8. Common pathogens of neonatal sepsis in developed countries
Early-onset Late-onset
Pathogen Frequency
(%)
Pathogen Frequency
(%)
Group B Streptococcus 43–58 Coagulase-negative Staphylococcus 39–54
E. coli 18–29 E. coli 5–13
Other gram-negative bacteria 7–8 Klebsiella sp. 4–9
S. aureus 2–7 S. aureus 6–18
Coagulase-negative Staphylococcus 1–5 Candida albicans 6–8
L. monocytogenes 0.5–6 Enterococcus sp. 6–8
P. aureginosa 3–5
Other Candida species 3–4
a
Common pathogens of neonatal sepsis in developing countries
Community-acquired Hospital-acquired
Pathogen Frequency (%) Pathogen
Klebsiella sp.
S. aureus
E. coli
Group B Streptococcus
S. pneumonia
Salmonellasp.
14–21
13–26
8–18
2–8
2–5
1–5
Klebsiella sp.
S. aureus
E. coli
Coagulase-negative Staphylococcus
Pseudomonas sp.
Enterobacter sp.
Candida sp.
16–28
8–22
5–16
8–28
3–10
4–12
0.3–3
Frequency (%)
JournalofTropicalPediatrics,2015, 61, 1–13 doi: 10.1093/tropej/fmu079
Clinical Review
9. Early onset sepsis among very low birth weight infants in the developed countries
10. LOS
• 2 TYPES- A)HEALTHY TERM INFANTS IN COMMUNITY
B) HOSPITAL ACQUIRED PREMATURE INFANTS IN NICU
• Acc to NICHD- 77%-Gram positive org
18%-Gram negative org
8%-Fungal
18. NEONATAL MENINGITIS
The clinical presentation is usually nonspecific.
• Meningitis must be excluded in any infant being evaluated for
sepsis or infection.
Forced posture of newborn with meningitis
19. Meningitis
The principal pathogens in neonatal meningitis are GBS (36% ), E coli
(31%), and Listeria species (5-10%). Other organisms :
S pneumoniae
S aureus
S epidermidis
H influenzae
Pseudomonas species
Klebsiella species
Serratia species
Enterobacter species
Proteus species
21. Meningitis
• Ventriculitis
• Arachnoiditis
• Vasculitis
• Cerebral edema
• Infarction
Mortality rate in neonatal meningitis is approximately 10 percent
Survivors– Neurological sequelae & lifelong impairments
20% of survivors- severe disability,
35% of survivors-mild to moderate disability
22. Neonatal Pneumonia
Infectious
GBS
Haemophilus influenzae
Gram neg bacilli
Listeria monocytogens
Enterococci
Staphylococcus aureus
Non infectious
Diffuse alveolar damage
Organising pneumonia
Aspiration
Non specific interstotial
Klebsiella & S aureus- generate severe lung damage, microabscesses and empyema
Early onset GBS pneumonia has fulminant course, with mortality in first 48 hours of life.
If the infant has remained hospitalized in NICU with endotracheal intubation and
mechanical ventilation, the organisms may include Staphylococcus or Pseudomonas .
30. Twoor more parameters of thesepsisscreenare
positive ->sepsisscreenpositive
If all the parameters of the sepsisscreenare negative
in aneonate ->low probability ofsepsis, antibiotics
need not be started and the neonate must be
monitoredclinically.
Thescreenmust be repeated after 12hours.
Twoconsecutive completely negative screens are
suggestiveof nosepsis.
30
34. 34
Micro-ESR
• Measures ESR in vertically placed capillary tube in
1 hour.
• Normal: day of life plus 3 mm/ hr, up to a
maximum of 14 mm/ hr
• > 15mm is abnormal in 1st hour
• Poor sensitivity and specificity
– False positive tests with hemolysis
– False negative tests with DIC
36. 36
BLOOD CULTURE
Gold standard for diagnosis of bacteremia
• Add at least 1.0 ml blood obtained by sterile
venipuncture to 5-10 ml culture broth (ideally 2
bottles)
• Most bacteria grow within 24 to 36 hours
• BACTEC and BACT/ALERT blood culture system
37. Baby has risk factors and clinical signs of sepsis but
blood culture is negative
Blood cultures are positive in only 2 to 25% of babies with clinically suspected sepsis.
