Post on 30-May-2018
8/14/2019 Early-onset sepsis :clinical and laboratory challenge
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Ear ly -onse t sepsis :cl in ica l a nd
la bo ra tory c hal le ng e
By
Shadia El Sallab
Prof. of pediatrics
Mansoura
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A pretem baby 34w
gestation,1.5 kgPresented 4h after birth with severe R.D
What is your diagnosis ?
RDS
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Baby put on ventilator
Given surfactant
with clinical deterioration
x-ray was repeated
A 2nd dose of surfactant wasgiven
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6h later , as there is no clinicalimprovement
A sepsis work-up was doneThe diagnosis is changed toprobably
EARLY-ONSET PNEUMONIA
Antibiotics was instituted , but the babydeteriorated with poor perfusion andhypotension & Death occurs at 24 h of life
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WHAT IS EARLY-
ONSET SEPSIS
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Definition of early –onset sepsis
Sepsis appearing within 72 h of life
50% appear within 6h. of birth , 85% within
24h.
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Causative organisms:
EOS is usually due to organisms transmittedfrom mother to baby
GBS & gram-ve enteric organisms(predominantly E.Coli) accounts for 70% of early-onset sepsis
H.influenza , klebsiella
Listeria monocytogenes ,Enterococci ,Staph.
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Clinical presentation
Most neonates with early onset sepsis presents withrespiratory distress (fulminant pneumonia):90%
Temperature instability ,Poor perfusion ,hypotensionand shock
Meningitis is very rare
Mortality rate even with treatment is 15-50%
Sometimes ,the signs and symptoms areinconspicuous and can be easily confused with other non-infective causes :
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D.D. of EOS
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s y m p t o m a t i c n e w b o r n s a t b i r t h w i t h r i s k
f a c t o r s
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3groups
1-asymtomatic babies with maternal risk factors
2- symptomatic babies at or shortly after birth
3-babies with equivocal signs and symptoms;suspected infection
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In view of the potentially serious outcome
associated with delayed treatment and thedifficulty in distinguishing infected from
non-infected cases, it has becomecommon practice to prescribe antibiotics for :
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So the current practice is characterized byfrequent antibiotic treatment despite low
incidence of true infection
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Why empiric antibiotic therapy is dangerous ?
The high prevalence of unnecessary antibiotic therapyaugments the risk of emerging resistant bacterialstrains
Prolonged duration of initial empiric antibiotic therapy> 5days started in in the 1st 3days of life is associatedwith increased rate of NEC& death for extremely low
birth weight and should be used with caution .(a retrospective cohort study by COTTON et al .pediatrics(January 2009 )
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Diagnostic challenge
Accurate and timely diagnosis of early –onsetsepsis remains challenging to the clinician andlaboratory as if patient escapes early diagnosisEOS may progress to septic shock
So a test with rapid turnaround time with100% sensitivity,rather than high specificity which allows accuratediagnosis and appropriate antimicrobial treatment or
which allow antibiotics to be safely withheld in non-infected infants,,is desirable
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Sepsis work-UP
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CBC
CDC in 1996 recommended obtaining CBC from allclinically septic & asymtomatic at risk newborns
Total WBCs >.30.000 or <5000/mm3
Absolute neutophil count (ANC) :<1500/mm3
Band /Neutophil ratio (I:T ) >0.2
Thrombocytopenia
Sensitivity & specificity of WBCs in predicting which newbornswould develop sepsis were 41% and 73%respectively
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Limited accuracy of WBCs
large overlap with normal values for WBCs33% of septic infants had normal I:T initially but allseptic infants had abnormal I:T ratio at 12-24h
36% of healthy neonates at 4h of age haveabnormal leukocyte indices
The sensitivity of physical examination andsymptoms is greater than that of I/T ratio or ANC
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Blood culture
Culture –proven sepsis: symptoms of bacterialinfection + positive blood culture
Culture- negative : (blood culture misses 18% of
sepsis)1- probable sepsis :clinical symptoms + host
response
2- possible sepsis :equivocal clinical findings
