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1、 Most common cause of neonatal mortality in developing countries.Up to 20% of neonates develop sepsis and 1% die of sepsis related causes.Incidence of systemic infection is 3% (India) with septicemia (75%) and pneumonia (25%) NNP Network, 2005 3.6 3:4.1 0 to 10.5 25.0 23.6:26.3 0 to 53.7 26.4 19.1:3
2、3.7 20 to 57.1 13.3 11.2:15.4 1.8 to 35.6*Intra units (5 or more cases)Data from Valls-e-Soker A, et al. 2021 (5)NeoReviews, Vol.11, No.8, August 2021SepticemiaPneumoniaMeningitisArthritisOsteomyelitisUrinary tract infection NNP Network, 2005Intramural admissions -Klebsiella pneumoniae (32.5%) -Stap
3、hylococcus aureus (13.6%)Extramural admissions -Klebsiella (27.5%) -S aureus (38%) Sankar et al. Indian j Pediatr.2021;75:261-6 Culture positive sepsis -Isolation of the pathogen from blood, CSF, urine or abscess 72 hours of age Pathological evidence of sepsis on autopsy NNF, IndiaIncidence of EOS i
4、s 1-2 cases/1000 live births.This incidence is 10 fold higher in the VLBW infants.Incidence of early onset GBS has declined 80% from 1.7 cases /1000 live births (1993) to 0.34/1000 live births (2005) due to intrapartum antibiotic prophylaxis.Mortality 2.6% in term and 35% in VLBW infants.Survivors o
5、f EOS may have severe neurologic sequelae attributable to meningitis, hypoxemia, septic shock, PPHN etc. Puopolo KM. NeoReviews 2021;9:e571-579Early onset sepsis (24 hours)More than three vaginal exam during laborProlonged and difficult delivery with instrumentationPerinatal asphyxia (apgar 72 hours
6、) usually nosocomial or community acquired) Risk factors:NICU admissionPoor hygieneLow birth weightPoor cord carePrematurityBottle feedingInvasive procedureSuperficial infection (pyoderma, umbilical sepsis)VentilationAspiration of feedsPuopolo, K., NeoReviews 2021, 9;571-e579 Puopolo, K., NeoReviews
7、 2021, 9;571-e579 Puopolo, K., NeoReviews 2021, 9;571-e579 Puopolo, K., NeoReviews 2021, 9;571-e579 Group B Strep (GBS)Incidence used to be 4-6/1000 live births (0.4%)Now 0.1% after prenatal screening guidelinesE. coliEvery few decades flips back and forth with GBS as most common causeGram negative
8、rods (esp. in urine)Occasional Salmonella sepsisListeria monocytogenesHerpes SimplexEnterovirusGBS or group A strepEnterics/Enterococcus in urineHSVEnterovirus, RSV, FluPneumococcusMeningococcusGABHSHaemophilus influenzae (HIB) not really a problem anymoreTemperature irregularityFeverHypothermiaTone
9、 and BehaviorPoor toneWeak suckShrill cryWeak cryIrritabilitySkinPoor perfusionCyanosisMottlingPallorPetechiaeUnexplained jaundiceFeeding ProblemsVomitingDiarrheaAbdominal distensionHypo or HyperglycemiaCardiopulmonaryTachypneaRetractionsTachycardia for ageBradycardia in first few days of lifeHypote
10、nsion for ageLow PO2Sunken fontanelleBulging or pulsating fontanelleNeck stiffness CAN NOT be usedBabies can be bacteremic but look wellPresence of a “cold does not change anythingStudy in India found that any two of these signs had an almost 100% sensitivity for sepsis and over 90% mortalityReduced
11、 suckingWeak cryCool extremitiesVomitingPoor toneRetractionsBlood culture (1ml sample adequate) possible to detect growth in 24 hours using BACTEC or BACT/ALERT systemsTotal WBC count (0.2CRP 1mg/dl or Micro- ESR 15mm/hrLP (incidence of meningitis 0.3-3%)In EOS LP is indicated in the presence of + b
12、lood culture or symptoms of septicemiaIn LOS, LP should be done in all infants prior to starting antibioticsLP should not be done in the following cases: -Asymptomatic babies investigated for maternal risk factors -Premature babies with RDS -Critically ill and hemodynamically unstable babiesCellsWBC
13、sPolymorphonuclearcells7 (0-32)61%9 (0-29)57%Protein (mg/dl)90 (20-170)115 (65-150)Glucose (mg/dl)52 (34-119)50 (24-63)CSF glucose:Blood glucose81 (44-248)74 (55-105)Urine culture should not be part of sepsis evaluation in the first 72 hours of life.In LOS urine culture should be obtained by suprapu
