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Neonatal Sepsis and Recent
Challenges
Mohammad Khasswneh, MD
Assistant Professor of PediatricsJUST
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introduction
Common 20% of VLBW has sepsis In term 0.1%
Inter-institution difference 11-32% (NICHD net work)
Serious mortality is 3-5 times more for infant with sepsis in NICU
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Classification
Early onset sepsis (EOS):
bacteria acquired before and during delivery
5-7/1000 live birth 1.5% of VLBW infants had EOS (intrapartum antibiotics)
Late onset sepsis (LOS):
bacteria acquired after delivery (Nosocomialor community)
20% of VLBW infants
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Who is the septic
neonate? Positive blood culture with clinical
symptoms of infection
Coagulase-negative Staphylococcus (CoNS)
2 positive blood cultures
One positive blood culture and elevated CRP
Clinical sepsis or probable sepsis
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Adult and Pediatrics
Definitions
Systemic Inflammatory response
syndrome (SIRS) Sepsis
as SIRS plus infection
Severe sepsis: as sepsis associated with organ dysfunction,
hypo perfusion or hypotension, Septic shock
sepsis with arterial hypotension despite fluidresuscitation
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Blood CultureOne out of five evaluations for
sepsis has positive bloodculture
80% of the time, empiric
antibiotics will be given when noorganism is isolated fromculture
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Blood culture
In a 1999, autopsy study of ELBW
infants infection was primary cause of death
by pathologists in (56 of 111)
sepsis was not diagnosed prior todeath for 61% of these 56 neonates
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False negative Blood
Culture Maternal antibiotics
Small blood sample
in a prospective study of nearly 300 blood
cultures drawn from critically ill neonates,
55% of culture vials contained less than 0.5
ml of blood Bacteria load, timing of sampling
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Diagnosis
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Clinical Signs
according to WHO Integrated Management of
Childhood illness
Respiratory rate >60 breaths/min
Retraction, flaring, Grunting
Crepitation
Cyanosis
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Clinical Sings
according to WHO Integrated Management of
Childhood illness
Temperature >37.7C (or feels hot) or
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Other signs in NICU
abnormal heart rate characteristics Reduced digital capillary refill time
metabolic acidosis
Increase in weight
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Clinical signs of sepsis
in VLBW infants
NICHD network study
Apnea in 55%
gastrointestinal problems (46%), increased need for oxygen or ventilatory
support 36%
lethargy/hypotonia 23%
Hypotension 5%
The positive predictive value 14 to 20%.
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New Diagnostic Methods
CRP
Interleukin 6,8 IgM
Polymerase chain reaction (PCR)
DNA microarray technology Immunoassay
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CRP
Best discriminatory value for predicting
septicemia Expressed by all gestational age
sensitivity 48 to 63%
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Serial CRP
elevated CRP on day 1
and/or day 2, identify most
case of sepsis
sensitivity (90.2%)
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Serial CRP
When CRP is normal on days 1
and 2 ,neonatal sepsis can be
confidently excluded andantibiotic therapy ceased
negative predictive value
(97.7%).
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CRP
Sensitivity of serial CRP
testing is lower for
bacteremia due to gram-
positive than to gram-
negative bacteria
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CRP
Help in timing of discontinuation
of antibiotics when CRPnormalize
Further studies is needed
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Polymerase Chain
Reaction (PCR)
PCR: under investigation for
bacterial and fungal infection
amplification of16S rRNA,
a gene universally present in
bacteria but absent in humans
Results in 9 h of sample acquisition
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PCR
Sensitivity 96%Specificity 99.4%
positive predictive value 88.9%
negative predictive value 99.8%
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Microbiology in
Developing Country Gram negative organisms
Klebsiella, Escherichia coli,
Pseudomonas, and Salmonella.
Gram positive less common
Staphylococcus Aureus
Coagulase negative staphylococci (CONS) Streptococcus pneumoniae, and
Streptococcus pyogenes
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Microbiology In
Developing Country
Group B streptococcus (GBS) is rare
Maternal recto-vaginal Carriage rates
for GBS is similar to that in developed
country
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Meningitis
developing country 1st week mainly Gram negative.
