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Neonatal Sepsis and Recent Challenges Mohammad Khasswneh, MD Assistant Professor of Pediatrics JUST
 
introduction <ul><li>Common </li></ul><ul><ul><li>20% of VLBW has sepsis </li></ul></ul><ul><ul><li>In term 0.1% </li></ul...
Classification <ul><li>Early onset sepsis (EOS): </li></ul><ul><ul><li>bacteria acquired before and during delivery </li><...
Who is the septic neonate? <ul><li>Positive blood culture with clinical symptoms of infection </li></ul><ul><ul><li>Coagul...
Adult and Pediatrics Definitions <ul><li>Systemic Inflammatory response syndrome (SIRS) </li></ul><ul><li>Sepsis   </li></...
Blood Culture <ul><ul><li>One out of five evaluations for sepsis has positive blood culture  </li></ul></ul><ul><ul><li>80...
Blood culture <ul><li>In a 1999, autopsy study of ELBW infants </li></ul><ul><li>infection was primary cause of death by p...
False negative Blood Culture <ul><li>Maternal antibiotics </li></ul><ul><li>Small blood sample </li></ul><ul><li>in a pros...
Diagnosis
Clinical Signs  according to WHO Integrated Management of Childhood illness <ul><li>Respiratory rate >60 breaths/min </li>...
Clinical Sings  according to WHO Integrated Management of Childhood illness <ul><li>Temperature >37.7°C (or feels hot) or ...
Other signs in NICU <ul><li>abnormal heart rate characteristics </li></ul><ul><li>Reduced digital capillary refill time   ...
Clinical signs of sepsis  in VLBW infants   NICHD network study <ul><li>Apnea in 55% </li></ul><ul><li>gastrointestinal pr...
New Diagnostic Methods  <ul><li>CRP </li></ul><ul><li>Interleukin 6,8 </li></ul><ul><li>IgM </li></ul><ul><li>Polymerase c...
CRP <ul><li>Best discriminatory value for predicting septicemia  </li></ul><ul><li>Expressed by all gestational age </li><...
Serial CRP <ul><li>elevated CRP on day 1 and/or day 2, identify most case of sepsis </li></ul><ul><ul><li>sensitivity (90....
Serial CRP  <ul><li>When CRP is normal on days 1 and 2 ,neonatal sepsis can be confidently excluded and antibiotic therapy...
CRP <ul><li>Sensitivity of serial CRP testing is lower for bacteremia due to gram-positive than to gram-negative bacteria ...
CRP <ul><li>Help in timing of discontinuation of antibiotics when CRP normalize </li></ul><ul><li>Further studies is neede...
Polymerase Chain Reaction (PCR)  <ul><li>PCR: under investigation for bacterial and fungal infection </li></ul><ul><ul><li...
PCR <ul><ul><li>Sensitivity  96% </li></ul></ul><ul><ul><li>Specificity  99.4%  </li></ul></ul><ul><ul><li>positive predic...
Microbiology in Developing Country <ul><li>Gram negative organisms  </li></ul><ul><ul><li>Klebsiella ,  Escherichia coli ,...
Microbiology In Developing Country <ul><li>Group B streptococcus (GBS) is rare  </li></ul><ul><li>Maternal recto-vaginal C...
Meningitis developing country <ul><li>1st week mainly Gram negative. </li></ul><ul><li>Older than 1 week: </li></ul><ul><u...
Microbiology in Developed Country <ul><li>EOS  </li></ul><ul><ul><li>GBS and  E coli   </li></ul></ul><ul><ul><li>Recently...
New trends <ul><li>incidence of GBS sepsis decreased from 5.9 to 1.7 per 1,000  </li></ul><ul><li>the incidence of sepsis ...
Case Fatality <ul><li>EOS:  more severe and case fatality rate is higher( all-causes mortality was 37%)  </li></ul><ul><li...
Mortality Per Organisms percentages/ LBW infants <ul><li>Gram-negative  257cases   (36%) </li></ul><ul><ul><li>E coli  53 ...
Mortality Rate by Organisms in low birth weight infants <ul><li>Gram-positive  905 case 101 deaths  (11.2%) </li></ul><ul>...
