Part 12. Infection of Neonatal Infant

Part XII. Infection of the neonatal infant

Part XII. Infection Of The Neonatal Infant

Section 1. Unique Aspects Of Infection

Chapter 94. Epidemiology, Immunity And Pathogenesis

# The Uniqueness Of Neonatal Infection

    1. diverse mode of transmission

           ; transplacental hematogenous spreads

           ; vertical transmission

           ; after birth, exposed to infectious disease

    2. less capable of responding to infections owing to one or more immunologic deficiency

           ; RES system, complement, PMNL, cytokines, antibody, cell-mediated immunity

    3. coexisting ds. of the newborn often complicate the diagnosis and management of neonatal infection

           ; resp. distress such as HMD

           ; acidosis

    4. manifestation of infectious ds. in the newborn infant are extremly variable

           ; subclinical infection, congenital malformation, focal disease, poorly localized systemic infection

# 82 Transplacental Transmission Of Prenatal Infection

    ; Borrelia burgdorferi, Listeria monocytogenes, tuberculosis, syphilis

    ; rubella, CMV, parvovirus B19, HIV, varicella zoster

    ; toxoplasmosis

# 87 Results Of Infection In Utero

    ; resorption of the embryo, abortion, stillbirth, congenital malformation, IUGR, premature birth, acute disease in the neonatal period, asymptomatic persistent infection with neurological sequelae later in life

# 91 Vertical Transmission Of Perinatal Infection(Bacteria That Colonize The Birth Canal)

    ; group B streptococci, gonococci, L. monocytogenes, E. coli(K1 capsular strain), chlamydia, genital mycoplasma, ureaplasma

    ; enteroviruses, herpes simplex

# Maternal To Fetal Trasnfusion At Delivery

    ; *Hepatitis B virus & HIV

# Amniotic Infection Synd.

    ; amniotic fluid bacterial invasion으로 인해 발생하는 임상 증상

           - asymptomatic or maternal fever or systemic sg of chorioamnionitis

           - congenital pneumonia or systemic bacterial infection

                   / fetal distress, tachycardia prior to delivery

                   / perinatal asphyxia at delivery

                   / respiratory distress, shock after latent period of a few hours

    ; usually results of prolonged rupture of the chorioamniotic membrane

           - occasionally intact membrane

           - *uniformly exceeding 24hr

Fig 94-1

Table 94-1

Table 94-2 Patterns of Neonatal Infection

# ★▲important neonatal factor of infection

    ; prematurity, low birth weight (3-10)

# male female보다 2배높다

Nosocomial Nursery Infection

; uncommon in normal full term infant(0.5-1.7%)

    - low birth weight infant(20-33%)

; 90 usually involve the skin

    - caused by S.aureus, Candida

; the incidence increases with the duration of hospitalization and lower gestational age

; 93 Common Pathogen in NICU

    - coagulase-negative staphylococci, gram-negative bacilli(Klebsiella pneumoniae, E.coli, Salmonella, Campylobacter, Enterobacter, Citrobacter, Pseudomonas, aerusinosa, Serratia), enterococcus, S.aureus, Candida

    - enterovirus, CMV, hepatitis A, adenovirus, influenza, RSV, rhinovirus, parainfluenza, herpes simplex, rotavirus

; ★▲Common Infection

    - skin bacteremia ass. with catheter

    - pneumonia

; Risk factor

    - lowbirth weight, length of stay, invasive procedure, indwelling vascular catheter, ventricular shunt, endotracheal tube, alteration in the skin & mucous memb. barrier, frequent use of broad spectrum antibiotics

# Prevention

    ; colonization of infants skin, umbilicus, nasopharynx, GI tract

    ; antibiotics

    ; crowding & inadequate infection control (handwashing between patient examinations)

    ; *p747 Table 174-1. Incfectious disease control measures used to prevent spread of staphylococcus epidemics 참조

Immunology And Pathogenesis

# *dimiminished immunologic factors에도 불구하고 risk factors 없을때에 invasive infection 빈도가 낮은 이유

    ; maternal transplacental Ig transmission

Immunoglobulin

; IgG placenta 통과한다

; cord IgG level gestational age 비례한다

; 1500g 미만에서는 hypogammaglobulinemia 있다

; enteric bacteria 대한 specific bactericidal & opsonic Ab IgM이다. 그러므로 newborn infant E.coli 다른 Enterobacteriaceae protection못한다

Complement

; mediate bactericidal activity as opsonin with antibody

; placenta 통과하지 못하기때문에 fetus first trimester 자체생산한다

; full term

    - mild diminished classic pathway complement activity

    - *moderate diminished alternative pathway complement activity (35-60% of normal)

; *premature infant

    - *diminished both complement pathway activity

; opsonization

    - S.aureus : normal

    - *GBS, E.coli : impairment

Neutrophil

; *diminished chemotaxis of neonatal neutrophil

; decreased adherence, aggregation, deformability

; infant with RDS, hypoglycemia, hyperbilirubinemia, sepsis

  - impaired microcidal activity

Monocyte-Macrophage System

; consists of circulating monocyte + tissue macrophage in RES

; newborn

    - normal circulating monocyte number & function

    - macrophage

           / decreased number & function, esp. prematurity

Cytokines

; *interferon α  & β - normal

; *INF- γ - decrease

; *TNF- α - elevated

; IL-2

    - prematurity

           / higher level than adult

        / *no m-RNA for the IL-2 receptor

    - full-term

           / same level m-RNA as adult

; IL-6

    - *increased in sepsis & NEC

Chapter 95. Clinical Aspects

Clinical Menifestation

Table 95-1

; early manifestation

    - subtle, nonspecific (inability to tolerate feeding, irritability or lethargy)

# Fever

    ; 50% - more than 37.8

    ; DDx

           - increased ambient temperature, dehydration, CNS disorder, hyperthyroidism, familial dysautonomia, ectodermal dysplasia

