Prévenir les infections périnatales à streptocoques du groupe B: Stratégies & nouveautés - Mécanismes de résistance aux antibiotiques

(1)

1 Pierrette

Pierrette

Melin

Microbiologie m

é

dicale CHU de Li

è

ge

Laboratoire de r

Laboratoire de ré

éf

f

érence belge des GBS

é

rence belge des GBS

Pr

é

_é

venir

_venir

les

_les

infections

p

é

rinatales

à

streptocoques

du

_du

groupe

B

_B

Strat

(2)

2 Background

Background

_Important

_pathogen

_since

_the

_1970s

_Perinatal

_GBS

_disease

_burden

_Neonatal

_illness

_/

_death

_,

_long

_-

_term

_disability

_Belgium

_{: > 300}

_sepsis

₊

_meningitis

_/

_year

_34.8%

_of

_EOD

_through

₁₉₉₁

_-

₂₀₀₅

_{(No.2 =}

_E.coli

_{: 12.5%)}

_Maternal

_morbidity

(3)

3 GBS

GBS

Neonatal

Infections

A. A. Schuchat

Schuchat

, Clin Microb

, Clin

Microb

Rev

1998;11:497-

1998;11:497

-513

513

0

20

40

60

80

100 < 1

wk

1-3

wk

1

2

3

4

5

6

7

8

9 10 11

Age (months)

P

e

rc

e

n

t

o

f

c

a

s

e

s

0 20 40 60 80 100 0 1 2 3 4 5 6 Age (days) P e rc e n t o f c a s e s

80 % EOD

EOD : 80 %

occur

before

24 h

LOD

(4)

4 “

“

Evidence

-

based

”

Prevention of

perinatal

Group B

streptococcal infections

Guidelines from Belgian Council of Hygiene

-

July 2003

Gynecologists

-

obstetricians

Pediatrician

-

neonatologists

Microbiologists

French/

Flemish

University

/

non

-

university

Foulon W.

Hubinont

C.

C. Lepage

Lepage

P.

P. Levy

Levy

J.

J. Mahieu

Mahieu

L.

L. Alexander S.

Alexander S.

Beckstedde

I.

I. Claeys

Claeys

G.

G. De Mol P.

De Mol P.

Donders

G.

G. http://

http://

www.health.fgov.be

/CSH_HGR

General Recommendations

& Specific suggestions

WORKING GROUP :

Secr

Secr.: Dubois JJ, CSH

.: Dubois JJ, CSH

Melin

P.

P. Naessens

Naessens

A.

A. Potvliege C.

Potvliege C.

Temmerman

M.

M. Tuerlinckx

Tuerlinckx

D.

D. Van Eldere J.

Van Eldere J.

(5)

5

PRO

SCREENING

(6)

6 Gyneco

Gyneco

-

Obstetricians

Laboratory

microbiologist

Pediatricians

Labor

/

delivery

Ward

Intrapartum

antimicrobial

prophylaxis

-

IAP

Universal

prenatal

screening

at

35

35 -

-

37

37 weeks

weeks

gestation

Risk

-

based

approach

reserved

for

women

with

unknown

GBS

(7)

7 Adhesion to a common protocol is a key of success

Adhesion to a common protocol is a key of success

Multidisciplinary collaboration is mandatory

(8)

8 Why

Why

IAP ?

_{IAP ?}

Why

a

Screening

-

based

approach

?

_Risks

_{for GBS EOD}

_Goals

_of

_IAP

_{Effectiveness}

_Belgian

_choice

_Concerns

_{about use}

_of

_prophylaxis

(9)

9 GBS VERTICAL TRANSMISSION

GBS VERTICAL TRANSMISSION

GBS

colonized

mothers

Non-colonized

newborns

Colonized

newborns

40 40 -

-

60 %

2 2 -

-

4 %

GBS EOD

60

60 -

-

40 %

96

96 -

-

98 %

Asymptomatic

sepsis

pneumonia

meningitis

long

long term

term

disability

_CDC

Risk

factors

(10)