14、bic puncture or catheterization.UTI diagnosis: 10WBC/mm in a 10 ml centrifuged sample 10 organisms/mL in catheterized specimen Any organism in a suprapubic specimenChest X ray in case of respiratory distress or apneaAbdominal X Ray if suspecting necrotizing enterocolitisAcute phase reactantsCell sur
15、face markersGranulocyte colony stimulating factorCytokinesMolecular geneticsMol cell proteomicsThese endogenous peptides are produced by the liver as part of immediate response to infection or injuryC- reactive proteinProcalcitoninFibronectinHaptoglobinLactoferrinNeopterinOromucosoidFive identical s
16、ubunits (protomers) that are arranged around a central pore NeoReviews, 2005;6:e508-515Non- type- specific somatic polysaccharide fraction extracted from Streptococcus pneumoniae. “Fraction C as it was called was precipitated by sera of acutely infected patients and sera of convalescent patients los
17、t the ability to cause precipitation.Acute phase reactant protein composed of five identical nonglycosylated polypeptide subunits.It is synthesized in hepatocytes, regulated at the transcription level by interleukin (IL) -6 and IL -1- beta.The exact function of CRP is not known.CRP activates complem
18、ent and has a functional effect on phagocytic cells and play an important role in the first line of host defense.CRP may be a key component in lipid metabolism and contribute to the pathogenesis of atherosclerosis and myocardial infarction.In healthy adults: 0.8mg/ LIn infants: 10mg/LStarts with in
19、4-6 hours after stimulation and peaks around 36- 48 hours.Biologic half life is 19 hours with 50% reduction daily after the acute phase stimulus resolves.Measuring CRP concentration in CSF is unreliable.Neutrophil CD 11b and CD 64 appear to be promising markers.CD 64 had sensitivity of 80% and speci
20、ficity of 79% in culture proven sepsis.CD 11b had a sensitivity of 96- 100% and specificity of 81- 100% in culture proven sepsis.GSF, mediator produced by the bone marrow facilitates proliferation of neutrophils in sepsis. A concentration of 200pg/ml has a sensitivity of 95% and specificity of 99%.P
21、CT is produced by the monocytes and hepatocytes and is propeptide of calcitonin.PCT rises 4-6 hours after exposure to bacterial endotoxin peaking at 6- 8 hours.Half life of PCT 25- 30 hours.Elevated concentrations are found in RDS, IDM and hemodynamically unstable infants.PCT values of 2.3ng/ ml and
22、 CRP 30mg/ L indicates a high likely hood of late onset sepsis.Serial measurements in early and late onset sepsis showed the best cut off value of 10mg/ L (Stanford)CRP concentration was normal in 30% of all sepsis episodes.PPV was 5% for culture proven early onset sepsis and 43% in late onset sepsi
23、s.Greater elevation in CRP concentrations were associated with higher probability of infection.Negative predictive value was highest both for early and late onset sepsis after three values (99.7 and 98.7)Two CRP concentration 70pg/ml)and CRP (10mg/L) showed a sensitivity of 80% and a specificity of
24、87%.TNF and median IL6 values were significantly higher in patients with sepsis compared to controls.Franz et al. Pediatrics 2004;114:1-8Polymerase chain reaction (PCR) analysis relies on the fact that bacteria specific 16S rRNA gene is conserved in all bacterial genomes and is a useful method for i
25、dentification of bacteria in clinical samples.PCR assay is challenging due to small amount of residual DNA present reagents resulting in false positivity.Detection by PCR does not yield the antimicrobial pattern of the pathogen.Real time PCR combined with DNA Micro Array technology will allow identi
26、fication and antimicrobial sensitivity of the organism.Proteomics: Significant alterations in the levels of eight serum proteins were found in infected neonates.Culture - veCulture + ve NeoReviews, 2005;6:e508-515 NeoReviews, 2005;6:e508-515 Early onset sepsis: -Ampicillin and Gentamicin or CefotaximeHospital acquired infection: -Vancomycin/ Oxacellin/Ce
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