    ; *fever 1시간이상 sustain 경우 infection 가능성이 높다

    ; premature infant

           - *more common hypothermia, temperature instibility

# Useful Clue Of Cutaneous Manifestation

    ; *ecthyma gangrenosum - pseudomonal infection

    ; *small salmon-pink papule - Listeria monocytogenes

  ; vesicular rash - herpes virus

# progressive respiratory failure

    - pneumonia suspicion

Diagnosis

Table 95-2

; serologic screeing test

    - Treponema pallidum, rubella, hepatitis B

; maternal cultures

    - N. gonorrhoeae, GBS, herpes simplex, chlamydia

; TORCH

    - toxoplasmosis, other agent, rubella, cytomegalovirus, herpes simplex

    - STORCH ; include syphilis

# Diagnostic Dilemma Of Intrauterine Infection Due To STORCH

    ; their clinical feature overlap

  ; disease may be inapparent

  ; maternal infection is often asymptomatic

  ; special laboratory studies may be needed

    ; toxoplasmosis, syphilis, herpes simplex 대한 specific Tx 정확한 진단을 필요로 하며 long term morbidity 감소시킬 있다.

# Common Shared Features Of Intrauterine Infection

    ; prematurity

    ; IUGR

    ; hematologic involvement

           - anemia, neutropenia, thrombocytopenia, petechia, purpura

    ; ocular sign

           - chorioretinitis, cataract, keratoconjunctivitis, glaucoma, microphthalmia

    ; CNS symptom

           - microcephaly, hydrocephaly, intracranial calcification

    ; other organ systemic involvement

           - pneumonia, myocarditis, nephritis, hepatiits with hepatomegaly, jaundice

    ; non-immune hydrops

# 82 Serologic test

    ; IgG

           - transplacental passage 있으므로 해석에 주의

           - fetal-neonatal IgG titer > maternal IgG titer

    - rising IgG titer during infancy

    ; IgM

           - high specificity but low sensitivity

    ; total cord blood IgM, IgA or IgM rheumatoid factor

           - false positive & negative results

# Identification of bacterial or fungal infection

    1) isolating etiologic agents from body fluid sterile

    2) demonstrating endotoxin or bacterial antigen in body fluid

    3) demonstrating bacterial infection at autopsy

    ; Blood Culture

           - two specimen different site

           - sampling in umbilical artery insertion

           - sample size

                   / *as little as 0.2ml but more than 0.5-1ml is optimal

           - radiometric method

                   / growth within 24-72hr

    ; *latex particle agglutination & counterimmunoelectrophoresis

           - identification of GBS & E.coli K1 capsular polysaccharides

# When clininical presentation of infection but unclear focus

    ; blood culture, lumbar puncture, urine exam & culture, gastric aspirate for gram stain & culture, chest roentgenogram

# early-onset infection

    ; omitted urine culture due to rare culture

    ; detection of bacteria, inflammatory cell in 1st day gastric aspirtation

    ; buffy coat with gram or methylene blue stain

           - demonstration of intracellular pathogens

# more common neutropenia than neutrophilia in severe neonatal sepsis

    ; other condition

           - maternal hypertension, neonatal sensitization, NEC, periventricular hemorrhage, seizure, surgery, hemolysis

# *immature neutrophil-total ratio of 0.16 or greater suggests bacterial infection

# mother with chorioamnionitis

    - *two blood cultures & a gastric cultures

    - *presumptive treatment

; *PROM 18시간 이상이면 blood culture

Treatment

# Initial Empiric Tx

   ; *ampicillin + aminoglycoside (GM)

