Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection within the first month of life. It is a leading cause of neonatal mortality, responsible for about 52% of neonatal deaths. The presentation and risk factors differ based on whether the onset of sepsis is early (within 72 hours of life) or late (after 72 hours of life). Management involves screening protocols to determine the need for antibiotics and treatment, which typically involves empiric broad-spectrum antibiotics that may need to be adjusted based on culture and sensitivity results. Close monitoring is important as the condition can deteriorate rapidly.

1. Presented By :
Dr. Surendra Godara

2. AIIMS protocol NICU 2010
PGI Chandigarh Protocol NICU 2010
Manual of neonatal care
John P Cloherty
Avery’s Disease of newborn
8th Edition
Foranoff & Martin
Neonatal & perinatal medicine, Volume II 8th Edition

3. 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
include:-
septicemia,
meningitis,
pneumonia,
arthritis,
osteomyelitis, and
urinary tract infections.
Superficial infections like conjunctivitis and oral thrush are not usually included
under neonatal sepsis.

4. Neonatal sepsis
COMMONEST CAUSE Prematurity
15%
OF NEONATAL Others
13%
DEATHS
Asphyxia
Sepsis
20%
52%

5. Klebsiella pneumoniae
Escherichia coli
Staphylococcus aureus
Pseudomonas
Group b streptococus

6. Early Late
Onset Upto 72 hrs After 72 hrs
Source Maternal Postnatal environment
Presentation Fulminant multisystem Slowly progressive,focal
Pneumonia frequent Meningitis frequent
Mortality 15-50% 10-20%

7.  Lethargy  Cyanosis*
 Refusal to suckle  Tachypnea*
 Poor cry  Chest retractions*
 Not arousable, comatosed  Grunt*
 Abdominal distension  Apnea/gasping*
 Diarrhea  Fever+
 Vomiting  Seizures+
 Hypothermia  Blank look+
 Poor perfusion  High pitched cry+
 Sclerema  Excessive crying/irritability+
 Poor weight gain  Neck retraction+
 Shock  Bulging fontanel+
 Bleeding
 Renal failure
* Particularly suggestive of pneumonia
+ Particularly suggestive of meningitis

8. 1. Low birth weight (<2500 grams) or prematurity
2. Febrile illness in the mother with evidence of bacterial infection within 2
weeks prior to delivery.
3. Foul smelling and/or meconium stained liquor.
4. Rupture of membranes >24 hours.
5. Single unclean or > 3 sterile vaginal examination(s) during labor
6. Prolonged labor (sum of 1st and 2nd stage of labor > 24 hrs)
7. Perinatal asphyxia (Apgar score <4 at 1 minute)
Presence of foul smelling liquor or three of the above mentioned risk factors
warrant initiation of antibiotic treatment. Infants with two risk factors should
be investigated and then treated accordingly.

9. Risk factor Score
IP per vaginal examinations >3 6
Clinical chorioamnionitis 6
BW <1.5kg 3
Male gender 3
Not received IP antibiotics 2
Gestation <30 wks 2
If - score 0-6 monitoring
7 or >7 antibiotics , blood culture
Extreme risk factor – prom>72hr
-prolonged labor>24hr
-unclean vaginal exam’
- Maternal septisemia

10.  Neonates who become symptomatic after 72 h must be evaluated
for LOS..
 Based on clinical assessment the neonate must be categorized into
low probability of sepsis or high probability of sepsis. “Low
probability” represents situations where the clinician would be
willing to withhold antibiotics if-the sepsis screen is negative.
 Those with low probability of sepsis (e.g. single episode of
apnea, but otherwise well) should undergo a sepsis screen. The
purpose of the sepsis screen is to rule out sepsis rather than to rule
in sepsis. The sepsis screen consists of:TLC, CRP, ANC. ITR and
micro-erythrocyte sedimentation rate (m-ESR).

11. Components Abnormal values
Total leukocyte count <5000/mm3
Absolute neutrophil count <1750/mm3
Immature /total neutrophil >0.2
Micro-ESR >10 mm in 1st hour
C reactive protein (CRP) >1mg/dL
o CRP: It is done by quantitative ELISA or by a bedside semi-
quantitative latex agglutination kit. More than 1 mg/dL is
positive.
o ANC: It must be read off Manroe’s charts, Schelonka’s chart or
Mouzinho’s chart, depending on whether it is a term baby or a
preterm baby respectiveIy.

