facultative gram-positive diplococci that are grown easily on a variety of bacteriologic media. Isolated colonies are 3 ... group B streptococci include resistance to bacitracin or ...... What percent of these infections are preventable remains to be determined ..... participation in phagocytosis of type III group B streptococci. Infect.
Introduction (brief description of streptococci and clinical
significance). T h e ge n u s S t r e p t o c o c c u s i s a d i v e r s e c o l l e c t i o n o f G r a m - p o s i t i v e c o c c i t yp i c a l l y a r r a n ge d i n p a i r s o r c h a i n s ( F i gu r e 1 ) . w i d e l y d i s t r i b u t e d a n d a r e c o m m e nsa l s o f r e s p i r a t o r y, ga s t r o i n t e s t i n al species
are
important
facultative
anaerobes,
and
and human some
the
They are
hu m a n u p p e r
fe m a l e ge n i t a l t r a c t s . p a t h o ge n i c .
Most
gr o w
in
only
an
Certain
species
are
atmosphere
e n h a n c e d w i t h c a r bo n d i ox i d e ( c a p n o ph i l i c gr o w t h ) . T h e i r n u t r i t i on a l r e q u i r e m e n t s a r e c o m p l ex , n e c e s s i t a t i n g t h e u s e o f b l o o d - o r s e r u m -e n r i c h e d m e d i a f o r i s o l a t i o n . f e r m e n t e d , r e s u l t i ng i n t h e p r o d u c t i o n o f
C a r b o hyd r a t e s a r e
lactic acid, and
unlike
s t a p h yl o c o c c u s s p e c i e s . D e f i n i t i o n : G r am - p o s i t i v e c o c c i ca t a l a s e - n e ga t i v e . N o n - s p o r i n g; o c c a s i o n a l l y c a p s u l a t e ; o p t i m u m gr o w t h a t 3 7 C ; f a c u l t a t i ve a e r o b e s ; often require enriched media; many species show characteristic h e m o l ys i s ( 1 ) . s G r o u p A s t r e p t o c o c c i ( S . p y o g e n e s ) i s b e t a h e m o l yt i c , l a r ge c o l o n y- f o r m i n g s t r e p t o c o c c i w i t h La n c e f i e l d gr o u p A a n t i ge n a r e i n c l u d e d i n t h e s p ec i e s S . p yo ge n e s a n d r e p r e s e n t o n e of t h e m o s t i m p r e s s i v e h u m a n p a t h o ge n s . T h e n um e r o u s vi r u l e n c e fa c t o r s o f S . p yo g e n e s ( M p r o t e i n , l i p o t ei c h o i c a c i d, e n z ym e s , t o x i n s ) a l l o w i t t o p r o d u c e a w i d e a r r a y o f s e r i o u s i n f e c t i o n s , i n c l u di n g p h a r yn gi t i s , r e s p i r a t o r y i n f e c t i o n , s k i n ( i m p e t i go , e r ys i p e l a s ) a n d s o f t t i s su e i n f e c t i o n s , e n d o c a rd i t i s , m e n i n gi t i s , pu e r p e r a l s e p s i s a n d a r t h r i t i s . In f e c t i o n s w i t h t ox i n - p r o d u c i n g s t r a i n s c a n r e s u l t i n s c a r l e t f e v e r o r m o r e s e r i o u s t ox i c sh o c k - l i k e s yn d r o m e s . ( 2 ) B e t a - h e m o l yt i c s t r e p t o c o c c i w i t h La n c e f i e l d gr o u p B a n t i ge n ( S . a g a l a c t i a e ) a r e a n i m p o r t a n t c a u s e o f s e r i o u s n e o n a t a l i n f e c t i on c h a r a c t e r i z e d b y s e p s i s a n d m e ni n gi t i s . H e a v y c o l o n i z a t i o n o f t h e m a t e r n a l ge n i t a l t r a c t i s a s s o c i a t e d w i t h c o l o ni z at i o n o f i n f a n t s a n d
1
r i s k o f n e o n a t a l d i se a s e . E a r l y - o n s e t i n f e c t i o n o c c u r s w i t h i n t h e f i r s t f e w d a ys a f t e r d e l i ve r y a n d o f t e n i s a s so c i a t e d w i t h pn e u m o n i a , w hi l e late-onset disease usually appears after one week of age. Group B streptococcal infection includes diabetes mellitus, cancer, and human i m m u no d e f i c i e n c y v i r u s i n f e c t i on . A d u l t gr o u p B i n f e c t i o n s i n c l u d e bacteremia,
endocarditis,
skin
and
soft
t i s su e
i n f ec t i o n ,
a n d.