# nafcillin for S.aureus

# vancomycin for coagulase-negative staphylococci

# 최근에 항생제를 사용했거나 antibiotic-resistent infection 있을때는 amikacin,

  vancomycin

# necrotic skin lesion ; pseudomonas(ticarcillin or carbenicillin + GM)

# gram negative enteric bacteria ; ampicillin + AG, third-generation ceph

# enterococcus ; ampicillin or piperacillin + AG

# L. monocytogenes ; ampicillin

# GBS ; penicillin

# ♣㉿3rd generation cephalosporins 장점

    ; MIC needed for Tx of G(-) enteric bacilli are much lower than AG

    ; excellent penetration into CSF in presence of inflamed meninges

  ; much higher doses can be given

  ; 단점

           - modest activity against S.aureus, L.monocytogenes

    - enterococcus are uniformly resistant

           - rapid emergence of resistant organism

# total of 7-10days

  ; at least 5-7 days after a clinical response

    ; GBS meningitis ; 14 days

  ; G(-) meningitis ; CSF sterilization된후 적어도 14

# *치료 시작 24-48시간 reculture

    - negative 되어야한다. 만약 계속 culture(+)라면

    infected indwelling catheter

    endocarditis

    infected thrombus

    occult abscess

    subtherapeutic antibiotic level

    resistant organism 생각해보고 antibiotics change 고려해야한다

Prevention

# aggressive management of suspected maternal chorioamnionitis

# Prevention of nosocomial infection

  ; 2 min scrub before entering the nursing

  ; 15 sec washing between patient

  ; scrub suits for nurses & residents

  ; adequate nursing staff

  ; avoidance of overcrowding

  ; specific isolation precaution

SECTION 2. CLINICAL SYNDROMEs

Chapter 96. Intrauterine Infection And Prenatal Diagnosis

Technique For Prenatal Diagnosis

# amniocentesis

    ; 15 이후 36ml 채취

    ; risk of fetal loss < 1%, monitored by constant ultrasound visualization

# cordocentesis

    ; 15 이후

    ; high resolution ultrasound

    ; Cx

           -transient bleeding

         - rate of fetal loss < 2%

# chorionic villus sampling

    ; *7

    ; complication

           - *fetal death, subsequent fetal limb anomaly, cavernous hemangioma

    ; *littel useful due to complication

Direct Evidence Of Infection

Maternal Serology

# routine screening

    ; STORCH

    ; *now discouraged due to low yield of useful information

Fetal Serology

# specific IgM assay

# total IgM value

    ; normal fetal IgM level is less than 5 mg/dl

    ; any elevation in total IgM may indicate an underlying fetal infection

 ex)    20주에 chicken pox 감염  경우 32주에 total IgM 30mg/dl 34주에

        delivery 2주후에 low total IgM level

        toxoplasmosis 감염  경우 total IgM 높지 않다

      IgM 강양성 때만 유용하게 사용될 있다

Culture

# CMV, Toxoplasma

    ; *amniotic fluid

Electron Microscopy

# Parvovirus

Polymerase Chain Reaction

# HIV infection in blood samples taken from the neuborn infant

Diagnosis

Table 96-1

Prenatal Dx & Tx Of Congenital Toxoplasmosis

# 번째 임신때 infection되면 fetopathy 일으킨다

# route of infection

  ; toxoplasma cyst by eating rare or undercooked meat

  ; acidental contact with oocysts in contaminated cat feces

# tachyzoite forms of the parasite cross the placenta the fetal circulation

  tissue cysts form within the fetal tissue

    dysmorphogenesis

# fetopathy

    ; hepatosplenomegaly, chorioretinitis, hydrocephaly, microcephaly, meningoencephlitis, cerebral calcification

    ; first trimester primary maternal infection 되면 dysmorphogenesis 위험성이 커진다

# screening test toxo 대한 Ab 측정하여 임신하기 전에 sero positive이면 위험성이 적고 임신초기에 Ab 발견되지 않으면 위험성이 많아진다

# amniotic fluid, fetal blood에서 culture infected fetus identify 있다.

Chapter 97. Viral Infection Of The Fetus & Newborn

97.1 Cytomegalovirus

; *common cause of congenital infection

Epidemiology

; pregnant woman *primary CMV inf. 가졌을때 40%에서 fetal infection

; pregnant woman previous CMV inf. recur 경우는 1% fetal infection

; congenital infection

    - 5-10% symptomatic

    - *90-95% asymptomatic

91 Clinical Manifestation

; IUGR

; hepatosplenomegaly, jaundice

; thrombocytopenia, purpura

; interstitial pneumonitis

; CNS involvement

    - microcephaly, ventriculomegaly

    - *intracranial calcification in preventricular distribution

    - chorioretinitis, sensorineural deafness

; *purple skin lesion caused by dermal erythropoiesis

; main concern with asymptomatic infected newborns

    - *subsequent development of sensorineural hearing loss

    - 20%

Diagnosis

  ; *culture of the amniotic fluid

  ; postpartum isolation from the urine or saliva

  ; cell culture

  ; CMV-specific Ab

           - IgG-reliable, IgM-less sensitive

Treatment

# insensitive to acyclovir

# ganciclovir ; 6 mg/kg every 12hrs for 6 wks

     (evaluation 중에 있음, side eff ; BM suppression)

Prevention

; pregnant women should have CMV serologic tests

    - CMV positive women : low risk

    - CMV negative women

           --> counseled regarding hygienic measures

; *no efficacious CMV vaccine

Prognosis

# mortality rate ; 12%

# surviving infant

    ; mostly permanant sequele

       - visual deficit, hearing loss, seizure disorder, motor & intellectual retardation

97.2 Herpes Simplex Virus

# type 1 ; fever blisters or cold sores, genital inf. after orogenital sexual contact

# type 2 ; major cause of genital herpes

# Fetal infection

    ; by primary and reactivated HSV infection during pregnancy

    ; *more commonly from maternal genitourinary tract infection during parturition

Epidemiology

; if mother has primary infection

    - 44% risk

; if mother has recurrent infection

    - *3% risk

; HSV-2

    - *75% of neonatal HSV infection

Clinical Manifestation Of The Fetopathy

  - pricipal sites of involvement ; skin, eyes, CNS

  - skin ; very common, vesicular rashes, scarring over the scalp, trunk,

           extremities, vesicle around the scar

  - CNS ; microcephaly, atropy of the brain, cystic encephalomalacia, involvement

           of the spinal cord

  - eye ; chorioretinitis, microphthalmia

  - hepatitis, calcifications in the lungs & adrenal gland

Pathogenesis Of The Fetopathy

; the fetal ds probably is acquired by a transient maternal viremia, which seeds the placenta

Clinical Manifestation Of Perinatal Ds.

; *not symptomatic until late in the 1st wk or early in the 2nd wk

; predominantly due to HSV-2

    - HSV-1 10-20%

; Pattern

    1) disseminated pattern

           - seen in intrauterine disese

           - multiorgan involvement

    2) cutaneous HSV ds.

           - skin, mouth, eye

           - vesicle on the presenting part, keratoconjunctivitis

    3) encephalic pattern

           - *occur in late 2nd & 3rd wks

           - lethargy, irritability, seizure, often in absence of cutaneous lesion

Diagnosis

# cell culture

    ; vesicle fluid, nasopharyngeal or conjunctival swabs, urine, stool, tracheal secretion(pneumonia), duodenal aspirate(hepatitis), CSF(encephlitis)

# HSV-specific fluoroscein-conjugated monoclonal Ab

# Tzank cytologic test is non-specific and should be discontinued

Treatment

# acyclovir

    ; without CNS ds

           - 10 mg/kg every 8hr for 14 days

  ; with CNS ds

           - *10 mg/kg every 8hr >21 days

# 몇몇 infant에서 recurrent cutaneous vesicle 생기는 수가 있는데 대부분은 acyclovir resistant때문이 아니고 reduced HSV-specific immunity 때문이다

# acyclovir main Cx

    ; renal dysfunction as a result of crystal formation in the tubule(serum Cr level 3 마다 check, Cr level 증가하기 시작하면 acyclovir 줄인다)

