TOP PAPERS IN PEDIATRIC INFECTIOUS DISEASES

Susanna EspositoPediatric Highly Intensive Care Unit,

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

Milan, Italy

AGENDA

• Viral infections

• Bacterial infections

• Hot topics in antinfective treatment

VIRAL INFECTIONS

• Ebola virus

• Enterovirus D68

• Rhinovirus

• Parechovirus

• Norovirus

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

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

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

(Greninger et al., Lancet Infect Dis 2015)

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

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

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

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

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

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

October 2013 to January 2014

Main studies regarding norovirus infection in Europe

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

BACTERIAL INFECTIONS

• MRSA

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

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)

Predominant organismsaccording to groups

(From Irwin AD et al., Pediatrics 2015)

Proportion of bacteremia episodes of eachisolate according to age group

(From Irwin AD et al., Pediatrics 2015)

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)

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

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)

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

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

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

HOT TOPICS IN ANTINFECTIVE TREATMENT

• Vancomycin serum concentrations in neonates

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

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

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

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

Pediatrics 2015; January 1

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

(Hersh et al., Pediatrics 2015)

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

SUGGESTED USE OF FLUOROQUINOLONES IN PEDIATRIC AGE

(Principi & Esposito, Int J Antimicrob Agents 2015)

Participantcharacteristics for

receipt of fluconazole vs

placebo

(From Benjamin DK et al.,JAMA 2015)

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

(From Benjamin DK et al., JAMA 2015)

Primary and secondaryendpoints and neurodevelopentalendpoints for receipt of fluconazole or placebo

(From Benjamin DK et al.,JAMA 2015)

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