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Neonatal Sepsis and Recent Challenges

Neonatal Sepsis and Recent Challenges. Mohammad Khasswneh, MD Assistant Professor of Pediatrics JUST. introduction. Common 20% of VLBW has sepsis In term 0.1% Inter-institution difference 11-32% ( NICHD net work ) Serious mortality is 3-5 times more for infant with sepsis in NICU.

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Neonatal Sepsis and Recent Challenges

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  1. Neonatal Sepsis and Recent Challenges Mohammad Khasswneh, MD Assistant Professor of Pediatrics JUST

  2. introduction • Common • 20% of VLBW has sepsis • In term 0.1% • Inter-institution difference 11-32% (NICHD net work) • Serious • mortality is 3-5 times more for infant with sepsis in NICU

  3. Classification • Early onset sepsis (EOS): • bacteria acquired before and during delivery • 5-7/1000 live birth • 1.5% of VLBW infants had EOS (intrapartum antibiotics) • Late onset sepsis (LOS): • bacteria acquired after delivery (Nosocomial or community) • 20% of VLBW infants

  4. Who is the septic neonate? • Positive blood culture with clinical symptoms of infection • Coagulase-negative Staphylococcus (CoNS) • 2 positive blood cultures • One positive blood culture and elevated CRP • Clinical sepsis” or “probable sepsis

  5. Adult and PediatricsDefinitions • Systemic Inflammatory response syndrome (SIRS) • Sepsis • as SIRS plus infection • Severe sepsis: • as sepsis associated with organ dysfunction, hypo perfusion or hypotension, • Septic shock • sepsis with arterial hypotension despite fluid resuscitation

  6. Blood Culture • One out of five evaluations for sepsis has positive blood culture • 80% of the time, empiric antibiotics will be given when no organism is isolated from culture

  7. Blood culture • In a 1999, autopsy study of ELBW infants • infection was primary cause of death by pathologists in (56 of 111) • sepsis was not diagnosed prior to death for 61% of these 56 neonates

  8. False negative Blood Culture • Maternal antibiotics • Small blood sample • in a prospective study of nearly 300 blood cultures drawn from critically ill neonates, 55% of culture vials contained less than 0.5 ml of blood • Bacteria load, timing of sampling

  9. Diagnosis

  10. Clinical Signs according to WHO Integrated Management of Childhood illness • Respiratory rate >60 breaths/min • Retraction, flaring, Grunting • Crepitation • Cyanosis

  11. Clinical Sings according to WHO Integrated Management of Childhood illness • 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

  12. Other signs in NICU • abnormal heart rate characteristics • Reduced digital capillary refill time • metabolic acidosis • Increase in weight

  13. Clinical signs of sepsis in VLBW infantsNICHD network study • Apnea in 55% • gastrointestinal problems (46%), • increased need for oxygen or ventilatory support 36% • lethargy/hypotonia 23% • Hypotension 5% • The positive predictive value 14 to 20%.

  14. New Diagnostic Methods • CRP • Interleukin 6,8 • IgM • Polymerase chain reaction (PCR) • DNA microarray technology • Immunoassay

  15. CRP • Best discriminatory value for predicting septicemia • Expressed by all gestational age • sensitivity 48 to 63%

  16. Serial CRP • elevated CRP on day 1 and/or day 2, identify most case of sepsis • sensitivity (90.2%)

  17. Serial CRP • When CRP is normal on days 1 and 2 ,neonatal sepsis can be confidently excluded and antibiotic therapy ceased • negative predictive value (97.7%).

  18. CRP • Sensitivity of serial CRP testing is lower for bacteremia due to gram-positive than to gram-negative bacteria

  19. CRP • Help in timing of discontinuation of antibiotics when CRP normalize • Further studies is needed

  20. Polymerase Chain Reaction (PCR) • PCR: under investigation for bacterial and fungal infection • amplification of 16S rRNA, • a gene universally present in bacteria but absent in humans • Results in 9 h of sample acquisition

  21. PCR • Sensitivity 96% • Specificity 99.4% • positive predictive value 88.9% • negative predictive value 99.8%

  22. Microbiology in Developing Country • Gram negative organisms • Klebsiella, Escherichia coli, • Pseudomonas, and Salmonella. • Gram positive less common • Staphylococcus Aureus • Coagulase negative staphylococci (CONS) • Streptococcus pneumoniae, and Streptococcus pyogenes

  23. Microbiology In Developing Country • Group B streptococcus (GBS) is rare • Maternal recto-vaginal Carriage rates for GBS is similar to that in developed country

  24. Meningitisdeveloping country • 1st week mainly Gram negative. • Older than 1 week: • Streptococcus pneumonia, 50% of all bacterial meningitis occurring between 7 and 90 days of age • Fatality rate of 53%.

