changing spectrum of invasive bacterial diseasebundels are needed to limit nosocomial infections 2....

C.Berger, Kinderspital Zürich 2013 1

Changing spectrum of invasivebacterial disease

Christoph Berger, MDDivision of Infectious Diseases and Hospital Epidemiology

University Children‘s Hospital Zürich

PIGS course Basel November 8, 2013

Pneumococcal sepsis circulatory collapse

Pneumococcal sepsis circulatory collapse

Pneumococcal sepsis Waterhouse Friederichson

Diagnosis

S. pneumoniae inblood, lung

S. pneumoniae in lung

S. pneumoniae in blood, lung, spleen

Microbio(p.mortem)

51h shock52h pleuropneumonie53h exitusneutropenia

14h intubation18h shock: reanimation30h exitus (pneumonia)neutropenia

9.5h resuscitation

10h exitusLab

24h thorax rx: neg. 44h respiratory

distress (at home)

12h respiratory distress cyanosis (at home)

9h septical shock (at home)

Course

cough, feverrhinitis, fevervomiting, diarrheaOnset

Boy 6 months of age previously healthy

Boy 2 years of agepreviously healthy

Girl 3 years of age previously healthy

Overhelming sepsis in previously healthy children


• High incidence in the first 2(-5) years of life

encapsualted bacteria:Streptococcus pneumoniaeNeisseria meningitidisHaemophilus influenzae typ b

• Pneumonia• Sepsis • Meningitis• Arthritis

Invasive bacterial infections in children

Pathogenesis: Pneumococcal infection


Bacterial Meningitis: EpidemiologyAfter introduction of conjugate vaccines- Haemophilus influenzae type b (1990)- Pneumococci (2000 PCV7, PCV13 2010) - (GBS screening in pregnancy?)

• Reduction in incidence of meningitis at all agesexcept age < 2 months

• Age: median <5 years → 42 years

• Incidence (USA 2006/2007)< 2 months: 80 /100000

2-23 months: 6.9 /1000002-10 years: 0.56/100000

11-17 years: 0.43/100000

Trend in the incidence of IPD in the US: comparisonof prelicensure years to postlicensure years

PCV7 serotypes

all serotypes62.5

15.3

Inzi

denc

epe

r 105 50.1

4.9

Children <5 years of age

Bla

ck S

et a

l. P

edia

trIn

fect

Dis

J 2

007;

26: 7

71–7

77)


Hsu HE et al. N Engl J Med 2009;360:244

Serotype replacement in pneumococcal meningitis

US (1998-2005): overall reduction of cases - 30.1%

PCV7 (black), extra PCV13 (gray), remaining (white) pneumococcal serotypes

Pichon B et al J. Clin. Microbiol. 2013;51:820

England and Wales (2004 - 2009): overall, no significant reduction of cases

IPD attributed to clinical syndromes and serotypes in Utah in pre- (1997–2000)and postvaccine (2001–2010) periods.

Ampofo K et al. Pediatr Infect Dis J 2012;31: 228


Pneumonia with effusion

- 1 week + 3 months

PredominantelypneumococcalInfection:

Serotypes1, 3, 7F, 19A

and after PCV13 ?

• Antimicrobial treatment targeted against S. pneumoniae:Amoxicillin

• Conservative management• Minimize interventions• Excellent long term follow up

33

< 5 y: 8

Invasive Pneumococcal Diseaseaccording to age in Switzerland 2001-2012

Inci

denc

epe

r 100

000

popu

latio

n

> 64 y: 35

total: 11

>64

<2

2-4Total

5-15 16-50

Age group


Inci

denc

epe

r 100

000

Changing epidemiology of paediatric bacteraemiain England and Wales 1998-2007

Hen

ders

on K

L et

al.

J M

ed M

icro

biol

2010

; 59:

213

1-11 months

1-4 years

5-15 years

CoNSS. pneumoniaeS. aureus

CoNSS. pneumoniaeNon pyogenic Streptococcus

S. aureusCoNS

S. aglactiae

N. meningitidis

N. meningitidis

N. meningitidis

E. coli

Klebsiella spp.

Klebsiella spp.E. coli

E. coli

S. aureus

Swiss Pediatric Sepsis StudyRecruitment: in 2 years SwissPediatricSepsisStudy

Recruitment: 2 years, mean monthly frequency: 20

476Blood sampling data435Outcome

495Infectious dataassessment

510EligibilityTotalCRF FormsAll 8 pediatric A clinics in CH

Children < 18 years of age with- positive blood culture- SIRS / sepsis

Start Novemver September 2011


Swiss Pediatric Sepsis StudyPathogens and SeverityCoNS 48 (13%) (3 died)S. aureus 69 (19%) (2 died)S. pneumoniae 42 (12%) (3 died)Group A strepto 30 (9%) (2 died)Group B strepto 31 (9%)Enterococcus 7 (2%) (2 died)E. coli 52 (14%) (4 died)Klebsiella 14 (4%) (1 died)P. aeruginosa 10 (3%)N. meningitidis 7 (2%)H. influenza 7 (2%)other gram-negative 23 (6%) (1 died)other gram-positive 45 (12%) (1 died)fungi 8 (2%) (1 died)

SwissPediatricSepsisStudy

• 25% required PICU/NICU admission• 19% mechanical ventilation

• Mortality: 7%

Del

linge

rRP

et a

l Int

ensi

ve C

are

Med

201

3; 3

9:16

5

Suriviving sepsis campaign: Antimicrobial therapy

Sepsis mortality is associated with:• multiple comorbid illnesses• multiple organ dysfunction• greater severity of illness

begin high flow O2give iv fluidadminister antiboitics <1h

Each hour of delay in administering effective antibiotics increases mortalityGoal: administration < 1 hour.

