PERINATAL INFECTION

FOR C- 1
Infections in the Newborn
The fetus and the newborn are very susceptible to
infections.
There are three major routes of perinatal infection.
Blood borne transplacental infection( e.g., CMV,
rubella, syphilis)
Ascending infection ( e.g., bacterial infections after
12-18 hours of ruptured membranes)
Infection on passage through an infected blood at
delivery ( e.g., herpes simplex, hepatitis B, HIV,
bacterial infections).
 Intrauterine infection
• Transplacental infection may occur at any time during
gestation
• The signs & symptoms may be present at birth or delayed for
months or years.
• The timing of infection during gestation affects the outcome.
• 1st trimester infection may alter embryogenesis, with
resulting congenital malformations (congenital rubella)
• 3rd trimester infection often results in active infection at the
time of delivery (toxoplasmosis, syphilis) and
• Infections that occur late in gestation may lead to a delay in
clinical manifestations until some time after birth (syphilis).
 Intrauterine infection
• Effect
• no evidence of damage
• subclinical infection without evidence of damage
• abortion
• fetal death
• stillbirth
• death in infancy
• intrauterine growth retardation (IUGR) resulting in low
birth weight (LBW)
• congenital defects
• late onset of congenital disease or defects
 Intrauterine & Perinatal Infection

Diagnosed in utero
Parvovirus B19

Manifest at Birth
Toxoplasma gondii
Cytomegalovirus Varicella/Zoster
Rubella
Treponema pallidum
hepatitis C
 Intrauterine & Perinatal
Infection
Acquired around the time of birth and symptomatic
later
Herpes simplex
hepatitis B/C
HIV
Group B  haemolytic streptococci
E. coli
Listeria monocytogenes
Chlamydia trachomatis
Neisseria gonorrhoea
 Torch Syndrome
Toxoplasma
Others (Varicella/Zoster & Tr. pallidum
Rubella
CMV
Herpes simplex
Clinical suspicion
• Maternal laboratory results
• Hydrops fetalis
• Microcephaly
• Seizures
• Cataract
• Hearing loss
• Congenital heart disease
• Hepatosplenomegaly
• Jaundice
• Rash
• Thrombocytopenia
Rubella
• Is RNA togavirus
• Rubella (German measles or 3-day measles)
• a mild, often exanthematous disease of infants and children
• Its major clinical significance is transplacental infection and
fetal damage as part of the congenital rubella syndrome
(CRS).
• The pathologic findings for CRS are often severe and may
involve nearly every organ system
• The most distinctive feature of congenital rubella is
chronicity, well beyond delivery (brain)
Timing of infection:
Risk of damage
The most important risk factor for severe congenital
defects is the stage of gestation at the time of
infection
Infection at
• 0-8 weeks 80% detectable defects
• 9-12 weeks 52% detectable defects
• 13-20 weeks 16% ?
• 20+ weeks no increased risk
Rubella: Nature of Damage
SYSTEM PATHOLOGIC FINDINGS Hepatic giant cell transformation
PDA Fibrosis
Pulmonary artery stenosis Liver Lobular disarray
Cardiovascular (PS)
VSD
Bile stasis
Myocarditis Kidney Interstitial nephritis
Chronic meningitis Adrenal
Cortical cytomegaly
Central nervous Parenchymal necrosis gland
system Vasculitis with Malformed osteoid
calcification Bone Poor mineralization of osteoid
Microphthalmia Thinning cartilage
Cataract
Spleen,
Iridocyclitis
Eye lymph Extramedullary hematopoiesis
Ciliary body necrosis
Glaucoma
node
Retinopathy Histiocytic reaction
Thymus
Cochlear hemorrhage Absence of germinal centers
Ear
Endothelial necrosis Skin Erythropoiesis in dermis
Chronic mononuclear
Lung
interstitial pneumonitis
Diagnosis of CRS
• Isolation of virus
• Demonstration of rubella-specific immunoglobulin
M (IgM)
• Infant rubella IgG antibody level that persists at a
higher level and for a longer time(ie, rubella titer
that does not drop at the expected rate of a
twofold dilution per month)
• PCR positive for rubella virus
 Rubella treatment and
prevention
• Supportive Care
• There is no specific treatment available for either
acquired rubella or CRS.