  25. Microbiology in Developed Country • EOS • GBS and E coli • Recently decrease in Gram positive organisms (GBS) and increase in Gram negative organisms • LOS: • Coagulase Negative Staph (CON), • GBS • Staph Aureus.

  26. New trends • incidence of GBS sepsis decreased from 5.9 to 1.7 per 1,000 • the incidence of sepsis from E. coli increased from 3.2 to 6.8 per 1,000 between 1991-1993 and 1998-2000

  27. Case Fatality • EOS: more severe and case fatality rate is higher( all-causes mortality was 37%) • LOS: less sever (CoNS) 18%.

  28. Mortality Per Organisms percentages/ LBW infants • Gram-negative 257cases(36%) • E coli 53 cases (34%) • Klebsiella 62 cases (22%) • Pseudomonas 43 cases (74%) • Enterobacter 41 cases (26%) • Serratia 39 cases (35%) • fungal 151cases(31%)

  29. Mortality Rate by Organisms in low birth weight infants • Gram-positive 905 case 101 deaths (11.2%) • CoNS . 606 cases (9.1%) • S aureus 99 cases (17.2%) • GBS 32 cases (21.9%) • All other streptococci 65 cases (10.8%)

  30. Sepsis Risk Factors • Prematurity • Birth weight • Term 0.1% • 1,000 -1,500 g 10% • <1,000 g 35% • <750 g. 50% • Delay enteral feeding and Prolonged TPN

  31. Frequent Blood Drawing??

  32. Group B streptococcus (GBS) • Maternal colonization 15 to 40% • 50% of infants acquire surface colonization at delivery • 1% of colonized full-term infants develop EONS

  33. GBS • In 1996, GBS guidelines • Incidence declined from 5.9-1.7 per 1,000 in 1992 and 1999 respectively • Emergence of penicillin resistance among GBS (Japan)

  34. GBS Guideline • the incidence of infections with gram-negative bacteria increased • antibiotic resistance among gram-negative pathogens has increased

  35. Coagulase-Negative Staphylococci • commonest cause of nosocomial bacteremia • ventriculoperitoneal shunt infection • Endocarditis with umbilical lines • S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus,

  36. Coagulase-Negative Staphylococci • Sepsis with CoNS is often indolent • nonspecific symptoms

  37. Coagulase-negative staphylococci • a positive blood culture for CoNS may represent either contamination • 26 cases, in only 16 cases were cultures from two sites positive, and the other 10 cases were considered to represent contamination

  38. Coagulase-negative staphylococci • Studies have shown that initial therapy of suspected LONS with nafcillin or oxacillin and an aminoglycoside,rather than vancomycin did not change outcome (decrease resistance)

  39. Staphylococcus aureus • Less commonly seen • S. aureus strains remained sensitive to extended-spectrum penicillins (oxacillin or nafcillin)

  40. Gram Negative bacteria • Klebsiella pneumoniae in our area • E. coli in united states • Increase in incidence • Multiresistance • Invasion of CNS, Citrobacter koseri

  41. Gram Negative • P. aeruginosa • conjunctivitis • systemic disease high mortality • Haemophilus influenzae. • Non typeable • Fulminant, simulating RDS. • Mortality 90%

  42. Antibiotics Resistance • Induced by antibiotic pressure (over use) • Broad-spectrum cephalosporin induce chromosomal ESBLs in gram-negative bacilli

  43. Antibiotics Resistance • Ampicillin and Amikacin for empiric treatment of EONS • Oxacillin and amikacin for empiric treatment of LONS reduce colonization with resistant gram-negative bacilli from 32 to 11%

  44. Practical points • LP should be done in evaluation of sepsis even with negative blood culture • Urine culture is not part of work up for EOS • Vesicoureteral reflux was present in 14% of VLBW infants with UTI.

  45. Conclusions • Gram negative organism is becoming more common worldwide • GBS is not common in our area • Multi-resistance organism mandate different approaches for N. sepsis treatment

  46. Conclusions • CRP can help in early discontinuation of antibiotics • New Diagnostic Technology will play role in both • Early diagnosis and treatment • Restrict antibiotics over use

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