10 GBS

GBS

maternal

_maternal

colonization

_colonization

Risk

factor

for

early

-

onset

disease

(EOD)

:

vaginal GBS

colonization

_colonization

at

_at

delivery

_delivery

_{GBS carriers}

₁₀

_-

_{30 %}

_of

_women

_Clinical

_signs

_not

_predictive

_Dynamic

_condition

_Prenatal

_cultures

_late

_in

_pregnancy

_can

_predict

delivery

(11)

11 Additional Risk Factors

for Early-Onset GBS Disease

Obstetric factors:

Prolonged rupture of membranes,

Preterm delivery,

Intrapartum

fever

GBS

bacteriuria

Previous infant with GBS disease

Immunologic:

Low specific

IgG

to GBS capsular

polysaccharide

No difference in occurrence either in GBS

Positive or Negative women, except

intrapartum

fever

Lorquet S., Melin P. & al.

J

(12)

12 GBS EOD

GBS EOD

-

_-

Belgian data

_Incidence

_{1985: 3/1000 live births}

_{1990: 3 cases + 4 likely cases/1000 live births}

_{1999, estimation : 2/1000 live births}

_{Meningitis : 10 %}

_{Mortality > 14 %}

_{60 % EOD}

_{(130 cases)}

_{: WITHOUT any}

maternal/obstetric risk factor

_{Prenatal screening}

_Recto

_-

_{vaginal cultures : 13}

_-

_{25 % GBS Positive}

P. Melin, 2001

(13)

13 Prevention

Prevention

of

_of

perinatal

_perinatal

GBS EOD

_{GBS EOD}

_Intrapartum

_antibiotics

_Highly

_effective

_at

_preventing

_EOD

_in

_women

_at

_risk

_of

transmitting

GBS

to

their

newborns

(

>

4 h)

INTRAPARTUM ANTIMICROBIAL

PROPHYLAXIS (

IAP

)

_{Main goal}

_:

_To

_prevent

_{70 to 80 %}

_of

_{GBS EO cases}

_Secondary

_:

(14)

14 How best to

How best to

identify women

at risk ?

CDC 1996

recommendations

«

IAP

»

35

35 -

-

37

37 wks

wks

Screening

-

based

strategy

Or

Risk

(15)

15

0 0,5

1 1,5

2 2,5

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Year

Early-onset

Late-onset

Impact of prevention practices

Rate of Early

-

and Late

-

onset GBS

Disease in the 1990s, U.S.

Consensus

guidelines

Group B Strep

Association

formed

1st ACOG & AAP

statements

CDC draft

guidelines published

S.

(16)

16 Screening

Screening

for GBS

or

risk

-

factors

?

P.Melin

, 40th ICAAC, 2000

L.Mahieu

L.Mahieu, 2000, J

, 2000, J Obst

Obst

Gyn;5:460

Gyn

;5:460-

-4

4

90

44

0

20

40

60

80

100 Screening-based

%

O

b

st

e

tr

ic

ia

ns

French C. Flemish C.

(17)

17 Effectiveness

Effectiveness

of

_of

both

_both

CDC 1996

_{CDC 1996}

approaches

Schrag

S. et

al

. N

Engl

J

Med

2002; 347:233

-

9

9 “

“

RF

”

easier and cheaper than

“

screening

”

BUT

_Population

_-

_{based surveillance study, U.S.}

_{312 GBS EOD ;}

₊

_{600 000 live births}

_AUDIT

_{(5144 files)}

_:

_«

_{IAP given when mandatory}

_»

_{52 %}

_of

_all

_deliveries

_had

_screening

_IAP

_given

_more

_often

_if

_«

_{GBS Positive}

_screening

_»

_than

if

presence

of

>= 1 RF

“

(18)

18 Why

Why

is

Screening

more

protective

than

the

risk

-

based

approach

?

