Chapter 14

Neonatal Sepsis
Introduction
Sepsis is the most common cause of neonatal deaths worldwide including India, contributing to almost one-
third of all neonatal deaths. World Health Organization estimates that 1 million deaths per year are due to
neonatal sepsis. If diagnosed early and treated with good supportive care and antibiotics, it is possible to save
most cases of neonatal sepsis. Decreasing invasive interventions, promoting breastfeeding and maintaining
proper hand hygiene are the best preventive strategies to reduce the occurrence of neonatal sepsis.

Learning Objectives
The participant after completing this module should be able to:-
1) Identify neonate with sepsis
2) Enumerate the important etiological organisms
3) Interpret the ‘sepsis screen’
4) Treat neonatal sepsis

Definition
Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without
accompanying bacteremia in the first month of life. It encompasses various systemic infections of the newborn
such as septicemia, meningitis, pneumonia, arthritis, osteomyelitis and urinary tract infections (UTIs).

Classification
Depending on the age of onset, two patterns of the disease have been recognized:
i) Early onset sepsis (EOS), where the signs and symptoms of sepsis appear within 72 hours of birth. The
source of pathogens is the maternal genital tract or the delivery area. Respiratory distress due to congenital
(intrauterine) pneumonia is the predominant manifestation of EOS.

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ii) Late onset sepsis (LOS), where the signs and symptoms of sepsis appear after 72 hours of age. The
pathogens are acquired from community or hospital (nosocomial). LOS commonly presents as septicemia,
pneumonia or meningitis.

Etiology
Most cases of neonatal sepsis are caused by Escherichia coli, Klebsiella and Staphylococcus aureus.

Risk Factors
Early-onset sepsis is caused by organisms prevalent in the maternal genital tract or in the delivery area. The
risk factors for early-onset sepsis include:
 Very low birth weight (<1500 g), prematurity, spontaneous preterm delivery
 Prolonged rupture of membranes (>24 hours)
 Foul smelling liquor
 Multiple (>3) per vaginum examinations in 24 hours/single unclean p/v examination
 Intra-partum maternal fever (>380C)

Late-onset sepsis 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:
 Very low birth weight, prematurity
 Lack of breastfeeding
 Delayed enteral feeding
 Frequent handling
 Disruption of skin integrity with needle pricks and use of intravenous fluids
 Poor hygiene
 Poor maintenance of asepsis in neonatal units including improper hand washing techniques
 Superficial infections (pyoderma, umbilical sepsis)
 Previous or prolonged hospitalization

Clinical Features
The clinical picture of neonatal sepsis is highly variable. The signs and symptoms may be minimal, subtle, or
nonspecific.

Common clinical features of neonatal sepsis are listed in Table 14.1.

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Table 14.1: Clinical manifestations of neonatal sepsis

Lethargy Cyanosis*
Refusal to feed Tachypnea*
Poor cry Chest retractions*
Not arousable, comatose Grunt*
Abdominal distension Apnea/gasping*
Vomiting Fever+
Hypothermia Seizures+
Poor perfusion Blank look+
Scleremab High pitched cry+
Poor weight gain Excessive crying/irritability+
Shock Neck retraction+
Bleeding Bulging fontanel+
Diarrheaa Renal failurec

*Particularly suggestive of pneumonia.

+ Particularly suggestive of meningitis.
a Diarrhea should be suspected if there is passage of watery stool or an increase in usual stool frequency.
b Sclerema Neonatorum manifests as diffuse hardening of the subcutaneous tissue resulting in a tight smooth skin that feels bound
to the underlying structures.
c Renal failure can be suspected clinically by presence of edema/excessive weight gain and oliguria/anuria.

Meningitis
About 25-30% of septicemic neonates may have meningitis which is often silent without signs of meningeal
irritation. Symptoms suggestive of meningitis are excessive or high-pitched cry, fever, seizures or bulging
anterior fontanel.

Diagnosis
Direct Method
Isolation of microorganisms from blood, CSF, urine or pus is diagnostic. In clinically suspected cases of sepsis,
blood culture should be sent prior to starting antibiotics.