• Routine infant immunisation, now as MMR at 15

months and 4 years
• Routine screening test in pregnancy
• Women who are non-immune are offered vaccine
postnatally
• [pre-conceptual screen, premarital screen]
 Cytomegalovirus
• CMV is the largest of the herpesviruses with a double-
stranded DNA enclosed by an icosahedral capsid
• The most common congenital infection worldwide;
predominantly due to primary maternal infection
• Incidence= 0.2% to 2.2% (avg 1%) of all live births
• The risk for fetal infection is greatest with maternal
primary CMV infection (30%) and much less with
recurrent infection (<1%)
• occasionally causes the syndrome of cytomegalic
inclusion disease
C/M of Congenital CMV
• 90% are asymptomatic at birth, 10 may develop
symptoms(5% mild other 5% severe)
• Includes:
• IUGR
• Microcephaly, hydrocephaly
• periventricular cerebral calcification
• Deafness (10 %), cerebral palsy
• Seizures
• microphthalmia
• chorioretinitis, blindness
• interstitial pneumonia
• petechiae/purpura
• anaemia, jaundice, HSM, lymphadenopathy
Dx of congenital CMV infection
• virus DNA by PCR—definitive diagnosis
• Urine and saliva are the best specimens for culture
and saliva, and cord blood is best for PCR.
• Infants with congenital CMV infection may excrete
CMV in the urine for several years
• Negative IgG result excludes the diagnosis of
congenital CMV infection
• IgM tests ---- unreliable
• Fetal infection can be confirmed by viral isolation from
amniotic fluid
IMAGING
• ultrasonography or computed tomography (CT) of the head
• findings:
Microcephaly
Intracranial calcifications (classically with periventricular
distribution)
Lissencephaly
Polymicrogyria
• CBC-- thrombocytopenia
 Congenital CMV
• Prevention - there is no proven preventive
intervention
• ?screening
• Hygiene