Prevention

# *C-sec if documented primary gental genital herpes infection

# asymptomatic woman with recurrent history

  ; vaginal delivery & birth canal culture

        - if delivery culture is positive

                   --> cultures from skin, eye, pharyx, rectum of newborn

                   --> if initial culture is positive of mother or infant

                   --> second exam & repeat culture

; 몇몇 specialist recurrent genital herpes 있는 pregnant woman에게

     suppressive oral acyclovir therapy(400 mg twice daily) 하는 경우도 있다

Prognosis

 - considerable morbidity & mortality rate

  - the prognosis for neonatal encephalitis ; HSV-1 2 보다 예후가 좋다

97.3 Varicella-Zoster Virus

Epidemiology Of Fetal Infection

    ; 산모가 chicken pox 앓을때 fetus *25%정도 영향을 받는다

        - *infected fetus 모두가 congenital varicella syndrome 일으키지 않는다 (3%)

Clinical Manifestation Of The Fetopathy

Table 97-1 stigmata of varicella-zoster virus fetopathy

; *characteristic cutaneous lesion

    - *cicatrix, zigzag scarring

; other hallmark

    - *shortened & malformed extremities

Pathogenesis Of The Fetopathy

  - virus-induced injury to the nervous system

  - the limb & eye manifestations ; caused by denervation secondary to VZV

     invasion of fetal nerve (cervical or lumbosacral cord or the optic stalk)

  - the virus may select tissues that are in a rapid developmental stage(limb bud)

  - necrotizing cerebral lesion involving the leptomeninges, the cortex, the adjacent

     white matter

  - pathologic change in the spinal cord (shrunken & gliotic posterior horn & lat. column)

  - gestation 6-12주에 감염되면 limb development 가장 심하게 영향을 준다

  - 16-20주에 감염되면 eye & brain involvement

Diagnosis

# history of gestational chicken pox + stigmata seen in the fetus

# viral DNA ; tissue sample by hybridization technique

Treatment & Prevention Of Fetal Ds.

# does not progress postpartum antiviral treatment is not indicated

Neonatal Chickenpox

; postpartum clinical chickenpox

; incubation period

    - 10-14days

Treatment & Prevention In The Newborn Infant

# Indication of VZIG

    ; 분만 1 이내에 chicken pox 걸린 산모에서 태어난 full term infant

    ; active chicken pox 산모에서 태어난 모든 premature

# oral acyclovir

    ; infant chicken pox develop 되자마자

    ; pneumonia, hepatitis, encephalitis IV acyclovir

97.4 Parvovirus

; HPV - B19

Epidemiology

    ; fifth ds, erythema infectiosum

  ; transmission

           - respiratory route, droplet aerosol

  ; spontaneous abortion & still birth

Clinical Manifestation

; *hydrops, CHF due to fetal anemia

Pathogenesis

# detection of viral DNA & viral particle

# cytopathic effect in erythroblast of the bone marrow & extramedullary hematopoiesis in the liver & spleen

Diagnosis

  - 산모 ; detection of virus specific IgM Ab

           detection of viral DNA in fetal blood or visualization of viral particles

           by immune electron microscopy

97.5 Rubella

; enveloped RNA virus, 3-day measles or German measles

Epidemiology Of The Fetopathy

# transmission

    ; *1st trimester - 80%, 2nd trimester - 50%

Clinical Manifestation In The Fetus

; IUGR

    - *common

; cataract, microphthalmia

; *myocarditis, PDA, Pulmonary artery stenosis,

; *Blueberry muffin skin lesion

; hearing loss(sensorineural deafness)

; meningoencephalitis at birth

    --> later sequelae motor & mental retardation

; persistent infection

    - pneumonia, hepatitis, bone lucencies, thrombocytopenia, purpura, anemia

Diagnosis

# clinical basis

# virus specific IgM Ab in neonatal serum

# culturing rubella virus in infants urine or tissue

Treatment

  - immunization으로 예방

  - 임신초기에 감염되면 fetal infection 가능성이 높으므로 termination 고려

97.6 Human Immunodeficiency Virus

Epidemiology Of Fetal HIV Infection

  - 소아 AIDS 거의 항상 infected mother 부터 감염된다

    (by intrauterine, by intrapartum trasmission)

  - mother risk group ; IV drug user, prostitutes, recipients of contaminated blood 

     transfusion, women married to men who were HIV seropositive

# transmission rate

    ; fetal & perinatal transmission rate 70%

    ; vertical transmission rate 25%

           -early gestation 첫감염되면 25%이상이다

# Intrauterine HIV Transmission Mechanism

    1) virus in the maternal system is released from decidual cells & subsequently phagocytosed by syncytiotrophoblast

           - *important mechanism of intrauterine transmission

    2) trophoblast that are invading decidual tissue come into contact with HIV-infected maternal CD4 lymphocyte

    3) infected maternal macrophages invade the villous stroma

Diagnosis

; viral culture, HIV-specific, PCR assay

Treatment

# zidovudine

    ; mother treatments 100 mg five times daily

    ; during labor, administrated iv

           - loading dose of 2 mg/kg over 1 hr

                   and then continuous infusion 1mg/kg/hr until delivery

    ; newborn medication

           - *6 wks of antiviral therapy (zidovudine syrup at 2 mg/kg every 6 hr)

# 67.5% relative risk reduction

Chapter 98. Neonatal Sepsis And Meningitis

98.1 Sepsis

Table 98-1

Epidemiology

; 1-4/1000 live birth

# Predisposing Factors

    ; low birth weight infant

    ; presence of maternal(obstetric) risk factor

           - prolonged rupture of memb. (>18hr)

    - maternal intrapartum fever(37.5)

    - maternal leukocytosis (>18000)

    - uterine tenderness

    - fetal tachycardia(>180)

# Host Risk Factor

  ; male, developmental or congenital immune defect, galactosemia(E. coli), administration of intramuscular iron(E. coli), congenital anomaly(urinary tract, asplenia, meningomyelocele, sinus tract), omphalitis, twinning(second twin)

