How to detect and prevent bacterial and bacterial-like sepsis in children and adolescents? Professor Susanna Esposito presents in this slideset data on epidemiology, etiology and mortality rates of pediatrical sepsis, and then discusses the possible treatment and the more efficient way of preventing the burden of pediatric sepsis. To learn more, visit www.waidid.org.

1. BACTERIAL AND BACTERIAL-
LIKE SEPSIS: DETECTION AND
PREVENTION
Susanna Esposito
Pediatric Highly Intensive Care Unit
Fondazione IRCCS Ca’ Granda Ospedale Maggiore
Policlinico, Università degli Studi di Milano
Milano

2. Which is the definition of sepsis in
children?
1. Proved infection with high fever
2. Systemic inflammatory response
3. Systemic inflammatory response in
presence of infection
4. Systemic inflammatory response with
cardiovascular dysfunction

3. DEFINITIONS OF SEPSIS IN CHILDREN
(From Goldstein B et al. Pediatr Crit Care Med 2005)

4. SEPSIS IN CHILDREN: THE BOTTOM LINE

5. COLD AND WARM SEPTIC SHOCK
(From Plunkett A and Tong J, BMJ 2015)

6. EVENTS LEADING TO DEATH AFTER
INFECTION

7. STANDARDISED CRITERIA FOR ORGAN DYSFUNCTION
(From Goldstein B et al., Pediatr Crit Care Med 2005)

8. Which is the age group at highest
risk of sepsis?
1. Infants <1 year
2. Children 1-5 years
3. Children 6-10 years
4. Adolescents

9. Watson RS et al. The epidemiology of severe sepsis in children in the
United States. Am J Respir Crit Care Med 2003;167:695–701
Epidemiology

10. Epidemiology of severe sepsis in children in USA
( Watson RS et al. Am J Respir Crit Care Med 2003;167:695–701)

11. Number of cases of pediatric severe sepsis diagnosed
in the USA from 2004 to 2012
(From Ruth A et al. Pediatr Crit Care Med 2014)

12. CHARACTERISTICS OF PATIENTS WITH
SEVERE SEPSIS
(From Weiss SL et al., Am J Crit Care Med 2015)

13. SITE OF INFECTION
IN SEVERE SEPSIS OF CHILDREN
(From Weiss SL et al., Am J Crit Care Med 2015)

14. Differential diagnosis
of severe sepsis in children
(From Plunkett A and Tong J, BMJ 2015)

15. Which is the most frequent
etiologic pathogen in pediatric
sepsis?
1. Streptococcus pneumoniae
2. Neisseria meningitidis
3. Staphylococcus aureus
4. Haemophilus influenzae

16. Typical or important pathogens
in pediatric sepsis
(From Plunkett A and Tong J, BMJ 2015)

17. Early recognition of sepsis and septic shock
in children
Recognize signs of poor perfusion (0-5 min)
• Decreased mental status
• Cold extremities
• Delayed capillary refill
• Weak pulses, differential central and
peripheral pulses
• Low urine output
• Hypotension or low BP: minimum systolic
BP by age, < 1mo 60 mmHg; 1mo to 10y:
70 + (2 × age in years); ≥10y: 90 mmHg

18. Treatment of sepsis and septic shock in
children (I)
Assess ABCs (0-5 min)
• Provide 100% oxygen at high flow rate
(15 L)
• Early intubation may be necessary in
neonates and infants
• Breathing assistance as necessary,
including mechanical ventilation

19. Treatment of sepsis and septic shock
in children (II)
Establish IV access and place on monitor (0-5
min)
• 2 large-bore peripheral IVs (PIVs) preferred: if
difficult IV, place IO access per PALS
guidelines; 1 PIV may be sufficient unless
vasoactive drugs needed
• Consider labs on IV placement: blood gas,
lactate, glucose, ionized calcium, CBC, cultures
(glucose check through finger stick preferred
for rapid result)

20. Treatment of sepsis and septic shock in
children (III)
Fluid and electrolyte resuscitation (5-15min)
Fluids:
• Push 20 mL/kg fluid (isotonic crystalloid) IV/IO over 5-20min or faster if needed (reassess
for signs of shock; see Step No. 11, below)
• Repeat 20 mL/kg bolus push of fluid (up to 60 mL/kg) until clinical symptoms improve or
patient develops respiratory distress/rales/ hepatomegaly
• May continue to require additional fluid above 60 mL/kg (fluid refractory) (see Step No. 6,
below)
• Fluid needs may approach 200 mL/kg in warm septic shock (warm extremities, flash capillary
refill)
Correct hypoglycemia:
• Glucose levels in hypoglycemia: Neonates < 45 mg/dL; infants/children < 60 mg/dL
• Glucose dosage: 0.5-1 g/kg IV/IO (max that can be administered through a peripheral vein is
25% dextrose in water) (see alternative treatments immediately below)
• Treatment options to provide 0.5-1 g/kg glucose: For infant/child: dextrose 25% in water: 2-
4 mL/kg IV/IO; dextrose 10% in water: 5-10 mL/kg IV/IO; for neonate: dextrose 10% in
water: 2-4 mL IV/IO; consider maintenance fluid containing dextrose
Correct hypocalcemia for low ionized calcium:
• Calcium gluconate 100 mg/kg IV/IO (max 2g) PRN
• Calcium chloride 20 mg/kg IV/IO PRN ( Note: central line administration preferred over 60
min in nonarrest situation)

