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-C.S.N.Vittal
Vijayawada
Bacterial Sepsis in Neonate
Definition :

Clinical syndrome of
infection with bacterimia in
first month of life.
• May get predominantly localized to lung (Pneumonia)
• May be localized to meninges (meningitis)
Bacterial Sepsis in Neonate
Incidence :

24 / 1000 live births
Single most important cause of neonatal deaths in the
community (>50%)
Bacterial Sepsis in Neonate
Patterns
Late Onset

Early Onset
•Within 72 hrs of birth
• Complicated pregnancy +
• Maternal Genital tract

• Symptoms beyond 72 hrs
of birth
• Complicated pregnancy +

• Fulminant course

• Maternal Genital tract /
Environmental

• Pneumonia

• Slower progression

• 5-50 % mortality

• Meningitis
• 2-6 % mortality
Neonatal Sepsis
Major Risk Factors
• Ruptured membranes > 24 hrs.
• Maternal Fever (100.4oF(38oC)
• Chorionamnionitis
• Sustained fetal heart rate
>160/min
• Multiple obstetric procedures

Minor Risk Factors
• Ruptured membranes > 12 hrs.
• Foul smelling liquor
• Maternal Fever > 99.5oF (37.5oC)
• Low APGAR < 5 at 1 min,
< 7 at 5 min
• Prematurity
• Multiple gestation

Presence of 1 major or 2 minor risk factors ->
High Risk of Sepsis
NNF CRITERIA
SUSPECT SEPSIS
1 out of 3 parameters is an indication for antibiotic therapy

• PREDISPOSING FACTORS like PROM, Foul
smelling liquor, amnionitis, gastric aspirate
showing polymorphs 5 / HPF
• POSITIVE SEPSIS SCREEN (2/4 parameters)
– TLC <5000 per cubic ml
– Bandemia 20%
– CRP >10 ng per ml
– Micro ESR >10mm fall in 1hr
• CXR showing Pneumonia
Neonatal Sepsis
Pathogenesis
• Infection in the birth canal
• Colonization of skin, umbilical stump,
nasopharynx, conjunctiva, etc.
• Transient bacteremia
• Invasion of blood stream
• Metastatic foci
• Meningitis, etc.
Neonatal Sepsis
Risk factors for Late onset sepsis (LOS)
• Prolonged hospitalization
• Prematurity
• LBW
• Previous antibiotic use
• Invasive procedures
• Presence of foreign material (ET Tubes/
catheters)
• Lack of disposables
• Over crowding / understaffing
Neonatal Sepsis
Risk factors for Community acquired sepsis
• Bottle feeding
• Poor hygiene
• Poor cord care
• Over crowding
Pathogenesis ...

• SIRS
• CARS
• MARS
Infection
Systemic Inflammatory Response Syndrome (SIRS)
Resp:
Tachypnoea
Hypoxia PaO2

> 2 SD
< 70 mm Hg

CVS :
Tachycardia
> 2 SD
Hypothermia
< 2 SD or hyperthermia
Peripheral Perfusion:
Delayed Capillary Filling
> 3 Sec.
Oliguria
< 0.5 ml / kg / hr
Lactic acidosis
Altered mental status
Increased or decreased white blood count:
Infection > SIRS
Sepsis –
• Systemic response to infection with bacteria :
SIRS with hypotension

Severe Sepsis –
• Sepsis with organ dysfunction, hypoperfusion or hypotension
• Changes in mental status, oliguria, hypoxemia or lactic acidosis
Septic shock –
Severe Sepsis with persistent hypotension
despite adequate fluid resuscitation

Multiple Organ Dysfunction Syndrome
(MODS) –
Presence of altered organ function such that
homeostasis
can not be maintained without intervention

Death
Local
Initial insult
pro-inflammatory (bacterial, viral
response
thermal, traumatic)
Systemic spillover of proInflammatory mediators

Systemic Reaction

Local
anti-inflammatory
response

Systemic spillover of antiInflammatory mediators

SIRS : Pro
CARS : Anti
MARS : Mixed

C

H

CV Compromise Homeostasis

A

Aptosis

O
MODS

S
Suppression of immunity
Clinical Features
• General :

• Skin:

– Lethargy, jaundice
– Temperature instability

• Respiratory
– Distress after a period of
normalcy
– Apnea

• GI:
– Poor feeding, vomiting,
abdominal distention, bilious
aspirates
– Temperature labiality

– Petechial rashes, bleeding from
puncture sites
– Sclerema

• CNS:
•

– Lethargy, irritability, seizures
Metabolic:
– Unexplained metabolic acidosis
– Hyperglycemia
– Hypoglycemia

• Features to system
involvement
Sepsis Screen
• Total neutrophil count :
• Immature to total ratio :
•Acute Phase Reactions
• Micro ESR
• C Reactive Protein
• Hepatoglobin

:
:

Laboratory Studies

< 5000 / mm3
> 0.2
> 15 mm in 1st hour
> 10 mg/L

• Cultures
• Chest X-Ray
• Grams Stain of gastric aspirate
• Antigen detection methods
• Lumbar Puncture
Neonatal Sepsis
Total neutrophil count & Immature to total ratio:
• TWBC
• Tot. neutrophil count

: < 5000 / micro liter or >24000
: < 1000 / micro liter
( Normal= 1,750 /µL)

• Band / Total Neutrophil

: > 0.2
( Normal = 0.16 in 1st Day,
0.12 after 24 Hrs.)

• Platelet Count

: < 1 Lakh/mm3
(Normal = 1.5 to 4 Lakhs /mm3)

- Increased risk of infection
Repeat TWBC & DC at 8 - 12 hrs in a symptomatic neonate
may have more predictable value than single record.
Neonatal Sepsis
Cultures

• Blood
• Urine
• CSF ( For Late Onset type)]

Two positive cultures are more significant
Neonatal Sepsis
Chest X-Ray

• Persistent focal changes with
infiltrative process
• Findings similar to RDS in GBS
infection
Neonatal Sepsis
Acute Phase Reactants - Sepsis Screen
Positive CRP ( > 6 mg/ L or 10 times normal)
Elevated hepatoglobin level
Micro ESR After 14 days of age 15 mm or
more for the first hour is abnormal.
(Normal ESR = Age in days + 2)
If all results are -ve : Probability that infection absent = 99%
If all results are +ve : Probability of infection = 90%
Neonatal Sepsis
Grams Stain of gastric aspirate

Positive Result :
If > 5 neutrophils / hpf
or
Large number of bacteria (esp. Gram+ve cocci) in
large clumps and chains
Predictive value less
Neonatal Sepsis
Antigen detection methods

• Latex particle aggulutination assays
for GBS and ECK1
• Counter immuno electrophoresis
Neonatal Sepsis
Lumbar Puncture
• Valuable in symptomatic infants
who have risk factors for sepsis.
• CSF studies prior to antibiotic
therapy is preferable
LP in RDS is difficult
Interpretation is difficult if LP is traumatic
Sometimes meningitis may be present with normal
CSF picture
Normal Neonatal CSF
TEST

TERM

PRETERM

WBCs (per cm)
Polymorphs

Up to 30
60%

Up to 90
60%

Protein (mg/dL)

Up to 150

Up to 150

Glucose (mg/dL)

35-120

25-65
Neonatal Sepsis
Miscellaneous Investigations
• DIC Profile
• Culture of catheters/ ET Tubes
• Maternal vaginal swab cultures, etc.
Supportive therapy
•
•
•
•
•
•
•
•
•

Thermoneutral environment
IV Fluids
Electrolyte and acid base balance
Maintain oxygen saturation
Circulatory support
Glucose homeostasis
Treat anemia with packet
Rbc
Treat bleeding diathesis with FFP / platelets
Antibiotic Therapy
Indications:
•
•
•
•
•

PROM > 12 hrs.
Evidence of Chorioannionitis
Delivery outside labour room
Infants with 1 major or 2 minor risk factors
Positive Sepsis Screen
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•

Sulfa Drugs
Folic Acid Analogs
The Beta-Lactams
Aminoglycosides
Tetracyclines
Macrolides
Lincosamides
Streptogramins
Fluoroquinolones
Polypeptides
Rifampin
Mupirocin
Cycloserine
Aminocyclitol
Glycopeptides
Oxazolidinones

