Neonatal sepsis

1. Neonatal infections/ sepsis:
More than just treating with antibiotics
Dr. Stefan Weichert
Consultant Paediatrician
Paediatric Infectious Diseases
University Children‘s Hospital Mannheim, Germany

2. Why relevant? Have we not been successful?

3. “… 44% of child deaths under the age of 5 take place during the
neonatal period…”
Weekly Epidemiological Record, no. 38, 19 SEPTEMBER 2014
Of the 5.8 million children who died before 5 years of age in 2015
worldwide, approximately 2.6 million died in the neonatal period
GBD 2015 Child Mortality Collaborators, Lancet 2016

4. Oza S et al., Bull World Health Organ 2015;93:19–28

5. For more information: See the Every Newborn website:
www.everynewborn.org.

6. Prevention
Awareness
Treatment
Neonatal infections/ sepsis
Child health AND maternal health!

7. Prevention
• Immunization maternal, childhood, general population
• Nutrition breast-feeding, weight, Kangaroo Mother Care
• Hygiene perinatal, use of chlorhexidine for cord care
• Education health professionals (neonatal resuscitation),
leaflets, trainings, workshops

8. Prevention
• Immunization maternal, childhood, general population
“immunologic immaturity”: ineffective clearing of intracellular
pathogens, only moderate antibody generation against bacterial
polysaccharides, …
Palmeira P et al., Clin Dev Immunol 2012
Neonates/ young babies:
1. Unprotected (insufficient maternal protection, e.g. pertussis)
2. More robust protection after several months of life (ca. 6 months)
3. Lack of vaccinations licensed for this young age group (e.g. influenza)

9. Increase in steroid hormones
Immune system: Shift TH1 to TH2
(„antiinflammatory“)
--I cytotox. T-lymphocytes
 B-lymphocyte stimulation
Increase of diaplacental
IgG-transfer
Omer SB, NEJM 2017

10. Prevention
• Immunization counselling of women, who wish to
have children! (check immunization status)

11. World Health Organization. WHO vaccine-preventable diseases: monitoring
system. 2016 global summary [Internet]. 2016 [cited 2016 Feb 26]. Available from:
http://apps.who.int/immunization_monitoring/ globalsummary/schedules
Maternal Vaccination

12. Tetanus
• Propagated by WHO since 1974 to reduce the risk of
neonatal tetanus
• Vaccination against tetanus during pregnancy is safe!
“…Although this approach has decreased neonatal tetanus by 96%
compared to the late 1980s, the WHO estimated that 34,000 new-borns
still died from the disease in 2015 …”
Blencowe H et al., Int J Epidemiol 2010
WHO (2017) Tetanus vaccines: WHO position paper –
February 2017. Wkly Epidemiol Rec 92:53-76.
“… Transplacental antibody transfer can be significantly reduced by a
short interval between the last dose of TTCV before delivery (<14 days),
prematurity, and conditions such as maternal HIV infection,
hypergammaglobulinemia in the context of malaria and chronic placental
malaria infection …”

13. Omer SB, NEJM 2017

14. • California, US-cohort of 74.504 mother-child pairs
• Risk of symptomatic pertussis infection during the first 2 months of life
• Prenatal vs. postnatal vaccination
 Vaccination during 27th–36th week of pregnancy improved
propability of childhood protection against pertussis by 85% as
compared to vaccination during 14 days postpartum!
Winter K et al., Clin Infect Dis 2017

15. Mothers vaccinated:
49 infants diseased  43% hospitalization rate
3 days average duration of hospitalization
no deaths
Mothers non-vaccinated:
371 infants diseased  73% hospitalization rate
6 days average duration of hospitalization
6 deaths
Winter K et al., Clin Infect Dis 2017

16. Prevention
• Immunization maternal, childhood, general population
• Nutrition breast-feeding, Kangaroo Mother Care
• Hygiene perinatal, use of chlorhexidine for cord care
• Education health professionals (neonatal resuscitation),
leaflets, trainings, workshops

