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Neonatal sepsis ppp

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    Neonatal sepsis ppp Neonatal sepsis ppp Presentation Transcript

    • بسم الله الرحمن الرحيم Neonatal Sepsis BKTH Department of Pediatrics Dr. magdah & Dr. Amal Unite April 2010 By: Dr. Mohamed Eisam Elhag Mahmoud MBBS, Alneelain University Faculty of Medicine Note: Dr. Mohammed Isam Al-Hajj does not have any financial relationships to disclose nor will he discuss any non-approved drug or device uses.
    • Babies and Bacteria... What will I learn ? Pathology * Causes * Symptoms * Diagnosis * Treatments
    • Definition
      • Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia occurring in the first month of life.
    • Epidemiology
      • Incidence : 1-8 cases per 1000 live births
      • Mortality: 50%
        • 13-69% world wide
        • 13-15% of all neonatal deaths (US) (8 th cause)
      • Morbidity: Meningitis occurs in one third of sepsis cases
      • Sex : males more
        • Culture proven 2/1000 (3-8% of infants evaluated for sepsis); 10-20/1000 VLBW
      • Age : premature infants
      • (1000-2000 g : 8-9/1000
      • <1000 g : 26/1000)
    • Pathophysiology
      • Neonate immune deficiency
      • neutrophil, monocyte, macrophage, T cell, immunoglobulin, complement
      • physical and chemical barriers
      •  Because of the interdependence of the immune response, these individual deficiencies of the various components of immune activity in the neonate cospire to create a hazardous situation for the neonate exposed to infectious threats !!
    • Classification
      • Early onset sepsis (EOS):
        • bacteria acquired before and during delivery
        • 5-7/1000 live birth
      • Late onset sepsis (LOS):
        • bacteria acquired after delivery (Nosocomial or community)
        • 20% of VLBW infants
    • Early onset sepsis Late onset sepsis Pathogens Group B Streptococcus E. coli Haemophilus influenzae Listeria Virus, STD Coagulase negative staphylococcus Staphy. aureus E. coli Klebsiella Pseudomonas Enterobacter Baby in risk Term, near-term baby Preterm baby
    • Predisposing Factors
      • General Host Factors
      • Prematurity (OR 25 if < 1,000 gms)
      • Race – GBS sepsis blacks>whites (x4)
      • Sex – sepsis & meningitis more common in males, esp. gram negative infections
      • Birth asphyxia, meconium staining, stress
      • Breaks in skin & mucous membrane integrity (e.g. omphalocoele, meningomyelocoele)
      • Environmental exposure
      • Procedures (e.g. lines, ET-tubes)
    • Predisposing Factors
      • Maternal/Obstetrical Factors
        • General – socioeconomic status, poor prenatal care, vaginal flora, maternal substance abuse, known exposures, prematurity , twins
        • Maternal infections – chorioamnionitis (1-10% of pregnancies), fever (>38° C/100.4° F), sustained fetal tachycardia, venereal diseases, UTI/bacteriuria, foul smelling lochia, GBS+ (OR 204), other infections
        • Obstetrical manipulation – amniocentesis, amnioinfusion, prolonged labor, fetal monitoring, digital exams, previa/abruption?
        • Premature & Prolonged ROM, preterm labor
    • pathogens can enter a neonate’s body in many ways ! Prenatal Maternal Substance Abuse Premature Rupture of Membranes (>18 Hours) Maternal Infection Perinatal Microbial Colonization at Birth Maternal Infection Vaginal Exam of Mother Postnatal Invasive Catheters Endotracheal Intubation Exposure to Nosocomial Microorganisms
    • Predisposing Factors
      • Overall sepsis rate 2/1000
      • Maternal Fever 4/1000
      • PROM 10-13/1000
      • Fever & PROM 87/1000
    • Preterm Labor/PROM
      • Prematurity (~10%) 15-25% due to maternal infection
      • >18-24h term; >12-18h preterm
      • Bacterial infection
        •  synthesis of PG
        • Macrophage TNF/IL stimulate PG synthesis, cytokine release **
        • Release of collagenase & elastase  ROM
      • + Amniotic fluid cultures 15% (with intact membranes)
    • S EPSIS
      • ORGANISMS (all babies)
      • Group B strep (most common G+) 41 %
      • Other strep 23%
      • Coliforms (E. coli most common G-) 17%
      • Staph aureus 4%
      • Listeria 2%
      • Nosocomial infections
      • Candida
      • Note: 73% G+ and 27% G-
    • S EPSIS
      • ORGANISMS (VLBW)
      • Group B strep (most common G+) 12%
