1. CHANGES IN ETIOLOGIC PATTERNS OF NEONATAL SEPSIS
Presenter: Dr. Yaser Abdallah
MB.Ch.B, M.Med, M.Phil, Cert (Neon)

2. Order of presentation
Relevance of this review
Brief epidemiology of neonatal sepsis
Etiology of neonatal sepsis by regions over time
Previous and current diagnostic challenges
Conclusion

3. How long should we treat clinical sepsis????
Neonatal sepsis = clinical syndrome of systemic illness + bacteremia (in the first 28 days of life).
Short falls of this definition?
-many clinical signs and symptoms in the newborn are non specific
-low incidence of bacteremia among symptomatic neonates. 38% of neonates with meningitis have negative blood culture.
-non-bacterial pathogens??
Clinical sepsis = symptomatic + negative blood culture.
How long should we treat clinical sepsis????

4. Why this review?
Neonatal sepsis is one of the major causes of neonatal mortality and morbidity
High index of suspicion is important
Presumptive treatment is always considered as results pend. choice of treatment
Getting it early and right can be life saving

5. Epidemiology:
Developed countries
Early onset sepsis- 1/1000 live births
Late onset sepsis- 6/1000 live births
Ref: Andi L. Shane, Barbara J. Stoll Am j Perinatol 2013;30:
Developing countries
Estimated 5-20/1000live births.
Account for >1,000,000 neonatal deaths
Ref: Anna C Seale et al Lancet Infect Dis 2009;9:428-38
>90% of all neonatal deaths occur in the developing countries
Epidemiology in the developing countries is largely an underestimation since many births and deaths occur outside health facilities.

6. Early / Late onset neonatal sepsis
-different authorities have different definitions
-NICHD, NICE, VON define EOS as sepsis ≤ 72hrs and LOS >72hrs
-NeoIN surveillance network (UK) - 48hrs/>48hrs
-<7day and ≥7days used by many researchers
Implication of definition disparity
- Epidemiological difference
EOS is from vertically acquired microbes and LOS from environment. Spectrum of responsible organisms may vary.
Rational for choice of presumptive antibiotic
Preventative interventions e.g IAP for GBS
LETS HARMONIZE

7. MICRO-ORGANISMS ISOLATED FROM NEONATES WITH SEPSIS GBS E.coli S.aureus
CoNS
S.viridans
Other G-ve
others
Fungal
USA <2002
EOS/LOS
44.7% 2%
22.9% 4% 5% 9% -
55%
5.9%
8.9%
12.5%
14%
8.8% 7%
USA ≥2002
43%
2.3%
29%
4.9%
2.4%
7.8%
0.6%
47.9%
5.4%
5.1%
13%
12.1% 3%
12.2%
Europe (UK)
2006 EOS/LOS
50% 8%
18%
20%†
54%†
1.3%
0.8%
10%
47%
12%*
21% 1%
Asia/pacific
>2004
38%
0.7%
6.4%
17%
33.5%
23%
2.5%
6.2%
*Listeria 6%
†CoNS occurred concurrently with other pathogens
Ref:-NeoIN surveillance network
-NICHD 1996, 2006
-Asia-Pacific neonatal infection study 2008

8. MICRO-ORGANISMS ISOLATED FROM NEONATES WITH SEPSIS Africa GBS E.coli
S.aureus
Klebs
Other G-ve
others
Fungal
Kenya <2000
EOS/LOS -
3.3%
7.4%
31.4%
38.8%*
19%
Kenya >2000 8%
15.5%
21.6%
6.6%
4.3%
12%
13.5% 9%
33%
28.1%
19.6%
Nigeria <2000
EOS+LOS
37%
26%
+ Ecoli
Nigeria>2000
EOS+LOS†
8.4%
16.4%
33.6%
25.4%
28.6%
10.9%
17.6%
25.5%
1.7%
3.6%
S.Africa <2000
35%
17%
28%
S.Africa >2000
1.5%
14.2%
9.5%
23%
CoNS33% & 49%
7.8%
Other gram negative-enterobactor, citrobacter, campylobactor, proteus, niserria, pseudomonus
Others- group D strep, strep pneumoniae, strep viridans
*includes citrobacter (21.5%), enterobacter (15.7%)
†based on 1 study 2011 looking at 174 cases of neonatal sepsis

9. Why the disparity in etiology of neonatal sepsis?
Is GBS sepsis under-estimated in developing countries?
Rates of maternal colonization same (Stoll BJ et al 1998)
Same serotypes in mothers in last 30yrs (Kirsty Le Daore 2013)
High correlation between black and hispanic race and neonatal invasive GBS infection (Dori F 2000)
BACTEC versus manual method (Vaciloto et al 2002, Miura E 2001)
Spectrum of disease caused by GBS- IUFD, chorioamnionitis, EOS, LOS- without full investigation in the developing countries, the count might be low!!
Home/ TBA’s, home neonatal deaths????
Maternal anibiotics for other reasons (UTI….)