21. Treatment of sepsis and septic shock
in children (IV)
Infection control (5-60min)
Immediate considerations:
• Administer antibiotics immediately after cultures obtained
(blood, urine, +/- CSF/ sputum)
• Do not delay antibiotics because of delay in obtaining cultures;
initial antibiotics should be given within 1h
General treatment recommendations:
• Empiric therapy should be used for unknown etiology of sepsis;
• Tailoring of therapy to address suspected pathogens or to
achieve adequate drug penetration may be necessary;
• Broader initial coverage may be needed for initial stabilization
• Dosing varies by age and weight (consult institution pharmacist
and primary medication references for your institution practice
and for preterm infants and neonates <2kg)

22. Which is the recommended
antibiotic treatment in a 12-month-
old child with suspected sepsis?
1. Ampicillin + gentamycin
2. Ceftriaxone
3. Ceftriaxone + vancomycin
4. Cefepime + vancomycin

23. Treatment of sepsis and septic shock in
children (V)
Neonates >2kg:
• Ampicillin plus gentamicin: Ampicillin for 0-7d: 50 mg/kg IV/IM/IO q8h;
ampicillin >7d: 50 mg/kg IV/IM/IO q6h plus gentamicin (dosing institution
dependent): 4mg/kg IV/IO/IM q24h (alternative for 0-7d: 2.5 mg/kg
IV/IO/IM q12h; alternative for >7d: 2.5 mg/kg IV/IO/IM q8h) or
• Ampicillin plus cefotaxime: Ampicillin for 0-7d: 50 mg/kg IV/IM/IO q8h;
ampicillin >7d: 50 mg/kg IV/IM/IO q6h plus cefotaxime 50 mg/kg IV/IO
q8h
Infants (>1mo) and children:
• Ceftriaxone 75 mg/kg (max 2g) IV/IO/IM q24h plus vancomycin 15mg/kg
(max 1g) IV/IO q8h
Immunosuppressed patients:
• Vancomycin 15 mg/kg IV/IO (max 1 g/dose) q8h plus cefepime 50 mg/kg
IV/IO (max 2g/dose) q8h; consider antifungal therapy
Duration of therapy:
• Determined by ultimate source of infection; 7-10d is typically sufficient
• Above regimens may be empiric therapy for 48-72h
• If culture-negative sepsis, antibiotic choice and duration determined by
severity of presentation and most likely pathogen

24. Treatment of sepsis and septic shock
in children (VI)
Fluid-refractory shock (persisting after 60 mL/kg fluid; 15-
60 min)
• Continue fluid resuscitation and initiate vasopressor
therapy to correct hypotension/poor perfusion
• Central line placement and arterial monitoring if not
already established; vasopressors should not be delayed
for line placements
• Normotensive shock (impaired perfusion but normal blood
pressure): dopamine 2-20 mcg/kg/min IV/IO, titrate to
desired effect; if continued poor perfusion, consider
dobutamine infusion 2-20 mcg/kg/min IV/IO, titrate to
desired effect (may cause hypotension, tachycardia)
• Warm shock (warm extremities, flash capillary refill):
Norepinephrine 0.1-2 mcg/kg/min IV/IO infusion, titrate
to desired effect
• Cold shock (cool extremities, delayed capillary refill):
Epinephrine 0.1-1 mcg/kg/min IV/IO infusion, titrate to
desired effect

25. Treatment of sepsis and septic shock
in children (VII)
Shock persists following vasopressor initiation (60 min)
• Continued fluid replacement; obtain CVP measurement to guide
• SvO2 < 70% (cold shock): transfuse Hgb >10 g/dL; optimize arterial
saturation through oxygen therapy, ventilation; epinephrine 0.1-1
mcg/kg/min IV/IO infusion, titrate to desired effect
• SvO2 < 70% (normal BP but impaired perfusion): transfuse Hgb >10
g/dL; optimize arterial saturation through oxygen therapy,
ventilation; consider addition of milrinone 0.25-0.75 mcg/kg/min
IV/IO (titrate to desired effect) or nitroprusside 0.3-5 mcg/kg/min
IV/IO (titrate to desired effect)
• SvO2 >70% (warm shock): norepinephrine 0.1-2 mcg/kg/min IV/IO
infusion

26. Therapy of sepsis and septic shock
in children (VIII)
Fluid refractory and vasopressor-dependent shock) (60
min)
• Consider adrenal insufficiency
• Hydrocortisone 2 mg/kg (max 100mg) IV/IO bolus;
obtain baseline cortisol level; if unsure, consider
ACTH stimulation test; duration depends on response,
laboratory evaluation
Continued shock
• Consider cardiac output measurement to direct
further therapy
• Consider extracorporeal membrane oxygenation
(ECMO)