Sepsis Risk Factors <ul><li>Prematurity </li></ul><ul><li>Birth weight </li></ul><ul><ul><li>Term  0.1% </li></ul></ul><ul...
Frequent Blood Drawing??
Group B streptococcus (GBS) <ul><li>Maternal colonization 15 to 40% </li></ul><ul><li>50% of infants acquire surface colon...
GBS <ul><li>In 1996, GBS guidelines </li></ul><ul><li>Incidence declined from  5.9-1.7 per 1,000  in 1992 and 1999 respect...
GBS Guideline  <ul><li>the incidence of infections with gram-negative bacteria increased </li></ul><ul><li>antibiotic resi...
Coagulase-Negative Staphylococci <ul><li>commonest cause of nosocomial bacteremia </li></ul><ul><ul><li>ventriculoperitone...
Coagulase-Negative Staphylococci <ul><li>Sepsis with CoNS is often indolent </li></ul><ul><li>nonspecific symptoms   </li>...
Coagulase-negative staphylococci <ul><li>a positive blood culture for CoNS may represent either contamination  </li></ul><...
Coagulase-negative staphylococci <ul><li>Studies have shown that initial therapy of suspected LONS with  nafcillin  or  ox...
Staphylococcus aureus   <ul><li>Less commonly seen </li></ul><ul><li>S. aureus  strains remained sensitive to extended-spe...
Gram Negative bacteria <ul><li>Klebsiella pneumoniae  in our area </li></ul><ul><li>E. coli  in united states </li></ul><u...
Gram Negative <ul><li>P. aeruginosa   </li></ul><ul><ul><li>conjunctivitis  </li></ul></ul><ul><ul><li>systemic disease hi...
Antibiotics Resistance <ul><li>Induced by antibiotic pressure (over use) </li></ul><ul><li>Broad-spectrum cephalosporin in...
Antibiotics Resistance <ul><li>Ampicillin and Amikacin for empiric treatment of EONS </li></ul><ul><li>Oxacillin and amika...
Practical points <ul><li>LP should be done in evaluation of sepsis even with negative blood culture </li></ul><ul><li>Urin...
Conclusions <ul><li>Gram negative organism is becoming more common worldwide  </li></ul><ul><li>GBS is not common in our a...
Conclusions <ul><li>CRP can help in early discontinuation of antibiotics </li></ul><ul><li>New Diagnostic Technology will ...
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Neonatal Sepsis And Recent Challenges

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  1. 1. Neonatal Sepsis and Recent Challenges Mohammad Khasswneh, MD Assistant Professor of Pediatrics JUST
  2. 3. introduction <ul><li>Common </li></ul><ul><ul><li>20% of VLBW has sepsis </li></ul></ul><ul><ul><li>In term 0.1% </li></ul></ul><ul><ul><li>Inter-institution difference 11-32% ( NICHD net work ) </li></ul></ul><ul><li>Serious </li></ul><ul><ul><li>mortality is 3-5 times more for infant with sepsis in NICU </li></ul></ul>
  3. 4. Classification <ul><li>Early onset sepsis (EOS): </li></ul><ul><ul><li>bacteria acquired before and during delivery </li></ul></ul><ul><ul><li>5-7/1000 live birth </li></ul></ul><ul><ul><li>1.5% of VLBW infants had EOS (intrapartum antibiotics) </li></ul></ul><ul><li>Late onset sepsis (LOS): </li></ul><ul><ul><li>bacteria acquired after delivery (Nosocomial or community) </li></ul></ul><ul><ul><li>20% of VLBW infants </li></ul></ul>
  4. 5. Who is the septic neonate? <ul><li>Positive blood culture with clinical symptoms of infection </li></ul><ul><ul><li>Coagulase-negative Staphylococcus (CoNS) </li></ul></ul><ul><ul><ul><li>2 positive blood cultures </li></ul></ul></ul><ul><ul><ul><li>One positive blood culture and elevated CRP </li></ul></ul></ul><ul><li>Clinical sepsis” or “probable sepsis </li></ul>