• Treatment
• ganciclovir (6 mg/kg/dose every 12 hr IV for the 1st
6 wk of life)
Congenital toxoplasmosis
Toxoplasma gondii
• Toxoplasma gondii is an obligate intracellular
protozoan
• The cat is the primary host
• Other animals and birds
• Human infection is result from eating undercooked
infected meat or handling infected soil or cat litter
• Transmission to the fetus usually follows acquisition
of infection by an immunologically normal mother
during gestation
Congenital Toxoplasmosis
• Infection may be transmitted to the fetus
transplacentally or during vaginal delivery.
• in the 1st trimester, approximately 17% of fetuses
are infected, usually with severe disease
• for 3rd trimester, approximately 65% of fetuses are
infected, usually is mild or inapparent at birth
Clinical manifestation
• has three general categories of clinical presentation:
1. Subclinical infection
2. Clinically apparent disease observed in the fetus,
neonate, or young infant (10 to 30% newborn)
3. Late sequelae in later infancy, childhood, or adolescence
• Classic triad
• hydrocephalus, intracranial calcification & chorioretinitis
• non-specific signs
• hepatosplenomegaly, jaundice
• thrombocytopenia, anemia
• growth retardation, rash
• Chorioretinitis
• Is he most common and late manifestation
• Occurs in 90 % or more of children with untreated
congenital Toxoplasma infection, regardless of the initial
clinical presentation.
• The peak incidence during the second to third decades
of life
• Symptoms include blurred vision, photophobia,
epiphora, and vision loss.
• The typical lesion is a unilateral
Others
• Microcephaly
• Convulsions
• Psychomotor retardation
• Microphthalmia
• Strabismus
• myocarditis, pneumonitis, nephrotic syndrome
• Jaundice and conjugated hyperbilirubinemia may persist for
months
• CSF abnormalities occur in at least 30% of infants with
congenital toxoplasmosis.
• A CSF protein level of >1 g/dL is characteristic of severe CNS
toxoplasmosis
Diagnosis
• Fetal ultrasound examination, performed every 2 wk
during gestation and PCR analysis of amniotic fluid
are used for prenatal diagnosis
• T. gondii may also be isolated from the placenta at
delivery
• Either persistent or rising titers in the dye test or IFA
test, or a positive IgM-ELISA or IgM-ISAGA result is
diagnostic of congenital toxoplasmosis
• increase in the ratio of specific serum IgG antibody
titer to the total IgG
• head CT scan
• CSF analysis
 Treatment of CT
• All newborns infected with T. gondii should be
treated whether or not they have clinical
manifestations
• Infants should be treated for 1 yr with
• pyrimethamine +
• sulfadiazine +
• Leukovorin
• Prednisone when active chorioretinitis involves
the macula or otherwise threatens vision or the
CSF protein is >1,000 mg/dL at birth
Congenital Syphilis
• Syphilis is a chronic systemic sexually transmitted infection
caused by T. pallidum subspecies pallidum
• Treponema pallidum is a long, motile spirochete with finely
tapered ends belonging to the family Spirochaetaceae
• Congenital syphilis results from transplacental transmission
of spirochetes
• Women with primary and secondary syphilis and
spirochetemia are more likely to transmit infection
• Transmission can occur at any stage of pregnancy.
Clinical Manifestations and Laboratory Findings
• Untreated syphilis during pregnancy has a vertical
transmission rate approaching 100%
• Fetal or perinatal death occurs in 40% of affected infants
• Most infected infants are asymptomatic at birth(2/3)
• symptoms develop within weeks or months
• Clinical manifestations is divided into early and late stages.
• All stages are characterized by a vasculitis, with progression
to necrosis and fibrosis
• The placenta of neonates with congenital syphilis is often
large, thick, and pale
• Early stage
• appear during the first 2 yr of life
• involve multiple organ systems, resulting from
transplacental spirochetemia and are analogous to the
secondary stage of acquired syphilis
• Hepatosplenomegaly, jaundice, and elevated liver
enzymes
• Lymphadenopathy
• Coombs-negative hemolytic anemia
• Thrombocytopenia
• Characteristic osteochondritis and periostitis and
• a mucocutaneous rash
• Central nervous system (CNS) abnormalities,
• failure to thrive,
• chorioretinitis,
• nephritis, and nephrotic syndrome may also be seen.
• gastroenteritis, peritonitis, pancreatitis,
• pneumonia,
• eye involvement (glaucoma and chorioretinitis),
• nonimmune hydrops, and testicular masses
Rash - congenital syphilis
Congenital syphilis