Start empiric treatment with one ore more antimicrobials- effective against the likely pathogens- reaching adequate concentration in the tissue to be the source of sepsis

Reassess antimicrobial treatment daily- combination therapy < 3-5 days, duration of treatment 7-10 days-non infectious SIRS: stop antimicrobials

Pediatric Sepsis


Swiss Pediatric Sepsis StudyRisk groups / acquisition SwissPediatricSepsisStudy

• Hospitalized prior to sepsis (nosocomial sepsis): 42%• Neonates 31%• NICU/PICU prior to sepsis 23%• Chronic disease 22%• Immunosuppression 15%• Surgery 7%• Primary ID 3%

community acquired „no risk“?

risk: „nosocomial“ and „health-care-associated“

→ GWAS, EUCLIDS…

Acquisition of infection

Community-acquired (CAI)

Nosocomial (NI)

Health-care-associated (HCAI)

Hospital admission

>2days


The changing burden of pediatric bloodstreaminfections in Calgary 2000-2006

Laupland KB. et al PIDJ 2009; 28:114……..

BSI incidence: 53 per 100000, highest in neonates,Decreasing incidence of community acquired disease over time

Incidence ofpneumococcalBSI with PCV7:

Overall:13.6 → 4.7/105

CA-BSI11.3 → 3/105

<2 years of age:58.9 → 7.3/105

Febrile neutropeniain children treated for cancer

Fletcher M et al Pediatr Blood Cancer 2013;60:1299

Possible infectionProbable infectionBacteremiaSepsis

Immediate empirical treatmentto prevent invasive infection

Increasing time to antibiotic administration isassociated with poor outcomes of FN in children

Shift from Gram- to Gram + infections in the 1980 and 1990High prevalence of streptococcal infectionsCoNS (catheter associated infections)Antibiotic-resistant Gram negative bacteria

Risk stratificationDe-escalationAntibiotic stewardship

Treatment


Gram-negative bacteremia* in paediatric oncologic patients

Hae

usle

rGM

et a

l Ped

iatr

Infe

ctD

is J

201

3;32

: 723

Antibiotic resistant (= resistant to ticarcillin-clav + gentamicin) Gram-negative bacteremia is associated with increased adverse outcomes

- after high-intensity chemotherapy,- in patients that have been in hospital beyond 48 hours- in patients with previous AR GN infection or colonization

*28% of bacteremias(2003-2010)

Incidence of neonatal invasive groupB streptococcal (GBS) disease (US)

Early onset neonatal sepsis

EO sepsis: Incidence/1000 live births and mortalityBirth weight >1500 1500 >2500 all

(g) -2500 All 10.96 1.38 0.57 0.98 62/389 (16%)GBS 2.08 0.38 0.35 0.41 15/160 (9%)E coli 5.09 0.54 0.07 0.28 35/107 (33%)

Sto

ll B

et a

l Ped

iatri

cs20

11;1

27:8

17–8

26; M

MW

R 2

010;

59(N

o. R

R59

10)

• Intrapartum prophylaxis reduced

GBS early onset sepsis

• the burden of GBS and E. coli

disease continues.


Late onset neonatal sepsisnosocomial ! can it be prevented ?

•SOPs: standardized procedures•Accurate diagnosis (CONS)•Surveiilance

•Hand hygiene !

• Remove catheters as soon as possible

• Early enteral feeding

• restrict vancomycin use• careful with H2 blockers• fluconazole prophylaxis cave !

Mean age: 2-3 weeks

↑ Sepsis incidence• birth weight ↓• CVC days ↑• ventilation days ↑• parenteral hyperalimentation

Antimicrobial resistance

Mortality:Gram-pos << Gram-neg, fungi

NN

IS 2

000;

Sai

man

Cur

rOpi

nPe

d20

06; 1

8:10

1

Extensively-drug-resistant i.e. metallo-β-lactamase (MBL) positive Pseudomonas aeruginosa were resistant to all antibioticsexcept colistin

Increases in the use of colistin will probably result in furtherspread of ST235 P aeruginosa resistant to all drugs

Antimicrobial resistance


Acquisition of infection matters forprevention and empirical treatment

Community-

acquired (CAI)

Nosocomial (NI)

Health-care-associated (HCAI)

Hospital admission

>2days

Early recognitionVaccine-preventable ?

Antibiotic stewardshipHygiene precautions

Need recognition !and smart empiricaltreatment

The changing spectrum of invasive bacterial infection

The introduction of conjugate vaccines has reduced the burdenand changed the spectrum of community-aquired bacteremia

Up to half of pediatric sepsis is health-care and hospital acquired.

1. Antibiotic stewardship and infection prevention / hygienebundels are needed to limit nosocomial infections

2. Children with severe comorbidity account for a larger % of invasive infections. Recognizing those as „health-care-associated infections“ may allow to optimize their needs

changing spectrum of invasive bacterial diseasebundels are needed to limit nosocomial infections 2....

Documents