  5. 6. Adult and Pediatrics Definitions <ul><li>Systemic Inflammatory response syndrome (SIRS) </li></ul><ul><li>Sepsis </li></ul><ul><ul><li>as SIRS plus infection </li></ul></ul><ul><li>Severe sepsis : </li></ul><ul><ul><li>as sepsis associated with organ dysfunction, hypo perfusion or hypotension, </li></ul></ul><ul><li>Septic shock </li></ul><ul><ul><li>sepsis with arterial hypotension despite fluid resuscitation </li></ul></ul>
  6. 7. Blood Culture <ul><ul><li>One out of five evaluations for sepsis has positive blood culture </li></ul></ul><ul><ul><li>80% of the time, empiric antibiotics will be given when no organism is isolated from culture </li></ul></ul>
  7. 8. Blood culture <ul><li>In a 1999, autopsy study of ELBW infants </li></ul><ul><li>infection was primary cause of death by pathologists in (56 of 111) </li></ul><ul><li>sepsis was not diagnosed prior to death for 61% of these 56 neonates </li></ul>
  8. 9. False negative Blood Culture <ul><li>Maternal antibiotics </li></ul><ul><li>Small blood sample </li></ul><ul><li>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 </li></ul><ul><li>Bacteria load, timing of sampling </li></ul>
  9. 10. Diagnosis
  10. 11. Clinical Signs according to WHO Integrated Management of Childhood illness <ul><li>Respiratory rate >60 breaths/min </li></ul><ul><li>Retraction, flaring, Grunting </li></ul><ul><li>Crepitation </li></ul><ul><li>Cyanosis </li></ul>
  11. 12. Clinical Sings according to WHO Integrated Management of Childhood illness <ul><li>Temperature >37.7°C (or feels hot) or <35.5°C (or feels cold) </li></ul><ul><li>Convulsions ,Lethargic or unconscious </li></ul><ul><li>Reduced movements and activity) </li></ul><ul><li>Not able to feed (sustain suck) </li></ul><ul><li>Bulging fontanels </li></ul>
  12. 13. Other signs in NICU <ul><li>abnormal heart rate characteristics </li></ul><ul><li>Reduced digital capillary refill time </li></ul><ul><li>metabolic acidosis </li></ul><ul><li>Increase in weight </li></ul>
  13. 14. Clinical signs of sepsis in VLBW infants NICHD network study <ul><li>Apnea in 55% </li></ul><ul><li>gastrointestinal problems (46%), </li></ul><ul><li>increased need for oxygen or ventilatory support 36% </li></ul><ul><li>lethargy/hypotonia 23% </li></ul><ul><li>Hypotension 5% </li></ul><ul><li>The positive predictive value 14 to 20%. </li></ul>
  14. 15. New Diagnostic Methods <ul><li>CRP </li></ul><ul><li>Interleukin 6,8 </li></ul><ul><li>IgM </li></ul><ul><li>Polymerase chain reaction (PCR) </li></ul><ul><li>DNA microarray technology </li></ul><ul><li>Immunoassay </li></ul>
  15. 16. CRP <ul><li>Best discriminatory value for predicting septicemia </li></ul><ul><li>Expressed by all gestational age </li></ul><ul><li>sensitivity 48 to 63% </li></ul>
  16. 17. Serial CRP <ul><li>elevated CRP on day 1 and/or day 2, identify most case of sepsis </li></ul><ul><ul><li>sensitivity (90.2%) </li></ul></ul>
  17. 18. Serial CRP <ul><li>When CRP is normal on days 1 and 2 ,neonatal sepsis can be confidently excluded and antibiotic therapy ceased </li></ul><ul><ul><li>negative predictive value (97.7%). </li></ul></ul>
  18. 19. CRP <ul><li>Sensitivity of serial CRP testing is lower for bacteremia due to gram-positive than to gram-negative bacteria </li></ul>
  19. 20. CRP <ul><li>Help in timing of discontinuation of antibiotics when CRP normalize </li></ul><ul><li>Further studies is needed </li></ul>