Collection of sample for blood culture: Inoculation of 1-2 mL of blood (at least 1 mL) is recommended for
adequate and appropriate growth in a pediatric blood culture bottle. The ideal ratio of blood to culture medium
should be 1:10. The physician should ensure proper aseptic technique during collection of blood to avoid
contamination. Before collection of blood, automated system’s blood culture bottles should be kept in a fridge
maintaining a temperature below 250C and that of conventional broth may be left at room temperature.
However, after inoculation of blood in the culture bottle, it should be kept outside at room temperature till it is
dispatched to the laboratory for facilitation of growth of microorganisms. Dispatch at the earliest. (This skill will
be demonstrated during the skill station on IV Cannulation)

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Indirect Method
There are a variety of tests which are helpful for screening of neonates with sepsis.
 Total leukocyte count (TLC): A total leucocyte count below 5000/cu mm.
 An absolute neutrophil count (ANC) of <1800 per cu mm is an indicator of infection. Neutropenia is more
predictive of neonatal sepsis than neutrophilia.
 Immature neutrophils (Band cells + myelocytes + metamyelocytes) to total neutrophils ratio (ITR)
>0.20 means that immature neutrophils are over 20 percent of the total neutrophils. This happens because
bone marrow pushes even the immature cells into circulation to fight infection.
 Micro-ESR may be elevated with sepsis and a fall of >15 mm during first hour indicates infection.
 C-reactive protein (CRP): A CRP value of >10mg/L is taken as positive. A negative CRP is reassuring
The CRP can also be positive in other conditions like perinatal asphyxia, shock and meconium aspiration
syndrome.
A negative sepsis screen helps to rule out sepsis however a positive screen may not be confirmatory as the
screen parameters may be positive due to many other clinical conditions like PIH, Perinatal asphyxia, shock,
meconium aspiration syndrome etc. Neonate with a positive sepsis screen may have an infection or it could
be positive due to other reasons.
A practical positive “sepsis screen” takes into account two or more positive tests out of the five given below:
1. Leukopenia (TLC <5000/mm3)
2. Neutropenia (ANC <1800/ mm3)
3. Immature neutrophil to total neutrophil (I/T) ratio (> 0.2)
4. Micro ESR (> 15 mm 1st hour)
5. CRP +ve (>10mg/L)
Perform Sepsis Screen if
 Early onset Sepsis is suspected clinically or
 There are two or more risk factors in an asymptomatic baby.
CSF Examination and Values of CSF for Diagnosing Meningitis
 Lumbar puncture (LP) must be performed in all neonates with late-onset sepsis. In EOS, CSF examination
may be deferred in a neonate with RDS without any risk factors for sepsis. In all cases it must be done
preferably before starting antibiotics.
 In a neonate with meningitis not showing clinical recovery after institution of antibiotics, LP should be
repeated after 48 hours.
 Ideally, the CSF WBC count & CSF sugar must be performed within 30 minutes of drawing the sample. It must
be noted that CSF WBCs and glucose rapidly fall with time, giving spurious results.
Treat for Meningitis if
In Preterm In Term
WBC count >/=10/mm3 WBC count >8/ mm3
OR OR
Glucose <24mgs/dl Glucose <20mgs/dl
OR OR
Proteins >170mgs/dl Proteins >120mgs/dl

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Management
Table 14.2: Supportive care of a septic neonate

1. Maintain TABC
2. Ensure optimum oxygenation (maintain SpO2 91-95%)
3. Maintain normoglycemia
4. Give Inj Vit K 1mg if required
5. Avoid enteral feed if hemodynamically compromised, give maintenance IV fluids but start orogastric feeds as
soon as hemodynamically stable
6. Consider exchange transfusion if there is sclerema

Supportive care and antibiotics are two equally important components of the management.

Antibiotic Policy
Antibiotic therapy should cover the common causative bacteria, namely, Escherichia coli, Staphylococcus
aureus and Klebsiella pneumonia (Table 14.3).

Table 14.3: Antibiotic Therapy for Neonatal Sepsis

I. Septicemia or Pneumonia

B wt < 2 kg

Frequency
Antibiotic Each dose Route Duration
0 – 14 days age >14 days age

Inj Ampicillin* 50 mg/kg/dose 12 hrly 8 hrly IV 7-10 days

Inj cloxacillin# 50 mg/kg/ dose 12 hrly 8 hrly IV 7-10 days

AND

Inj Gentamicin 5 mg/kg/ dose 24 hrly 24 hrly IV 7-10 days

B wt ≥ 2 kg
Frequency
Antibiotic Each dose Route Duration
0 – 7 days age >7 days age

Inj Ampicillin* or 50 mg/kg/dose 12 hrly 8 hrly IV 7-10 days

Inj cloxacillin# 50 mg/kg/ dose 12 hrly 8 hrly IV 7-10 days

AND

Inj Gentamicin 5 mg/kg/ dose 24 hrly 24 hrly IV 7-10 days

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II. Septicemia IInd Line Drugs
B wt < 2 kg
Frequency
Antibiotic Each dose Route Duration
0 – 14 days age >14 days age
Inj Piperacillin+
Tazobactum*** 50 mg/kg/dose 12 hrly 8 hrly IV 7-10 days

