Transcript Neonatal sepsis early detection and antibiotics choice

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 Pediatrics
Definitions
• 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
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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
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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 grampositive than to gramnegative 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
Meningitis
developing 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
– E coli
53 cases
– Klebsiella
62 cases
– Pseudomonas 43 cases
– Enterobacter 41 cases
– Serratia
39 cases
• fungal
151cases
(36%)
(34%)
(22%)
(74%)
(26%)
(35%)
(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
– 1,000 -1,500 g
– <1,000 g
– <750 g.
0.1%
10%
35%
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 extendedspectrum penicillins
(oxacillin or nafcillin)
Gram Negative bacteria
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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 gramnegative 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