37
42. • Culture positive after 72 hours
• Polymicrobial culture
• Growth of purely skin organisms
43. 43
Lumbar Puncture
Possibility of meningitis 1-10%
Sepsis & meningitis overlap
INDICATIONS
Blood culture positive
Symptomatic infants with high risk for EOS condition stable
to tolerate LP
Negative blood culture treated empirically for clinical
diagnosis of sepsis
LOS- prior to starting antibiotics
15% of babies with meningitis will have negative blood
cultures
45. 45
Urine culture
Sterile specimen obtained by sterile
catheterization or by suprapubic bladder
aspiration(ideal)
UTI-single uropathogenic pathogen >50000
CFU/ml
10000-50000CFU/ml with associated
pyuria(WBC>5/HPF)
Any 1 organism from suprapubic aspiration
46. • Cultures from central lines
• Surface cultures
• Endotracheal cultures
• Gastric aspirate cultures>More than 5 neutrophils/HPF
indicate exposureto chorioamnionitis.
Poor Sensitivity and Specificity
46
47. DEVELOPING BIOMARKERS
SERUM AMYLOID A
LIPOPOLYSACCHARIDE BINDING/MANNOSE BINDING
PROTEIN
47
OTHER BIOMARKERS
Alpha-1 antitrypsin
Fibronectin
Haptoglobulin
Lactoferrin
neopterin
49. CYTOKINES &CHEMOKINES
• IL-6,8,10,TNF-alpha,IFN-gamma,TGF-beta
• Increase very rapidly
• Normalise within 24 hrs
• Increase IL-10 to TNF-alpha ratio severe LOS in VLBW
infants
• IL-6,IL-10 & RANTES morbidity in sepsis with DIC
49
Combination of cytokine profiles inc likelihood of identifying infection more than
single measurements
50. CELL SURFACE ANTIGENS
• CD 11b, 14,16, 64 etc
• CD 64 sensitive biomarker for EOS & intraabdominal
infections even before rise of CRP
• Pentraxin 3 (PTX3)
• Angiopoietins 1 & 2 low ang1 & high ang2 predict
poor prognostic outcome of sepsis
• STREM-1
• SuPAR
50
52. MOLECULAR TECHNOLOGY
• q PCR- Detect bacterial DNA in body fluid of host suspected of
infection
• FISH
ADVANTAGE
Underlying pathological events
Development of new diagnostic approaches
Algorithms
Score systems
BIOFLUID ANALYSIS saliva,urine
52
53. GENOMICS
• To identify genes that demonstrate altered regulation during
infection
• Focus on chemokine mRNA expression & its relation to infection
• Inc IL8 Perinatal infection
• Inc IL8 & MCP-1Perinatal asphyxia
PROTEOMICS
Involve separation of proteins based n intrinsic properties like
molecular weight, isoelectric point or affinity to metals or
antibodies
Identify protein signatures & functionally expressed metabolites
during specific disease states
53
61. In 2018, the stewardship and charge for updating the GBS prophylaxis guidelines
were transferred from the CDC to ACOG and the American Academy of Pediatrics
62. Prevention of LOS
• IV IG
• G-CSF / GM-CSF
• Probiotics
• Lactoferrin
• Antistaphylococcal monoclonal antibodies
• Prophylactic vancomycin
• Establishment of early enteral feedings
• Antibiotic restriction
• Surveillance practices
65. Sepsis Calculator - Assessment of EarlyOnset
Sepsis in Infants > 35 Weeks
• Three groups of infants require a blood culture and antibiotic treatment
without delay:
Unwell appearing infants.
Infants whose sibling had EOS.
Infants whose mother currently has Group A Streptococcal infection.
calculation of EOS score:
Gestational age.
Highest maternal antepartum temperature
Duration of rupture of membranes.
GBS status
Maternal intrapartum antibiotics.
66. NEWBORN CLINICAL PRESENTATION
The EOS risk score then incorporates the newborn clinical presentation as:
Well appearing.
Equivocal signs.
Clinical illness.
Definition of Equivocal Clinical Signs
Clinical Parameters Assessed Equivocal signs
Heart rate > 160/min 2 clinical parameters abnormal for >2hrs
Respiratory rate > 60/min or
Temperature > 38.0°C or <36.4 C 1 clinical parameter abnormal for 4 hrs
Respiratory distress
67. Interpretation of EOS Risk Score Results and
Management
• Management Plan for GREEN Group:
• Routine care.
• Early discharge possible
• Management Plan for YELLOW Group:
• BLOOD CULTURE AND OBSERVATION.
• No routine full blood count or CRP.
• Infants with equivocal signs - observation in neonatal unit; when signs normalised.
• Infants with medium risk, but normal exam may be observed (3 hourly vital signs) on
postnatal wards until blood culture result available.