  20. 21. Polymerase Chain Reaction (PCR) <ul><li>PCR: under investigation for bacterial and fungal infection </li></ul><ul><ul><li>amplification of 16S rRNA , </li></ul></ul><ul><ul><li>a gene universally present in bacteria but absent in humans </li></ul></ul><ul><ul><li>Results in 9 h of sample acquisition </li></ul></ul>
  21. 22. PCR <ul><ul><li>Sensitivity 96% </li></ul></ul><ul><ul><li>Specificity 99.4% </li></ul></ul><ul><ul><li>positive predictive value 88.9% </li></ul></ul><ul><ul><li>negative predictive value 99.8% </li></ul></ul>
  22. 23. Microbiology in Developing Country <ul><li>Gram negative organisms </li></ul><ul><ul><li>Klebsiella , Escherichia coli , </li></ul></ul><ul><ul><li>Pseudomonas , and Salmonella . </li></ul></ul><ul><li>Gram positive less common </li></ul><ul><ul><li>Staphylococcus Aureus </li></ul></ul><ul><ul><li>Coagulase negative staphylococci (CONS) </li></ul></ul><ul><ul><li>Streptococcus pneumoniae, and Streptococcus pyogenes </li></ul></ul>
  23. 24. Microbiology In Developing Country <ul><li>Group B streptococcus (GBS) is rare </li></ul><ul><li>Maternal recto-vaginal Carriage rates for GBS is similar to that in developed country </li></ul>
  24. 25. Meningitis developing country <ul><li>1st week mainly Gram negative. </li></ul><ul><li>Older than 1 week: </li></ul><ul><ul><li>Streptococcus pneumonia , 50% of all bacterial meningitis occurring between 7 and 90 days of age </li></ul></ul><ul><ul><li>Fatality rate of 53%. </li></ul></ul>
  25. 26. Microbiology in Developed Country <ul><li>EOS </li></ul><ul><ul><li>GBS and E coli </li></ul></ul><ul><ul><li>Recently decrease in Gram positive organisms (GBS) and increase in Gram negative organisms </li></ul></ul><ul><li>LOS: </li></ul><ul><ul><li>Coagulase Negative Staph (CON) , </li></ul></ul><ul><ul><li>GBS </li></ul></ul><ul><ul><li>Staph Aureus . </li></ul></ul>
  26. 27. New trends <ul><li>incidence of GBS sepsis decreased from 5.9 to 1.7 per 1,000 </li></ul><ul><li>the incidence of sepsis from E. coli increased from 3.2 to 6.8 per 1,000 between 1991-1993 and 1998-2000 </li></ul>
  27. 28. Case Fatality <ul><li>EOS: more severe and case fatality rate is higher( all-causes mortality was 37%) </li></ul><ul><li>LOS: less sever (CoNS) 18%. </li></ul>
  28. 29. Mortality Per Organisms percentages/ LBW infants <ul><li>Gram-negative 257cases (36%) </li></ul><ul><ul><li>E coli 53 cases (34%) </li></ul></ul><ul><ul><li>Klebsiella 62 cases (22%) </li></ul></ul><ul><ul><li>Pseudomonas 43 cases (74%) </li></ul></ul><ul><ul><li>Enterobacter 41 cases (26%) </li></ul></ul><ul><ul><li>Serratia 39 cases (35%) </li></ul></ul><ul><li>fungal 151cases (31%) </li></ul>
  29. 30. Mortality Rate by Organisms in low birth weight infants <ul><li>Gram-positive 905 case 101 deaths (11.2%) </li></ul><ul><ul><li>CoNS . 606 cases (9.1%) </li></ul></ul><ul><ul><li>S aureus 99 cases (17.2%) </li></ul></ul><ul><ul><li>GBS 32 cases (21.9%) </li></ul></ul><ul><ul><li>All other streptococci 65 cases (10.8%) </li></ul></ul>
  30. 31. Sepsis Risk Factors <ul><li>Prematurity </li></ul><ul><li>Birth weight </li></ul><ul><ul><li>Term 0.1% </li></ul></ul><ul><ul><li>1,000 -1,500 g 10% </li></ul></ul><ul><ul><li><1,000 g 35% </li></ul></ul><ul><ul><li><750 g. 50% </li></ul></ul><ul><li>Delay enteral feeding and Prolonged TPN </li></ul>
  31. 32. Frequent Blood Drawing??