17. Raihana S et al., PLoS Med 2019; 16(8): e1002904
• Study from Bangladesh
• Neonatal sepsis: 24% of neonatal deaths
• Only 50% of newborns in Bangladesh initiated breastfeeding
within 1 hour of birth
• Initiation of breastfeeding and severe illness
• the earlier the initiation of breastfeeding, the lower the risk
of having severe illnesses in the early newborn stage

18. Prevention
• Immunization maternal, childhood, general population
• Nutrition breast-feeding, Kangaroo Mother Care
• Hygiene perinatal, use of chlorhexidine for cord care
• Education health professionals (neonatal resuscitation),
leaflets, trainings, workshops

19. Awareness
• Public awareness neonatal care
• Easy access to medical care midwifes, community nurses
• Education red flags (outpatient/ inpatient)
Treatment
• Know your microbes (and your antimicrobial resistance)
• Empirical, promt treatment (right drug, dose, duration)
• Antibiotic Stewardship

20. Increased antibiotic consumption is associated with increasing
numbers of resistance against antibiotics
Goossens 2009
Up to 50% of all prescribed antibiotics in hospitals are unneccessary!
Dellit et al., Clin Inf Dis 2007
Antibiotics account for the most prescribed medications in children
(outpatient: up to 30%; inpatient: 30-72%)
Pakyz et al., Infect Hosp Epidemiol 2009
Gerber et al., Pediatrics 2010
Missuse of Antibiotics Increases Antimicrobial Resistance

21. Sir Alexander Fleming
(1881 – 1955)
Quelle: medienwerkstatt-online.de
„… the thoughtless person playing with penicillin is morally
responsible for the death of the man who finally succumbs to
infection with the penicillin-resistant organism. I hope this evil
can be averted.“
New York Times, 26 June 1945
SHEA / IDSA / PIDS policy statement,
Infect Control Hosp Epidemiol 2012

22. www.amr-review.org
Missuse of Antibiotics Increases Antimicrobial Resistance

23. „rational use of antibiotics“
„optimal choice, dose and duration of antimicrobial therapy or
prophylaxis, with minimal toxicity for the patient as well as with the
lowest potential for developing resistance“
Gerding DN, Jt Comm J Qual Improv 2001
What are Antimicrobial Stewardship Programs?

24. 1. 4 D‘s Drug, Dose, De-escalation, Duration
Joseph and Rodvold, Expert Opin Pharmacother 2008
2. Stop overuse (wrong indication)
wrong use (missing adaptation)
missuse („favoured drug“)
3. Minimize development of resistance
antibiotics risk for colonization or infection with
resistant organisms
Dellit et al., Clin Infect Dis 2007
What are Antimicrobial Stewardship Programs?

25. Neonatal infections/ sepsis
• Antibiotic Stewardship
Diagnostics:
- blood culture(s) (1ml!) (low grade bacteremia)
- supportive role of biomarkers (CRP, IL-6, IL-8, PCT)
( good negative predictive value; can help to
reduce antobiotic consumption)

26. • Neonates with suspected bacterial infection:
Test: combination of CRP and IL-8 (vs. CRP and I/T neutrophil
ratio)
Outcome: Reduction of antibiotics by 73%!
• Neonates with suspected early onset sepsis (EOS):
Test: IL-8 and CRP (vs. CRP alone)
(IL-8 > 70 pg/mL and/ or CRP > 10 mg/L)
Outcome: 50% reduction (vs. 36%), without an increase in
missed infections
Franz et al., 2001
Franz et al., 2004

27. Neonatal infections/ sepsis
• Antibiotic Stewardship
Therapy:
- dosage and monitoring of antimicrobial levels
- e.g. gentamicin: higher doses at longer intervalls
- detect toxicity „trough levels“ and access potency
„peak levels“ (e.g. vancomycin 10-20 mg/l)
Gkentzi D and Dimitriou G, Current Pediatric Reviews, 2019, Vol. 15, No. 1

28. Kearns GL et al., N Engl J Med 2003;349:1157-67.

29. Neonatal infections/ sepsis:
More than just treating with antibiotics
For more information: See the Every Newborn website:
www.everynewborn.org.
Thank you for your attention!