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TOP PAPERS IN PEDIATRIC INFECTIOUS DISEASES Susanna Esposito Pediatric Highly Intensive Care Unit, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan, Italy
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Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Jul 20, 2015

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Page 1: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

TOP PAPERS IN PEDIATRIC INFECTIOUS DISEASES

Susanna EspositoPediatric Highly Intensive Care Unit,

University of Milan, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

Milan, Italy

Page 2: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

AGENDA

• Viral infections

• Bacterial infections

• Hot topics in antinfective treatment

Page 3: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

VIRAL INFECTIONS

• Ebola virus

• Enterovirus D68

• Rhinovirus

• Parechovirus

• Norovirus

Page 4: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 5: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Pediatric cases of Ebola virus infection(From Agua-Agum J et al., NEJM 2015)

Page 6: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Incubation period and case fatality rate of Ebola virus infection in children(From Agua-Agum J et al., NEJM 2015)

Page 7: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 8: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

DESCRIPTION OF THE PATIENTS WITH EVD68 INFECTION ASSOCIATED WITH ACUTE FLACCID MYELITIS

(Greninger et al., Lancet Infect Dis 2015)

Page 9: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 10: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Clinical characteristics of human rhinovirus infectionaccording to infecting HRV species and types

(From Principi N et al., J Clin Virol. 2015)

Page 11: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Median shedding time by type of human rhinovirus(From Principi N et al. , J Clin Virol 2015)

Page 12: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Cases oh human rhinovirus infection with viralshedding of the same viral type ≥3 weeks

(From Principi N et al., J Clin Virol 2015)

Page 13: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 14: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Number of confirmed HPeV cases admitted to 5 hospitals in New South Wales each week between

October 2013 to January 2014

Page 15: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 16: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
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Page 18: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Main studies regarding norovirus infection in Europe

(From Kowalzik F et al., Pediatr Infect Dis J 2015)

Page 19: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 20: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

BACTERIAL INFECTIONS

• MRSA

• Streptococcus pneumoniae• Neisseria meningitidis• ESBL producing Enterobacteriaceae• XDR TB

Page 21: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 22: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Proportion of households contaminated with an environmental strain type of Staphylococcus aureus

correlating with the participants’ baseline colonizing or infecting strains type, by household surface

(From Fritz SA et al., JAMA Pediatr 2014)

Page 23: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 24: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Predominant organismsaccording to groups

(From Irwin AD et al., Pediatrics 2015)

Page 25: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Proportion of bacteremia episodes of eachisolate according to age group

(From Irwin AD et al., Pediatrics 2015)

Page 26: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Fitted likelihood over time that an isolate was susceptibleto empirical therapy (top) and that an episode occurred in

a child with an indwelling chronic disease (bottom) (From Irwin AD et al., Pediatrics 2015)

Page 27: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 28: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Laboratory –confirmed cases of invasive meningococcaldisease by capsular group in England and Wales during the

2000-2001 to 2013-2014(From Ladhani SN et al., Clin Infect Dis 2015)

m

Page 29: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Laboratory-confirmed cases of invasive meningococcalgroup W disease by phenotype, age groups, and year

of diagnosis in England and Wales (From Ladhani SN et al., Clin Infect Dis 2015)

Page 30: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 31: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 32: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

ESBL producing Enterobacteriaceae in pediatric age(Lukac et al., Clin Infect Dis 2015)

Page 33: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Esposito S, D'Ambrosio L, Tadolini M, Schaaf HS, Caminero Luna J, Marais B, Centis R, Dara M, Matteelli A, Blasi F, Migliori GB.

Eur Respir J 2014 Sep;44:811-5.

First case in which delamanid was used in pediatric age

Page 34: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Index caseFAMILY

Male, 12 yearsLaryngeal + PTBLong diagnostic delayDirect Sputun examination +++Resistant to SHREZ+FQ+Inj+EtoHaarlem strain Mother, TST+, QF+

PTB, immigrant, histopathology+, CXR improved Cat 1

21 classmates tested:1 monolateral pleurisy (immigrant)10 TST+, QF+ (7 native, 3 immigrant)

2 dental hygienists tested: 2TST+, QF+

56 playmates tested:3 TST+, QF-(BCG vaccinated)

24 students tested in parallel class performing common activities:1 TST+, QF+1TST+, QF-