Arm
a

me
nt

ariu
m

… and the list is
incomplete …
Which
one
would
you
choose ?
Factors to be considered in the choice of
Antibiotic
Gram + ve

Gram _ ve

Anaerobes
Antibiotic Selection
Presumptive therapy directed to most commonly
encountered pathogens.
1st Line :
Ampi/Sulbactum+Aminoglycoside

2nd Line
2nd gen. Cephalosporins + Aminoglycosides

3rd Line
Vancomycin + Cephalosporins
Newer antibiotics
er
ew
fN
le o
Ro
s?
r ug
d
Antibiotic Evolution
When you can’t decide , you tend to …

Resort to “Shotgun Therapy”
Bauer-Kirby Method
(Agar gel diffusion method)
Duration of Antibiotic Therapy
Culture Positive Sepsis
Pyogenic Meningitis

- 14 Days
- 21 Days /
2 weeks after CSF sterile
Culture – ve/ clinically probable sepsis screen +ve:7-10 d.
Culture – ve/ clinically probable sepsis screen -ve:5-7 d.
Septic Arthritis
- 6 Weeks
Immunotherapy
• Immunoglobulin : IVIG 500-1000 mg/kg/dose
• Specific Immunoglobulins : Anti GBS Ig.
• Oral administration of IgA and IgG in NEC
• Granulocyte infusions
• G – CSF 10 µg/kg/d for 3 days
• GM – CSF 10 µg/kg/d for 5 days
• Double volume exchange transfusions
Supportive Therapy
• Continued Breast Feeding
• Nutrition : TPN / Aminoplasma
• Fluid / Electrolyte balance
• Treatment of acidosis
Preventive Aspects of Neonatal Sepsis
• Obstetric Management strategies
• Screening based approach
• Risk factor approach
• Exclusive breast feeding
• No prelacteals
• Keeping the cord dry
• Hand washing by care givers before and after handling the baby
(Single most effective measure)
• Hygiene of the baby
• Avoid unnecessary intravenous fluids, needle pricks etc.
Algorithm for early prevention of GBS
Risk Factors
Give intrapartum
Previous GBS
penicillin
Preterm delivery
Bacteremia

Rectal & Vaginal swab
c/s. at 35-37 wks.
Risk Factors
Intrapartum Temp.
PROM > 18 hrs
No intrapartum prophylaxis needed

