An Overview of Neonatal Sepsis

Dr.M.Mizanur RahmanNeonatal and Pediatric Specialist

King Khaled Civilian HospitalTabuk, Saudi Arabia

BackgroundNeonatal sepsis is one of the leading problem

of neonatal death, causes the neonatal morbidity and mortality.

The incidences of neonatal death due to neonatal sepsis varies from 3 – 14 per 1000 newborns.

It is higher in preterm babies(up to 26 per 1000 live babies).

Incidence is even higher in the underdeveloped countries like Bangladesh, where the proper treatment facility is not sufficient

DefinitionNeonatal sepsis is a clinical syndrome of

systemic illness accompanied by bacteremia in the first 28 day’s of life.

Early Onset Sepsis (EOS):Culture proven infection within the first 72

hours of life85% present within 24 hrs ,5% present in

between 24-48 hrs, a small % present in between 48-72 hrs.

Late Onset Sepsis (LOS):Culture proven infection after 72 hours of life

Etiology Infectious agents associated with neonatal sepsis

have changed since the mid-20th century1950 - S. aurus, E. coli; later s. aurus replaced by GBS1990 – GBS and E .coliNow – coagulase-negative S. epidamis frequently

observedCan also be caused by adenovirus, enterovirus,

coxsakie virus.Gonorrhea, syphilis, herpes simplex virus, CMV,

hepatitis, HIV, TORCH infection have also been implicated in neonatal infection.

Early-onset SepsisAssociated with acquisition of microorganisms

from the mother – transplacental infection or ascending infection

Onset is most rapid in premature neonatesGBS, E. coli, Coagulase-negative Staphylococcus,

Stepto coccus , H. influenzae, L. monocytogenes are common pathogens.

In Bangladesh context Klebsiella, Pseudomonas, E.coli, Acinobactor are commonPneumonia is more common in early-onset sepsis

Risk Factors of Early-onset SepsisMaternal GBS colonization (especially

if untreated during labor)Premature rupture of membranes

(PROM)Prolonged rupture of membranesPrematurityMaternal urinary tract infectionChorioamnionitis

AcinetobacterKlebsiellaE coliSerratiaPseudomonasS. aureusEnterobacterCandidaGBSAnaerobesCoagulase negetive staphilococcus

Etiology of Late-onset Sepsis

Meningitis and bacteremia are more common in late-onset sepsis

Risk Factors of Late-onset Sepsis

PrematurityCentral venous catheterization

(duration >10 days)Nasal cannula or continuous positive airway

pressure (CPAP)H 2 -receptor blocker or proton pump inhibitor

(PPI)GI tract pathology

Numerous host factors in Neonatal sepsis

Cellular immunity Humeral immunity Complement factors And other Barrier function

Clinical ExaminationClinical signs of neonatal sepsis are nonspecific

and are associated with Characteristics of the causative organism Body’s response to the invasion.

These nonspecific clinical signs are also associated with other neonatal diseasesRespiratory distress syndrome (RDS)Metabolic disordersIntracranial hemorrhageTraumatic delivery

Clinical SymptomsCommon /Non-specific

Respiratory distress (90%) - RR, apnea (55%), hypoxia/vent need (36%), flaring/gruntingTemperature instability, feeding problemsLethargy-irritability (23%)Gastrointestinal – poor feeding, vomiting, abdominal distention, ileus, diarrheaColor—Jaundice, pallor, mottlingHypo- or hyperglycemia,MetabolicacidosisCardiovascular – Hypotension (5%), hypo perfusion, tachycardia,overt shock with pallor & odema.This late signs of shock are indicative of severe compromise & strongly associated with mortality

NICHD data

Less comSeizureDICPetechiaeHepatosplenomegalySclerema

Meningitis symptomsBuiging anterior frontaneleIrritability, lethargy, poorly responsiveChanges in muscle tone, etc.

Differential DiagnosesBowel Obstruction in the Newborn Congenital PneumoniaHeart Failure, Congestive Hemolytic Disease of Newborn Meconium Aspiration Syndrme Necrotizing Enterocolitis Pediatric Congenital Diaphragmatic

Hernia Pediatric Infective Pericarditis Pulmonary Hypoplasia Imaging Respiratory Distress Syndrome

Approach ConsiderationsComplete blood count (CBC) and differentialBlood cultureQuantity measurement of CRP and possibly other

infection markersIn some cases, serial CBC and CRP studies may be

appropriateGram stain provides early identification of the

gram-negative or gram-positive status of the organism for preliminary identification

CSF analysis and culture

Approach Considerations contd…Emerging technology using PCR could eventually

help achieve faster identification of causative organism. Rapid pathogen detection with multiplex PCR may facilitate more timely selection of targeted antibiotic therapy while limiting exposure to broad-spectrum antibiotics

Imaging studies may include:Chest radiography to evaluate pulmonary

involvementCT scan, MRI and ultrasonography of the head in

cases of meningitis

Results “Trigger Points” CBC

WBC <5.0, or > 22.0, abs neutro <1,750, bands >2.0

I/T ratio > 0.2*Platelets < 100,000

CRP > 1.0 mg/dlCSF > 20 WBC’s with few or no RBC’s Radiographs: infiltrates on CXR, ileus on

KUB, periosteal elevation, etc.