Etiology

# early onset

    ; GBS(*common cause), enteric bacteria

# late onset

    ; GBS, HSV, enterovirus, E.coli

# VLBW

    ; candida, coagulase-negative staphylococci

Pathogenesis

; neonatal sepsis & NEC IL-6, TNF, platelet-activating factor 증가한다

Clinical Manifestation

    ; multiorgan system ds., metabolic acidosis

  ; late manifestation

           - sign of cerebral edema and thromboses, respiratory failure as a result of acquired respiratory distress syndrome, pulmonary hypertension, cardiac failure, renal failure, hepatocellular disease with hyperbilirubinemia and elevated enzymes, prolonged prothrombin time and PTT, septic shock, adrenal hemorrhage with adrenal insufficiency, bone marrow failure, DIC

Diagnosis

  - inflammatory resp. test ; ESR, CRP, haptoglobin, fibrinogen, nitroblue

                               tetrazolium dye, leukocyte alkaline phosphatase

  - total WBC with differential, ratio of immature to total nutrophil( >0.16)

  - severe sepsis일때 neutropenia 더욱 흔하다. 그러나 다음과 같은 경우에도

     neutropenia 있다.(maternal hypertension, neonatal sensitizaqtion,

                    periventricular hemorrhage, seizure, surgery, hemolysis)

Treatment

  - correction of hypovolemia, hyponatremia, hypocalcemia, hypoglycemia, limitation of fluid

  - fluid resuscitation, mechanical ventilation

  - hyperbilirubinemia should be monitored

  - DIC sepsis 치료해야 호전되지만 bleeding 있는 경우에는 FFP, platelet,

    whole blood transfusion

# GM-CSF, IVIG

    ; 지속적인 neutropenia 있으면서 antibiotics 반응이 없는 경우에 granulocyte transfusion indication 수있다(GM-CSF, IVIG)

98.2 Neonatal Meningitis

; caused by bacteria, virus, fungi, protozoa

; 0.2-0.4/1000 live birth, higher in preterm infant

Etiology

; *GBS, E.coli K1, Listeria

    - *common bacteria causes

; other streptococci, hemophilus influenza, coagulase negative, positive staphylococci, Klebsiella, Enterobacter, Pseudomonas, Treponema pallidum, M. tuberculosis,

; Cytrobacter diversus  ; important cause of brain abscess

; Mycoplasma hominis, Ureaplama urealyticum, candida albicans, Toxoplasma gondii, virus (enterovirus, HSV, rubella, CMV, HIV)

Pathology & Pathogenesis

  - hematogenous dissemination

  - 드물게 다음과 같은 경우에 contiguous spread 수있다

     (contamination of neural tube defect, congenital sinus tract, penetrate wound

      from fetal scalp sampling or internal fetal electrocardiographic monitor)

  - cerebritis, septic infarct, abscess, ventriculitis, hydrocephalus, subdural effusion

     들은 newborn에서 더흔히 나타난다

Clinical Manifestation

; lethargy(50-90%), bulging or full fontanel(20-30%), focal, generalized, subtle seizure(30-50%), nuchal rigidity(10-20%)

Diagnosis

# blood culture positive

    ; 70-85%

  ; early onset sepsis & meningitis일때 culture율이 증가

# CSF analysis

    ; lumbar puncture respiratory status 변화시킬것이 예상되는 severely ill infant에서는 lumbar puncture 하지않고 blood culture Ag detection assay만을 한후에 meningitis 대한 치료를 시작하고 안정화되면 lumbar puncture 시행한다

# 87주★Normal Uninfected Neonate CSF Finding

  ; protein

           - term - 90 mg/dl (20-170)

       - preterm - 115 mg/dl(65-150)

  ; glucose

           - term - 52 mg/dl(34-119)

    - preterm - 50 mg/dl(24-63)

  ; CSF-to-blood glucose ratio

           - term - 51%

    - *preterm - 75%

  ; CSF leukocyte count

           - term - 7/ l (0-32)

    - preterm - 8/ l(0-29) with 57-61% neutrophil

# gram staining

    ; GBS - 85%, gram negative - 65% 에서 양성

# leukocyte

    ; 보통 neutrophil( >70-90%)

        > 1000 ; gram negative

        <100 ; GBS

# ultrasound, CT

    ; ventriculitis, brain abscess

# culture positive without CSF abnormalities

    ; GBS meningitis

# Culture Negative Meningitis

    ; pretreatment of AB

    ; infection with M. hominis, U. urealyticum, Bacteroides fragils

    ; brain abscess

    ; enteroviral infecton

    ; HSV infection

Treatment

# 91 Presumptive Therapy

    ; ampicillin + cefotaxime + GM

  - cephalosporin monotherapy 사용해서는 않된다. 왜냐하면 Listeria

     monocytogenes 모든 cephalosporin resistant하기 때문

# GBS meningitis

    ; 24-48hr 후에 반응이 있고, 14-21일간 써야함

# gram negative meningitis

    ; *21일간 계속치료 또는 CSF sterilization된후 14

  - Pseudomonas aeruginosa ; ceftazidime

  - B. fragilis ; metronidazole

# CT Ix ; suspected ventriculitis, hydrocephalus, cerebral abscess, unexpectedly

             complicated course(prolonged coma, focal neurologic deficits, persistent

                                or recurrent fever)

98.3 Group B Streptococcus

 - major cause of severe systemic & focal infection in the newborn

Etiology

Table 98-2

    ; *Streptococcus agalactiae

           - faculative, encapsulated gram-positive diplococcus

           - hemolysis

  - type ; Ia, Ib, Ia/c, II, III, IV, V

  - early onset disease may be due to any serotype

    late onset  ; type III in 90%

  - IV, V, nontypeable stain ; neonatal ds와의 연관성이 적다

  - extracelluar substance 생성한다 ; hemolysin, CAMP factor, hippuricase,

                                       nuclease, protease, neuraminidase,

                                       lipoteichoic acid

  - neuraminidase, lipoteichoic acid virulence 관련이 있다

Epidemiology

  - maternal genitourinary, GI tract, pregnant woman 20%에서 colonize

  - 보통은 pregnant woman asymptomatic 하지만 UTI, chorioamnionitis,

     endometritis 일으킬 수도있다.