• If abnormal clinical parameters develop, the infant requires urgent paediatric review
• If equivocal signs develop, infant requires transfer to neonatal unit
• Management Plan for RED Group:
• TAKE BLOOD CULTURE AND TREAT WITH EMPIRIC ANTIBIOTICS.
• With the blood culture, take full blood count and CRP.
68. Treatment of neonatal sepsis may
be divided into
antimicrobal therapy supportive care
(for the suspected or
known pathogen)
The initial diagnosis of sepsis is, by necessity, a clinical one
because it is imperative to begin treatment before
the results of culture appear
69. Supportive therapy
Respiratory
Oxygen and ventilation as necessary
Cardiovascular
Volume expanders,Dopamine, FFP to correct
perfusion
Hematologic
Treat bleeding- vit k,FFP, fresh blood, platelet
CNS
Treat seizures with phenobarbital
Metabolic
Treat hypoglycemia/hyperglycemia and
metabolic acidosis
70. Principles for antibiotic use
• Empiric initiation of
antibiotics
• Switch antibiotics based
on susceptibility patterns
• Define duration of
antibiotic therapy
• Use only when bacterial infections
are likely and discontinue empiric
treatment when they have not
been identified.
• Change the antibiotic agents to
those with the narrowest
spectrum.
• Establish a final duration of
antibiotic management based on
the disease process.
75. Duration of Antibiotic therapy
• Gram negative septicemia: 14 days
• Group B Strep septicemia: 10-14 days
• Gram negative meningitis: 21 days minimum
• Group B Strep meningitis: 14 - 21 days
• Culture negative sepsis
• Asymptomatic neonate at risk of EOS ?
• Suspected EOS/ LOS & neonate asymptomatic over time ?
• Suspected EOS/ LOS & neonate improves but doesnot become
asymptomatic ?
• Osteoarticular infection should be treated for 3 to 4 weeks
• Ventriculitis should be treated for at least 4 weeks.
76. Upgradation of Empirical Antibiotics
NO CLINICAL IMPROVEMENT IN 48-72 hrs
Extremely sick babies start with higher antibiotics
as per clinical situation
DEVELOPMENT OF SCLEREMA
77. Newer antibiotics-Beta lactamase
inhibitors
• Production of beta lactamase by gram
negative bacteria greatest threat to efficacy of
antibiotics
• To counteract this-Beta lactamase inhibitors
combined with Beta lactam antibiotics
• New- Avibactam, Relebactam, Vaborbactam
78. ADJUNCTIVE IMMUNOTHERAPIES for EOS
• DVET
• Granulocyte transfusion
• IV IG
• Recombinant G-CSF & GM-CSF
• Activated protein C
• Pentoxifyllin
79. Background
• Neonatal sepsis may be categorized as early-onset or
late-onset. Of newborns with early-onset sepsis, 85%
present within 24 hours, 5% present at 24-48 hours,
and a smaller percentage present within 48-72
hours.
• Onset is most rapid in premature neonates.
• Early-onset sepsis is associated with acquisition of
microorganisms from the mother.
• Late-onset sepsis occurs at 4-90 days of life and is
acquired from the caregiving environment.
84. TAKE HOME MESSAGES
Gram negative organisms MCC for neonatal sepsis in India
PCT superior to CRP in early diagnosis of Neonatal sepsis
serial C-reactive protein levels and serial assessment of
immature:total neutrophil counts provide the best negative
predictive value for neonatal sepsis.
Hematological scoring system –screening test for early
diagnosis of neonatal infections
PCR reduces antibiotic use & length of stay in hospital
1st line drug-Ampicillin+Gentamicin
Treatment should be according to antibiotic susceptibility to
prevent emergence of MRSA, VRSA, VRE
85. REFERENCES
• CLOHERTY AND STARK’S MANUAL OF NEONATAL CARE 8th
EDITION
• AIIMS PROTOCOL,2nd EDITION
• NELSON TEXTBOOK OF PAEDIATRICS,21st INTERNATIONAL
EDITION
• Neonatal Infectious DiseasesEvaluation of Neonatal Sepsis,
Andres Camacho-Gonzalez, MD, MSca,*, Paul W. Spearman,
MDa
, Barbara J.Stoll, MDb
• Biomarkers for neonatal sepsis: recent developments
Authors Mally P, Xu J, Hendricks-Muñoz K
86. “ I am not sure exactly what heaven will be like,
but i do know that when we die and it comes time
for god to judge us, He will not ask, How many
good things have you done in your life, rather he
will ask, HOW MUCH LOVE did u put into what you
did?”