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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