Inj Amikacin** 15 mg/kg/ dose 24 hrly 24 hrly IV 7-10 days

B wt ≥ 2 kg
Frequency
Antibiotic Each dose Route Duration
0 – 7 days age >7 days age
Inj Piperacillin+
50 mg/kg/dose 12 hrly 8 hrly IV 7-10 days
Tazobactum***
Inj Amikacin** 15 mg/kg/ dose 24 hrly 24 hrly IV 7-10 days

III. Meningitis (For confirmed meningitis)

B wt < 2 kg
Frequency
Antibiotic Each dose Route Duration
0 – 7 days age >7 days age
Inj Cefotaxime* 50 mg/kg/dose 12 hrly 8 hrly IV 3 weeks
Inj Amikacin** 15 mg/kg/ dose 24 hrly 24 hrly IV 3 weeks

B wt ≥ 2 Kg
Frequency
Antibiotic Each dose Route Duration
0 – 7 days age >7 days age
Inj Cefotaxime* 50 mg/kg/dose 8 hrly 6 hrly IV 3 weeks
Inj Amikacin** 15 mg/kg/ dose 24 hrly 24 hrly IV 3 weeks

IV. Meningitis – IInd Line

Frequency
Antibiotic Each dose Route Duration
0 – 7 days age >7 days age
Inj Meropenem**** 40 mg/kg/dose 8 hrly 8 hrly IV 3 weeks
Inj Amikacin** 15 mg/kg/ dose 24 hrly 24 hrly IV 3 weeks
# Start if pustules/umbilical sepsis.
* Infuse as an IV infusion using syringe infusion pump over 30 minutes or longer
Use a concentration not higher than 100 mg/ml for infusion.
** Infuse as an IV infusion using syringe infusion pump over 30 minutes or longer
Use a concentration not higher than 5mg/ml for infusion.
*** Infuse as an IV infusion using syringe infusion pump over 30 minutes or longer
Use a concentration not higher than 50 mg/ml for infusion.
**** Infuse as an IV infusion using syringe infusion pump over 30 minutes or longer
Use a concentration not higher than 10mg/ml for infusion.

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 The above tables are suggested guidelines to begin with as it is not possible to advocate a single
antibiotic policy for use in all newborn units.

 Every newborn unit must have its own antibiotic policy based on the profile of pathogens and
local sensitivity patterns.
 Preferably choose Penicillin plus an Aminoglycoside combination for sepsis and not
cephalosporins as they rapidly induce the production of extended spectrum ß-lactamases (ESBL),
cephalosporinases and fungal colonization leading to increased resistance and fungal sepsis.
 IIIrd generation Cephalosporins like cefotaxime should be reserved for meningitis in view of good
CSF penetration. Avoid using ceftriaxone in neonates as it may displace bilirubin from albumin
binding sites and may also induce cholestasis.

Duration of Antibiotic Therapy

Positive sepsis screen: 5-7 days. Stop earlier if culture is sterile and baby is well.

Positive blood culture: 10 -14 days.

Change of Antibiotics

 Empirical upgradation can be considered if there is no clinical improvement by 48 hours of institution

of antibiotics or there are signs of deterioration earlier than that.
 In such circumstances (presence of signs of deterioration) one must look for alternate explanation
(hypoglycemia, hypothermia, MAS, TTNB, RDS, Perinatal asphyxia) for the clinical signs and augment
supportive care. However, despite this, if improvement does not occur in 48-72 hrs one may consider
changing to IInd line antibiotics. Current evidence does not support the use of serial CRP as a guide
for deciding whether or not antibiotics should be upgraded empirically.
Following conditions do not require antibiotics for their management (unless workup for sepsis is positive).
 Meconium Stained Amniotic Fluid
 Meconium Aspiration Syndrome
 Respiratory Distress
 Perinatal Asphyxia
 Asymptomatic neonates with presence of 1-2 risk factors for EOS
 Jaundice
 Prematurity
 Cyanotic heart disease

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When to Stop Antibiotics

Culture negative sepsis: If the blood culture is reported sterile at 48 hours, the following guidelines must be
adhered to:

 Asymptomatic neonate (at risk of EOS) with positive sepsis screen/screen not performed initiated on
antibiotics: stop antibiotics.
 Symptomatic neonate with positive sepsis screen becomes completely asymptomatic: stop antibiotics by
5-7 days.

Culture positive sepsis: Stop antibiotics after 10-14 days.

