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 *NeoReviews,Vol.11,No.8,August 2010SepticemiaPneumoniaMeningitisA
2、rthritisOsteomyelitisUrinary tract infection NNP Network,2005Intramural admissions -Klebsiella pneumoniae(32.5%)-Staphylococcus aureus(13.6%)Extramural admissions -Klebsiella(27.5%)-S aureus(38%)Sankar et al.Indian j Pediatr.2008;75:261-6 sepsis(any one criteria):-Maternal fever or foul smelling amn
3、iotic fluid -PROM(24 hrs)or gastric polymorphs(5 hpf)-Positive sepsis screen(any two criteria)-Total WBC count(0.2)-Total WBC count 1mg/dl,micro ESR 10 mm-first hour -Radiological evidence of pneumonia NNF,India Culture positive sepsis -Isolation of the pathogen from blood,CSF,urine or abscess 72 ho
4、urs of age Pathological evidence of sepsis on autopsy NNF,IndiaIncidence of EOS is 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 antibi
5、otic prophylaxis.Mortality 2.6%in term and 35%in VLBW infants.Survivors of EOS may have severe neurologic sequelae attributable to meningitis,hypoxemia,septic shock,PPHN etc.Puopolo KM.NeoReviews 2008;9:e571-579Early onset sepsis(24 hours)More than three vaginal exam during labor Prolonged and diffi
6、cult delivery with instrumentation Perinatal asphyxia(apgar 72 hours)usually nosocomial or community acquired)Risk factors:NICU admission Poor hygiene Low birth weight Poor cord care Prematurity Bottle feeding Invasive procedure Superficial infection(pyoderma,umbilical sepsis)Ventilation Aspiration
7、of feedsPuopolo,K.,NeoReviews 2008,9;571-e579 Puopolo,K.,NeoReviews 2008,9;571-e579 Puopolo,K.,NeoReviews 2008,9;571-e579 Puopolo,K.,NeoReviews 2008,9;571-e579 Group B Strep(GBS)Incidence used to be 4-6/1000 live births(0.4%)Now 0.1%after prenatal screening guidelinesE.coli Every few decades flips b
8、ack and forth with GBS as most common causeGram negative rods(esp.in urine)Occasional Salmonella sepsisListeria monocytogenesHerpes SimplexEnterovirusGBS or group A strepEnterics/Enterococcus in urineHSVEnterovirus,RSV,FluPneumococcusMeningococcusGABHSHaemophilus influenzae(HIB)not really a problem
9、anymoreTemperature irregularity Fever HypothermiaTone and Behavior Poor tone Weak suck Shrill cry Weak cry IrritabilitySkin Poor perfusion Cyanosis Mottling Pallor Petechiae Unexplained jaundiceFeeding Problems Vomiting Diarrhea Abdominal distension Hypo or HyperglycemiaCardiopulmonary Tachypnea Ret
10、ractions Tachycardia for age Bradycardia in first few days of life Hypotension for age Low 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 sign
11、s had an almost 100%sensitivity for sepsis and over 90%mortalityReduced 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
12、of meningitis 0.3-3%)In EOS LP is indicated in the presence of+blood 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 R
13、DS -Critically ill and hemodynamically unstable babiesCellsWBCsPolymorphonuclearcells7(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 lif
14、e.In LOS urine culture should be obtained by suprapubic 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 nec
15、rotizing enterocolitisAcute phase reactantsCell surface markersGranulocyte colony stimulating factorCytokinesMolecular geneticsMol cell proteomicsThese endogenous peptides are produced by the liver as part of immediate response to infection or injury C-reactive protein Procalcitonin Fibronectin Hapt
16、oglobin Lactoferrin Neopterin OromucosoidFive identical subunits(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 infe
17、cted patients and sera of convalescent patients lost 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 func
18、tion of CRP is not known.CRP activates complement 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 adu
19、lts:0.8mg/LIn infants:10mg/LStarts with in 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 marke
20、rs.CD 64 had sensitivity of 80%and specificity 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 sensitivit
21、y of 95%and specificity of 99%.PCT 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 infant
22、s.PCT values of 2.3ng/ml and 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
23、43%in late onset sepsis.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
24、 a specificity of 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 usef
25、ul method for identification 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 wi
26、ll allow identification 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 C
27、efotaximeHospital acquired infection:-Vancomycin/Oxacellin/Cefotaxime(6070%of Gm negative organisms are resistant)MRSA:-Vancomycin/Ciprofloxacin/AmikacinEnterococus:-Ampicillin and Gentamicin Psuudomonas:-Piperacilli-tazobactam with Amikacin Penicillin resistant staphylococcus:Cloxacillin,Nafcillin
28、or MethicillinIntravenous Immune Globulin(IVIG):There is insufficient evidence to support the routine use of IVIG in suspected or proven sepsis.Granulocyte colony stimulating factor(G-CSF):Insufficient evidence to support the use of G-CSF.Exchange transfusion:Has not been well studied in neonatal se
29、psis.May be used with caution in certain situations(DIC,severe metabolic acidosis)Pentoxifylline:This is a methylxanthine that has been postulated to modulate the activity of RES and decrease the neutrophil activation that contributes to acute injury.Tripathi S et al.Internet Journal of medical update 2010;5:45-54
