A careful clinical examination and
relevant investigations are necessary to differentiate these
conditions from NNS and avoid unnecessary antibiotics
therapy. Babies who are clinically stable can be observed,
without admission and intravenous antibodies, while
providing good supportive care

10. Investigations
No investigation is required to start treatment in a sick
baby
who has high probability of sepsis. Blood culture
provides
definitive diagnosis of NNS and should be taken before
starting antimicrobial therapy. After cleaning the skin
(alcohol, povidone-iodine and again alcohol, a
specimen
of 0.5 to 1.0 ml of blood can be taken in a small culture
media bottle containing 5 to 10 ml of the liquid broth .

11. Sepsis screen should be performed in equivocal cases.
A panel of tests (sepsis screen) consisting of total leukocyte
count (TLC; <5000/mm3), absolute neutrophil count
(ANC; <1800/mm3), immature to total neutrophil ratio
(I/T ratio; more than 20%), CRP (more than 1 mg/ dl) and
micro ESR (15 mm or more in the first hour) constitutes a
useful sepsis screen for clinically doubtful cases. Sepsis
screen is considered positive if two of these parameters
are positive. Value of sepsis screen is more for exclusion
of diagnosis of NNS.

12. Lumbar puncture should be performed in all cases
suspected of NNS except in asymptomatic babies being
investigated for maternal risk factors.

13. Treatment
Institution of prompt treatment is essential for ensuring
optimum outcome of neonates with sepsis who often reach
the health care facilities late and in a critical condition.
Supportive care and antibiotics are the two equally
important components of treatment. Antibiotics take at
least 12 to 24 hr to show any effect, optimum supportive
care improves the outcomes in sick septic babies.

14. Supportive care Good supportive care requires
meticulous attention to various aspects:
• Provide warmth; ensure normal temperature (36.5°-
37.50C).
• Start oxygen by hood or mask, if the baby is cyanosed
or grunting. Provide bag and mask ventilation if
breathing is inadequate. Instilling normal saline drops
in nostrils may help clear the nasal block.
Assess peripheral perfusion by palpating peripheral
pulses, capillary refill time (normally <2-3 seconds) and
skin color. Serial measurement of urine output is helpful
for this purpose.

15. Infuse normal saline or Ringer lactate
10 ml/kg over 5-10 minutes, if perfusion is poor. Repeat
the same 1-2 times over the next 30-45 minutes, if
perfusion continues to be poor. Dopamine and
dobutamine
may be required to maintain normal perfusion
Insert intravenous line. If hypoglycemia is suspected,
infuse glucose (10%) 2 ml/kg stat. Do not use glucose
boluses routinely. Provide maintenance fluid, electrolytes
and glucose (4--o mg/kg/min). Add potassium
to IV fluids once normal flow of urine has been
documented.

16. Ensuring optimal nutrition is extremely helpful in sick
babies. Enteral feeds should be initiated early if there
is no abdominal distension and baby is hemodynamically
stable. Feed mother's milk. Consider
parenteral nutrition, if baby is not expected to receive
enteral feeds for prolonged period.
• Administer vitamin K 1 mg intramuscularly.
• Transfuse packed cells, if baby has a low hematocrit
(less than 35-40%). Do not use blood/plasma transfusion
on routine basis for 'boosting' immunity

17. Specific care Antimicrobial therapy constitutes the
mainstay of treatment of sepsis. In a seriously sick neonate
suspected of sepsis, appropriate antibiotics therapy should
be initiated without any delay after obtaining blood
samples for culture and sepsis screen. One need not await
for the results of sepsis screen for antibiotics treatment.
However, in a baby who is otherwise stable or suspected
of sepsis because of maternal risk factors, it is desirable to
await results of sepsis screen before initiation of
antibiotics.
Since symptoms suggestive of sepsis may be caused by a
variety of other illnesses, confirmation of sepsis by sepsis
screen may help avoiding unnecessary antibiotics therapy.

18. Empiric therapy when etiologic agent is not knownThe
empiric therapy of NNS should cover the major causative
pathogens while awaiting reports of culture studies.
Since the antimicrobial spectrum and susceptibility
profile is different in different settings, there cannot be a
universal policy of empiric regimen. Antibiotics are often
used in neonates on the slightest suspicion of sepsis
because of the grave and fulminant nature of neonatal
sepsis. But unbridled overuse of antibiotics is associated
with the serious risk of emergence of resistant strains of
pathogens. Most newborn units in the country are facing
the problem of overwhelming resistance to practically all
antibiotics including third generation cephalosporins.
Rational use of antibiotics is, therefore, the responsibility
of every physician.

19. Each treating unit should adopt a suitable policy.
Based
on changes in the spectrum of etiologic agents and the
antibiotics sensitivity pattern, the choice of antibiotics
must be periodically reviewed and modified.

20. Choice of initial antibiotic therapy
Clinical situation Septicemia and
pneumonia
Meningitis
Community acquired;
resistant
strains unlikely
Ampicillin or penicillin
and gentamicin
(First line)
Cefotaxime and
gentamicin
Hospital acquired or
when there is
a low to moderate
probability of
resistant strains
Hospital acquired sepsis
or when
there is a high probability
of
resistant strains
Ampicillin or cloxacillin
and amikacin
(Second line)
Cefotaxime and amikacin
(Third line
Cefotaxime and amikacin
Cefotaxime and amikacin

21. Therapy after an etiologic agent is known.
Antimicrobial
therapy can be made specific once a positive culture
and
sensitivity report is available. However, this would be
known only after 2-3 days. Even in best institutions,
only
approximately one-fourth of babies suspected of sepsis
have positive blood culture.

22. Mode of Administration and Dos age
Antibiotics should preferably be administered
parenterally.
In a baby with septicemia or pneumonia (but not
meningitis), who has received intravenous ampicillin
and gentamicin initially and is clinically well after 3
days, the
physician may consider an individual basis switching
over
to oral amoxycillin along with single-dose
intramuscular
gentamicin therapy for the rest of the course

23. Monitoring
Intensive care and monitoring is the key determinant of
improved survival of neonates. The elements of monitoring
in sepsis are not different from those in other
lifethreatening
conditions. Proper monitoring of sick babies
enables care providers detection of complications at the
earliest. The periodicity of documenting the various
parameters should be individualized.

24. Prognosis
The outcome depends upon weight and maturity of the
infant, type of etiologic agent, its antibiotic sensitivity
pattern; and adequacy of specific and supportive therapy.
The early-onset septicemia carries higher risk of adverse
outcomes. The reported mortality rates in neonatal sepsis
in various studies from India ranges between 45-58%. The
institution of sepsis screen for early detection of infection,
judicious and early antimicrobial therapy, close monitoring
of vital signs and intensive supportive care are the
most crucial factors responsible for a better outcome.