12. o ITR: It is considered to be positive if>20%. ITR is defined as
 Immature PMN (band forms, metamyelo & myelocytes)
 Mature + immature neutrophils
Mature neutrophil Band cell
12

13. o mESR, Value (in mm in first hour)> “3+age in days” in the 1
wk of life or >10 thereafter is considered positive.
 Two systematic reviews on sepsis screens reached the same
conclusions- that there is no ideal test or combination of tests.
Among the various tests, quantitative CRP is the best, followed by
qualitative CRP and ITR.
 If all the parameters of the sepsis screen are negative in a neonate
assessed to have low probability of LOS, antibiotics may not be
started and the neonate must be monitored clinically. The screen
must be repeated after 12-24h. Two consecutive completely
negative screens are suggestive of no sepsis.

14.  Since CRP is the key parameter in the sepsis screen, a pragmatic
approach is that if the CRP alone is positive or any two
parameters of the sepsis screen are positive, a blood culture must
be drawn and empirical antibiotics must be started. A CSF
examination must be performed.
 Neonates assessed to have a high clinical probability of sepsis
may not be subjected to a sepsis screen, because a negative screen
would not alter the decision to start antibiotics. A CSF
examination must be performed.

15. Sepsis screen
Blood culture
LP Revised guideline for empirical treatment of meningitis based on csf parameter
Among neonates with Among neonates with
suspected sepsis blood culture proven
sepsis
Preterm babies
•WBC >25 AND protein >170 •WBC >10
OR • OR
•WBC>100 •Glucose <25
Cut-off values to •OR OR
diagnose meningitis •Glucose <25 •Protein >170
Term babies
•WBC >21 •WBC >8 OR
• OR •Glucose <20 OR
•Glucose <20 •Protein >120

16. Radiology
 X-ray chest
 X-ray Abdomen
 CT scan
 Neurosonogram
Urine analysis

18.  First line: Ciprofloxacin + Amikacin (covers - 75% isolates) .
If meningitis is suspected, replace Ciprofloxacin. by Cefotaxime-
sulbactam (see section D24)
 Second line: Vancomycin + Piperacillin-Tazobactam (covers -
90% isolates)
 Third line: Vancomycin + Meropenem (covers - 95-100%)
The antibiotic policy is reviewed periodically and may change after
the next review. Cephalosporins rapidly induce the production of
extended spectrum b-lactamases, cephalosporinases and fungal
colonization, and hence, are best avoided as empirical antibiotics.

19.  Empirical upgradation must be done if the expected clinical
improvement with the ongoing line of antibiotics does not occur.
A minimum of 48-72 h of observation should be allowed before
declaring the particular line as having failed. The duration may
be longer for Vancomycin compared to the Penicillin group and
Aminoglycosides
 In case the neonate is extremely sick or deteriorating very
rapidly and the treating team feels that the neonate may not able
to survive 48 h in the absence of appropriate antibiotics, a
decision may be taken to bypass the first line of antibiotics and
start with the second- line of antibiotics

20.  If the growth is a non-contaminant, the antibiotic sensitivity must
be assessed to decide whether antibiotics need to be changed or
not. The following guidelines must be adhered to:
o If the organism is sensitive to an antibiotic with a narrower
spectrum or lower cost, therapy must be changed to such an
antibiotic, even if the neonate was improving with the
empirical antibiotics.
o If possible, a single sensitive antibiotic must be used, the
exception being Pseudomonas for which 2 sensitive
antibiotics must be used. Two sensitive antibiotics (a
Penicillin + an Aminoglycoside) may also be used for S
aureus and E. fecalis.

21. o If the empirical antibiotics are reported sensitive, but the neonate has
worsened on these antibiotics, it may be a case of in vitro resistance.
Antibiotics may be changed to an alternate sensitive antibiotic with the
narrowest spectrum and lowest cost.
o If the empirical antibiotics are reported resistant but the neonate has
improved clinically, it may or may not be a case of in-vivo sensitivity. In
such cases a careful assessment must be made before deciding on
continuing with the empirical antibiotics. One must not continue with
antibiotics with in vitro resistance in case of Pseudomonas, Kiebsiella and
MRSA; and in cases of CNS infections and deep-seated infections.
o If no antibiotic has been reported sensitive, but one or more has been
reported moderate1y sensitive’, therapy must be changed to such
antibiotics at the highest permissible dose. Use a combination, in such
cases.