• discrete
macular
lesions similar
to those seen
IN secondary
syphilis
Congenital syphilis
• Interstitial keratitis
• Late manifestations
• appear gradually during the first 2 decades.
• These result primarily from chronic granulomatous
inflammation of bone, teeth, and CNS
• persistent or recurrent periostitis and associated thickening
of the involved bone.
• Dental abnormalities such as Hutchinson teeth
• Saddle nose
• unilateral or bilateral interstitial keratitis and the Clutton
joint
• Soft tissue gummas
• Eighth nerve deafness
• Juvenile paresis- Latent meningovascular infection;
typically occurs during adolescence with behavioral
changes, focal seizures, or loss of intellectual function
• Juvenile tabes- Rare spinal cord involvement and
cardiovascular involvement with aortitis
• Hutchinson triad
• Hutchinson teeth,
• interstitial keratitis, and
• 8th nerve deafness
• choroiditis, retinitis, vascular occlusion, and
optic atrophy.
LABORATORY EVALAUTION
• CBC– leukocytosis/leukopenia, anemia and thrombocytopenia
• Coombs test--- non immune hemolytic anemia
• Liver enzyme and bilirubin
• Urinalysis
• Long bone x-ray
• CXR
• CSF analysis including VDRL
• Non- treponemal test---- VDRL and RPR
• Treponemal test----- FTA-ABS, MHA-TP, TP-PA, TP-EIA
• fluorescent antitreponemal antibody staining
• Darkfield microscopy
Approach
• Infant with positive non treponemal test, further
detailed work up is necessary if:
• Abnormal physical finding or
• Titer > 4x maternal
• Inadequate maternal treatment defined as:
1. Not treated or treat inadequately or not documented
2. Treated with non-pencilline regimen
3. received treatment with completion up to 4 weeks
prior to delivery
CDC surveillance case definition for congenital syphilis*
Probable
• Infant whose mother had untreated or inadequately • treated syphilis at
delivery, regardless of signs in the infant, or
• Infant or child who has a reactive treponemal test for syphilis and any one of
the following:
- Any evidence of congenital syphilis on physical examination:
> For children 0 to 2 years: Hepatosplenomegaly, rash, condyloma
lata, snuffles, jaundice, pseudoparalysis, edema
> For children >2 years: Interstitial keratitis, sensorineural hearing
loss, "saber shins" , frontal bossing, Hutchinson teeth , mulberry
molars , saddle nose, rhagades , Clutton joints
- Any evidence of congenital syphilis on radiographs of long bones
- A reactive cerebrospinal fluid (CSF) venereal disease research laboratory
(VDRL) test
- An elevated CSF cell count or protein (without other cause)
Confirmed
• Case that is laboratory confirmed

Laboratory criteria for diagnosis

• Demonstration of Treponema pallidum by darkfield
microscopy, fluorescent antibody, or other specific stains in
specimens from lesions, placenta, umbilical cord, or autopsy
material
Treatment
• Neonates congenital syphilis should be treated
either with:
1. aqueous penicillin for a total of 10 days; or
2. procaine penicillin for 10 days.
• If normal physical examination (asymptomatic) and
VDRL titers < 4x maternal titer and whose mother
not adequately treated a single dose of benzathine
penicillin G IM.
• If asymptomatic and VDRL titers < 4x maternal titer
and whose mother adequately treated a single
dose of benzathine penicillin G IM OR no
treatment.
Varicella zoster virus
• VZV is a neurotropic human herpesvirus with
similarities to herpes simplex virus
• Cause for varicella (chickenpox) and herpes zoster
(shingles)
• Infection in the first 20 weeks may result in the
congenital varicella syndrome
• The risk of CVS with chickenpox in the first 20 weeks
is approx. 2%
• Acute varicella in the time period from 2 days before
to 5 days after delivery is associated with a high risk
of severe disseminated varicella in the newborn
Varicella zoster
• The congenital varicella syndrome is characterized by
• cicatricial skin scarring in a zoster-like distribution,
• limb hypoplasia,
• neurologic (e.g., microcephaly, cortical atrophy, seizures, and
mental retardation),
• eye (e.g., chorioretinitis, microphthalmia, and cataracts),
• renal (e.g., hydroureter and hydronephrosis) and
• autonomic nervous system abnormalities (neurogenic bladder,
swallowing dysfunction, and aspiration pneumonia).
• The diagnosis of VZV fetopathy is based mainly on the
history of gestational varicella combined with the
presence of characteristic abnormalities in the newborn
infant
Varicella zoster: Prevention
• because the damage caused by fetal VZV infection
does not progress in the postpartum period,
antiviral treatment of infants with congenital VZV
syndrome is not indicated
• Specific VZ immunoglobulin if administered within
96 hours of exposure will usually modify the
illness
• If administered up to 9 days there may be
attenuation
Varicella zoster: Prevention
• The principal reason for VZIG administration in
pregnancy is to modify the illness in the mother
• there is little evidence that it will influence the
development of the congenital varicella syndrome