O s t e o m ye l i t i s ( 3 ) . Group C
and G
streptococci
that
form
l a r ge
colonies
are
p yo g e n i c s t r e p t o c o cc i s i m i l a r t o S . p y og e n e s a n d c a u s e a w i d e r a n ge o f s e r i o u s i n f e c t i on s s u c h a s b a c t e r e m i a , e n d o c a r d i t i s , m e n i n gi t i s , s e p t i c a r t h r i t i s , a nd i n f e c t i o ns o f t he r e s p i r a t o r y t r a c t a n d s k i n. A l t h o u gh t h e cl i n i c a l s ym p t o m s o f ph a r yn ge a l i n f e c t i o n c a u s e d b y t h e s e s t r e p t o c o c c i ar e s i m i l a r t o t h o s e o f gr o u p p h a r yn gi t i s , gr o u p C a n d G s t r e p t o c o c c i l a c k a s t r o n g a s s o c i a t e d w i t h ou t b r e a k s o f gr o u p C p h a r yn gi t i s ( 4 , 5 ) . S m a l l - c ol o n y- f o r m i n g b e t a - h e m o l yt i c s t r e p t o c o c c i s t r a i n s m a y express
La n c e f i e l d
n o n gr o u p a b l e .
gr o u p
A,
C,
F,
or
G
a n t i ge n
or
may
be
T h es e s t r e p t o c o c c i a r e u s u a l l y i d e n t i f i e d as m e m b e rs
o f t h e ― S . m i l l e r i ‖ gr o u p o f s p e c i e s . A l t h o u gh t h e s e o r ga n i s m s c a n b e i s o l a t e d f r o m p yo g e n i c i n f e c t i o n ( n ot a b l y a b s c e s s e s ) , t h e y a p p e a r t o r e s i d e i n t h e p h a r yn x a s c om m e n s a l s a n d a r e p r o b a b l y n o t a ge n t s o f p h a r yn gi t i s ( 6 ) . The
p n e u m o c oc c u s
is
an
i m p or t a n t
of
communituacquired
p n e u m o n i a t h a t m a y b e a c c o m p a n i e d b y b a c t e r e m i a . O r o p h a r yn ge a l c a r r i a g e o f p n e u m oc o c c i i s c om m o n a nd c o n t r i b u t e s t o t h e d i f f i c u l t y o f i n t e r p r e t i n g t he s i gn i f i c a n c e o f p n e u m o c o c c i
in cultures of
e x p e c t o r a t e d s p u t um . O t h e r p n e um o co c c i i n f e c t i o ns i n cl u d e o t i t i s m e d i a ’ s i n us i t i s , m e n i n gi t i s , a n d e n d oc a r d i t i s . V a c c i n e s d e s i gn e d t o p r o t e c t a ga i n s t i n f e c t i o n b y p n e u n o c o c c i w i t h p r e d o m i n a nt c a p s u l ar p o l ys a c c h a r i d e t yp e s a r e n o w a v a i l a b l e . S t r a i n s o f vi r i da n s s t r e p t o c o c c i a r e n o r m a l i n h a b i t a nt s o f t h e m a m m a l i a n o r a l c a v i t y, ga s t r o i n t e s t i n a l t r a c t , a n d f e m a l e g e n i t a l t r a c t . A l t h o u gh t h es e s t r e p t o c o c c i o f t e n a p p e a r a s c o n t a m i n a n t s i n b l o o d c ul t u r e s , t he i r p r e s e n c e m a y b e a s s o c i at e d w i t h s ub a c u t e 2
bacterial
e n d o c a r d i t i s,
especially
in
patients
with
da m a ge d
or
p r o s t h e t i c v a l v e s . T h e v i r i d a n s s t r e pt o c o c c i a r e a l s o i s o l a t e d f r o m i n f e c t i o n s i n o t h e r o r ga n s ys t e m s a n d s e e m t o b e a ss u m i n g a n i n c r e a s i n g r o l e i n i n f e c t i o n i n n e u t r o p en i c p a t i e n t s ( 7 ) . B a c t e r e m i a c a u s e d b y S . b o v i s i s o l a t e s , p a r t i c u l a r l y b i o t yp e I, i s a s s o c i a t e d w i t h m a l i gn a n c i e s o f t h e ga s t r o i nt e s t i n a l t r a c t ( 8 ) . T h e s e o r ga n i s m s a r e a l s o a ge n t s o f e n d o c a r d i t i s a n d h a v e b e e n i s o l a t ed f r o m p a t i e n t s w i t h m e n i n gi t i s ( 9 ) . T h e n u t r i t i o n al l y v a r i a n t s t r e p t o c o cc i a r e n o r m a l r e si d en t s o f t h e o r a l c a v i t y b u t h a v e b e e n i d e n t i fi e d a s a ge n t s o f e n d o c a r d i t i s i n v o l vi n g b o t h n a t i v e a n d p r o s t h e t i c v a l v e s . T h e s e o r g a n i s m h a v e a l s o b e e n i so l a t e d fr o m p a t i e nt s w i t h op h t h a l m i c i n f e c t i o ns ( 1 0 )
( Figure 1) Streptococci, Gram-positive cocci arranged in pairs or chains
3
1 Theoretical part of work 1. 1
Classification and Morphologic characteristics
Streptococcus agalactiae is the species designation for streptococcal belonging to Lancefield group B. the serologic differentiation of hemolytic streptococci by groups was described in 1933. It is based on the capillary precipitin reaction between the group-specific carbohydrate antigens in the cell wall, which is solubilized by acid treatment of the organisms. With hyperimmune antisera that is prepared by immunization of rabbits with formalin-killed whole cells. (11) Group B streptococci are facultative gram-positive diplococci that are grown easily on a variety of bacteriologic media. Isolated colonies are 3 – 4 mm in diameter and grayish white in color when cultivated on sheep blood agar ( Figure 2) . T h e f l a t , s o m e w h a t m u c o i d c o l o n i e s ar e s u r r o u n d e d b y n a r r o w z o n e o f β - h e m o l ys i s t h a t , f o r s o m e s t r a i n s , i s d e t e c t a b l e o nl y o n l i f t i n g a colony
from
the
a ga r .