      • Other strep 9%
      • Coliforms ( E. coli most common G-) 41%
      • CONS 15%
      • Listeria 2%
      • Nosocomial infections
      • Candida 2%
      • Note: 45% G+ and 53% G-
      • Source: Stoll et al Ped Inf Dis 2005, 24:635
    • Routes of Infection
      • Transplacental/Hematogenous
      • Ascending/Birth Canal
      • Aspiration
      • Device Associated Infection
      • Nosocomial
      • Epidemic
    • Transplacental/Hematogenous
      • Organisms (Not just “TORCHS”)
        • Toxoplasmosis Parvovirus
        • Rubella Gonorrhea
        • Cytomegalovirus Mumps
        • Herpes* TB
        • Syphilis Varicella
        • Acute Viruses HIV
        • Coxsackie Polio
        • Adenovirus GBS
        • Echo Malaria
        • Enterovirus Lyme
    • Ascending/Birth Canal
      • Organisms - GI/GU flora, Cervical/Blood
        • E. Coli Herpes
        • GBS Candida
        • Chlamydia HIV
        • Ureaplasma Mycoplasma
        • Listeria Hepatitis
        • Enterococcus Anaerobes
        • Gonorrhea Syphilis
        • HPV
    • Nosocomial
      • Organisms –
      • Skin Flora, Equipment/Environment
      • Staphylococcus – Coagulase neg & pos
      • MRSA
      • Klebsiella
      • Pseudomonas
      • Proteus
      • Enterobacter
      • Serratia
      • Rotavirus
      • Clostridium – C dificile
      • Fungi
    • Coagulase-Negative Staphylococci
      • commonest cause of Nosocomial bacteremia
        • ventriculoperitoneal shunt infection
        • Endocarditis with umbilical lines
      • S. epidermidis , S. haemolyticus , S. hominis , S. saprophyticus
    • Infection
      • Timing
      • Onset
        • Early Onset 1 st 24 hrs 85 %
        • 24-48 hrs 5%
        • Late Onset 7-90 days
    • Clinical Presentation
      • initial diagnosis of sepsis is, by necessity, a clinical one because it is imperative to begin treatment before the results of culture are available
      • Clinical S/Sx of sepsis are nonspecific , and the differential diagnosis is broad
    • Non-specific/Common
      • Temperature irregularity . Hypo- or hyperthermia (greater heat output required by the incubator or radiant warmer to maintain a neutral thermal environment or frequent adjustments of the infant servo control probe).
      • Change in behavior . Lethargy, irritability (23%), or change in tone.
      • Skin . Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, rashes, sclerema, or jaundice.
      • Skin . Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, rashes, sclerema, or jaundice.
      • Feeding problems . Feeding intolerance, vomiting, diarrhea (watery loose stool), or abdominal distention with or without visible bowel loops/ ileus,.
      • 5 -Cardiopulmonary . Tachypnea, respiratory distress (90%)(grunting, flaring, and retractions), apnea within the first 24 h of birth or of new onset (especially after 1 week of age), tachycardia, or hypotension (5%),, which tends to be late sign.
      • 6- Metabolic . Hypo- or hyperglycemia or metabolic acidosis.
    • Symptoms
      • Less common
        • Seizures
        • DIC
        • Petechiae
        • Hepatosplenomegaly
        • Sclerema
      • Meningitis symptoms
        • Irritability, lethargy, poorly responsive
        • Changes in muscle tone, etc.
    • Evaluation
      • Non-specific
        • CBC/diff, platelets – ANC, I/T ratio
        • Radiographs
        • CRP
        • Fluid analysis – LP,  U/A
        • Glucose, lytes, gases
      • Specific – Cultures, stains
      • Other – immunoassays, PCR, DNA microarray
    • Results “Trigger Points”
      • CBC
        • WBC <5.0, abs neutro < 1,750 , bands >2.0
        • I/T ratio > 0.2*
        • Platelets < 100,000
      • CRP > 1.0 mg/dl
      • CSF > 20 WBC’s with few or no RBC’s
      • Radiographs: infiltrates on CXR, ileus on KUB, periosteal elevation, etc.
    •  
    • Lumbar puncture (CSF)
      • Indications
      • -- Sepsis is considered primary diagnosis
      • -- Blood culture positive
      • -- Neurologic signs or symptoms
      • Specific Tests
      • -- CSF examination
      • -- CSF Culture
      • --CSF antigens
      • pneumonia  CXR
      • Meningitis  CT, head ultrasound
      • Late onset sepsis:
      • In addition to the above consider
      • Blood culture taken through central line.
      • Urine by suprapubic aspirate [preferable] or catheter.