  - colonized mother에서 태어난 infant 40-70% colonization된다

  - colonization rate 영향을 주는 factor

     ; maternal factor (low socioechonomic status, teenage status, sexual acitvity)

       choice of media, the number and location of body site sampled in the

       mother

       newborn infant ; external auditory canal

       48hr-old neonate ; throat, anorectum, umbilicus

  - vertical transmission (50%)

     ; ascending infection through ruptured amniotic membranes or contamination

       after passage through the colonized birth canal

  - ruptured membrane없이도 infection 있다

  - ruptured membrane 시간과 early onset GBS infection과는 직접적인 연관성이

    

  - infant-to-infant, adult-to-adult transmission late onset GBS infection 원이

     이며 드물게 nursery epidemic 원인이 수도 있다

  - Early onset GBS ; first 5 days of life

    ·incidence ; 0.7-3.7/1000 live birth or 0.5-2% of newborn infant born to

                  colonized mother

    ·50% 태어날 당시에 symptomatic 하다

    ·VLBW infant에서는 high attack rate ; 8/1000 live birth( <1500 g)

    ·감염에 영향을 주는 인자

          prolonged rupture of amniotic membrane

          prolonged labor

          maternal endometritis-chorioamnionitis (fever, tender uterus, leukocytosis)

  - late onset GBS

    ·not associated with obstetric risk factor

    ·0.5-1.8/1000 live birth

Pathology

  - intrauterine death 언제든지 있다

  - intrauterine, early onset inf 에서는 pulmonary inflammation 특징적으로 온다

     ; interstitial, alveolar neutrophil exudate, vascular congestion, edema,

       pulmonary hemorrhage

  - late onset ; substantial inflammatory response, abscess formation 흔하다

Pathogenesis

  - early onset ; immature host defense mechanism

                 exposure to heavily colonized maternal genitourinary tract

  - GBS intact membrane local inflammation 일으켜서 rupture of membrane,

     premature 유발 시킬 도있다

  - 드물게 infected amniotic fluid aspiration하여 pneumonia, bacteremia, septic

     shock 일으킨다

  - early onset ; pneumonia, bacteremia, pulmonary hypertension

  - late onset ; initial colonization, alteration of the mucosal barrier by a prior viral

                respiratory tract infection, elaboration of large amount of GBS type

                III, capsular poly saccharide, possibly reduced amount of maternal

                Ab

Clinical Manifestation

  - early onset infection ; from asymptomatic bacteremia to septic shock

                          symptom 태어날 때부터 있고 대부분은 6시간 이내에

                          타난다

    ·respiratory symptom are prominent (cyanosis, apnea, tachypnea, grunting,

                                         flaring, retraction)

    ·roentgenographic finding ; reticulogranular pattern(50%)

                                patch pneumonic infiltration(30%)

                                pleural effusion, pulmonary edema, cardiomegaly,

                                increased pumonary vascular marking

    ·PFC, ARDS

    ·meningitis ; <10%, seizure, lethargy, coma, bulging fontanel

  - late onset GBS ; meningitis in 60%, type III serotype

Diagnosis

# Differential Diagnosis

    ; HMD, amniotic fluid aspiration syndrome, sepsis from other vertically transmitted ascending infection(E. coli, HSV), metabolic disease(hypoglycemia, hyperammonemia), congenital heart disease, diaphragmatic hernia

Laboratory

  - isolation and identification of the organism

     (blood, CSF, urine, flural fluid, abscess material, cellulitis aspirate, bone and

      joint aspirate)

  - isolation of GBS from skin or mucous membranes indicates colonization and

    not invasive infection

  - latex particle agglutination ; antigen detection, less sensitive than culture

  - positive urine latex test result is suggestive but not diagnostic of systemic

     infection

  - CSF should be examined in all patients suspected of having meningitis or

     sepsis

Complication

  - mortality rate for early-onset GBS ; 10-20%

  - mortality rate is highest in very low birthweight infants

  - 20-30%에서는 neurologic sequale 심하다 (mental retardation, quadriplegia,

     repeated uncontrolable seizure, hypothalamic dysfunction, cortical blindness,

     hydrocephalus, bilateral deafness, hemiplegia)

  - mild mental retardation, mild cortical atropy, a stable seizure disorder, delay in

     receptive and expressive speech and language development, other learning

     disability

Prevention

# Recommendation

    ; *selective chemoprophylaxis

           - *high risk, colonized pregnant woman with premature labor, fever, prolonged rupture of membrane( >12hr), suspected chorioamnionitis

    ; intravenous ampicillin(2g initially and then 1g every 4hr)

           - labor시작부터 infant 태어날 때까지

  - immunoprophylaxis ; active immunization of the mother or possibly passive

                         IgG administration to the newborn infant might prevent

                         GBS disease

Treatment

# emperic AB

    ; PC + AG

    ; sensitive to penicillin G

  ; penicillin G MIC group A streptococci보다 4배에서 10 높다

    ; vancomycin, semi-synthetic penicillin, cefotaxime, ceftriaxone, imipeneme에도 susceptible 하다. 그러나 penicillin보다는 효과가 좋지 못하므로 documented GBS infection 사용해서는 않된다.

# GBS meningitis

    ; 300,000 units/kg/24hr of penicillin G or 300 mg/kg/24hr of ampicillin

  ; usual dose보다 높은 dose 사용하는 이유

         higher than usual MIC

         high CSF inoculation size

         20 unit 사용했을 경우 relapse 보고되었다

         relative safty of penicillin in the neonate

  ; *치료 48시간 후에 CSF study 해야한다

    ·duration of treatment ; 2-3wk

    ·48시간후에 CSF sterile해지지 않은 경우

       ; subdural empyema, brain abscess, ventriculitis, supprative dural sinus

         thrombosis, insufficient dose of a bactericidal antibiotic

  - recurrence or relapse ; uncommon, 만약 있다면 치료 2-43(평균 16)후에

                            어난다

                           치료기간이 짧았거나 dose 낮았다

    ·reinfection may result from maternal mastitis

    ·late complication ; brain abscess, endocarditis

    ·repeat therapy with higher dose of penicillin, for a longer course

 - current IVIG protective Ab 양이 적기 때문에 효과가 적다

    hyperimmune IVIG, human monoclonal Ab 문제를 극복

98.4  E. coli

 - neonatal meningitis 일으키는 strain 80%이상이 K1 capsular Ag 생성한다

Epidemiology

  - meningitis ; K1 88%

    bacteremia ; K1 30%

  - obstetric and/or neonatal risk factor

     ; UTI during the last month of pregnancy, intrapartum fever, prolonged

       rupture of membranes, postpartum endometritis, assisted delivery,

       prematurity, multiple birth, postmaturity, congenital abnormality, congenital

       defect(spina bifida, sacrococcygeal teratoma, gastroschisis, duodenal atrsia in

       Down synd, galactosemia, pyruvate kinase deficiency)