  32. 33. Group B streptococcus (GBS) <ul><li>Maternal colonization 15 to 40% </li></ul><ul><li>50% of infants acquire surface colonization at delivery </li></ul><ul><li>1% of colonized full-term infants develop EONS </li></ul>
  33. 34. GBS <ul><li>In 1996, GBS guidelines </li></ul><ul><li>Incidence declined from 5.9-1.7 per 1,000 in 1992 and 1999 respectively </li></ul><ul><li>Emergence of penicillin resistance among GBS ( Japan ) </li></ul>
  34. 35. GBS Guideline <ul><li>the incidence of infections with gram-negative bacteria increased </li></ul><ul><li>antibiotic resistance among gram-negative pathogens has increased </li></ul>
  35. 36. Coagulase-Negative Staphylococci <ul><li>commonest cause of nosocomial bacteremia </li></ul><ul><ul><li>ventriculoperitoneal shunt infection </li></ul></ul><ul><ul><li>Endocarditis with umbilical lines </li></ul></ul><ul><li>S. epidermidis , S. haemolyticus , S. hominis , S. saprophyticus , </li></ul>
  36. 37. Coagulase-Negative Staphylococci <ul><li>Sepsis with CoNS is often indolent </li></ul><ul><li>nonspecific symptoms </li></ul>
  37. 38. Coagulase-negative staphylococci <ul><li>a positive blood culture for CoNS may represent either contamination </li></ul><ul><ul><li>26 cases, in only 16 cases were cultures from two sites positive, and the other 10 cases were considered to represent contamination </li></ul></ul>
  38. 39. Coagulase-negative staphylococci <ul><li>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 ) </li></ul>
  39. 40. Staphylococcus aureus <ul><li>Less commonly seen </li></ul><ul><li>S. aureus strains remained sensitive to extended-spectrum penicillins (oxacillin or nafcillin) </li></ul>
  40. 41. Gram Negative bacteria <ul><li>Klebsiella pneumoniae in our area </li></ul><ul><li>E. coli in united states </li></ul><ul><li>Increase in incidence </li></ul><ul><li>Multiresistance </li></ul><ul><li>Invasion of CNS, C itrobacter koseri </li></ul>
  41. 42. Gram Negative <ul><li>P. aeruginosa </li></ul><ul><ul><li>conjunctivitis </li></ul></ul><ul><ul><li>systemic disease high mortality </li></ul></ul><ul><li>Haemophilus influenzae . </li></ul><ul><ul><li>Non typeable </li></ul></ul><ul><ul><li>Fulminant, simulating RDS. </li></ul></ul><ul><ul><li>Mortality 90% </li></ul></ul>
  42. 43. Antibiotics Resistance <ul><li>Induced by antibiotic pressure (over use) </li></ul><ul><li>Broad-spectrum cephalosporin induce chromosomal ESBLs in gram-negative bacilli </li></ul>
  43. 44. Antibiotics Resistance <ul><li>Ampicillin and Amikacin for empiric treatment of EONS </li></ul><ul><li>Oxacillin and amikacin for empiric treatment of LONS reduce colonization with resistant gram-negative bacilli from 32 to 11% </li></ul>
  44. 45. Practical points <ul><li>LP should be done in evaluation of sepsis even with negative blood culture </li></ul><ul><li>Urine culture is not part of work up for EOS </li></ul><ul><li>Vesicoureteral reflux was present in 14% of VLBW infants with UTI. </li></ul>
  45. 46. Conclusions <ul><li>Gram negative organism is becoming more common worldwide </li></ul><ul><li>GBS is not common in our area </li></ul><ul><li>Multi-resistance organism mandate different approaches for N. sepsis treatment </li></ul>
  46. 47. Conclusions <ul><li>CRP can help in early discontinuation of antibiotics </li></ul><ul><li>New Diagnostic Technology will play role in both </li></ul><ul><ul><li>Early diagnosis and treatment </li></ul></ul><ul><ul><li>Restrict antibiotics over use </li></ul></ul>
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