    • False negative Blood Culture
      • Maternal antibiotics
      • Small blood sample
      • Bacteria load, timing of sampling
    • D ifferential D iagnosis
      • Respiratory distress syndrome (RDS)
      • Metabolic diseases
      • Hematologic disease
      • CNS disease
      • Cardiac disease
      • other infectious processes (ie. TORCH infections)
    • Treatment First five days. After first five days. Start ampicillin and gentamicin for 1.all VLBW neonates and 2. any infant who --Appears septic or is sicker than would be usually anticipated. --Has any vascular catheter Start amoxycillin and cefoxitin in all other babies Start vancomycin and amikacin in all babies (Almost all Coag negative Staph is sensitive to Amikacin but resistant to gentamicin. ) ( Flucloxacillin being used at present because of an increased number of Staph aureus isolates within the unit ) Add amoxycillin if specific cover for Enterococci, Strep fecaelis [suspected NEC], Listeria or Group B Strep is needed.
    • Treatment
      • Ampicillin and Amikacin for empiric treatment of EONS
      • Oxacillin and amikacin for empiric treatment of LONS reduce
    • Treatment
      • Prevention – vaccines, GBS prophylaxis, HAND-WASHING
      • Supportive – respiratory, metabolic, thermal,nutrition( Encourage breast milk provide immunologic protection ) , monitoring drug levels/toxicity
      • Specific – antimicrobials, immune globulins
      • Non-specific – IVIG, NO inhibitors & inflammatory mediators
    • Neonatal Sepsis: the special case of Group B Strep Sepsis
      • RISK FACTORS
      • Previous GBS-infected baby
      • Gestational age <37 wks
      • Maternal disease (esp. GBS UTI)
      • Ruptured membranes > 18 hours
      • Location of delivery (e.g., home)
      • Infant/Fetal symptommatology
      • Clinical suspicion
      • Note: incidence has fallen 80% since CDC prevention guidelines were published in 1996
      GBS S EPSIS
    • Mothers in labor or with ROM should be treated if:
      • Chorioamnionitis
      • History of previous GBS+ baby
      • Mother GBS+ or GBS-UTI this preg.
      • Mother’s GBS status unknown and:
        • < 37 wks gestation
        • ROM ≥ 18 hrs
        • Maternal temp ≥ 38 o (100.4 o F)
      • INFANTS TO BE SCREENED
      • Maternal “chorioamnionitis”
      • Maternal illness (i.e. UTI, pneumonia)
      • Maternal peripartum fever > 38 o (100.4 o F)
      • Prolonged ROM ≥ 18 hrs ( ≥ 12 hrs preterm)
      • Mother GBS+ with inadequate treatment ( < 4 hrs )
        • No screening necessary if C-section delivery with intact membranes
      GBS S EPSIS
      • INFANTS TO BE SCREENED
      • Prolonged labor (> 20 hrs)
      • Home or contaminated delivery
      • “ Chocolate-colored”/foul smelling amniotic fluid
      • Persistent fetal tachycardia
      • SYMPTOMATIC INFANT
        • treat immediately (in DR if possible)
      GBS S EPSIS
      • SEPSIS SCREEN
      • CBC with differential
      • Platelet count
      • Blood culture x 1-2 (ideally 1 ml)
      • Chest X-ray &/or LP if symptommatic
      • Close observation and frequent clinical evaluation
      • Role of CRP
      GBS S EPSIS
    • GBS prophylaxis
      • The guidelines recommended one of two approaches:
      • 1- the prenatal screening approach (screening all pregnant women for GBS infection at 35—37 weeks gestation and treatment of those women with positive cultures )
      • 2- identifying women who present with risk factors treating them during labor
    •  
    • Diagnosis
    • S EPSIS
      • SIGNS and SYMPTOMS
      • temp instability • lethargy
      • poor feeding/residuals • resp distress >60
      • glucose instability • poor perfusion
      • hypotension • bloody stools
      • abdominal distention • bilious emesis
      • apnea • tachycardia
      • skin/joint findings
    • Clinical Signs according to WHO Integrated Management of Childhood illness
      • Respiratory rate >60 breaths/min
      • Retraction, flaring, Grunting
      • Crepitation
      • Cyanosis
      • Temperature >37.7°C (or feels hot) or <35.5°C (or feels cold)
      • Convulsions ,Lethargic or unconscious
      • Reduced movements and activity)
      • Not able to feed (sustain suck)
      • Bulging fontanels
      • LABORATORY EVALUATION
      • Provide added value when results are normal
        • high negative predictive value
        • low positive predictive value
          • abnl results could be due to other reasons and not infection