57 students tested in other classes:1TST+, QF+13 TST+, QF-

TB disease TST+, QF+ TST+, QF -

18 school staff tested:4TST+, QF+5TST+, QF-

Sister 6 yrs, PTB

Brother 10 yrs, PTB

Father, TST-, QF-

19 school canteen staff tested:3 TST+, QF -

37 educators tested:1 TST+, QF-

Summer camp circle

27 tested: All TST-, QF-

Sport related circle

Catechism related circle

50 tested: 1 TST+, QF+4 TST+, QF-

Other contacts

Page 35: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

HOT TOPICS IN ANTINFECTIVE TREATMENT

• Vancomycin serum concentrations in neonates

• Antimicrobial stewardship programmes• Use of off label antibiotics• Antifungal therapies

Page 36: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 37: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Baseline characteristics of neonates(From Ringerberg T et al., Pediatri Infect Dis J 2015)

Mean ± SD

Gestational age (weeks)

% patients born at:< 28 weeks28-34 weeks> 34 weeks

59.131.69.3

% male 46.1

PNA at vancomycin start (days) 34.1 ± 34.6

PMA at vancomycin start (weeks) 33.1 ± 6.3

Birth weight (grams) 1155 ± 782.8

Weight at vancomycin start (grams) 1602. 1014.5

Total length of stay* (days) 91.1 ± 51.3

SCr at vancomycin initiation (mg/dL) 0.51 ± 0.28

WBC (x103/mcL) at vancomycin initiation 17.2 ± 9.8

Duration of antibiotics (days) 6.5 ± 4.5

Page 38: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Achievement of vancomycin trough concentrations(From Ringerberg T et al., Pediatric Infect Dis J 2015)

Trough value Number of patients(%)

Initial trough (N = 171) 0-10 mcg/mL10-20 mcg/mL> 20 mcg/mL

123 (71.9)43 (25.1)5 (2.9)

Overall trough (N = 168)0-10 mcg/mL10-20 mcg/mL> 20 mcg/mL

92 (54.8)75 (44.6)

1 (0.6)

Dose adjustments to attain trough 10-20 mcg/mL(N = 75)

012

48 (64.0)22 (29.3)5 ( 6.7)

Duration of therapy to achieve trough 10-20 mcg/mL (mean ± SD)

2.27 ± 1.76 days

Page 39: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Differences in characteristics of patients whoachieved a trough of greater than 10 mcg/mL and

those who did not (n=178)(From Ringerberg T, et al. Pediatric Infect Dis J 2015)

Baseline characteristics

Trough < 10Median (IQR)

Trough > 10 Median (IQR)

P value

GA (weeks) 26.7 (25.6-32.0) 26.1 (24.7-29.9) 0.118

PMA (weeks) 32.6 (28.7-36.3) 30.4 (28.6-34.4) 0.107

PNA (days) 22 (10-40) 24 (16-41.5) 0.523

Birth weight (g) 900 (664-1651) 755 (666-1103) 0.103

Weight at start vancomycin (g)

1,385 (890-2130) 1,070 (803-1567) 0.046

SCr (mg/dL) 0.44 (0.30-0.64) 0.50 (0.31-0.80) 0.098

Aminoglycoside - - 0.549

Total daily dose(mg/kg/day)

20 (20-30) 30 (30-45) <0.001

Dosing intervals(hours)

12 (8-12) 8 (8-12) 0.026

Page 40: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Pediatrics 2015; January 1

Page 41: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

DDT/1000 pts days for all and selected antibioticsfor ASP- (grey lines) and ASP+ (black lines) hospitals

(Hersh et al., Pediatrics 2015)

Page 42: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

DDT per 1000 pt-days for all and selected antibiotics(Hersh et al., Pediatrics 2015)

Page 43: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 44: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

SUGGESTED USE OF FLUOROQUINOLONES IN PEDIATRIC AGE

(Principi & Esposito, Int J Antimicrob Agents 2015)

Page 45: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics
Page 46: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Participantcharacteristics for

receipt of fluconazole vs

placebo

(From Benjamin DK et al.,JAMA 2015)

Page 47: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Safety end points and other secondary end points for receipt of fluconazole vs placebo

(From Benjamin DK et al., JAMA 2015)

Page 48: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

Primary and secondaryendpoints and neurodevelopentalendpoints for receipt of fluconazole or placebo

(From Benjamin DK et al.,JAMA 2015)

Page 49: Susanna Esposito (president WAidid) - Infections and vaccines in pediatrics

SEE YOU IN MILAN!

THANK YOU VERY MUCH FOR

YOUR ATTENTION