Treatment & ManagementWhen neonatal sepsis is suspected, treatment should

be initiated immediately because of the neonate’s relative immunosuppression

Begin antibiotics as soon as diagnostic tests are performed

Cardiopulmonary support and parenteral nutrition may be required during the acute phase of the illness until the infant’s condition stabilizes

Monitoring BP & vital signs, HCT, platelets, and coagulation studies is vital

Not uncommonly, blood product transfusion, including packed red blood cells, platelets and FFP are indicated

Treatment & Management contd…Infant with temperature instability needs

thermoregulatory support with a radiant warmer or incubator. Once the infant is stable from a cardiopulmonary point, parental contact is important, kangaroo management can be applicable in this regard

Surgical consultation for central line placement may be necessary in infants who require prolonged IV antimicrobial therapy

If an abscess is present, surgical drainage may be necessary; IV antibiotic therapy cannot adequately penetrate an abscess, and antibiotic treatment alone is ineffective

Treatment & Management contd…The infant may require transfer to a level III

perinatal center, especially if he or she requires cardiopulmonary support, parenteral nutrition, or prolonged IV access. The multidisciplinary services available at larger centers may be necessary if the neonate’s condition is acutely compromised

Additional therapies can be apply for the treatment of neonatal sepsis, including granulocyte transfusion, IVIg infusion, exchange transfusion, and the use of recombinant cytokines

Antibiotic TherapyIn the United States and Canada, the current

approach to the treatment of early-onset neonatal sepsis includes combined IV aminoglycoside and expanded-spectrum penicillin antibiotic therapy

The specific antibiotics to be used are chosen on the basis of maternal history and prevalent trends of organism colonization and antibiotic susceptibility in individual nurseries

Antibiotic Therapy contd…If an infection appears to be nosocomial (late-onset sepsis), antibiotic coverage should be directed at organisms implicated in hospital-acquired infections, including S. aureus, S epidermidis, and pseudomenous sp.

Vancomycin has been favored for this coverage; however, concern exists that overuse of this drug may lead to vancomycin-resistant organisms, For this reason, some clinicians prefer oxacillin therapy in this setting.

Antibiotic Therapy contd…Cephalosporins are attractive in the treatment of nosocomial infection because lack of dose-related toxicity and ability to reach adequate serum and CSF concentrations; however, their use has led to resistance in gram-negative organisms. Ceftriaxone displaces bilirubin from serum albumin and should be used with caution in infants with significant hyperbilirubinemia

Aminoglycosides and vancomycin both have the potential to produce ototoxicity and nephrotoxicity and should therefore be used with caution

PrognosisMortality from neonatal sepsis may be as high as 50%

for infants who are not treated. Low birth weight and gram-negative infection are

associated with adverse outcomes.In preterm infants who have had sepsis, impaired

neurodevelopment is a concern.Residual neurologic damage occurs in 15-30% of

neonates with septic meningitis.preterm infants with sepsis who did not have meningitis

had higher rates of cognitive deficits, cerebral palsy, and other neuro developmental disabilities than infants who did not have sepsis.

Infants with meningitis may acquire hydrocephalus or periventricular leukomalacia. They may also have complications associated with the use of aminoglycosides, such as hearing loss or nephrotoxicity.

Long time -Follow UpFollow up- The primary care provider (PCP) should evaluate

the infant with neonatal sepsis within 1 week of discharge from the hospital.1st week, Then Two weekly up to 3 Month

Monthly up to 18 month If need to continue

The PCP should evaluate growth and determine whether the feeding regimen and activity have returned to normal.

ROP Screening,Hearing test- audiology test, audio screenRSV prophylaxisNeonatal sepsis is associated with meningitis, prolong hypoxia,

ECMO therapy or brain abscess should be folowed for several yrs,

PreventionHAND-WASHING- the gold slandered measure for

prevention Aseptic precaution during examination For GBS antibiotic treatment & prophylaxis during labor

and deliveryPediatrician especially neonatologist all over the world continuously pay great attention to the

unsolved questions of new born babies with sepsis, to

reduce neonatal morbidity & mortality of this contingent of babies, hope to reduce to single digit.

THANK YOU