27. Therapy of sepsis and septic shock
in children (IX)
Supplemental therapies
• Blood transfusion considered for Hgb < 10 g/dL
(ideal threshold for transfusion unknown)
• Sedation/analgesia while ventilated
• Optimize oxygenation through ventilation
• IV immunoglobulin can be considered (unknown
benefit)

28. THERAPEUTIC ENDPOINTS
Clinical
• Heart Rate normalized for age
• Capillary refill < 2sec
• Normal pulse quality
• No difference in central and peripheral pulses
• Warm extremities
• Blood pressure normal for age
• Urine output >1 mL/kg/h
• Normal mental status
• CVP >8 mmHg
Laboratory
• Decreasing lactate
• SvO2 >70%

29. Which is the mortality rate in
children with sepsis in absence of
comorbidities?
1. 5-10%
2. 10-20%
3. 20-30%
4. 30-40%

30. Mortality for pediatric sepsis according to age and
presence of at least one comorbidity
(Weiss SL et al., Am J Crit Care Med 2015)

31. Outcomes of pediatric sepsis according to
age
(Weiss SL et al., Am J Crit Care Med 2015)

32. Which is the best way to reduce
the burden of pediatric sepsis?
1. Correct diet and life-stype
2. Large use of antibiotics
3. No vaccination
4. Universal vaccination against Hib,
pneumo and meningo

33. Norvegia
VT-IPDd
100%
(<2 anni)
Danimarca
VT-IPDd
84%
(<2 anni)
Germania
VT-IPDc
83%
(<2 anni)
Spagna
VT-IPDd
84%
(<15 anni)
Nicaragua
Polmonitea
33%
(<1 anno)
USA
Polmoniteb
27%
(<2 anni)
UK
VT-IPDc
89%
(<2 anni)
USA
VT-IPDb
93%
(<5 anni)
Israele
VT-IPDb
79%
(<5 anni)
Israele
OM pneumococcica
66%
(<2 anni)
Francia
VT-IPDd
84%
(<2 anni)
Francia
VT-Polmonitec
74%
(<16 anni)
Impact of PCV13 on IPD
a Ospedalizzazioni per polmonite
b 5 sierotipi addizionali per IPD: 1, 3, 5, 7F e19A
c 6 sierotipi addizionali per IPD/CAP: 1, 3, 5, 6A, 7F e 19A
d Tutti i sierotipi inclusi in PCV13
IPD
Polmonite
Otite Media

34. Impact of Synflorix™ on IPD
Quebec (Canada)
IPD
COMPAS
Panama
Colombia
Argentina
CAP, NP carriage,
AOM
Chile
IPD, CAP
Clinical trial
Impact / effectiveness
FinIP (Finland)
IPD, Antibiotics, CAP,
Antibiotic use, NP
carriage
Finland
IPD
2+1
After PCV7
3+1
No PCV7
3+1
No PCV7
3+0
No PCV7
2+1
No PCV7
3+1 & 2+1
No PCV7
The Netherlands
IPD, AOM
3+1
After PCV7
New Zealand
IPD, AOM
3+1
After PCV7
Iceland
IPD, meningitis, CAP,
AOM, antibiotic use
Bangladesh
IPD, pneumonia
3+0
NoPCV7
3+1
No PCV7
Brazil
IPD, meningitis, CAP,
carriage
3+1
No PCV7
Kilifi (Kenya)
IPD, carriage

35. INCIDENCE OF SEROGROUP C DISEASE IN
COUNTRIES THAT HAVE INTRODUCED PUBLIC
MCC VACCINATION PROGRAMMES
Trotter & Ramsay, FEMS Microbiol Rev 2007

36. 36 MEN-BEX-P-S-573-152012
MATS Concept
Are any of the 4CMenB components in the circulating strains:
(i) expressed to a sufficient degree, and
(ii) similar enough to the antigens in the vaccine
such that the antibodies generated by 4CMenB will kill the bacteria?
MATS can determine the minimum amount of recognizable antigen
needed to result in bacterial killing, for each of the four components*
1. fHbp, NHBA and NadA assessments use ELISA  PHENOTYPIC
2. PorA assessment uses PCR sequencing  GENOTYPIC
*individually

37. 37 MEN-BEX-P-S-573-152012
 Based on MATS, 4CMenB is predicted to cover 78% of strains
†Coverage based on MATS from pooled sera from 13-mo-old infants vaccinated at 2,4, 6, and 12 mo of age tested on
1,052 strains isolated during the 2007-2008 epidemiological year.
Boccadifuoco G, et al. Presented at: Meningitis and Septicaemia in Children and Adults 2011 (Organized by Meningitis Research
Foundation); 8–9 November 2011; London, UK. Poster V36.
Norway: 85% [95% CI: 76%, 98%]
n=41
France: 85% [70%, 93%]
n=200
Germany: 82% [69%, 92%]
n=222
Italy: 87% [70%, 93%]
n=54
England & Wales: 73% [59%, 88%]
n=535
4CMenB European coverage estimates†
4CMenB Has the Potential to Cover the Majority of
MenB Strains in 5 European Countries

39. Gràçie
[in zeineise]