• If a mother has chickenpox in the time period 2

days before to 5 days after delivery, the infant
should be given VZIG and carefully observed
• if any lesions develop, iv aciclovir should be given
CONGENITAL Herpes Simplex Virus (HSV)
• HSV is is a member of the Herpesviridae family of
viruses.
• It is a enveloped double-stranded linear DNA virus
• Two types: type 1 and type 2
• Incidence
• Occur 1/3000-20,000 live births
• neonatal HSV accounts for 0.2 percent of neonatal
hospitalizations in USA
• 75% HSV II
• Transmission
• Three rout of transmisson: intrauterine, perinatal and
postnatal
• 5-8% transplacental (congenital)
• 85-90% perinatally– during delivery
• Primary infection (risk 30-50%)
• Secondary infection (risk <5%)
• Impossible to distinguish 1o vs 2o
• 5-10% postnatally– from caretaker
 Clinical manifestation
INTRAUTERINE HSV
• hydrops fetalis, and fetal in utero demise.
• triad of skin vesicles, ulcerations, or scarring; eye
damage; and severe CNS manifestations, including
microcephaly or hydranencephaly
NEONATAL HSV
• may be classified into three main categories :
1. localized skin, eye, and mouth (SEM);
2. central nervous system (CNS) with or without SEM;
3. disseminated disease, which may involve the CNS and
SEM in addition to other organs
1. Disseminated Disease--- 1/4
• Multi-organ involvement including liver, CNS, skin, eye,
adrenal
• Sepsis syndrome, DIC
• Liver, CNS (60 to 75 %), lung predominance
• Severe liver & CNS dysfunction common
• Wide temp variations characteristic
• > 80 % mortality without treatment
2. Localized Central Nervous System Disease– 1/3
• Presnt in two to three weeks
• Seizures common, lethargy, irritability, temp instability, …
3. Disease localized to the skin, eye and mouth --- occur in 45 % of
cases
• Vesicles, cloudy cornea, conjunctivitis, ulcers
• Occur in first 2 weeks but up to 6 weeks
• Without treatment can progress to cns or disseminated
HSV Diagnosis
• High index of suspicion
• History ±
• Age (1-4 weeks)
• Sepsis Syndrome unresponsive to antibiotic therapy
• PE - classic vesicular lesions
• Culture - readily grows within 1-3 days
• Mouth, nasopharynx, conjunctivae rectum -- swabs >48 hours of age
• Skin vesicles, urine, stool, blood and CSF
 PCR - diagnostic method of choice - best on CSF, other fluids possible
• CSF pleocytosis (especially monos) and elevated protein
• Coagulopathy/DIC, thrombocytopenia, severe liver dysfunction
• EEG
HSV Therapy and Prognosis
• Acyclovir IV
• 21 days for disseminated or CNS
• 14 days for skin, eye and mouth
• Decreases mortality with disseminated disease from ~75% to
25-40%
• Decreases morbidity from 90% to 65%
• Improvements in both mortality and morbidity dependent upon
early initiation of Acyclovir
Neonatal sepsis
Neonatal Immune System
• All neonates relatively immunocompromised

• Immature and Ineffective:

– Antibodies

– Complement
– Neutrophils

– Skin / mucosal barriers

Immunoglobulins
• Ig G is actively transported across the placenta, with
concentrations in a full-term infant comparable to or higher
than those in mother
• In premature infants, cord IgG levels are directly proportional
to gestational age, ratio of cord to maternal serum
concentrations is 1.0 at term, 0.5 at 32 wk of gestation, and
0.3 at 28 wk
• Other classes of immunoglobulins are not transferred across
the placenta
• Specific bactericidal and opsonic antibodies against enteric
gram-negative bacteria are predominantly in the IgM class.
• Newborn infants usually lack antibody-mediated protection
against Escherichia coli and other Enterobacteriaceae
Maternal Transfer of Antibody
• Antibody transfer
increases with GA
• Most during 3rd
trimester
• No guarantee maternal
antibodies present to
the infecting organism