Older than 1 week:Streptococcus pneumonia, 50% of
all bacterial meningitis occurring
between 7 and 90 days of age
Fatality rate of 53%.
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Microbiology in Developed
Country EOS
GBS and E coli
Recently decrease in Gram positive organisms (GBS)and increase in Gram negative organisms
LOS:
Coagulase Negative Staph (CON),
GBS
Staph Aureus.
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New trends
incidence of GBS sepsis decreasedfrom 5.9 to 1.7 per 1,000
the incidence of sepsis from E. coli
increased from 3.2 to 6.8 per 1,000between 1991-1993 and 1998-2000
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Case Fatality
EOS: more severe and casefatality rate is higher( all-causes
mortality was 37%)
LOS: less sever (CoNS) 18%.
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Mortality Per Organisms
percentages/ LBW infants
Gram-negative 257cases (36%)
E coli 53 cases (34%) Klebsiella 62 cases (22%)
Pseudomonas 43 cases (74%)
Enterobacter 41 cases (26%)
Serratia 39 cases (35%)
fungal 151cases (31%)
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Mortality Rate by Organisms in
low birth weight infants
Gram-positive 905 case 101 deaths (11.2%) CoNS . 606 cases (9.1%)
S aureus 99 cases (17.2%)
GBS 32 cases (21.9%)
All other streptococci 65 cases (10.8%)
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Sepsis Risk Factors
Prematurity
Birth weight
Term 0.1%
1,000 -1,500 g 10%
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Frequent
BloodDrawing??
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Group B streptococcus
(GBS)
Maternal colonization 15 to 40% 50% of infants acquire surface
colonization at delivery
1% of colonized full-term infants developEONS
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GBS
In 1996, GBS guidelines
Incidence declined from 5.9-1.7 per
1,000 in 1992 and 1999 respectively
Emergence of penicillin resistance
among GBS (Japan)
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GBS Guideline
the incidence of infections with
gram-negative bacteria increased
antibiotic resistance among
gram-negative pathogens hasincreased
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Coagulase-Negative
Staphylococci
commonest cause of nosocomial
bacteremiaventriculoperitoneal shunt infection
Endocarditis with umbilical lines
S. epidermidis, S. haemolyticus, S.
hominis, S. saprophyticus,
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Coagulase-NegativeStaphylococci
Sepsis with CoNS is often
indolent
nonspecific symptoms
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Coagulase-negativestaphylococc i
a positive blood culture for CoNS mayrepresent either contamination
26 cases, in only 16 cases were cultures
from two sites positive, and the other 10cases were considered to represent
contamination
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Coagulase-negative
staphylococc i
Studies have shown that initial
therapy of suspected LONS withnafcillin oroxacillin and an
aminoglycoside,rather than
vancomycin did not changeoutcome (decrease resistance)
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Staphylococcus aureus
Less commonly seen
S. aureus strains remainedsensitive to extended-
spectrum penicillins(oxacillin or nafcillin)
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Gram Negative bacteria
Klebsiella pneumoniae in our area
E. coliin united states Increase in incidence
Multiresistance
Invasion of CNS, Citrobacter koseri
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Gram Negative
P. aeruginosa
conjunctivitis
systemic disease high mortality
Haemophilus influenzae.
Non typeable
Fulminant, simulating RDS.
Mortality 90%
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Antibiotics
Resistance
Induced by antibiotic pressure
(over use)
Broad-spectrum cephalosporin
induce chromosomal ESBLs ingram-negative bacilli
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Antibiotics
Resistance
Ampicillin and Amikacin for empiric
treatment of EONS Oxacillin and amikacin for empiric
treatment of LONS reduce
colonization with resistant gram-negative bacilli from 32 to 11%
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Practical points
LP should be done in evaluation of sepsis
even with negative blood culture Urine culture is not part of work up for
EOS
Vesicoureteral reflux was present in 14%of VLBW infants with UTI.
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Conclusions
Gram negative organism is becoming
more common worldwide GBS is not common in our area
Multi-resistance organism mandate
different approaches for N. sepsistreatment
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Conclusions
CRP can help in early discontinuation of
antibiotics New Diagnostic Technology will play role
in both
Early diagnosis and treatment Restrict antibiotics over use