CHAIR OF PAEDIATRICS WITH

MEDICAL GENETICS
THEME OF LECTURE
“Neonatal sepsis”
 Determination
Sepsis – generalized infectious acyclic disease, basis of which
is made by the system inflammatory response of organism
(SIRS), bacterial infection, which is manifestated with
generalized defeat of bloodstream, intoxication, disorders
of hemostasis with DIC and development of POI.
 Epidemiology
 Frequency of neonatal sepsis is 2-10 on 1000 live-born;
 In hyperpremature – 1-2 on 100 live-born;
 Lethality is 13-50%, maximal –among premature children
with the early symptoms of infection and at its fulminant
motion.
 In the structure of neonatal death rate lethality from a sepsis
occupies 3 places.
 For the last 20 years frequency of gram-negative neonatal
sepsis grew in 10 times.
 Etiology
Early neonatal sepsis: Streptococcus A and B, E.coli, Klebsiela spp.,
Enterococcus, Listeria monocytogenes, Streptococcus
pneumoniae, Hem. Influenzae, Clostridium spp., Bacteroides
spp.
Late neonatal sepsis: Staphilococcus aureus (in premature – 73%),
E.coli, Klebsiela spp., Streptococcus epidermidis, Candida
albicans, Pseudomonas spp., Serratia spp.
At transplacental infection: viruses, treponema, listeria, candida.
At the intranatal infecting: bacterial agents.
For children with an immunodeficit: nosocomial cultures gram+
and грам- bacteria (Pseudomonas spp., Acinetobacter spp.,
Klebsiela spp., E.coli, Enterobacter spp., St. aureus).
 Main factors of risk
1.Chorioamnionitis (ten-fold risk):
temperature of body > 37,8 0С plus two of list of symptoms:
pulse of mother > 100/min.
pulse of fetus > 160/min.
pain at palpation of lower part of abdomen.
odor noisome of amniotic fluid.
leykocytosis > 15*109/л.
2.Prematurity (seven-fold risk).
3.Waterless interval >24 hours (seven-fold risk).
4.Men sex (six-fold risk compared with girls).
5.Fever for a mother in births 38,3 0С and more (four-fold risk).
6.Meconium, stinking, dirty amniotic fluid.
7.Maternal infections, especially of urinary system (double risk).
8.Colonization of cervix uteri by β-hemolytic streptococcus group B.
Combination of 2 and more factors increase risk of arising of sepsis in
4-8 ones.
 Pathogenesis
Basic components
 Entrance gate of infection.
 Overcoming of protective barriers of macroorganism by a
microorganism.
 Presence in the microorganism of factors of virulence
(lipopolysaccharides, peptidoglycan, exotoxine).
 Inadequate immunological answer of “host”:
surplus inflammatory reaction with septic shock and POI
(mature and immunocompetent children) - phase of
“hyperinflammation”;
deficient inflammatory reaction with the secondary suppurative
focus on background of septic katabolism (premature and
immuneincompetent children) is phase “immuneparalysis”
 Pathogenesis
 Infectious hearth

Penetration of microorganisms and toxins

 Microorganisms

 Gram- Gramm- Fungus Viral-
 negative positive bacterial
 bacteria bacteria association

 Toxins

Endotoxin- Exotoxin Endotoxines-
 lypopolysaccharide hemolysines
peptidoglycane

Activating of the immune system and reactions of inflammation
 Humoral system: Cellular system:
 system of complement macrophages, cells of endothelia, thrombocytes
 system of coagulation, bradykinin granulocytes, microcyte
 T- and B-lymphocytes

Release of mediators:
 cytokines (TNF, Il-1, Il-6) activating of granulocyte of freeing of mediators of ІІ
 degree
 (PG, leukotrien, NO, free radicals of oxygen)