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Value of Bc in asymptomatic at risk
Non of the babies at risk who remainedasymptomatic had +veblood culture (ortollani et
al 1999)
blood culture did not aid in diagnosis of sepsisamong asymptomatic at risk newborns and
24h of close observation is mandatory
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lumbar puncture
Menigitis is rare & non is asymtomatic
LP is Controversial
L.P. may be postponed or excluded from theevaluation of infant with suspected EOS
Meningitis cannot be diagnosed or excluded
solely on the basis of CNS symptoms and so LPis mandatory in symptomatic EOS
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CRP
Is produced by the liver under the influence of IL-1 &TNF-alpha when inflammation is present. rise begins in 4-6hpeaks at 2-3 days , remain elevated with ongoinginflammation but with resolution they decline rapidly due toshort half life
A single normal value cannot rule out infections becausethe sampling may have preceded the rise in CRP, serialdetermination are therefore indicated at 12,24 &48h
(Benitz et al 1998)
3 serial CRP had sensitivity of 97.8% & specificity of 98% for proven or probable sepsis
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Value of CRP
2 CRP under 10mg/l 24hs apart make sepsishighly unlikely
False positive rate of 8% is found in healthy
neonatesCRP is a valuable adjuncts1. in the diagnosis of sepsis ,
2. In monitoring the response to treatment
3. guiding the duration of treatment
NPV is 97-99% so can be used to determinewhen antibiotics can be safely discontinued
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New markers
Many new markers,including cytokines andcell surface markers have been suggested toimprove decision making ,but the clinical
efficacy of these techniques remain uncertainand combination of markers will ensuregreater diagnostic accuracy
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cytokines
IL-6 and TNF-alpha :Giardian&collegues: European j.ped.149:1990
when both tests are positive ,the diagnosis of neonatal sepsis is almost certain.
sensitivity is 60% ,specificity is 100%Ng (2004 )
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:
IL-6&CRP:Buck& co-workers : ped.93,1990:
The combination of both may be helpful in earlydiagnosis of sepsis while awaiting for cultureresults
G-CSFRussel et al BR.j.Hematology 86 1994
Infected newborns had a much peak conc.thannon-infected infants
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G-CSF and IL-8(Fisher et al. intensive care medicine 2002)
High level is associated with likely sepsis
Tracheal aspirate levels of G-CSF(Fisher et al :lancet 1998)
Used to diagnose localized lung infection aslocalized infections cannot be diagnosed onbasis of blood- derived cytokines
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A study comparing CRP, TNF receptors andsoluble adhesion molecules (ICAM-1,E-Selectin)Hench&et al(j.clinical epidemiology December2001)
concluded thatCRP was the best simple test to predict sepsis
Diagnostic accuracy was improved by combiningIL-6 to CRP whereas the other parameters addedno further diagnostic information
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IL-6 and IL-10(Ehab khairy et al , egyptian j.of neonatology vol 8,,may 2007)
(Ng et at al(2003) archives of disease in , fetal & neonataled.88:F209)
Early estimation of IL-6 & IL-10 in neonates withsuspected sepsis is of diagnostic value and
increased IL-6/IL-10 ratio is correlated with poor outcome and with prolonged hospital stay
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CRP,IL-6,and Procalcitonin
(Chiesa et al,clinical chemisty 2003,49:60-68)
Increased levels in the presence of bacterialinfections and that the increase isindependent of illness severity
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cell surface markers
Surface neutophil CD11 (Ng 2004)
Has been shown to be an excellent marker of early infection that correlates well with CRP
but peaks earlier Surface neutrophil CD64 (Safaa Meneza et al .thesis
2009):
Was found as useful marker to differentiateinfectious from non-infectious causes of RD
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In most tests ,evaluation of the results havebeen conflicting and the results of diagnostic
tests must be evaluated in the light of clinicalcondition of the baby
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conclusion
In all symptomatic cases ,start empiric antibiotictherapy &-ve WBCs &CRP screen do not overrulesymptoms
Asymtomatic at risk of EOS : WBCs &CRPat 12, 24 & 48h of age
-ve diagnostic screen : clinical observation
+ve diagnostic screen empiric antibiotictherapy for 48-72h pending -ve blood culture
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THANK
YOU