23. The survival of a sick septic newborn often depends upon
aggressive supportive care.
 Oxygen saturation should be maintained in the normal range and
mechanical ventilation may be required in case of increased work
of breathing.
 Anemia, thrombocytopenia, and DIC are treated with appropriate
transfusions. Packed red cells and FFP might have to be used.
 Septic infants should be screened for hypoglycemia and treated
appropriately.
 Management of Septic Shock

24. IVIG
The currently available evidence does not support the use
of IVIG. IVIG may be used in a difficult situation, after
discussion with the consultant.
Dose : pentaglobin 5 mL/kg/d for 2 d (IgM 6 mg, IgA 6
mg and IgG 38 mg/ml).
Among patients with clinically suspected infection, the
reduction of mortality with IVIG is of borderline
significance [typical RR 0.63 (95% CI; 0.40, 1.00)]. In
cases of subsequently proven infection the reduciton in
mortality is statistically but has very wide Cl [typical RR
0.55 (95% Cl; 0.31, 0.98)].

25. Exchange transfusion (ET): Sadana et al have evaluated the role
of double volume exchange transfusion in septic neonates with
sclerema and demonstrated a 50% reduction in sepsis related
mortality in the treated group. We perform double-volume
exchange transfusion with cross-matched fresh whole blood as
adjunctive therapy in septic neonates with sclerema.
.Granulocyte-Macrophage colony stimulating factor (GM-CSF):
This mode of treatment is still experimental.

26. Prevention of infections
Exclusive breastfeeding
Keep cord dry
Hand washing by care givers
Hygiene of baby
No unnecessary interventions
Teaching Aids: NNF NS- 26

27. Control of hospital infections
Hand washing by all staff
Isolation of infectious patient
Use plenty of disposable items
Avoid overcrowding
Aseptic work culture
Infection surveillance
Teaching Aids: NNF NS- 27

28. Work culture
Sterile gowns and linen for babies
Hand washing by all
Regular cleaning of unit
No sharing of baby belongings
Dispose waste-products in separate bins
Teaching Aids: NNF NS- 28

30. Definition
Defined as total serum calcium concentration of <7 mg/dL or an
ionized calcium concentration of <4 mg/dL (i.e. 1 mEq/L).
umbilical calcium level is 10-11mg/dL
first 24-48h-7.5-8.5 mg/dL .
Classification: early onset (<3 d) and late onset (>3 d)
Causes:
Early onset: Prematurity, 1DM, perinatal asphyxia, maternal intake
of anticonvulsants, IUGR. If hypocalcemia does not resolve within
72 h of therapy investigate for causes of late onset hypocalcemia.

31. Treatment
Maintenance: 4-6 mL/kg/d of Ca gluconate IV (added in last 2 h of
6 hourly IVF)
Preparation: Ca-gluconate 10% (IV)- 9 mg/mL (preferred), Ca-
chloride (IV)-27 mg/mL
Therapeutic:
Asymptomatic: increase maintenance to 8-12 mL/kg/d of Ca-
gluconate
Symptomatic: 2 mL/kg of Ca-gluconate diluted in 1:1 dilution with
NS or 5% D IV over 10-15 mm under strict cardiac monitoring
(stop infusion if HR drops for >20 beats/mm than baseline or any
other arrhythmia appears on ECO). Start maintenance calcium after
bolus dose.

32. Hypocalcemia
Total serum Cal <7 mg/dl
Asymptomatic
80 mg/kg/day for 48 hrs
(8 mL/kg/day of 10% calcium gluconate )
Taper to 40 mg/kg/day for one day
Then stop
Symptomatic
Bolus of 2 mL/kg calcium gluconate 1:1 diluted with 5 % dextrose over 10 minutes under cardiac monitoring
Followed by continuous infusion 80 mg/kg/day for 48 hrs (8 mL/kg/day of 10% calcium gluconate )
Document normal calcium at 48 hrs
Then taper to 40 mg/kg/day for one day
Then stop
Prophylactic
Preterm< 32 wks, sick IDM, severe asphyxia 40 mg/kg/day for 3 days
(4ml/kg/day of 10% calcium gluconate ) IV or oral if can tolerate per oral
Treatment is for 72 hours
 Continuous infusion is better than bolus
 Symptomatic babies treatment is 48 hrs continuous infusion

33. Prolonged or resistant hypocalcemia
This condition should be considered in the following
situations:
 Symptomatic hypocalcemia unresponsive to adequate
doses of calcium therapy
 Infants needing calcium supplements beyond 72 hours
of age
 Hypocalcemia presenting at the end of the first week.
 These infants should be investigated for causes of LNH

34. Causes of late onset hypocalcemia
 Increased phosphate load--Cow milk, renal insufficiency
 Hypomagnesemia
 Vitamin D deficiency
 Maternal vitamin D deficiency
 Malabsorption
 Renal insufficiency
 Hepatobiliary disease
 PTH resistence--Transient neonatal pseudohypoparathyroidism
 Hypoparathyroidism
 Primary
 Hypoplasia, aplasia of parathyroid glands - (Di George’s
 syndrome), CATCH 22 syndrome (cardiac anomaly, abnormal
 facies, thymic aplasia, cleft palate, hypocalcaemia with deletion
 on chromosome 22)
 Activating mutations of the calcium sensing receptor (CSR)
 Secondary
 Maternal hyperparathyroidism