10. Intrapartum antibiotic prophylaxis Are we doing it unknowingly???
-observed low rate of GBS sepsis in developing countries IAP (Boyer KM 1986)
-IAP associated with emergency of ampicillin resistant E.coli(Bizzaro MJ 2008) same in developing countries.
Way forward
-studies to establish GBS maternal and neonatal colonization rates including placenta, IUFD, FSB
-improve on culture techniques - BACTEC
-using penicillin for IAP- to minimize ampicillin resistance
-???vaccine

11. CoNS and Fungal sepsis
More prevalent in very low birth weight (VLBW) neonates.
What does this translate to?
Good neonatal care- saving many VLBW babies
Bad neonatal care- broad spectrum antibiotic use, prolonged indwelling catheters, poor aseptic techniques…….

12. Conclusion:
Evidence based clinical guidelines and audits to regulate antibiotic use should be in place.
Institute better laboratory techniques to enable fast and accurate microbe isolation and identification.
Neonatal infection surveillance is necessary to accurately describe neonatal sepsis in the developing countries.

13. THANK YOU SHUKURANI SANA

14. Diagnostic Challenges of neonatal sepsis Presenter: Dr
Diagnostic Challenges of neonatal sepsis Presenter: Dr. Yaser Abdallah MB.Ch.B, M.Med, Mphil, Cert(Neon)

15. Introduction Neonatal sepsis : 1) Clinical syndrome of systemic illness: the diagnosis is first and foremost clinical 2) And bacteremia: demonstration through lab test with gold standard being proof of presence of bacteria in blood.

16. Clinical diagnosis

17. Table 4. Association of admission clinical features with presence of bacteriologically Confirmed invasive disease
Clinical feature
OR for presence of bacteriologically confirmed invasive disease
p value
Omphalitis
2.4 (1.2 to 4.7)
0.008
Prostration
2.2 (1.3 to 3.6)
0.001
Oxygen saturation <90%
2.0 (1.2 to 3.5)
0.01
Weak or absent movements
2.9 (1.8 to 4.8)
<0.0001
Abnormally irritable or sleepy
2.3 (1.4 to 3.7)
0.005
Abnormal feeding
1.6 (1.0 to 2.6)
0.05
Inability to console infant
2.4 (1.1 to 5.1)
0.02
Bulging fontanelle
7.5 (3.1 to 18.0)
M Engilsh et al Cuases and outcome of young infant admissions to kenya distric Hospital. Arch dis child 2003;8: 438

18. Diagnostic challenges
Clinical signs
- not specific.
- highly depends on circumstance and care provider
consequences: un necessary test and antibiotics
way forward: Heart rate ECG monitoring for varibility. Detects risk for sepsis earlier and more objective.
Draw back – need training and equipment.
- Procedures may briefly affect index.

19. Heart rate characteristic index
Pre-sepsis
After retinal laser

20. Blood culture: gold standard
Lab tests:
Blood culture: gold standard
Challenges:-Low catch rate with small volume (depends on technique, micro organism load and bld volume)
-Turn around time
- false negative, contaminants, prior ABXC!!
Consequence: blood loss, presumptive treatment, prolongation of presumtive antibiotic therapy
Way forward: Automated culture BACTEC system, small bld volume, faster turn around time, better recovery rate
Drawback: expensive, no control over contaminants

21. Hematologic scoring system (RODWELL Score)
Use FBC and I/T neutrophil counts. Score of <3 has NPV of 99%
Challenges: only 78% specific, specimen handling affects results, maternal condition affect
neonatal indices- not reliable for EOS
Way forward:- training on how to handle specimen
- use microtainer 250µl of bld
- research on utility of serial FBC??

22. ACUTE PHASE REACTANTS