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, 2019 *NeoReviews, Vol.11, No.8, August 2019SepticemiaPneumonia
2、MeningitisArthritisOsteomyelitisUrinary tract infection NNP Network, 2019Intramural admissions -Klebsiella pneumoniae (32.5%) -Staphylococcus aureus (13.6%)Extramural admissions -Klebsiella (27.5%) -S aureus (38%) Sankar et al. Indian j Pediatr.2019;75:261-6 sepsis (any one criteria): -Maternal feve
3、r or foul smelling amniotic 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
4、 blood, CSF, urine or abscess 72 hours 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 li
5、ve births (2019) due to intrapartum antibiotic 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 2019;9:e571-579Early onset sepsis (24 hours) More than
6、three vaginal exam during labor Prolonged and difficult 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 infe
7、ction (pyoderma, umbilical sepsis) Ventilation Aspiration of feedsPuopolo, K., NeoReviews 2019, 9;571-e579 Puopolo, K., NeoReviews 2019, 9;571-e579 Puopolo, K., NeoReviews 2019, 9;571-e579 Puopolo, K., NeoReviews 2019, 9;571-e579 Group B Strep (GBS) Incidence used to be 4-6/1000 live births (0.4%) N
8、ow 0.1% after prenatal screening guidelinesE. coli Every few decades flips back 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,
9、FluPneumococcusMeningococcusGABHSHaemophilus influenzae (HIB) not really a problem anymoreTemperature irregularity Fever HypothermiaTone and Behavior Poor tone Weak suck Shrill cry Weak cry IrritabilitySkin Poor perfusion Cyanosis Mottling Pallor Petechiae Unexplained jaundiceFeeding Problems Vomiti
10、ng Diarrhea Abdominal distension Hypo or HyperglycemiaCardiopulmonary Tachypnea Retractions 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 wellPresenc
11、e 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 suckingWeak cryCool extremitiesVomitingPoor toneRetractionsBlood culture (1ml sample adequate) possible to detect growth in 24 hours using BA
12、CTEC 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 + blood culture or symptoms of septicemiaIn LOS, LP should be done in all infants prior to starting antibioticsLP should not be done in the follo
13、wing cases: -Asymptomatic babies investigated for maternal risk factors -Premature babies with RDS -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 gluco
14、se81 (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 suprapubic puncture or catheterization.UTI diagnosis: 10WBC/mm in a 10 ml centrifuged sample 10 organisms/mL in catheterized specimen Any organism in
15、 a suprapubic specimenChest X ray in case of respiratory distress or apneaAbdominal X Ray if suspecting necrotizing enterocolitisAcute phase reactantsCell surface markersGranulocyte colony stimulating factorCytokinesMolecular geneticsMol cell proteomicsThese endogenous peptides are produced by the l
16、iver as part of immediate response to infection or injuryC- reactive proteinProcalcitoninFibronectinHaptoglobinLactoferrinNeopterinOromucosoidFive identical subunits (protomers) that are arranged around a central pore NeoReviews, 2019;6:e508-515Non- type- specific somatic polysaccharide fraction ext
17、racted from Streptococcus pneumoniae. “Fraction C” as it was called was precipitated by sera of acutely infected 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 synth
18、esized 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 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 i
19、n lipid metabolism and contribute to the pathogenesis of atherosclerosis and myocardial infarction.In healthy adults: 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 stimu
20、lus 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 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, mediato
21、r 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%.PCT is produced by the monocytes and hepatocytes and is propeptide of calcitonin.PCT rises 4-6 hours after exposure to bacterial endotoxin pea
22、king 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 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 val
23、ue 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 sepsis.Greater elevation in CRP concentrations were associated with higher probability of infection.Negative predictive value was highest both for
24、 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 87%.TNF and median IL6 values were significantly higher in patients with sepsis compared to controls.Franz et al. Pediatrics 2019;114:1-8Poly
25、merase 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 identification of bacteria in clinical samples.PCR assay is challenging due to small amount of residual DNA present reagents resulting in fals
26、e positivity.Detection by PCR does not yield the antimicrobial pattern of the pathogen.Real time PCR combined with DNA Micro Array technology will allow identification and antimicrobial sensitivity of the organism.Proteomics: Significant alterations in the levels of eight serum proteins were found i
27、n infected neonates.Culture - veCulture + ve NeoReviews, 2019;6:e508-515 NeoReviews, 2019;6:e508-515 Early onset sepsis: -Ampicillin and Gentamicin or CefotaximeHospital acquired infection: -Vancomycin/ Oxacellin/Cefotaxime (6070% of Gm negative organisms are resistant)MRSA: -Vancomycin/Ciprofloxaci
28、n/ AmikacinEnterococus: -Ampicillin and Gentamicin Psuudomonas: -Piperacilli-tazobactam with Amikacin Penicillin resistant staphylococcus: Cloxacillin, Nafcillin or MethicillinIntravenous Immune Globulin (IVIG): There is insufficient evidence to support the routine use of IVIG in suspected or proven
29、 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 sepsis. 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 2019;5:45-54谢谢！