Remington and Klein, Sixth Edition, 2006

Complement
• No transplacental passage of complement from the
maternal circulation takes place
• Full-term newborn infants have slightly diminished
classical pathway complement activity and
moderately diminished alternative pathway activity
• Premature infants have lower levels of complement
components and less complement activity than full-
term newborns do
• Opsonization of Staphylococcus aureus is normal in
neonatal sera, but various degrees of impairment
have been noted with GBS and E. coli
Neutrophils
• Neutrophil migration (chemotaxis) is abnormal at birth in both
term and preterm infants
• Neonatal neutrophils have decreases in adhesion, aggregation,
and deformability, all of which may delay the response to
infection
• With adequate opsonization, phagocytosis and killing by
neutrophils are comparable in newborn infants and adults
• the ability of neonatal neutrophils to phagocytose gram-
negative (but not gram-positive) bacteria is decreased
• The number of circulating neutrophils is elevated after birth in
both term and preterm infants, with a peak at 12 hr that
returns to normal by 22 hr.
• Band neutrophils constitute less than 15% in normal newborns
Neutrophils
• Neutropenia, which is frequently observed in
preterm infants and infants with intrauterine
growth restriction, increases the risk for sepsis.
• The neutrophil storage pool in newborn infants is
20-30% of that in adults and is more likely to be
depleted in the face of infection.
• The number of circulating monocytes in neonatal
blood is normal
• The mass or function of macrophages in the
reticuloendothelial system is diminished,
particularly in preterm infants
Neonatal Neutrophils
• Immature
•  Chemotaxis
•  Deformability
•  Phagocytosis
•  Storage pool
• Adults 14-fold
> circulating
pool
• Neonates only
2-fold
Manroe et al, J Pediatr, 1979
 “Normal” VLBW neonates

Mouzinho et al, Pediatr 94:76, 1994

Neonatal Anatomic Barriers
• Immature skin and mucosal surfaces
• layers
• junctions between cells
• secretory IgA
• Umbilical cord
• Breaches - catheters, tape
Neonatal Sepsis: Incidence
• 2/1000 live births with culture proven sepsis
• Bacterial / Viral / Fungal
• 80% infants develop bacterial sepsis
• 20% infants perinatally acquired viral infections
• ~ 25% of infected infants have meningitis

• Higher rate with preterm birth

• 26/1000 preterm infants with BW < 1000g
• 8-9/1000 preterm infants with BW 1000-2000g
Neonatal Bacterial Sepsis:
Disease Patterns
•• Late
EarlyOnset
Onset Neonatal
Neonatal SepsisSepsis
(LONS)(EONS)
•• Sepsis or meningitis
Fulminant, multi-system illness
•• 7
< days to 3old
7 days months old
• Perinatal or postnatal acquisition
• Obstetrical complications
• Lower mortality, 2-6%
• Prematurity
• Perinatal acquisition
• High mortality, 5-50%
Etiologic Agents of Neonatal
Sepsis
Frequency(%)
 Group B Streptococci 40
 Escherichia coli 17
Streptococcus viridans 7
Staphylococcus aureus 6
Enterococcus spp 6
Coagulase-negative staphylococci 5
Klebsiella pneumoniae 4
Pseudomonas spp 3
Serratia marcescans 2
Others 10

*Schuchat et al, Pediatrics 105: 21-26, 2000

Etiologic Agents of Neonatal Meningitis
Gram Positive Bacteria; Frequency (%)
 Group B Streptococci 53
Listeria monocytogenes 7
Miscellaneous gram-positives 6

Gram Negative Bacteria:

