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a
 

 

 a

| 
 is a clinical syndrome
of systemic illness accompanied by
bacteremia occurring in the first month
of life.
 

! primary sepsis is 1 - 8 per 1000 live

births
! as high as 13-
13-27 per 1000 for infants
weighing <1500 g
! mortality rate is high (13-
(13-25%)
! higher rates are seen in premature
infants and in those with early fulminant
disease
  
 

  

?. Early
Early-- Onset Disease

B. Late - Onset Disease

C. Nosocomial Sepsis
  
 

  
 
a
! first 5 ± 7 days of life
! is usually a multi-
multi-system fulminant illness
with prominent respiratory symptoms
! Typically, the infant has acquired the
organism during the intrapartum period from
the maternal genital tract«
  
 
÷n this situation, the infant is colonized with the
pathogens in the perinatal period..
Several infectious agents«.
u Treponemes
u Viruses
u m
 
u  
can be acquired transplacentally via
hematogenous routes
  
 

! acquisition of other organisms is associated

with the birth process.
! with rupture of membranes, vaginal flora or
various bacterial pathogens may ascend to
reach the amniotic fluid and the fetus



 
develops, leading to fetal
colonization and infection.
! aspiration of infected amniotic fluid by the fetus
or neonate may play a role in resultant
respiratory symptoms.
  
 
! presence of vernix or meconium impairs the
natural bacteriostatic properties of amniotic
fluid.

Ñ  

 
 
    


PR÷ ?RY S÷TES of colonization :

1. nasopharynx
2. oropharynx
3. conjuctiva
4. umbilical cord
  
 

Trauma to these mucosal surfaces infection

Early-onset disease is characterized by a Ú



Early-
Ú

 Ú
  ÚÚ 
ÚÚ

   
  
 




a
! as early as 5 days of age but common 1st
week of life
! although these infants may have a history of
obstetric complications less frequent than
early--onset disease
early

! infants usually have an identifiable focus, most

often meningitis in addition to sepsis
  
 

bacteria responsible for late-

late-onset sepsis
and meningitis include those :
1. acquired after birth from the maternal
genital tract
2. acquired after birth from human contact
or from contaminated equipment
  
 

! The reasons for   

   


  








 





 

 
 


are
unclear.
  
 

| 


! occurs in high-
high-risk newborn infants
They are related to :
1. to the underlying illness and debilitation of the
infant
2. the flora in the N÷CU environment
3. invasive monitoring and other techniques used
in neonatal intensive care
  
 

Breaks in the natural barrier function of the

skin and intestine allow this opportunistic
organism to overwhelm the neonate

÷nfants, especially premature infants, have an

increased susceptibility to infection
underlying illnesses and immature defenses
that are less efficient at localizing and clearing
bacterial invasion.
 Causative Organisms
?gents associated with primary sepsis are usually
from the vaginal flora :
À




 most common
2. 


 
 
3 Ú 
Ú
   Ú

 
  





 Ú 
 Causative Organisms

The flora causing nosocomial sepsis vary in

each nursery«
The ?gents are :
1. Staphylococci (especially S 
S 

)
  
)
2. gram
gram--negative rods (including
P




  and
P

and fungal organisms predominate
  

! initial diagnosis of sepsis is, by necessity, a

clinical one because it is imperative to begin
treatment before the results of culture are
available

! Clinical S/Sx of sepsis are nonspecific, and the

differential diagnosis is broad
  

À

  
 

 ypo-- or
 ypo
hyperthermia (greater heat output required by
the incubator or radiant warmer to maintain a
neutral thermal environment or frequent
adjustments of the infant servo control probe)
probe)..
 
Lethargy, irritability, or

   

change in tone
tone..


Poor peripheral perfusion, cyanosis,


mottling, pallor, petechiae, rashes, sclerema,
or jaundice
jaundice..
  

Ñ
 


 
Ñeeding intolerance,
vomiting, diarrhea (watery loose stool), or
abdominal distention with or without visible
bowel loops
loops..


 


 
Tachypnea, respiratory
distress (grunting, flaring, and retractions),
apnea within the first 24 h of birth or of new
onset (especially after 1 week of age),
tachycardia, or hypotension, which tends to be
late sign
sign..

