Sepsis

Neonatal

13 June 2012
By MEDSWU Extern

SIGN & SYMPTOM

DEFINITION, INCIDENT

Neonatal sepsis
By MEDSWU Extern

Definition and Incidence

Early-onset bacterial infection
2006

0.40 case per 1000 live births Late-onset GBS disease

2006

0.30 case per 1000 live births

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 mothers 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 Intrapartum complication transmission

Early onset Often present Vertical Organism from mothers genital tract Fulminant course Multisystem involvement Respiratory distress, apnea Pneumonia: common Reduce incidence by 8590% 5-20 %

Late onset Usually absent Vertical Nosocomial infection Insidious onset Focal infection Irritable, fever, poor feeding Meningitis: common No effect 5%

Clinical manifestation

Effect of intrapartum IV antibiotic prophylaxis Case fatality rate

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 Respiratory system (sepsis with or without pneumonia)

Differential diagnosis Respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTNB), aspiration pneumonia, meconium aspiration syndrome (MAS) Birth trauma, intracranial hemorrhage, inborn errors of metabolism, drug withdrawal, congenital malformation

Neurological system

Signs and symptom Cardiovascular system Hematologic system

Differential diagnosis Hypoplastic left heart syndrome, myocarditis Severe anemia, hemolytic anemia, methemoglobinemia, congenital leukemia Gut obstruction(congenital/ac quire), necrotizing enterocolitis (NEC)

Gastrointestinal system

Signs and symptom Temperature instability Metabolic disorder

Differential diagnosis Environmental temperature, dehydration 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.

INVESTIGATION

LABORATORY

Neonatal sepsis
By MEDSWU Extern

Investigation
Grams stain & Culture PCR Antigen detection CBC Platelet count Acute phase reactant
CRP 1-Antitrypsin

ESR Procalcitonin Cytokine

25000

WBC, ANC, I:T ratio

20000 15000 10000 5000 0

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

Index WBC

Birth

12 hrs

24 hrs

48 hrs

72 hrs

>120 hrs

9000 30000

ANC

1800 5400

7800 14400

7200 12600

4200 9000

1800 7000

1800 - 5400

I:T

< 0.16

<0.16

<0.13

< 0.13

< 0.13

< 0.12

Averys Diseases of the Newborn, 9th ed. Early diagnosis of neonatal sepsis using a hematologic scoring system.

by Rodwell RL, Leslie AL, Tudehope DI.

Sensitivity & Specificity

Sense. ANC < 1750 /mm3 ANC < 10% I:T Ratio 0.2 I:T Ratio 0.3 38-96 48 90-100 35 Spec. 61-92 73 30-78 89 PPV 20-77 4 11-51 7 NPV 96-99 98 98 98

CRP > 1 mg/dL

PCR for Gram Pos. PCR for Gram Neg. TNF- PCT hematologic scoring system >3

70-93
74 86 73-82 73-78

78-94
98.5 99 80-94 72-81

27
98 98.9 78-84 72-80

100
79.1 87.6 74-84 73-78

96

78

81.4

95

Hematologic Scoring System

WBC Degen. PMNs. ANC

Plt. < 150,000 /mm3

HSS
I:T 0.3 I:T

i.PMN

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.

TREATMENT

SEPSIS

Neonatal sepsis
By 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 Ampicillin Route IV, IM Wt 1200 - 2000 g 07 days 25 q12h > 7 days 25 q8h Wt > 2000 g 07 days 25 q8h > 7 days 25 q6h

Ampicillin (Meningitis)
Cefotaxime Gentamicin Vancomyci n

IV, IM
IV, IM IV, IM IV

50 q12h 50 q12h
2.5 q12h 10 q12h

50 q8h 50 q8h
2.5 q8h 10 q12h

50 q8h 50 q12h
2.5 q12h 10 q8h

50 q6h 50 q8h
2.5 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 patients immune system such as IVIg, 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 weeks 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

SUMMARY

NEXT SECTION IS

Neonatal sepsis
By 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. Dont 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.