SEPTICEMIA NEONATAL MGV MAIO 2007 Martha V. Gonçalves Hospital Regional da Asa Sul/SES/DF .
Neonatal Septicemia - Diagnostic Dilemma
Transcript of Neonatal Septicemia - Diagnostic Dilemma
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Neonatal Septicemia - Diagnostic Dilemma
Dr.Ravikumar ChodavarapuM.B.B.S, D.C.H, D.N.B (Pediatrics), F.I.A.P (Nephrology)
Professor & HOD (emeritus)
Department of Pediatrics
Kakatiya Medical College & M.G.M.Hospital
Warangal
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Antibiotic Use or Overuse?
Presumptive treatment with antibacterials iscommon leading to over treatment of about
11 to 23 non-infected newborns for every one with
proven sepsis
Antibiotic therapy is associated with side-effects,alteration of normal flora, development of
resistant bacteria, medication errors, intravenousinfiltrates, financial and emotional cost to parentsand emotional cost to baby.
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To rationalize antibiotic usediagnostic strategy has its primary goals
To identify and treat all septic neonates.
To limit the duration of treatment forbabies who are quickly determined not tobe infected.
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Perinatal Risk factors for neonatal sepsis
Conditions Incidence of proven sepsis______ PROM >18 hours 1%
Maternal + GBS (preprophylaxis era) 0.5%1%
Maternal + GBS (in prophylaxis era) 0.2%0.4%
Maternal + GBS and PROM, fever or preterm 4%7%
Chorioamnionitis 3%8%
+GBS and chorioamnionitis 6%20%
PROM + preterm 4%6%
PROM + low Apgar score (5 minute
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Risk factors from perinatal history Help manageasymptomatic infants
Objectives.
Low risk may receive routine newborncare;
Medium-risk infants should be carefullyobserved under a specific protocol;
Highest risk babies should receive empiricantibiotic treatment pending cultureresults and clinical course.
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Symptomatic Septicemia(EOS)
Incidence of neonatal sepsis or bacteremia inasymptomatic infants is low, but not negligible.
Over 90% of neonates with sepsis have at leastone symptom, and the majority has three or more
symptoms.Over 90% of early onset septic neonates present
with symptoms in the first 24 hours of life, withthe remainder presenting before 48 hours.
So, careful observation for symptoms in the first48 hours of life is the most important aspect in adiagnostic strategy for neonatal sepsis.
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Signs and symptoms of sepsis include:
Respiratory distress or grunting, apnea.
Cyanotic spells, persistent pulmonary hypertension, poorperfusion or shock.
Lethargy or irritability, hypotonia, seizures.
Vomiting, poor feeding activity.
Petechiae or purpura, unexplained jaundice.
Fever or hypothermia.
Hypo- or hyperglycemia, acidosis.
Most important, not looking well
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Predictive clinical signs for the diagnosis of late onset neonatal septicemia in aprospective fashion; S. Amuchou Singh1, Sourabh Dutta1 and Anil Narang
Journal of Tropical Pediatrics 2003 49(4):235-239
Occurrence of 16 pre-defined clinical signs monitored
Symptomatic episodes (105 episodes in 80 neonates) were investigated forsepsis. Diagnosed as definite sepsis (n = 30), most probable sepsis (n = 17), and no
sepsis (n = 58).
Seven clinical signs (grunting, abdominal distension, increased pre-feedaspirates, tachycardia, hyperthermia, chest retractions, and lethargy) had
positive likelihood ratios (PLR) greater than 1, and were combined to make acomposite score. When a weighted clinical score (WCS) was used to diagnose
Definite sepsis - a cut-off score of 2 gave the best positive predictive value(PPV) and PLR (52 per cent and 2.65, respectively), anda cut-off score of 1 gave the best negative predictive value (NPV) and negative
likelihood ratio (NLR) (85 per cent and 0.44, respectively). Definite and/or probable sepsis - A cut-off score of 2 had a PPV of 65 per cent. In conclusion, physicians who attempt to make a diagnosis of neonatal sepsis
on purely clinical grounds can use a seven-item weighted clinical score.