  - most frequently between 3 days and 2wk of age

Etiology

  - cell wall ; lipid-linked polysaccharide or O antigen(150 종류)

  - capsular polysaccharide or K antigen(100 종류) ; virulence and invasiveness

  - K1, K2, K3, K5, K12, K13

  - K1 stain ; neonatal bacteremia, neonatal meningitis, childhood pyelonephritis

Pathogenesis and pathology

  - K1 polysaccharide ; a unique virulence factor

  - Ab to K1 capsule ; IgM, do not cross the placent

  - capsule antiphagocytic barrier 작용하여 Ab complement-mediate

     mechanism에의한 opsonization 손상받는다

Clinical manifestation

  - bacteremia, sepsis, meningitis

  - pneumonia, soft tissue abscess, UTI, arthritis, osteomyelitis, ascending

     cholangitis

Diagnosis

  - culture,

  - K1 strain ; latex agglutination test

98.5 Coagulase-Negative Staphylococci

; *common organisms associated with late-onset infections in neonatal intensive care unit

Etiology

  - Micrococcaceae, gram positive cocci in cluster

  - 21 species of CONS, 11 are found in human flora

  - S. epidermidis, S.saprophyticus, S.hemolyticus ; most common

Epidemiology

  - ubiquitous and are acquired early in life in essentially all infant

  - skin, respiratory, GI tract

  - most common cause of bacteremia in low birth weight infant

  - GBS, gram negative enteric infection 보다는 mortality rate 낮다

  - VLBW infant survival rate 증가하면서 prevelence 증가한다

      ·contributing factor ; prolonged hospitalization, heavy exposure to broad

                            spectrum antibiotics, use of invasive prosedure, use of

                            intravenous lipid emusion

Pathogenesis

  - Breakdown of the mucocutaneous barriers is the usual initial step

  - S. epidermidis ; most common

# exopolysaccharide

    ; production of a slimelike substance

    ; enhance colonization & infection

# slime

    ; enhances adherence to catheters

    ; inhibits neutrphil, chemotaxia & phagocytosis

    ; may affect resistence to glycopeptide antibiotics

# lack of optimal opsonophagocytosis ; most important immunologic defect

  - other possible virulence factor ; cytotoxins, hemolysins, proteinases

  - NEC ; delta toxin

Clinical manifestation

  - respiratory distress, apnea, bradycardia, GI abnormality, thermoregulatory

     problem, evidence of poor perfusion, cerebral dysfunction

  - pneumonia, pleural effusion, meningitis, endocarditis, NEC, omphalitis, abscess,

     osteomyelitis

Treatment

    ; Vancomycin

           - choice of initial therapy of suspected or proved CONS infection

  ; synergistic therapy

           - rifampin and vancomycin (infection 계속지속될때)

98.6 Candidiasis

  - common cause of oral mucous membrane & perineal skin infection

  - incidence ; as high as 5% in very low-birth weight infant

Etiology

  - Candida albicans ; 80-90% of human infection

  - three predominant morphologic form

       Yeast cell ; 1.5-5 m, blastospore, bud asexually

       chlamydospores ; 7-17  m,

       hyphae (pseudomycelia) ; filamentous process

Epidemiology

  - commonly isolated from GI and vaginal flora of adult

  - 임신을 하면 vaginal colonization 증가한다 (20%미만 33%)

  - term infant 10% 5 이내에 colonization 된다

    <1500 g ; 30%

  - early colonization ; GI, respiratory tract

  - 2주후에 skin involve한다

  - postnatal infection ; 가장 흔하게 생후 1주에 thrush 나타난다

  - monilial diaper dermatitis ; 3-4mo peak incidence

  - systemic candidiasis ; VLBW infant 2-5%

Pathogenesis

  - hematogeous spread ; vasculitis, miliary nodule

  - lung, kidney, GI, heart, meninges

Clinical manifestation

  - thrush, erythematous base

  - candida dermatitis ; erythematous scaling rash in intertringinous area

  - congenital candidiasis ; generalized, intensely, erythematous eruption in the first

                           12hr of life, desquamated, pustular

  - preterm infant일수록 더자주 systemic infection 발생한다

  - fungemia ; asymptomatic or sepsis, septic shock

  - vascular ds ; vasculitis of the aorta or vena cava, endocarditis, infected

                  thrombi

  - upper urinary tract involvement ; flank mass, hypertension, renal failure, renal

            abscess, papillary necrosis, fungal ball in the collecting system with

            obstruction and hydronephrosis

  - CNS candidiasis ; involve meninges, ventricle, cerebral cortex with abscess

                       formation

  - VLBW infant에서 systemic candidiasis 있을때 endophthalmitis 있다

Diagnosis

  - isolation of fungi from culture

  - buffy coat smears of blood may show yeasts

  - CSF culture are positive in 33% of infants with systemic infection

  - catheter associated transient candidemia disseminated candidiasis 구별하는

    것은 중요하다. catheter associated transient candidemia positive blood culture

    이지만 focal or disseminated ds. 증거가 없다.

