Early-onset sepsis :clinical and laboratory challenge

8/14/2019 Early-onset sepsis :clinical and laboratory challenge

http://slidepdf.com/reader/full/early-onset-sepsis-clinical-and-laboratory-challenge 1/34

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



A pretem baby 34w

gestation,1.5 kgPresented 4h after birth with severe R.D

What is your diagnosis ?

RDS



Baby put on ventilator

Given surfactant

with clinical deterioration

x-ray was repeated

A 2nd dose of surfactant wasgiven



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



WHAT IS EARLY-

ONSET SEPSIS



Definition of early –onset sepsis

Sepsis appearing within 72 h of life

50% appear within 6h. of birth , 85% within

24h.



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.



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 :



D.D. of EOS



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



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



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 :



So the current practice is characterized byfrequent antibiotic treatment despite low

incidence of true infection



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 )



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



Sepsis work-UP



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



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



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



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



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



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



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



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



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 )



:

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



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



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



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



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



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



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



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



THANK

YOU

Documents

Early-onset sepsis :clinical and laboratory challenge