neonatal sepsis
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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.
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