 Escherichia coli 19
Klebsiella species 8
Haemophilus influenzae 1
Miscellaneous gram-negatives 8

Anaerobes 3

Feigen & Cherry, Fifth Edition, 2004

Risk Factors for Early Onset Neonatal Sepsis

• Primary (significant)
Prematurity or low birth weight
• Preterm labor
• Premature or prolonged rupture of membranes
Maternal fever / chorioamnionitis
• Fetal hypoxia
• Traumatic delivery
• Secondary
• Male
• Lower socioeconomic status
• African-American race
 Early Onset Neonatal Sepsis:
Signs/Symptoms

• 60-80 % PRESENT AT FIRST 24 HRS

• MEDIAN AGE AT ONSET
-TERM 8 HOURS
-PRETERM 6 HOURS

• Respiratory distress due to pneumonia is the most

common
Early Onset Neonatal Sepsis:
Signs/Symptoms

Strongly suggestive Nonspecific

• Hypo/hyper-glycemia • lethargy, irritability
• hypotension
• metabolic acidosis • temperature instability
• Apnea =hypothermia or fever
• Shock • poor feeding
• DIC
• Hepatosplenomegaly • cyanosis
• bulging fontanelle • tachycardia
• Seizures • abdominal distention
• Petechiae
• Hematochezia • jaundice
• respiratory distress • tachypnea
Early Onset Neonatal Sepsis:
Signs/Symptoms - Fever

• The infant with sepsis may have an elevated, decreased or

normal temperature.
• Fever is seen in up to 50% of infected infants.
• Fever is more common in term infants, while hypothermia is more
common in preterm infants
• A single elevated temperature reading or fever as an isolated
finding is infrequently associated with sepsis.
• Persistent fever for greater than 1 hour is more frequently
associated with infection.
• Fever occurs more frequently with LONS
Early Onset Neonatal Sepsis:
Laboratory Evaluation
• Complete Blood Cell Count
• WBC( absolute neutropenia < 1000/ml)
• Ratios of immature to mature neutrophils elevated(>0.2)
Normal < 0.15
• Platelet count ( thrombocytopenia)
• Chest Radiograph
• Glucose
• Bilirubin
• Liver Function Tests
• Coagulation studies
• C-reactive Protein (CRP)
Early Onset Neonatal Sepsis:
Laboratory Evaluation
• Blood culture -- indicated in ALL infants with
suspected sepsis. Repeat cultures indicated if initial
culture positive.
• Urine culture -- low yield in EONS
• + in 1.6% EONS compared to 7.47% LONS
• CSF culture -- should always be considered
Meningitis frequently accompanies sepsis
- 50-85% meningitis cases have + blood culture
- Specific signs & symptoms occur in less than 50% of infants with
meningitis
Early Onset Neonatal Sepsis:
Laboratory Evaluation

CSF - - > 30 WBC/mm3

> 60% PMN
glucose < 50% - 75% of serum
protein > 150 mg/dl
organisms on gram stain
Early Onset Neonatal Sepsis:
Empiric Treatment
Initial:
Ampicillin and Gentamicin IV ? or third generation
cephalosporin
Duration:
“Rule out sepsis” 48 - 72 hours
Pneumonia 5 - 7 days
Sepsis 7 - 10 days
Meningitis 14 - 21 days
Primarily determined by etiologic organism cultured
Secondarily determined by clinical course/response
Early Onset Neonatal Sepsis:
Supportive Therapy
• Ventilation
• BP support - fluids,
Dopamine/Dobutamine/HCTZ
• TPN
• FFP - clotting factors, C3, antibodies
• G-CSF - stimulate WBC production/release
• Steroids not indicated as anti-inflammatory
 Treatment of GBS Infections

Initial
- Ampicillin and Gentamycin IV
(Gent synergy for first 3 days)
- May switch to Penicillin G IV
(with confirmation of diagnosis/sensitivities)

Duration (from first negative culture)

