Neonatal Sepsis and Recent Challenges
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Transcript of 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
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
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
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
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
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
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
Diagnosis
Clinical Signs according to WHO Integrated Management of
Childhood illness
• Respiratory rate >60 breaths/min
• Retraction, flaring, Grunting
• Crepitation
• Cyanosis
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
Other signs in NICU
• abnormal heart rate characteristics• Reduced digital capillary refill time
• metabolic acidosis
• Increase in weight
Clinical signs of sepsis in VLBW infants NICHD 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%.
New Diagnostic Methods
• CRP• Interleukin 6,8• IgM• Polymerase chain reaction (PCR)• DNA microarray technology • Immunoassay
CRP
• Best discriminatory value for predicting septicemia
• Expressed by all gestational age
• sensitivity 48 to 63%
Serial CRP
• elevated CRP on day 1 and/or day 2, identify most case of sepsis
– sensitivity (90.2%)
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%).
CRP
• Sensitivity of serial CRP testing is lower for bacteremia due to gram-positive than to gram-negative bacteria
CRP
• Help in timing of discontinuation of antibiotics when CRP normalize
• Further studies is needed
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
PCR
–Sensitivity 96%
–Specificity 99.4%
–positive predictive value 88.9%
–negative predictive value 99.8%
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
Microbiology In Developing Country
• Group B streptococcus (GBS) is rare
• Maternal recto-vaginal Carriage rates for GBS is similar to that in developed country
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%.
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.
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
Case Fatality
• EOS: more severe and case fatality rate is higher( all-causes mortality was 37%)
• LOS: less sever (CoNS) 18%.
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%)
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%)
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
Frequent Blood Drawing??
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
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)
GBS Guideline
• the incidence of infections with gram-negative bacteria increased
• antibiotic resistance among gram-negative pathogens has increased
Coagulase-Negative Staphylococci
• commonest cause of nosocomial bacteremia
– ventriculoperitoneal shunt infection
–Endocarditis with umbilical lines
• S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus,
Coagulase-Negative Staphylococci
• Sepsis with CoNS is often indolent
• nonspecific symptoms
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
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)
Staphylococcus aureus
• Less commonly seen• S. aureus strains remained
sensitive to extended-spectrum penicillins (oxacillin or nafcillin)
Gram Negative bacteria
• Klebsiella pneumoniae in our area
• E. coli in united states
• Increase in incidence
• Multiresistance
• Invasion of CNS, Citrobacter koseri
Gram Negative
• P. aeruginosa – conjunctivitis – systemic disease high mortality
• Haemophilus influenzae. – Non typeable– Fulminant, simulating RDS. – Mortality 90%
Antibiotics Resistance
• Induced by antibiotic pressure (over use)
• Broad-spectrum cephalosporin induce chromosomal ESBLs in gram-negative bacilli
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%
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.
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
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