Broader

coverage

of

«

at

-

risk

»

population

_Captures

_colonized

_women

_without

obstetric

RF

_High

_level

_of

_compliance

_with

recommendations

_Enhanced

_compliance

_with

_risk

_-

_based

approach

cannot

prevent

as

many

cases

as

(19)

19 CDC

CDC

The Recommendations

MMWR,

Vol

51

51 (RR

(RR

-

11) August 2002

Universal prenatal

screening

& RF reserved for unknown

GBS culture results

Endorsed

by AAP

and

by ACOG

in 2002

(20)

20 Screening

Screening

-

based

strategy

for

prevention

of GBS

perinatal

disease

(

Belgian

CH, 2003)

Recto-vaginal GBS screening culture at 35-37 weeks of gestation

For ALL pregnant women

Recto-vaginal GBS screening culture at 35-37 weeks of gestation

For ALL pregnant women

> 1 Risk factor:

- Intrapartum fever > 38°C***

- ROM > 18 hrs

> 1 Risk factor:

- Intrapartum fever > 38°C***

- ROM > 18 hrs

Intrapartum prophylaxis

NOT

indicated

IN

T

R

A

P

A

R

T

U

M

A

N

T

IB

IO

P

R

O

P

H

Y

L

A

X

IS

IN

D

IC

A

T

E

D

Neg

Pos

if NO

if YES

Unless patient had a previous infant with GBS invasive disease

or GBS bacteriuria during current pregnacy

or delivery occurs < 37 weeks’ gestation *

GBS

Neg

if YES

GBS POS

Not done, incomplete

or unknown GBS result

! Facultative !

Intrapartum

(21)

21 GBS Screening: Predictive Value of

GBS Screening: Predictive Value of

Antenatal Cultures by Interval to

Delivery

0

20

40

60

80

100

120

6

5

4

3

2

1 Weeks before delivery

P

e

r

c

e

n

t

PPV

NPV

N=826; 26.5% GBS carriers

Yancey et al., OB GYN 1996;88:811

-

5.

(22)

22 WHEN

_WHEN

35 ₃₅

-

_-

37 ₃₇

weeks

_weeks

WHO

_WHO

ALL

_ALL

the

_the

pregnant

_pregnant

women

_women

Specimen

_Specimen

Vaginal + rectal

_{Vaginal + rectal}

swab

_swab

(s)

_(s)

Collection

_Collection

WITHOUT

_WITHOUT

speculum

_speculum

Transport

_Transport

Transport/collection

_{Transport/collection}

device

_device

(non nutritive medium: Amies/Stuart)

Request

form

To

specify

prenatal

«

GBS

»

screening

+

expected

address

for

delivery

Crucial conditions to

optimize

_optimize

SCREENING

(CDC 2002

(23)

23 Prenatal

Prenatal

GBS

screening

:

Laboratory

procedure

_procedure

(

Belgian

HC, 2003)

35

35 -

-

37 wks

V+R

Selective enrichment broth (eg.LIM)

Overnight, 35

-

37

37 °

°

C

Sub-culture onto “Granada” agar

Overnight, 35

-

37

37 °

°

C

anaerobically

POSITIVE screening

Negative screening

Presence

of orange

colonies

= GBS

Absence of

orange

colonies

Minimum

:

(24)

24 Selective

Selective

enrichment

_enrichment

broth

_broth

Lim

Broth

=

Todd

Hewitt

broth

+

colistin

(15

µµµµ

g/ml)

+

nalidixic

acid

(10

µµµµg/ml)

µµµµ

g/ml)

Overnight

at

37

37 °

°

C

and

sub

-cultured

-

cultured

onto

«

(25)

25 Granada medium agar

Granada medium agar

or

BD

TM

_Group

B

Streptococcus

_{Streptococcus}

Differential

_Differential

Medium

_Medium

Orange

color

:

Specific

for GBS

//

(26)

26 Strepto

Strepto

B ID agar

-

BioM

é

rieux

High

sensitivity

for

for growth

growth

o

f GBS

GBS =

pink

to

red

colonies

Not 100 %

(27)

27 What

What

to do in case of Positive

_{to do in case of Positive}

GBS

screening

?