 
 

 ypo-- or hyperglycemia or
 ypo
metabolic acidosis
acidosis..
 Ñ

À
   



Premature or




prolonged (>18 h) rupture of membranes

 

 (•38 ÛC/100.4
ÛÑ) or infection. Chorioamnionitis, urinary
tract infection (UT÷), vaginal colonization
with Y
 and
and other obstetric
complications.
 
 

econium

 
  econium--
stained or foul-
foul-smelling, cloudy amniotic
fluid.
 Ñ



÷nfants who had

fetal distress, were born by traumatic
delivery or were severely depressed at birth
and required intubation and resuscitation.

 


 





 ÷nvasive monitoring


÷nvasive
and respiratory or metabolic support.

   (predisposition
to Y
 sepsis),
sepsis), immune defects, or
asplenia.
 

 
 (iron added to serum in vitro
enhances the growth of many organisms).
À

 

* males are 4 times more affected than
females
* more common in black than in white
infants
* Variations in immune function may play a
role
* N÷CU staff and family members are often
vectors for the spread of microorganisms,
primarily as a result of improper hand
 a



À
  
! Blood and other normally sterile body fluids
should be obtained for culture.. *Positive
bacterial cultures will confirm the diagnosis of
sepsis
Computer--assisted, automated blood culture
Computer
systems shown to identify up to 94% of all
microorganisms by 48 hr of incubation
 a
  «
! Results may vary because of a number of
factors, including maternal antibiotics
administered before birth, organisms that are
difficult to grow and isolate (ie., anaerobes),
and sampling error with small sample
volumes (the optimal amount is 1- 1- 2
mL/sample).
! Therefore, in many clinical situations, infants
are treated for ³presumed´ sepsis despite
negative cultures, with apparent clinical
benefit.
 a

 
! helpful for the study of CSÑ
! Gram
Gram--stained smears and cultures of
amniotic fluid or of material obtained by
gastric aspiration
 


 
! Neutropenia may be a significant finding
with an ominous prognosis when
associated with sepsis
! Serial white blood cell counts several hours
apart may be helpful in establishing a trend.
 a

  

* decreased platelet count is usually a
late*sign and is very nonspecific




* complex multifunctional group comprising
complement components, coagulation
proteins, protease inhibitors, C-
C-reactive
protein (CRP), and others that rise in
concentration in the serum in response to
tissue injury.
 a

! remain elevated with ongoing

inflammation, but with resolution they
decline rapidly due to a short half-
half-life of
4 ²7 h
! CRP demonstrates high sensitivity and
negative predictive value

  
! may be elevated but usually not until
well into the illness
 a

 
! increases the most in the presence of
inflammation caused by infection or tissue
injury
! highest concentrations in patients with
bacterial infections, whereas moderate
elevations chronic inflammatory conditions
! onset of inflammation, CRP synthesis
increases within 4²
4²6 h, doubling every 8
h, and peaks at about 36²
36²50 h
 a

À

 À

|Ñ
! major mediators of the systemic response
to infection
! Studies have shown that combined use of
÷L--8 and CRP as part of the workup for
÷L
bacterial infection reduces unnecessary
antibiotic treatment


 
! aÀÀ has been shown to be an
excellent marker of early infection that
correlates well with CRP but peaks earlier.
 a


 


! ?bnormal values for bilirubin,
glucose, and sodium may, in the proper
clinical situation, provide supportive
evidence for sepsis.
 a

 
  in case with respiratory
À

symptoms


  
  
 
 - should be part
of the evaluation when UT÷ accompanies
sepsis. Sterile urine for culture must be
obtained by either a suprapubic or catheterized
specimen
 a



 
Examination of the

placenta and fetal membranes may
disclose evidence of chorioamnionitis
and thus an increased potential for
neonatal infection
 Differential Diagnosis

1. Respiratory distress syndrome (RDS)

2. etabolic diseases
3.  ematologic disease
4. CNS disease
5. Cardiac disease
6. other infectious processes (ie. TORC 
infections)
 anagement

À



 
! major pathogen in the late 1960s and currently
remains the most common cause of early-
early-
onset sepsis
! 10 to 30% of pregnant women are colonized
with GBS in the vaginal or rectal area
! incidence of infection has been estimated at
0.8²
0.8²5.5/1000 live births (unchanged for the
past three decades).
! Case fatality rate ranges from 5²
5²15%
 anagement
 


  
a À



  

 
  


  
  
 

 
 




  

