Neonatal Sepsis

Neonatal

Sepsis 13 June 2012By MEDSWU Extern

DEFINITION, INCIDENT

SIGN & SYMPTOMNeonatal sepsisBy MEDSWU Extern

Definition and Incidence

Early-onset bacterial infection

0.40 case per 1000 live births

2006

Late-onset GBS disease

0.30 case per 1000 live births

2006

Pathogenesis• Early onset sepsis• Late onset sepsis

Pathogenesis of early onset

• Newborn infants are less capable of responding to infection because of 1 or more immunologic deficiencies.

• Maternal infection transplacental fetal infection

• Organism from mother’s genital tract

Pathogenesis of early onset

• A variety agents bacteria, viruses, fungi, protozoa, and mycoplasmas

• Mode of transmission: Intrauterine infection, ascending bacterial infection

Intrauterine infection• Hematogenous

transplacental transmission to the fetus.

• Depend on time of infection during gestation– 3rd trimester active infection

at the time of delivery (toxoplasmosis, syphilis)

Ascending bacterial infection

• Vertical transmission of bacterial agents that infect during labor and/or delivery

• Organism colonize at birth canal ascending amniotic infection and/or colonization of the neonate at birth

Ascending bacterial infection

• Chorioamnionitis results from microbial invasion of amniotic fluid, often as a result of prolonged rupture of the membrane (> 18 hr.)– maternal fever– uterine tenderness– foul-smelling vaginal

discharge/amniotic fluid– maternal and/or fetal

tachycardia.

Pathogenesis of early onset

• Maternal risk factors– GBS colonization – Asymptomatic UTI– Prolong PROM– Chorioamnionitis – Race– Age– STD infection

Pathogenesis of early onset

• Neonatal risk factors– Host defense mechanism– Cellular component

phagocytic cell• storage pool ↓ and opsonin ↓

– Complement • capsulated bacteria (GBS & E.coli

)

– Humoral immunity system – Cell- mediated immunity– Fibronectin

Pathogenesis of late onset

• Community- acquired infection• Nosocomial infection

– occur in preterm or term infants who require intensive care.

– Risk factors : prematurity, LBW, invasive procedures, indwelling vascular catheters, endotracheal tubes, ventricular shunts, frequent use of broad-spectrum antibiotics, and prolonged hospital stay

Nosocomial infection

• most common organism is Coagulase negative staphylococcus (Staphylococcus epidermidis)

• S. aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterobacter spp.

• methicillin-resistant S. epidermidis (MRSE), gram negative multi-drug resistance strain

Feature Early onset Late onset

Intrapartum complication

Often present Usually absent

transmission VerticalOrganism from mother’s genital tract

VerticalNosocomial infection

Clinical manifestation Fulminant courseMultisystem involvementRespiratory distress, apneaPneumonia: common

Insidious onsetFocal infectionIrritable, fever, poor feedingMeningitis: common

Effect of intrapartum IV antibiotic prophylaxis

Reduce incidence by 85-90%

No effect

Case fatality rate 5-20 % 5 %

Clinical manifestations• Abnormal neurologic status: irritability, lethargy,

poor feeding, seizures• Abnormal temperature: hyperthermia or

hypothermia• Bleeding problems: petechiae, purpura, oozing• Cardiovascular compromise: tachycardia,

hypotension, poor perfusion, cyanosis• Gastrointestinal symptoms: abdominal distention,

emesis, diarrhea, jaundice, hepatosplenomegaly• Respiratory distress: tachypnea, increased work

of breathing, hypoxemia, apnea

Signs and symptom Differential diagnosis

Respiratory system(sepsis with or without pneumonia)

Respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTNB), aspiration pneumonia, meconium aspiration syndrome (MAS)

Neurological system Birth trauma, intracranial hemorrhage, inborn errors of metabolism, drug withdrawal, congenital malformation

Signs and symptom

Differential diagnosis

Cardiovascular system

Hypoplastic left heart syndrome, myocarditis

Hematologic system Severe anemia, hemolytic anemia, methemoglobinemia, congenital leukemia

Gastrointestinal system

Gut obstruction(congenital/acquire), necrotizing enterocolitis (NEC)

Signs and symptom

Differential diagnosis

Temperature instability

Environmental temperature, dehydration

Metabolic disorder Hypoglycemia, hypocalcemia, hypokalemia, organic acidemia, congenital adrenal hyperplasia, neonatal abstinence syndrome

Pneumonia• Pathogenesis: aspiration or

ingestion of bacteria in amniotic fluid

• Early signs and symptoms : poor feeding, lethargy, irritability, cyanosis, temperature instability

• Respiratory symptoms and progressive respiratory failure.