_Send

_results

_to

_requesting

_doctor

_and

_a

copy to

expected

site for

delivery

_{DO NOT}

_treat

_during

_pregnancy

_if

asymptomatic

_{( ! To}

_treat

_{if GBS}

_bacteriuria

_{! )}

(28)

(29)

29 Intrapartum

Intrapartum

Antibio

-

Prophylaxis

(

Belgian

HC 2003)

Penicillin

_Penicillin

G

_G

5 millions U, IV initial dose, then

5 millions U, IV initial dose,

then

2,5

millions U IV

every

4

4 hours

hours

until

delivery

.

_Ampicilline

2 g IV initial dose,

_{2 g IV initial dose,}

then

_then

1 g IV every

_{1 g IV}

every

4 h until

_{4 h}

until

delivery

_delivery

.

_.

_Acceptable

_alternative

_{, but}

_broader

_spectrum

_,

_potential

selection

(30)

30 Intrapartum

Intrapartum

Antibio

-

Prophylaxis

If

penicillin

allergy

(

Belgian

HC 2003)

Patients

at low risk

for anaphylaxis

_Cefazolin

_{2 g IV initial dose, then 1g IV every 8 h until}

delivery.

Patients

_Patients

at high risk

_{at high risk}

for anaphylaxis

_{for anaphylaxis}

Clindamycin

_Clindamycin

_{900 mg IV every 8 hours until delivery.}

If GBS resistant to clindamycin : ask for infectiologist

_{If GBS resistant to clindamycin : ask for infectiologist}

opinion

(31)

31 Feasibility

Feasibility

in

_in

Belgium

_Belgium

_Screening

_Follow

_-

_up

_visit

_already

_scheduled

_around

₃₅

_-

-37

37 wks

wks

gestation

_{Accessability}

_to

_laboratories

_IAP

₍

_intra

_-

_venous

₎

(32)

32 Concerns

Concerns

about

_about

potential

_potential

adverse /

unintended

consequences

of

_of

prophylaxis

_prophylaxis

_Allergies

_Anaphylaxis

_occurs

_but

_rarely

_{Changes in incidence or resistance}

_{Changes in incidence or}

_resistance

_of

_other

pathogens

causing

EOD

_{Data are}

_complex

_…

_{BUT Most}

_studies

_{: stable rates}

_of

_«

_other

_»

sepsis

Changes in GBS

_{Changes in GBS}

antimicrobial

_{antimicrobial}

resistance

_resistance

profile

(33)

33 Susceptibility

Susceptibility

pattern of GBS

_{pattern of GBS}

0%

20%

40%

60%

80%

100%

Pen

Ampi

Céph.I

Ery/Clin

Susceptible

Resistant

15

15 -

-

30 % :

Melin

(34)

34 Interpretation

Interpretation

criterian

_criterian

(MH

with

blood

)

(CLSI 2006)

Zone

MIC

Diameter

(mm)

(mg/L)

S

I

R

S

I

R

Penicillin

>

24

24 -

-

<

0.12

0.12 -

-

-Erythromycin

Erythromycin

>

21

16

16 -

-

20

20 <

<

15

15 <

_<

0.25

0.5

0.5 >

>

1

1 Clindamycin

Clindamycin

>

19

16

16 -

-

18

18 <

<

15

15 <

<

0.25

0.5

0.5 >

>

1

1 Phenotypes

Phenotypes

of

resistance

to macrolide

-

lincosamide

:

Dtest

cMLS

Erythro

R &

Clinda

R

iMLS

Erythro

R &

Clinda

S/I/R

with

Dtest

+

M

(35)

-35

Concerns

about

_about

potential

_potential

adverse /

unintended

consequences

of

_of

prophylaxis

_prophylaxis

Management of

_{Management of}

neonates

_neonates

_Increase

_of

_unecessary

_evaluation

_Increase

_of

_unecessary

_{antimicrobial}

treatments

(36)

36 Management of

Management of

neonates

_neonates

at

_at

risk

for GBS EOD

Rem.