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Adjunctive tests for diagnosing neonatal sepsis
White blood cell (WBC) and differential counts
C-reactive protein (CRP) Mini-ESR (Erythrocyte sedimentation rate) Endotoxin Haptoglobin Acridine orange stain Fibronectin Nitro blue tetrazolium (NBT) test
Orosomucoid Soluble interleukin (SIL)-2 receptor Elastase alpha-1-proteinase inhibitor complex Interleukin 6 C3d Neutrophil CD11b Granulocyte-colony stimulating factor (CSF) Procalcitonin Bacterial polymerase chain factor (PCR) Inter-alpha-inhibitor proteins Interleukin 8 Tumor necrosis factor B
P di i l f dj i di i
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Predictive values of adjunctive diagnostic tests
Sensitivity(%) Specificity(%) PPV(%) NPV(%)______________________________________________________________________________________ TLC 1.0 mg/dL
(Screen + if 2/3 are abnormal)
Cord blood (Premature)IL-6 96 95IL-8 87 94
7 Weighted clinical score 52-65 85Cut-off score 2 Cut-off score 1
Blood Culture 50-80
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Poor specificity of CRP
Inflammatory response without having
proven infection such as
maternal fever,
prolonged rupture of membranes,
fetal distress or stressful delivery,
perinatal asphyxia,
intraventricular hemorrhage,meconium aspiration
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White blood cell count and related indicesNon-infectious influences
Neutropenia - Maternal hypertension, PIH & Preeclampsia(does not alter I/T ratio) and perinatal asphyxia.
I/T ratio elevated - asphyxia, maternal fever, or stressfullabor.
Total WBC can be higher in capillary than in arterial orvenous specimens.
Increased ANC and IG count - antenatal steroids.
Elevated IG counts might be a nonspecific response tophysiologic stresses associated with prematurity.
Inter-observer variability is also significant in the subjectivedifferentiation of immature from mature neutrophil forms.
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Performance of an Automated Immature
Granulocyte Count as a Predictor of Neonatal SepsisAm J Clin Pathol. 2005; 123 (4): 618-624. 2005 American
Society for Clinical PathologyA total of 233 blood cultures were obtained from 181infants. 121 blood cultures from 110 term infants and 112blood cultures from 71 preterm infants, ranging in
postnatal age from 0 to 253 days, with a median age of 8days on the day a blood culture sample was obtained.
A 1.7% (2/121) positive blood culture rate in term infants
A 0% (0/13) positive blood culture rate in preterm
neutropenic infantsA 0% (0/44) positive blood culture rate in preterm
nonneutropenic infants 7 days or younger
A 38% (21/55) positive blood culture rate in pretermnonneutropenic infants older than 7 days.
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White blood cell count and related indicesManual Vs Automated
Elevated IG counts by either method seemto be rather poor predictors of sepsis.
Perhaps their greatest use in this clinicalcontext is the negative predictive valueassociated with the absence of IGs inmanual differential counts or automated
values less than 0.5%.
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Timing of the sepsis screens should be taken intoconsideration.
WBC indices in the septic infant may be normal at the timeof initial evaluation but abnormal 4 to 12 hours later.
A commonly observed pattern in a non-infected infant bornfrom a stressful labor and delivery shows an elevation ofWBC or I/T at 12 hours of age with a normal CRP, and anincrease in CRP at 24 to 48 hours of age but withnormalizing WBC indices.
Most infants with sepsis have progressively abnormal WBCindices and CRP.
Obtaining a sepsis screen at birth in asymptomaticneonates is not useful.
An initial screen in an asymptomatic patient is
obtained at 12 to 24 hours of age
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Sepsis screen (screen positive if 2 points)
Test Point value____________________________________________________________ Absolute neutrophil count
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Is Blood culture a Gold standard?
Data from the era before widespread prophylactic antibiotic use inlaboring mothers show that even in neonates sick enough to die, only80% of autopsy proven sepsis was diagnosed by premortem bloodcultures.