Pneumonia• Physical examination • Radiographs of the chest

may reveal new infiltrates or an effusion

Neonatal meningitis• Incidence : 0.2-0.4/1,000 live

births

• It is associated with the same pathogens that cause bacterial sepsis GBS and E. coli and L. monocytogenes

• The underlying pathogenesis of bacterial meningitis is a seeding of the meninges during a bacteremic phase in the infant.

Clinical manifestations

• Lethargy, feeding problems, instability of temperature regulation, vomiting, respiratory distress, and apnea.

• A bulging fontanel and seizures may be seen, but this is usually a late manifestation.

Complications• Ventriculitis, brain abscess, communicating

or noncommunicating hydrocephalus, subdural effusions, deafness, and blindness.

• Infants who survive neonatal meningitis should have regular audiology, language, and neurologic evaluations until they enter school

Group B Streptococcal Sepsis in Neonates

Escherichia Coli infections

• The second-most common pathogen causing sepsis and meningitis in newborn infants.

• The strains causing bacteremia or sepsis express K1.

• Mostly women may have bacteriuria with strains of E. coli that express the K1 antigen or are colonized at the time of delivery.

LABORATORY

INVESTIGATIONNeonatal sepsisBy MEDSWU Extern

Investigation• Gram’s stain & Culture• PCR• Antigen detection• CBC• Platelet count• Acute phase reactant

– CRP– α1-Antitrypsin

• ESR• Procalcitonin• Cytokine

WBC, ANC, I:T ratio

Index

Birth 12 hrs 24 hrs 48 hrs 72 hrs >120 hrs

WBC 9000 – 30000

ANC 1800 – 54007800 – 14400

7200 – 12600

4200 – 9000 1800 – 7000 1800 - 5400

I:T < 0.16 <0.16 <0.13 < 0.13 < 0.13 < 0.12

Birth 12 hrs

24 hrs

48 hrs

72 hrs

>120 hrs

0

5000

10000

15000

20000

25000

Sensitivity & Specificity

Sense. Spec. PPV NPV

ANC < 1750 /mm3 38-96 61-92 20-77 96-99

ANC < 10% 48 73 4 98

I:T Ratio ≥ 0.2 90-100 30-78 11-51 98

I:T Ratio ≥ 0.3 35 89 7 98

CRP > 1 mg/dL 70-93 78-94 27 100

PCR for Gram Pos. 74 98.5 98 79.1

PCR for Gram Neg. 86 99 98.9 87.6

TNF-α 73-82 80-94 78-84 74-84

PCT 73-78 72-81 72-80 73-78

hematologic scoring system >3

96 78 81.4 95

Avery’s Diseases of the Newborn, 9th ed.Early diagnosis of neonatal sepsis using a hematologic scoring system.by Rodwell RL, Leslie AL, Tudehope DI.

Hematologic Scoring System

HSS

WBC

ANC

i.PMN

I:TI:T ≥ 0.3

Plt. < 150,000/mm3

Degen.

PMNs.

Recommendation• As in CDC guideline :

– In symptomatic case full workup• CBC c Platelet, Hemoculture, CXR, LP

– In suspected case Limited workup• CBC c Platelet, Hemoculture

• Some expert recommend CBC at 6-12 hr. of age

• CRP is useful for follow up, and sensitivity is increase when take as serial blood that conventional one.

SEPSIS

TREATMENTNeonatal sepsisBy MEDSWU Extern

Treatment• Antibiotic is the treatment of choice for neonatal

sepsis.• Choice of antibiotics depend on the predominant

organism and the susceptibility profile of the organism.

• Any decision to discontinue antimicrobial therapy should be based on the level of suspicion for sepsis at the time treatment was begun, the culture results, laboratory test results, and the clinical behavior and course of the infant

• If the infant is highly suspicion of neonatal sepsis, antibiotic should be given the full course despite the negative culture result

Antibiotic• Choice of antibiotics should be effective against

both gram positive and gram negative bacteria

• Commonly use combinations are– Ampicillin and Gentamicin– Ampicillin and 3rd generation Cephalosporin

(Cefotaxime)

• Ampicillin and Gentamicin are effective against common pathogen such as group B Streptococcus (GBS) and Escherichia coli (E. Coli)

Antibiotic• 3rd generation cephalosporin is another

choice because– the minimal inhibitory concentrations needed for

treatment of gram-negative enteric bacilli are much lower than those for the aminoglycosides,

– excellent penetration into CSF occurs– much higher doses can be given; can be well

tolerated in neonate than gentamicin

• 3rd generation cephalosporin is associated with drug resistance organisms and it is less effective against L. monocytogenes