35. Metabolic Syndromes
 Kenny-caffey syndrome
 Long-chain fatty acyl CoA dehydrogenase deficiency
 Kearns-sayre syndrome
Iatrogenic
 Citrated blood products
 Lipid infusions
 Bicrbonate therepy
 Diueretics (loop diuretics)
 Glucocorticosteriods
 Phosphate therepy
 Use of Aminoglycosides (mainly gentamicin) as single dose
 Alkalosis
 Phototherapy

36. Investigation required
First line Second line Others
Serum phosphate Serum magnesium CT brain for calcification
Serum alkaline Serum parathormone Echocardiography
phosphatase (SAP) levels (PTH) Vitamin D levels (1,25
Liver function tests Urine calcium creatinine D3)
Renal function tests ratio Hearing evaluation
X ray chest/ wrist Maternal calcium, Serum cortisol
Arterial pH phosphate, and alkaline Thyroid function tests
phosphatase
S.No. Disorder causing Findings
hypocalcemia
1 Hypoparathyroidism High : Phosphate
Low : SAP, PTH, 1,25 D3
2 Pseudo High : SAP, PTH, Phosphate
Hypoparathyroidim Low : 1,25 D3
3 Chronic renal failure High : phosphate, SAP, PTH, pH (acidotic), deranged RFT
Low : 1,25 D3
4 Hypomagnesemia High : PTH
Low : Phosphate, Mg,1,25 D3
5 VDDR1 High : SAP, PTH
Low : Phosphate, 1,25 D3
6 VDDR2 High : SAP, 1, 25 D3, PTH
Low : Phosphate

37. Treatment of LNH
The treatment of LNH is specific to etiology and may in certain
diseases be lifelong.
1. Hypomagnesemia: Symptomatic hypocalcemia unresponsive to
adequate doses of IV calcium therapy is usually due to
hypomagnesemia. It may present either as ENH or later as LNH.
The neonate should receive 2 doses of 0.2 mL/kg of 50% MgSO4
injection, 12 hours apart, deep IM followed by a maintenance dose
of 0.2 mL/kg/day of 50% MgSO4, PO for 3 days.
2. High phosphate load: These infants have hyperphosphatemia
with near normal calcium levels. Exclusive breast-feeding should
be encouraged and top feeding with cow’s milk should be
discontinued. Phosphate binding gels should be avoided.

38. Treatment of LNH
3. Hypoparathyroidism: These infants tend to be
hyperphosphatemic and hypocalcemic with normal renal function.
Elevated phosphate levels in the absence of exogenous phosphate
load (cow’s milk) and presence of normal renal functions indicates
parathormone inefficiency. It is important to realize that if the
phosphate level is very high, then adding calcium will lead to
calcium deposition and tissue damage. Thus attempts should be
made to reduce the phosphate (so as to keep the calcium and the
phosphate product less than 55). These neonates need
supplementation with calcium (50 mg/kg/day in 3 divided doses)
and 1,25(OH)2 Vitamin D3 (0.5-1 mg/day). Syrups with 125 mg
and 250 mg per 5ml of calcium are available.1,25(OH)2 vitamin
D3 (calcitriol) is available as 0.25 mg capsules. Therapy may be
stopped in hypocalcemia secondary to maternal
hyperparathyroidism after 6 weeks.

39. Treatment of LNH
4. Vitamin D deficiency states: These babies have hypocalcemia
associated with hypophosphatemia due to an intact parathormone
response on the kidneys. They benefit from Vitamin D3
supplementation in a dose of 30-60 ng/kg/day
Monitoring
The baby is monitored for the SCa, and phosphate, 24 hour urinary
calcium, and calcium creatinine ratio. Try to keep the calcium in
the lower range as defective distal tubular absorption leads to
hypercalciuria and nephrocalcinosis.

40. Treatment of LNH
Prognosis and outcome
Most cases of early neonatal hypocalcemia resolve within 48-72
hours without any clinically significant sequelae.
Late neonatal hypocalcemia secondary to exogenous phosphate
load and magnesium deficiency also responds well to phosphate
restriction and magnesium repletion. When caused by
hypoparathyroidism, hypocalcemia requires continued therapy with
vitamin D metabolites and calcium salts. The period of therapy
depends on the nature of the hypoparathyroidism which can be
transient, last several weeks to months, or be permanent.