  - ultrasonography is useful for localization of candida infection in the

     cardiovascular, renal, CNS

Treatment

  ; amphotericin B

           - initial dose 0.5-1.0 mg/kg/24hr

    - diluted in 5% dextrose in water without electrolytes (농도 <0.2mg/ml)

    - administered over 4-6hrs

    - total recommended dose ; 20-30 mg/kg

       - nephrotoxicity

                   / oliguria, azotemia, hyperkalemia

    ; flucytocin

    ·amphotericin B 같이 쓰면 synergistic effect 있다, CSF level증가

    ·단독으로 쓰면 resistent 증가한다

    ·bone marrow, GI, hepatotoxicity

Chapter 99. Pneumonia In The Neonate

Etiology and epidemiology

  - acquired transplacentally, perinatally, or postnatally

  - transplacentally 경우 more generalized congenital process

  - perinatal ; aspiration of infected amniotic fluid or maternal gastrointestinal or

               genitourinary secretion at delivery

  - microorganism ; GBS, gram-negative enteric aerobe, L.monocytogenes, genital

                     Mycoplasma, Chlamydia trachomatis, CMV, HSV

# 82,83 Risk Factor

    ; prematurity, prolonged rupture of membranes, chorioamnionitis, fetal distress

# respiratory virus ; RSV, parainfluenza, influenza, adeno virus

  - respiratory virus are the single most cause of community acquied pneumonitis

Clinical manifestation

  - poor feeding, lethargy, irritability, poor color, temperature instability, abdominal

     distension

  - tachypnea, tachycardia, flaring of alae nasi, grunting, retraction, cyanosis,

     apnea, progressive respiratory failure

  - fulminant infection ; GBS, indistinguishable from severe HMD

# Afebrile Pneumonia Syndrome

    ; older children

    ; preceded by URI symptoms or conjunctivitis

    ; no fever

    ; X-ray findings

           - focal or diffuse interstitial pneumonitis

    ; *C. trachomatis, CMV, U. urealyticum, resp.virus

Diagnosis

  - culture for respiratory virus and C. trachomatis may be valuable ; they are

                                                           never normal flora

  - serologic test

  - Eosinophilia ; caused by C. trachomatis

  - DDx ; HMD, meconium aspiration syndrome, TTN, diaphragmatic hernia,

           congenital heart ds, PFC, BPD

Treatment

  - same as antibiotics used for sepsis and meningitis

  - first 7-10 infection ; ampicillin + aminoglycoside

    nosocomial infection ; vancomycin + 3rd generation cepha

  - C. trachomatis ; EM or bactrim

  - U. urealyticum ; EM

  - RSV ; aerosolized ribavirin

  - influenza virus ; amantadine

Chapter 100. Hepatitis In Neonates

; caused by specific dtiologic factors usually is distinguished from the term

    neonatal hepatitis

Etiology And Epidemiology

  - hepatitis 원인중 sepsis 고려해야한다 특히 gram-negative bacterial infection

  - cholestatic effect of enterotoxin

  - five hepatotropic virus ; HAV, HBV, HCV, D, E

  - HAV rarely is transmitted cross the placenta

     transfusion fecal-oral contamination으로 드물게 전파됨

# HBV

    ; Transmission Route

           - *transplacental : uncommon

           - vertical

           - postpartum

    ; Infection Mechanism

           1) mother is chronic carrier

                   - asymptomatic

                   - chronic carrier if not treated

                   - mother-HBeAg(+) --> 90% infection

           2) mother is acute HBV infection

                   - 3rd trimester or shortly after birth --> 80% clinical hepatitis

                   - 1st two trimester --> 10-15% infection

           3) mother is chronic active hepatitis

                   - least common

                   - scanty data

# HCV

; infection primarily is acquired passively in utero, and

vertical transmission of HCV is uncommon

  - HEV ; similar to HAV

  - other virus ; enterovirus, CMV, HSV, HIV

  - nonviral cause ; congenital syphilis & congenital toxoplasmosis

Clinical Manifestation

  - jaundice, vomiting, poor feeding, elevated enzyme level

  - fulminant hepatitis ;

    ·rapid progression to very high hepatic enzyme]

    ·decreased production of coagulation protein

    ·elevated serum ammonia level

    ·shock, coma, death

    ·serum bilirubin, aminotransferase level ; poor predictor of outcome

    ·PT ; the best prognostic indicator

  - DDx ; anatomic(intra & extrahepatic biliary atresia, choledochal cyst)

           metabolic(cystic fibrosis, disorders of bile acid metabolism, galactosemia,

                     tyrosinosis,  -antitrypsin deficiency)

           toxic (drug, hyperalimentation)

Prevention & Treatment

  - acyclovir ; HSV, varicella

  - ganciclovir & foscarnet ; CMV

  - Zalcitabine & zidovudine ; HIV

  - HBsAg(+) mother ; hepatitis B immunoglobulin + hepatitis B vaccine

                         within 12hr of birth

Chapter 101. UTI

; *0.1 % of newborn infant

; more frequent in male

# 96Factor Predisposing To Infection

    ; P blood group secretor status

  ; VUR

  ; obstructive uropathy

  ; low birth weight

  ; meningomyelocele

  ; bladder catheterization

  ; male being uncircumcised

Etiology

    ; 75% E. coli

 - Other ; enterobacteria & gram positive cocci

 - 대부분 ascending, rarely hematogenous

 - renal growth retardation ; reflux 없으면 puberty이후에 reversible 있다

Clinical Manifestation & Diagnosis

  - FTT, weight loss, poor feeding, jaundice, diarrhea, fever(usually low grade)

  - palpable abdominal mass or weak urinary stream ; obstructive uropathy

  - Dx ; positive bladder urine culture(catheterization, suprapubic aspiration)

  - suprapubic aspiration에서 gram negative 나오면 infection 의미

  - small number gram(+) ; skin contamination

  - UTI infection 50%이상에서 WBC 10/HPF 나온다

  - pyuria 없다고 해서 infection rule out하지 못한다

  - blood culture ; 33%에서 positive

Evaluation

  - ultrasound(kidney, bladder)

  - VCU

  - in equivocal case, DMSA

Treatment

; ampicillin or cephalosphorin + AG