Likewise, only 50% of neonates with bacterial pneumonia diagnosedclinically and by tracheal aspirate cultures had positive blood cultures
Blood culture positive for bacteria, is only 50-80% at best.(Jeffrey S. Gerdes. Diagnosis and management of bacterial infections in the neonate. Pediatr Clin NAm 2004;51:939-959)
Currently, the increased use of maternal antibiotics has furtherreduced the rate of positive blood cultures in early-onset sepsis; as fewas 2.7% of neonates with clinical sepsis may have positive bloodcultures.
A positive blood culture with a pathogenic organism is diagnostic ofneonatal sepsis; however, a negative blood culture in no way rules outthe disease.
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Blood culture procedure & time
Sterile 0.5 mL to 1.0 mL of blood, placed in a standardtryptic soy broth culture bottle, is a standard microbiologictechnique.
The culture is incubated for up to 5 days, although themodern culture systems will identify almost all early-onsetneonatal pathogens within 48 hours.
Computer assisted continuous read culture systems mostblood cultures will be positive within 24-36 hours ofincubation if organisms are present.
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Negative blood culture results owing to
Partial treatment from maternal antibiotics,
Bacteremia may be transient in the earlystages of disease, and
Small blood volume typically taken frominfants for culture may be insufficient todetect low bacterial-density sepsis in infants
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M.G.M.H neonatology unit February to December 2005
Number of blood cultures/samples 55
Culture positive 45.5%
Culture negative 54.5%Staphylococci 48%
Klebsiella species 36%
E.coli 20%Pseudomonas 4%
A tibi ti St h Kl b i ll E C li P d
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Antibiotic Staphy-
lococci
S R
Klebsiella
S R
E.Coli
S R
Pseudo-monas
S R
Erythromy 2 6 - - -
Ampicill 1 1 - - -
Amoxicill - 4 - - -
Gentamyc 1 - 1 4 - 2 -
Amikacin 7 2 4 3 2 3 1 -
Ciproflox 2 5 6 - 2 2 1 -
Cefotaxim - 4 2 1 1 2 - 1
Ceftazidim 1 4 3 3 - -
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Lumbar puncture
An unpublished meta-analysis by Gerdes of these studies
found that one would need to perform between 1000 and2000 lumbar punctures to find one case of meningitis inneonates without symptoms of meningitis and with anegative blood culture.
C.S.F evaluation is required in neonates with
Symptoms of meningitis (lethargy, hypo- or hypertonia,seizures, apnea, excessive irritability, bulging fontanelle, orseptic shock)
Symptomatic babies in whom sepsis is the leading diagnosis
In babies with a positive blood culture.
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CSF bacterial cultures are very reliable in the absence ofpretreatment
As CSF infection tends to have highbacterial density
There are fewer interfering proteins thanare found in blood
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CSF cells & biochemistry
Interpretation of CSF cell counts and chemical analyses isdifficult.
The upper limit of the mean 2 standard deviations CSFcell count in term neonates is 25 cells/mm3, but white
blood cell counts up to 32/mm3 may be found inuninfected neonates.
At the low end, however, up to 30% of neonates with GBSmeningitis may have normal CSF counts below this upperlimit.
Glucose and protein concentrations are rarely useful, dueto wide normal ranges (24 to 119 mg/dL for glucose, and20 to 170 mg/dL for protein).
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Urine culture
Sterilely acquired bladder tap or catheterizedspecimens minimize false-positive cultures, but
they are difficult to obtain in the low-urine state ofthe newborn infant, and there is a very low yieldin the first 72 hours of life.
Therefore, a urine culture is not suggested as partof the work-up for early onset disease.
D i f b i l i
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Detection of bacterial antigens
Latex particle agglutination (LPA) test forGBS in urine has sensitivity as low as 67% and apositive predictive value of only 56%.
So there does not appear to be a place for urinebacterial antigen tests in the routine evaluation ofpotentially septic infants.
The LPA test for GBS and E.coli K1 may be useful,however, in CSF from patients with partiallytreated meningitis.