 Meningitis: Stop antibiotics after 21 days.

Antibiotic stewardship and rational use of Antibiotics:

WHO states that “Rational use of medicines requires that patients receive medications appropriate to their
clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at
the lowest cost to them and their community.”

 Emergence of multidrug resistant organisms (MDR) has been linked to the inappropriate use & overuse
of antibiotics.
 Broad spectrum antibiotic exposure is associated with development of necrotizing enterocolitis (NEC),
LONS, alteration of microbiota, invasive candidiasis, increased morbidity & mortality, duration of hospital
stay & healthcare costs.
 Antimicrobial stewardship is recognized as a critical patient safety & quality imperative to combat the
emergence of MDR.

Principles of Antibiotic Stewardship are:

 Timely & appropriate antibiotic utilization.
 Appropriate selection of a regimen.
 Optimization of the dose, route & duration of therapy.
These principles should be applied to empiric use as well as definitive use.

Best Practices to Prevent Neonatal Infections

 Safe delivery practices
 Maternal tetanus immunization
 Early diagnosis and prompt treatment of all maternal infections
 Early & Exclusive breastfeeding
 No pre-lacteal feeds
 Cord should be kept clean and dry
 Avoid overcrowding
 Maintain hygiene

Hand washing is the simplest and the most effective method for control of infection in the hospital.

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Prevention of Infection in Hospitals
 Nursery environment should be clean
 Ensure round the clock water supply
 Ensure adequate ventilation
 Maintain temperature 26-280C
 Avoid overcrowding
 Ensure strict asepsis during procedures
 Minimize invasive interventions such as needle pricks and IV alimentation
 Initiate early enteral feeds

The use of prophylactic antibiotics for prevention of nosocomial infections is strongly condemned. They
are not only useless but are dangerous due to the potential risk of emergence of resistant strains of bacteria.

When to Refer
After initial stabilization, if the baby’s condition worsens or no improvement is noted after 48 hours of
treatment, the baby could be considered for referral to higher center.

Worsening is Defined as Development of the Following Features

 Respiratory failure requiring mechanical ventilation
 Unresponsive shock
 Persistent or refractory convulsions
 Disseminated intravascular coagulation diagnosed by bleeding from puncture sites, gastro intestinal
hemorrhage or pulmonary haemorrhage
 Baby requiring exchange transfusion but facility is not available

Video on prevention of infection

This video will demonstrate the skill of proper hand washing for prevention of infection. It also includes the
methods of disinfecting instruments and equipment.

QI. INDICATORS:
1. Proportion of admitted neonates developing LONS.
2. Proportion of admitted neonates on antibiotics.
3. Average duration of antibiotics used in babies suspected of sepsis.
4. Proportion of admitted neonates started on antibiotics based on maternal risk factors alone.
5. Proportion of babies receiving second line antibiotics.

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EXCERCISE
1. Interpret the following Sepsis screen(s) as positive or negative –
a. TLC -3800/cu mm, CRP Positive, ANC 2020, IT ratio NA, µESR 12 mm.

b. TLC -9900/cu mm, CRP Positive, ANC 2020, IT ratio NA, µESR 12 mm.
c. TLC -9200/cu mm, CRP Negative, ANC 1270, IT ratio NA, µESR 18 mm.
d. TLC -8800/cu mm, CRP Positive, ANC 1920, IT ratio 0.02, µESR 14 mm.
e. TLC -22800/cu mm, CRP Positive, ANC 2020, IT ratio 0.10, µESR 12 mm.
f. TLC -2300/cu mm, CRP Positive, ANC 1870, IT ratio NA, µESR 12 mm.

2. Write treatment orders for a 2000 gm 9 days old baby diagnosed to have sepsis today.

3. Baby Tara has come to you with refusal to feed, fever and excessive crying. O/E the baby is irritable,
AF is full, CFT is 2 secs, and Temp is 390C. There is pus discharge from the umbilicus. The R/R is 70/min
and the HR is 180/ min. What is your initial impression? How will you prove your diagnosis and what
treatment will you start?

4. Baby Neha, a 15 days old neonate was born in the hospital at 35 weeks gestation with a birth weight
of 2100 gms. The baby was receiving breast feeds along with diluted animal milk with a bottle. She
has been brought to you with complaints of lethargy, not taking feeds well and loose motions. Mother
does not know when the baby last passed urine. On examination her weight is 2000 gms, she is
lethargic with cold hands and feet and a CFT of 4 seconds. Her temperature is 36.5 0C with a RR of
64/min and a HR of 180/min. What is your diagnosis and how will you manage this baby?

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