Uncomplicated sepsis 10 - 14 days
Meningitis 14 days minimum
Treatment of E. Coli Infections

Ampicillin and an Aminoglycoside IV

With confirmation of diagnosis /sensitivities:
- drop Amp
- substitute a third generation cephalosporin

Duration (from first negative culture)

Uncomplicated sepsis 10 -14 days
Meningitis 21 days minimum
Treatment of Listeria
Monocytogenes Infections
Ampicillin and an Aminoglycoside IV

Duration (from first negative culture)

Uncomplicated sepsis 10 -14 days
Meningitis 14 days minimum
Prognosis

Neonatal Sepsis
Mortality 20 - 30% overall - highest in premature infants
Morbidity ?? 25% ??

Neonatal Bacterial Meningitis

Mortality 15 - 30% - - 5% if infant survives the first 24 hr
Morbidity up to 50%
30 - 35% mild to moderate neurologic sequelae
5 - 10% severe neurologic impairment
Late Onset Neonatal Sepsis
• Perinatal acquisition with later onset
• Term or preterm
• ETIOLOGY: Coagulase negative staph, S. Aureus,
GBS, Enterococcus, pseudomonas & gram negatives.
• The most common source of postnatal infections in
hospitalized newborns is hand contamination of
health care personnel
• Health care associated infections
• Preterm or sick term infant
LONS….
• Presents in more subtle manner( poor feeding, lethargy,
hypotonic, temperature instability , altered perfusion,
increased 02 requirement & apnea).
• More often associate with meningitis or other localized
infections
• Most cases of neonatal meningitis result from
hematogenous dissemination
• Abscess formation, ventriculitis, septic infarcts,
hydrocephalus, & subdural effusions are complications
of meningitis that occur more often in newborn than in
older children
Risk Factors for Neonatal
Nosocomial Sepsis
• Prematurity
• ELBW > VLBW
• Increased LOS
• Abdominal surgery / NEC
• Hyperalimentaion / Intralipids
• Neutropenia, Thrombocytopenia
• Catheters
• UAC, UVC, ETT, Foley, CT, Peritoneal drains, etc
Late Onset Neonatal Sepsis:
Empiric Treatment
Initial:
Vancomycin and Aminoglycoside IV
(Cefotaxime discouraged)
Duration (from first negative culture):
“Rule out sepsis” 48 - 72 hours
Pneumonia 5 - 7 days
Sepsis 10 -14 days
Meningitis 14 - 21 days
Primarily determined by etiologic organism cultured
Secondarily determined by clinical course/response
Prognosis
Dependent upon organism and early initiation of
appropriate therapy

LOS increased in all cases

Morbidity also variable dependent upon organ

involvement - worse with meningitis
 Indications for GBS
Intrapartum Prophylaxis

AAP Redbook, 2006 Report of the Committee on Infectious Diseases

 Empiric management of the
infant after maternal IAP

AAP Redbook, 2006 Report of the Committee on Infectious Diseases

Guidelines for evaluation of bacterial
infection
Risk factor Clinical Evaluation
signs & Rx

Delivery 18hrs after none Observation

rupture of
membranes

> 18hrs & none CBC, blood

chorioamnionitis culture and
broad
spectrum
antibiotics for
48-72hrs
Continued
Delivery > 18hrs No CBC, blood
after rupture of clinical culture & broad
membranes, signs spectrum
chorioamnionitis & antibiotics for
maternal antibiotics 48-72hrs.

With or without risk With CBC, blood

factors clinical culture and CSF
signs & antibiotics
• Prevention through early, exclusive breast feeding
and feeding hygiene
• IMNCI
• management & care of LBW babies including kangaroo
mother care
• Emergency newborn care for illness, especially sepsis
• Maternal health programs such as antenatal care
( malaria control, tetanus immunization, PMTCT)
• Post natal care (Assess for danger signs, measure
weight, temperature, check feeding) & promote
hygiene, & skin, eye, cord care