: 90% of GBS EOD are

symptomatic

< 24 h of live

Neonates

born

to

women

who

received

IAP

Symptomatic

NN

/

asymptomatic

NN

At

low

/

at

high

risk

.

To

minimize

unnecessary

evaluation

and

antimicrobial

treatment

(37)

37 Management of

Management of

symptomatic

newborns

at

risk

for GBS EOD

Clinical

signs

of

sepsis

1

1 -

-

Full diagnostic

evaluation

*

2

2 -

-

Empiric

antibiotherapy

(

Ampicillin

+ aminoside)

*

:-

:

-

Full

blood

cell

count

(FBC) +

differential

--

CRP

--

Bloodculture

--

(

Lumbar

P.)

--

Chest

Xray

--

Endotracheal

culture (if

intubated

or if

resp.distress.

or

Rx

infiltrate

)

Rem

.

! NOT

recommanded

:

1

1 -

-

Urinary

GBS

Ag

2

(38)

38 Management of

Management of

asymptomatic

_asymptomatic

newborns

«

_«

at

_at

high

_high

risk

_risk

»

_»

for GBS

_{for GBS}

EOD

If

antibiotherapy

given

to

mother

for

--

Suspicion of

chorioamnionitis

or

--

Premature

AND

prolonged

rupture of

membranes

Full

evaluation

Empiric

(39)

39 Management of

Management of

asymptomatic

newborns

«

at

low

risk

»

for GBS

EOD

If IAP

given

to

the

mother

,

gestational

age :

< 35

wks

.

_Limited

_evaluation

_*

_Observation

If

sepsis

suspected

**

_Full

_evaluation

_Empiric

_therapy

>= 35

wks

.

Duration

of

IAP

>

4 h

No

evaluation

< 4 h

(40)

40 Threatened

Threatened

preterm

delivery

Planned

caesarean

_caesarean

delivery

_delivery

for

_for

GBS

colonized

_colonized

women

_women

Duration

(41)

41 Preventive

Preventive

strategies

Current

Belgian

benefits

0

8 1999

2000

2001

2002

2003

2004

2005

N

o

.c

a

s

e

s

E

O

D

/N

o

.c

a

s

e

s

L

O

D

SHC

guidelines

"Feed-back"

symposia &

Consensus

Prevention

"policy"

surveys

No.EOD /No.LOD

Melin

(42)

42 Conclusions & perspectives

Conclusions & perspectives

Prevention

of GBS

perinatal

Diseases

PRO

-

SCREENING

Currently

the

best choice

best

choice

but

NOT

the

ideal

strategy

Temporary

,

waiting

for vaccines,

other

approach

_To

_implement

_in

_the

_daily

_practice

_V+R

_Screening

_method

_{!! Transmission of}

_results

_!!

(43)

43 Alternative to prenatal GBS

Alternative to prenatal GBS

screening:

intrapartum

_intrapartum

screening

_screening

Specimen

analysis

Optimal

management

of patient

Results

Collect specimen at

admision

30

30 -

-

45 minutes

Benitz

(44)

44 Perspectives

Perspectives

_Other

_investigated

_approaches

_{Real time PCR for}

_intrapartum

_screening

(

(45)

45 Belgian

Belgian

Challenge =

To

prevent

annually

> 200 cases

of

neonatal

GBS EOD

GDLux

Challenge =

To

prevent

annually

> 10 cases

of

(46)

46 Key GBS Resources

Key GBS

Resources

_Resources

_{MMWR :}

_{August 16, 2002 / 51(RR11); 1}

_-

₂₂

_ACOG

_Comm

_Opin

_{2002, N}

_°

₂₇₉

_Obstet

_Gynecol

_{, 2002;100:1405}

_-

₁₂

_CDC

_’

_{s GBS Internet page}

_http://

_www.cdc.gov

_/

_groupBstrep

_/

_{Conseil sup}

_é

_{rieur d}

_’

_hygi

_è

_ne

_(brochure

_strep

_B)