 ))
 
 anagement

b) identifying women who present with risk

factors treating them during labor
! To ensure appropriate treatment for neonates
born to mothers who receive antibiotics for
fever and presumed choriomanionitis, as well
as for those born to mothers who receive
intrapartum antibiotic prophylaxis (÷?P)
because of GBS colonization, they are
clinically using an algorithm in their hospital
based on ??P guidelines, with some
alterations based on clinical experiences.
Ë aternal ÷?P aternal ÷?P
Ë other asymptomatic other w/ ssx of chorio-
Signs & Symptoms of amnionitis
sepsis in infant
aternal aternal
yes no temp <102 temp
Gestational Ñ >102Ñ
Ñull dx
age S/sx of sepsis in
eval.
infant
Emperic Tx
no yes
<37 wks >37
wks
Limited eval.
Limited eval No evaluation
Observe 48 
Observe 48  No therapy
÷f sepsis
÷f sepsis Observe min, 48 Ñull eval. w/
suspected, full
suspected, full   empiric Rx
eval & empiric
eval & empiric
Rx
Rx
 anagement




! have been mandated by the U.S.
Occupational Safety and  ealth
?dministration (OS ?) and apply to
blood, semen, vaginal secretions, wound
exudate and CSÑ and amniotic fluids
! caution to prevent injuries when using or
disposing of needles or other sharp
instruments
 anagement

  

! Treatment is most often begun before a
definite causative agent is identified.
!  usually 
  plus an
 usually
  such as Gentamicin.

! ÷n nosocomial sepsis flora of the N÷CU

must be considered: however, generally,
staphylococcal coverage with
! 
 
  

 

 anagement


 
 is based on culture
and sensitivity results, clinical course,
and other serial lab studies (eg., CRP).

onitoring for antibiotic toxicity is

important as well as monitoring levels of
aminoglycosides and vancomycin.
 anagement

When GBS is documented as the

causative agent   is the DOC
  is often given as well
because of documented synergism
 Complications and Supportive
Therapy
À
 

! Ensure adequate oxygenation with blood
gas monitoring and initiate O2 therapy or
ventilator support if needed

 a
 
! Support BP and perfusion to prevent
shock. Use volume expanders, 10- 10-20 mL/kg
(normal saline, albumin, and blood), and
monitor the intake of fluids and output of urine.
! Pressor agents such as dopamine or
dobutamine may be needed.
 Complications and Supportive
Therapy

 

a
‡ one may observe generalized bleeding at
puncture sites, the gastrointestinal tract, or
CNS sites. ÷n the skin, large vessel
thrombosis gangrene.

! Lab. parameters consistent with D÷C include :

thrombocytopenia, inc. PT, and inc. Partial
Thromboplastin Time
Complications and Supportive
Therapy
easures include treating the underlying
disease; fresh-
fresh-frozen plasma, 10 mL/kg;
vitamin K; platelet infusion; and possible
exchange transfusion.
 Complications and Supportive
Therapy
 |

! ultiple factors contribute to the increased
susceptibility of neonates to infection, including
developmental quantitative and qualitative
neutrophil defects.
! Studies suggest use of recombinant human
granulocyte colony-
colony-stimulating factor (rhG
(rhG--
CSÑ) or recombinant human granulocyte-
granulocyte-
macrophage colony-
colony-stimulating factor (rhG -
CSÑ) can partially counterbalance these
defects and reduce morbidity and mortality.
 Complications and Supportive
Therapy

|
! ÷mplement seizure control measures
   20 mg/kg loading dose
! monitor for the syndrome of inappropriate
antidiuretic hormone (S÷?D ) :
i. decreased urine output,
ii. hyponatremia,
iii. decreased serum osmolarity, and
iv. increased urine specific gravity and osmolarity
 Complications and Supportive
Therapy

 


! onitor for and treat hypo-
hypo- or
hyperglycemia. etabolic acidosis
may accompany sepsis and is treated
with bicarbonate and fluid replacement.
 Ñuture Developments
! ÷mmunotherapy progress continues in the
development of various hyperimmune
globulins, monoclonal antibodies to the specific
pathogens causing neonatal sepsis
! They may prove to be significant adjuvants to
the routine use of antibiotics for the treatment
of sepsis
! Research is also ongoing into blocking some
of the body's own inflammatory mediators that
result in significant tissue injury, including
endotoxin inhibitors, cytokine inhibitors, nitric
oxide synthetase inhibitors, and neutrophil
adhesion inhibitors.
««««««««««.Thank you