Damage of cells, violation of perfusion, death of cells

Shock and POI (acute kidney and hepatic insufficiency
 DIC, parafunction of CNS)
 Classification
Etiologic factor of sepsis (gram+, gram- microorganisms,
viral-bacterial associations, fungies).
Time of origin: intrauterine (antenatal, intranatal), postnatal
(early, late), nosocomial.
Entrance gate: umbilical, dermic, pulmonary, intestinal,
urosepsis, otogenic, criptogenic (in 40% an entrance gate is
impossible to be determined).
Clinical forms: septicemia (sepsis without purulent metastases),
septicopyemia (sepsis with purulent metastases).
Leading syndromes of sepsis: SIRS, bacteriemia, severe sepsis,
septic shock, syndrome of POI.
Leading syndromes of sepsis
SIRS (systemic inflammatory response syndrome) which is
started by various reasons, including by infection. For
diagnosing of SIRS it is necessary 2 or more of the followings
signs
 Leading syndromes of sepsis
SIRS (systemic inflammatory response syndrome) which is started by
various reasons, including by infection. For diagnosing of SIRS it is
necessary 2 or more of the followings signs .
Clinical criteria of SIRS: Laboratory criteria of SIRS
Disorders of temperature Metabolic lactate-acidosis.
homeostasis Leukocytosis or leukopenia
(hyperthemia>38°C, with a neutrophilia, or
hypothermia < 36°C) neutropenia.
Tachypnoea >60/min. Regeneratory changes of
leukocytar formula to the
Tachycardia >160/min. left, at the amount of
Oppression of CNS and/or cramps. immature forms >2*109/l.
Oligouria (<1 ml/kg/hour. in the Toxic granulosity of
first 3 days of life, <2 neutrophyles.
ml/kg/hour. in future) on Thrombocytopenia.
background of adequate Anaemia.
infusion therapy. Increase of level of acute stage
proteins.
Bakteriemia.
 Leading syndromes of sepsis
Bacteriemia - presence of viable bacteria in blood, which is
confirmed bacteriologically (positive result of bacterial
inoculation of blood).
SIRS + bacteriemia = sepsis.
SIRS + local hearth of infection (omphalitis) = sepsis.
SIRS + clinic of infection = sepsis.
SIRS and bacteriemia can exist for a child
independently, it is unconnected with a sepsis:
Local infection (pneumonia) + short-term bacteriemia
≠sepsis.
Only in 2% children with clinical-laboratory signs of
early sepsis there is the positive bacterial inoculation
of blood or liquor is marked.
 Leading syndromes of sepsis
Severe sepsis, septic shock
Severe sepsis is sepsis + one of Septic shock - sepsis +
criteria of severity: arterial hypotension:
 disturbance of  hypotension continues
consciousness; after entering of
 lactate-acidosis
crystalloid or colloid
(concentration of lactate in solutions in dose 20
arterial blood >1,6 mmol/l
ml/kg;
or in venous >2,2 mmol/l);
 combination of
 oliguria (diuresis less than,
1 ml/kg in a hour during 2 hypotension with any of
hours) criteria of severe sepsis.
 Leading syndromes of sepsis
Polyorganic disorders- any combination of DIC,
SRD, acute kidney insufficiency, hepatobiliar
Factor
disfunction, disfunction of CNS.
Children < 1 years Children > 1 years
Systolic AP < 40 mm.mer. col. < 50 mm. mer .col

Heart reat < 50 or > 220 < 40 or > 200

Breathing > 90 > 70
рН плазми < 7,2 (with normal РаО2)
AVL > 24 hour (for babies after surgery)
Інотропні препарати Необхідні для підтримки АТ та/або серцевого викиду (крім допаміну менше 5 мкг/кг/хв)

РаСО2 > 65 mm. mer. col.

РаО2 < 40 mm..mer..col

Nervous system
< 5 of Glazgo scale or fixed extension pupil
Haematological reading
Hb < 50g/l, leukocytes < 3х109/l, thrombocytes < 20х109/l
Kidnees Креатинин плазми > 40 micromol/l .

Liver
General bilirubin > 60 micromol/l
Alimentary canal Gastroduodenal bleeding
 Criteria of neonatal sepsis

 Presence of factors risk development of neonatal sepsis.

 Presence of respiratory dysfunctions (noisy breathing of child, intercostal
retraction, RR>60/min. or apnoea >15 sec.), circulatory dyfunctions (HR
>160/min. or < 100/min., oliguria, low perfusion of organs and tissues,
hypotension – systolic AP < 35 mm. Hg ).
 Presence of early nonspecific clinical signs of infection (microsymptoms of
sepsis): flabbiness, refuse of feeding, disturbance of thermoregulation,
abdominal distension , dyspepsia, icteritiousness, grayness of skin,
hepatomegaly) in combination with one of laboratory criteria SIRS.
 Combination of SIRS and pneumonias (lungs – main organ-target for
causative agent).
 Criteria of early and late sepsis
Early sepsis – it is arisen up
during 72 hours after birth.
 Transplacental or intranatal
way of infecting.
 Numerous hearths of
infection with predominance
in clinical course of signs RI
(pneumonia).
 Fulminant motion.
 Lethality 50% more.
Late sepsis –is arisen up
after the first 3 days life
of child.
 Intranatal or contact
way of infecting.
 Symptoms of oppression
of CNS prevail in clinic
(meningitis).
 Acute course.
 Lethality 20%.
 Nosocomial sepsis - arises up in newborns of risk group at
infecting of neonatal department by flora..
Ways of infecting:
Contact- through the hands of medical staff, through catheters, medical equipment.
Air-drop (at ALV).
Alimentary-through maternal milk.
Parenterally – through infusion solutions.
Risk factors:
Low weight at birth.
Peripheral venous catheter > 3 days.
Umbilical venous catheter > 7 days.
Subclavian venous catheter > 10 days.
RDS at entering of child into department.
Presence of nasogastric catheter.
Complete parenterally feeding.
UNEC
Localized infection of skin.
 Clinical picture

There are not characteristic

clinical signs of neonatal sepsis.
They are determined by etiology
of causative agent, time infecting
and by the features organism of
concrete baby.
 Clinical picture