Antibiotic• Ampicillin and Gentamicin is still recommended in

community acquired late neonatal sepsis• If Staphylococcal infection is suspected a

combination of Cloxacillin and Gentamicin is recommended

• If nosocomial infection is suspected an antipseudomonal penicillin such as Ceftazidime is recommended

• Vancomycin is recommended for MRSA or MRSE• If an intestinal source for sepsis is suspected,

clindamycin is added to cover anaerobic organisms• Antibiotic should be adjusted according to the culture

result and susceptibility profile

Antibiotic

Antibiotic Dose (mg/kg)

Antibiotic Route Wt 1200 - 2000 g Wt > 2000 g

0–7 days > 7 days 0–7 days > 7 days

Ampicillin IV, IM 25 q12h 25 q8h 25 q8h 25 q6h

Ampicillin (Meningit

is)

IV, IM 50 q12h 50 q8h 50 q8h 50 q6h

Cefotaxime

IV, IM 50 q12h 50 q8h 50 q12h 50 q8h

Gentamicin

IV, IM 2.5 q12h 2.5 q8h 2.5 q12h 2.5 q8h

Vancomycin

IV 10 q12h 10 q12h 10 q8h 10 q8h

Antibiotic• Duration of Antibiotic Course

– 7 – 10 days for neonatal sepsis without meningitis– If meningitis is suspected, duration depend on the

pathogen• continue therapy for approximately 2 weeks after

sterilization of the cerebrospinal fluid• minimum of 2 weeks for gram-positive meningitis • minimum of 3 weeks for gram-negative meningitis• In difficult situations, therapy may be required for as long

as 4 to 6 weeks

– If suspicion is very low and culture result is negative, duration of 48 – 72 hrs is suffice

• Antibiotic with nephrotoxicity should have its drug level monitor

Immunological Therapy

• Adjunctive therapies that aim to improve the patient’s immune system such as IV-Ig, granulocyte transfusions and G-CSF or GM-CSF treatment

• Insufficient data for recommendation for routine use

• Each therapy should be used in specific case only

• Granulocyte Transfusion shows effectiveness if the infant has neutropenia

• IV-Ig shows effectiveness in preterm with very low birth weight

Adjunctive Therapy• Pentoxifylline is a

phosphodiesterase inhibitor that inhibit the production of TNF–Alpha

• Reduce mortality and hospital stay when use in neonatal sepsis

• Only had a study with small population

Supportive Treatment• Ventilation and Oxygenation

Support as indicated• Parenteral nutrition as

indicated• Maintain fluid, electrolyte

and glucose balance• Jaundice should be treat

aggressively, risk of kernicterus increase with sepsis and/or meningitis

Guideline

Intrapartum Antibiotic Prophylaxis

• Culture base vs. Risk Base Screening

• Screened all pregnant women for vaginal and rectal GBS colonization between 35 and 37 week’s gestation

• Offer Antibiotic for woman with colonization at time of labor or at time of rupture of membrane before labor

Intrapartum Antibiotic Prophylaxis

• If culture status is unknown:– Preterm labor (<37 wks

gestation)– PPROM– Prolong PROM >18 Hr– Intrapartum maternal fever >

38 oC or 100.4 oF– GBS bacteriuria during current

pregnancy– Previously given birth to a

infant with early-onset invasive GBS disease

Intrapartum Antibiotic Prophylaxis

• Recommended– Penicillin G, 5 mU intravenously then 2.5 mU IV

every 4 hours until delivery

• Alternative– Ampicillin, 2 g intravenously then 1 g every 4 hours– Ampicillin, 2 g IV every 6 hours

• Penicillin allergy : High risk for anaphylaxis– Clindamycin, 900 mg intravenously every 8 hours– Erythromycin, 500 mg intravenously every 6 hours– Vancomycin, 1 g intravenously every 12 hours

NEXT SECTION IS

SUMMARYNeonatal sepsisBy MEDSWU Extern

In summary• Definition of early or late are

varied, in Thailand mostly use the 4th day as a cut point

• Infant is a immunocompromised person easy to be infected.

• Vertical vs. Horizontal infection• Most common organism :

– GBS,E. coli in early– CoNS, K. pneumoniae, L.

monocytogenase in late sepsis

• Clinical manifestation is unspecified.

In summary• Laboratory investigation is a

helpful tool, but use wisely• CBC c slide is a good things

for decision to Rx, CRP is good for follow up.

• Don’t forget to take a Hemoculture!

In summary• Rx. ABX• Tailored to your patient (and

organism)• Empirical Rx– Ampicillin + Gentamycin– Ampicillin + Cefotaxime

• IAP should be given in Risk mother.