      • IT < 0.3, ANC > 1,500 (normal) do not start abx, or d/c abx if started, if pt remains clinically stable
      • IT > 0.3, ANC < 1,500 consider initiation of abx pending bld cx in “at-risk” pt who was not already begun on antibiotics for other factors
      S EPSIS
      • LABORATORY EVALUATION
      • Positive screen
        • total WBC < 5,000 – I/T > 0.3
        • ANC < 1,500 – platelets < 100,000
      • Additional work-up
        • CXR , urine cx , and LP as clinically indicated
      • CRP
        • Best discriminatory value for predicting septicemia
        • no added value for diagnosis of early onset sepsis
        • best for negative predicative value or when used serially sensitivity 48 to 63%
        • not to be used to decide about rx, duration of rx or need for LP
        • positive results for a single value obtained at 24 hrs ranges > 4.0 - 10.0 mg/dL
    • New Diagnostic Methods
      • Interleukin 6,8
      • IgM
      • Polymerase chain reaction (PCR)
      • DNA microarray technology
      • Immunoassay
    • S EPSIS
      • TREATMENT
      • Review protocol
      • Antibiotics
        • Ampicillin 100 mg/kg/dose IV q 12 hours
        • Gentamicin 4 mg/kg/dose IV q 24 hours
          • IM route may be used in asymptomatic pt on whom abx are initiated for maternal risk factors or to avoid delays when there is difficulty obtaining IV
        • For meningitis: Ampicillin 200-300 mg/kg/d
      • Symptomatic management
        • respiratory, cardiovascular, fluid support
    • Prognosis
      • Fatality rate 2-4 times higher in LBW than in term neonates
      • Overall mortality rate 15-40%
      • Survival less likely if also granulocytopenic (I:T > 0.80 correlates with death and may justify granulocyte transfusion).
    • Infection and ND Outcome
      • IUI and postnatal infection both appear to increase the risk for adverse ND outcome
      • Role of inflammatory mediators/SIRS in brain injury in the preterm infant
        • Pressure passive CNS circulation
        • Direct cytotoxicity to the developing brain
        • Inherent vulnerability of the oligodendrocyte precursor
    • Clinical Infection Sepsis Alone Sepsis+NEC Sepsis+Meningitis
    • Late Onset Infection
      • Majority of ELBW infants will develop
      • late onset sepsis
      • Significant associated morbidity and mortality
      • CONS still the most common pathogen
      • Gram-negative pathogens increasing in prevelance and are associated with higher mortality rate
    • Prevention of Nosocomial Infections
      • HANDWASHING
      • HANDWASHING
      • Universal precautions
      • Limit use devices and catheters
      • Minimize catheter manipulation
      • Nursery design
      • Meticulous skin care
      • Education
    • Congenital Rubella Syndrome
      • • Microcephaly, IUGR
      • • Pulmonary stenosis, PDA
      • • Cataracts, chorioretinitis, microphthalmia
      • • Sensorineural Deafness
      • • Long bone radiolucencies
      • • Renal Anomalies
      • • Anaemia, low platlets, Hepatosplenomegaly
    • Chicken Pox
      • 95% pregnant women have immunity- no risk
      • Mat. Varicella: onset 7days pre to 5d post partum
      • - give ZIG asap to baby once born
      • - Acyclovir to Mum, to baby if ? infected
      • - Isolate
      • Small risk of syndrome in 1st and 2n d trimester
      • - scarring, skin defects, optic atrophy
      • ZIG to pregnant Mum if exposed and not immune
    • When to suspect Cong. Infection
      • • IUGR - all parameters
      • • Head Circ is <3rd or >97thile
      • • Anaemia, Thrombocytopaenia
      • • Hepatosplenomegaly, Rash
      • • Cataract, blindness, deafness ( late pick-up)
      • • Poor tone, poor suck, late milestones
      • • Stillbirth / FDIU / Neonatal death
    • How investigate Cong. Infection
      • • Cord blood : total IgM
      • • Cord /baby blood:TORCH screen IgM, IgG
      • • CMV: Urine culture Throat/ saliva PCR
      • • FBE, LFTs, EUC, RPR, VDRL +/- LP
      • • Toxo culture by inoculate mice with blood
      • • Cranial US , Cardiac ECHO ( rubella)
      • • Long Bone xrays ( rubella)
      • • Ophthalmological r/vHearing screen
    • How to treat
      • • Rubella - to late
      • • Toxo - Pyrimethamine, Sulphadiazine,
      • • Folinic Ac + regular FBE, LFTs
      • • CMU - Ganciclovir
      • • Syphilis - Penicillin for 10-14 days
      • • HSV - Aciclovir
    •  
      • I hope you have enjoyed your experience and have learned some new information about neonatal sepsis.
    • Thank You!!