Infant
Badly breathes!
Badly uses feed!
Looks seedy!
 Clinical picture
General appearance:
pallor, mottled of skin,
greyish or icteric tint.
Abdominal distension,
dilated venous network
of front abdominal wall,
hepatomegaly, areas of
sclerema . The infant has
suffering appearance,
inhibition or excitement.
 Clinical picture
Respiratory system:
Tachypnoea (especially
for the mature
infants);
Disorders rhythm of
breathing, apnoea;
Moan on expiration;
Increased requirement
in oxygen;
Diffuse changes on x-ray.
 Clinical picture
Cardiovascular system:
Tachycardia/bradycardia,
arrhythmia;
Cyanosys;
disturbance of
microcirculation (“white
spot – symptom” > 3 sec.);
Arterial hypotension (late
symptom);
Peripheral swelling;
 Clinical picture
Alimentary canal:
Refuse of feeding
Regurgitation, vomiting;
Meteorism;
Liquid, watery stool,
gastrointestinal
bleeding;
Hepatosplenomegaly.
 Clinical picture
Nervous system:
Inhibition or excitability; Thermoregulation:
Cramps or coma; Fever over 37,70С;
Oppression of physiology reflexes;
Tension of fontanel .
Hypothermia less than
36,50С;
Metabolism: Difference of axilla
Metabolic acidosis; (armpit) and rectal
Hyper- or hypoglycemia;
temperature more
Glucosuria;
Hyperbilirubinemia (due to direct
than 20С .
bilirubin).
 Diagnostics (plan of inspection):
 CBC.
 С-reactive protein (at entering and in 24 hours).
 Biochemical analysis of blood+ionogramm+indexes of
ABB.
 Clinical uranalysis.
 Lumbar punction.
 Coagulogramm – at development of DIC.
 NSG, US of abdominal region, chest x-ray.
 Bacteriologic examination of placenta, blood, urine,
liquor, excrements, excretions from nasopharynx, eyes,
endotracheal tube.
 On indications - specific virologic diagnostics (IFA and
PCR).
Laboratory signs of neonatal sepsis
Leukopenia < 5 000*109 /l
Leukocytosis
 to 4 days of life > 30 000 *109 /l
 after 4 days of life > 20 000 *109 /l
Absolute number of stab neutrophills
> 500/mm3
 to 4 days of life
> 1000/mm3
 after 4 days of life

Leukocyte index intoxication > 0,2

C – reactive protein > 20 mg/l
Thrombocytopenia < 150 000*109 /l
Procalcitonin (after 4 days of life) > 0,5 ng/ml
 Treatment
Therapeutic-protective regimen (adequate feeding and care).
Antibiotic therapy:
AB therapy is begun as earlier as possible at suspicion on a
sepsis;
Deescalation therapy is used – they prescribe the most
powerful, effective antibiotic during 4-7 days with the
subsequent passing to more simple drug, taking into
account the results of bacteriologic examination got on
this time.
At suspicion on nosocomial sepsis choice of AB depends on the
epidemiological situation of department.
AB are used i/v
Duration and efficiency of treatment depends on duration of
clinical-laboratory effect of drug.
 Treatment
Protocols of empiric antibacterial therapy:
 Cefuroxim (zinacef) 30-50 mg/kg + netromycin 7,5 mg/kg
 Ceftriaxon 100 mg/kg + netromycin 7,5 mg/kg
 Cefazidim (fortum) 100 mg/kg + clindamycin 20 mg/kg +
netromycin 7,5 mg/kg
In-hospital sepsis
 Tsefepim (maxipim) 150 mg/kg + vancomycin 10 mg/kg
+amikacin 10 mg/kg
 Vancomycin 10 mg/kg +amikacin 10 mg/kg + metronidazole 7,5
mg/kg
At duration of antibacterial therapy >5 days application of
flukonasol 10 mg/kg is necessary.
 Treatment
3. Infusion therapy
Conducted with the purpose of support of hemodynamics, VCB,
correction of plasma osmolality and violations of metabolic
processes, providing of disintoxication.
Standard solutions: 5 % glucose of 10 ml/kg, in the case of
hypovolemia - fresh-frozen plasma 10 ml/kg each 6-12
hours.
At development of septic shock is an intravenous reanimation of
volume with addition of dopamine or Dobutaminum.
 Treatment
4. Respiratory support
Indications:
Apnoe with bradycardia and cyanosys;
RR over 70/min.;
Cyanosys which conitinues after oxygenotherapy ;
Gasping breathing;
Arterial hypotension;
Pallor and decreased peripheral perfusion;
Severe lingering bradycardia ;
P CO2 >60 mm. Hg, P O2<50 mm. Hg., рН<7,25;
Mode of oxygenotherapy depends on the indexes of
saturation of blood by oxygen, respiratory gases of blood
and condition of child.
 Treatment
5. Immunotherapy
I/v immunoproteins (Pentaglobin, Sandoglobulin,
Gabriglobin, Polygam, Gammagard):
- Stimulate the process of opsonization;
- Stimulate the processes of phagocytosis;
- Activating of complement system;
- Alleviate motion of neutrophils to the antigen;
- Decrease toxicity of antigens;
- Neutralize viruses.
6. Local sanation of suppurative focus
7. Syndromal therapy
Thank you for your attention!