Give intrapartum
penicillin

Give intrapartum
penicillin
Neonatal Sepsis

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Neonatal Sepsis

  • 2. Bacterial Sepsis in Neonate Definition : Clinical syndrome of infection with bacterimia in first month of life. • May get predominantly localized to lung (Pneumonia) • May be localized to meninges (meningitis)
  • 3. Bacterial Sepsis in Neonate Incidence : 24 / 1000 live births Single most important cause of neonatal deaths in the community (>50%)
  • 4. Bacterial Sepsis in Neonate Patterns Late Onset Early Onset •Within 72 hrs of birth • Complicated pregnancy + • Maternal Genital tract • Symptoms beyond 72 hrs of birth • Complicated pregnancy + • Fulminant course • Maternal Genital tract / Environmental • Pneumonia • Slower progression • 5-50 % mortality • Meningitis • 2-6 % mortality
  • 5. Neonatal Sepsis Major Risk Factors • Ruptured membranes > 24 hrs. • Maternal Fever (100.4oF(38oC) • Chorionamnionitis • Sustained fetal heart rate >160/min • Multiple obstetric procedures Minor Risk Factors • Ruptured membranes > 12 hrs. • Foul smelling liquor • Maternal Fever > 99.5oF (37.5oC) • Low APGAR < 5 at 1 min, < 7 at 5 min • Prematurity • Multiple gestation Presence of 1 major or 2 minor risk factors -> High Risk of Sepsis
  • 6. NNF CRITERIA SUSPECT SEPSIS 1 out of 3 parameters is an indication for antibiotic therapy • PREDISPOSING FACTORS like PROM, Foul smelling liquor, amnionitis, gastric aspirate showing polymorphs 5 / HPF • POSITIVE SEPSIS SCREEN (2/4 parameters) – TLC <5000 per cubic ml – Bandemia 20% – CRP >10 ng per ml – Micro ESR >10mm fall in 1hr • CXR showing Pneumonia
  • 7. Neonatal Sepsis Pathogenesis • Infection in the birth canal • Colonization of skin, umbilical stump, nasopharynx, conjunctiva, etc. • Transient bacteremia • Invasion of blood stream • Metastatic foci • Meningitis, etc.
  • 8. Neonatal Sepsis Risk factors for Late onset sepsis (LOS) • Prolonged hospitalization • Prematurity • LBW • Previous antibiotic use • Invasive procedures • Presence of foreign material (ET Tubes/ catheters) • Lack of disposables • Over crowding / understaffing
  • 9. Neonatal Sepsis Risk factors for Community acquired sepsis • Bottle feeding • Poor hygiene • Poor cord care • Over crowding
  • 11. Infection Systemic Inflammatory Response Syndrome (SIRS) Resp: Tachypnoea Hypoxia PaO2 > 2 SD < 70 mm Hg CVS : Tachycardia > 2 SD Hypothermia < 2 SD or hyperthermia Peripheral Perfusion: Delayed Capillary Filling > 3 Sec. Oliguria < 0.5 ml / kg / hr Lactic acidosis Altered mental status Increased or decreased white blood count:
  • 12. Infection > SIRS Sepsis – • Systemic response to infection with bacteria : SIRS with hypotension Severe Sepsis – • Sepsis with organ dysfunction, hypoperfusion or hypotension • Changes in mental status, oliguria, hypoxemia or lactic acidosis
  • 13. Septic shock – Severe Sepsis with persistent hypotension despite adequate fluid resuscitation Multiple Organ Dysfunction Syndrome (MODS) – Presence of altered organ function such that homeostasis can not be maintained without intervention Death
  • 14. Local Initial insult pro-inflammatory (bacterial, viral response thermal, traumatic) Systemic spillover of proInflammatory mediators Systemic Reaction Local anti-inflammatory response Systemic spillover of antiInflammatory mediators SIRS : Pro CARS : Anti MARS : Mixed C H CV Compromise Homeostasis A Aptosis O MODS S Suppression of immunity
  • 15. Clinical Features • General : • Skin: – Lethargy, jaundice – Temperature instability • Respiratory – Distress after a period of normalcy – Apnea • GI: – Poor feeding, vomiting, abdominal distention, bilious aspirates – Temperature labiality – Petechial rashes, bleeding from puncture sites – Sclerema • CNS: • – Lethargy, irritability, seizures Metabolic: – Unexplained metabolic acidosis – Hyperglycemia – Hypoglycemia • Features to system involvement
  • 16. Sepsis Screen • Total neutrophil count : • Immature to total ratio : •Acute Phase Reactions • Micro ESR • C Reactive Protein • Hepatoglobin : : Laboratory Studies < 5000 / mm3 > 0.2 > 15 mm in 1st hour > 10 mg/L • Cultures • Chest X-Ray • Grams Stain of gastric aspirate • Antigen detection methods • Lumbar Puncture
  • 17. Neonatal Sepsis Total neutrophil count & Immature to total ratio: • TWBC • Tot. neutrophil count : < 5000 / micro liter or >24000 : < 1000 / micro liter ( Normal= 1,750 /µL) • Band / Total Neutrophil : > 0.2 ( Normal = 0.16 in 1st Day, 0.12 after 24 Hrs.) • Platelet Count : < 1 Lakh/mm3 (Normal = 1.5 to 4 Lakhs /mm3) - Increased risk of infection Repeat TWBC & DC at 8 - 12 hrs in a symptomatic neonate may have more predictable value than single record.
  • 18. Neonatal Sepsis Cultures • Blood • Urine • CSF ( For Late Onset type)] Two positive cultures are more significant
  • 19. Neonatal Sepsis Chest X-Ray • Persistent focal changes with infiltrative process • Findings similar to RDS in GBS infection
  • 20. Neonatal Sepsis Acute Phase Reactants - Sepsis Screen Positive CRP ( > 6 mg/ L or 10 times normal) Elevated hepatoglobin level Micro ESR After 14 days of age 15 mm or more for the first hour is abnormal. (Normal ESR = Age in days + 2) If all results are -ve : Probability that infection absent = 99% If all results are +ve : Probability of infection = 90%
  • 21. Neonatal Sepsis Grams Stain of gastric aspirate Positive Result : If > 5 neutrophils / hpf or Large number of bacteria (esp. Gram+ve cocci) in large clumps and chains Predictive value less
  • 22. Neonatal Sepsis Antigen detection methods • Latex particle aggulutination assays for GBS and ECK1 • Counter immuno electrophoresis
  • 23. Neonatal Sepsis Lumbar Puncture • Valuable in symptomatic infants who have risk factors for sepsis. • CSF studies prior to antibiotic therapy is preferable LP in RDS is difficult Interpretation is difficult if LP is traumatic Sometimes meningitis may be present with normal CSF picture
  • 24. Normal Neonatal CSF TEST TERM PRETERM WBCs (per cm) Polymorphs Up to 30 60% Up to 90 60% Protein (mg/dL) Up to 150 Up to 150 Glucose (mg/dL) 35-120 25-65
  • 25. Neonatal Sepsis Miscellaneous Investigations • DIC Profile • Culture of catheters/ ET Tubes • Maternal vaginal swab cultures, etc.
  • 26.
  • 27. Supportive therapy • • • • • • • • • Thermoneutral environment IV Fluids Electrolyte and acid base balance Maintain oxygen saturation Circulatory support Glucose homeostasis Treat anemia with packet Rbc Treat bleeding diathesis with FFP / platelets
  • 28.
  • 29. Antibiotic Therapy Indications: • • • • • PROM > 12 hrs. Evidence of Chorioannionitis Delivery outside labour room Infants with 1 major or 2 minor risk factors Positive Sepsis Screen
  • 30. • • • • • • • • • • • • • • • • Sulfa Drugs Folic Acid Analogs The Beta-Lactams Aminoglycosides Tetracyclines Macrolides Lincosamides Streptogramins Fluoroquinolones Polypeptides Rifampin Mupirocin Cycloserine Aminocyclitol Glycopeptides Oxazolidinones Arm a me nt ariu m … and the list is incomplete …
  • 32. Factors to be considered in the choice of Antibiotic Gram + ve Gram _ ve Anaerobes
  • 33. Antibiotic Selection Presumptive therapy directed to most commonly encountered pathogens. 1st Line : Ampi/Sulbactum+Aminoglycoside 2nd Line 2nd gen. Cephalosporins + Aminoglycosides 3rd Line Vancomycin + Cephalosporins Newer antibiotics
  • 36. When you can’t decide , you tend to … Resort to “Shotgun Therapy”
  • 37. Bauer-Kirby Method (Agar gel diffusion method)
  • 38. Duration of Antibiotic Therapy Culture Positive Sepsis Pyogenic Meningitis - 14 Days - 21 Days / 2 weeks after CSF sterile Culture – ve/ clinically probable sepsis screen +ve:7-10 d. Culture – ve/ clinically probable sepsis screen -ve:5-7 d. Septic Arthritis - 6 Weeks
  • 39. Immunotherapy • Immunoglobulin : IVIG 500-1000 mg/kg/dose • Specific Immunoglobulins : Anti GBS Ig. • Oral administration of IgA and IgG in NEC • Granulocyte infusions • G – CSF 10 µg/kg/d for 3 days • GM – CSF 10 µg/kg/d for 5 days • Double volume exchange transfusions
  • 40. Supportive Therapy • Continued Breast Feeding • Nutrition : TPN / Aminoplasma • Fluid / Electrolyte balance • Treatment of acidosis
  • 41. Preventive Aspects of Neonatal Sepsis • Obstetric Management strategies • Screening based approach • Risk factor approach • Exclusive breast feeding • No prelacteals • Keeping the cord dry • Hand washing by care givers before and after handling the baby (Single most effective measure) • Hygiene of the baby • Avoid unnecessary intravenous fluids, needle pricks etc.
  • 42. Algorithm for early prevention of GBS Risk Factors Give intrapartum Previous GBS penicillin Preterm delivery Bacteremia Rectal & Vaginal swab c/s. at 35-37 wks. Risk Factors Intrapartum Temp. PROM > 18 hrs No intrapartum prophylaxis needed Give intrapartum penicillin Give intrapartum penicillin