A l t h o u gh
1 –2
percent
of
strains
are
n o n h e m o l yt i c , t h e y a r e r a r e l y α - h e m o l yt i c . T o e n h a n c e t h e a c c u r a t e d e t e c t i o n o f e v e n l o w n u m b e r s o f gr ou p B s t r e p t o c o c c i f r o m s i t e s s u c h a s t h e ge n i t a l o r ga s t r o i n t e st i n a l t r a c t , a n u m b e r of s e l e c t i ve m e d i a h a v e b e e n e m p l o ye d . T h e s e u s u a l l y c o n t a i n T o d d -H e w i t t b r o t h w i t h o r w i t h o u t s he e p r e d b l o o d c e l l s ( 5 p e r c e n t ) a n d a nt i m i c r o b i al a ge n t s s u c h a s n a l i di x i c a c i d a n d ge n t am i c i n o r c ol i st i n ( 12 ) . S t r e p t o c o c c u s a g al a c t i a e i s t h e o n l y s p e c i e s t h a t c a r r i e s t h e gr o u p a n t i ge n B , g r a m - p o s i t i v e c o c c i ( 0 . 6 t o 1 . 2 μ m ) t h a t f o r m s h o rt c h a i n s i n cl i n i c a l s p e c i m e n s a n d l o nge r c h a i n s i n c u l t ur e , f e a t u r e s t h a t m a k e t h e m i nd i s t i n gu i s h a b l e o n G r a m s t a i n f r o m S . p yo g e n e s . T h e y gr o w w e l l o n n u t r i t i o n a l l y e n r i c h e d m e d i a , a n d i n c on t r e s t w i t h t h e c o l o ni e s o f S . pyo g e n e s , t h e c o l o n i e s o f S . a ga l a c t i a e a r e b u t t e r y w i t h a n a r r o w z o n e o f B - h e m o l ys i s ( Figure 3) . S o m e s t r a i n s ( 1 % t o 2%)
are
n o n h e m o l yt i c ,
underestimated
b ec a u s e
a l t h o u gh n o n h e m o l yt i c
s c r e e n e d f o r t h e gr o u p B a n t i ge n ( 1 3 ) .
4
their
prevalence
strains
are
no t
may
be
c o m m o nl y
( Figure 2) Group B Streptococcus (GBS) growing on a 5% sheep blood agar plate. The red background is the blood agar plate and the gray circular dots are colonies of GBS growing on the agar. The colonies of GBS are gray to whitish-gray surrounded by a weak zone of hemolysis of the red blood cells in the culture medium. Hemolysis is one of the traits that is used to help identify the bacteria. Hemolysis is the destruction of the red blood cells suspended in the agar medium. Before performing the tests in the following photos, a gram strain and catalase test should be performed. GBS are grampositive cocci in chains and catalase negative.
5
( Figure 3) Agar plate with growth and hemolytic activity of group A streptococci (on the left) and group B streptococci (on the right). Note that the colonies of both bacteria appear about the same color and size. The difference between these two bacteria is in the degree of hemolytic activity. The group A Streptococcus has more hemolytic activity than the group B Streptococcus. Experienced microbiologist use these traits to identify the two types of bacteria.
6
1. 2 Indentification Group
B
s t r ep t o c o c c i ,
S.
a g al a c t i a e ,
yi e l d
l a rge r ,
more
t r a n s l u c e n t t o o p a qu e , w h i t i s h gr a y, s o f t , s m o ot h c o l on i e s s u r r o u n d e d b y a m u c h s m a l l er z o n e o f b e t a h e m o l ys i s . t h e c ol o ni e s o f S . a ga l a c t i a e r e s e m b l e t h o s e o f l i s t e r i a s ., w h i c h a r e c a t a l a s e p o s i t i v e . S . a g a l a c t i a e s t r a i ne a r e p o s i t i v e i n t he G A M P t e s t ( ( Figure 4) ) a n d a b l e t o h yd r o l yz e h i p p u r a t e . T h e C A M P t e s t r e q ui r e s o v e r n i gh t i n c u b a t i on , b ut i t i s m o r e e x p e n s i v e t h an s e r o l o gi c t yp i n g. ( 1 5 )
( Figure 4). Blood Agar plate is shown after 24 hours of incubation at 37°C. The vertical streak is a beta-hemolysin-producing strain of Staphylococcus aureus, and at right angles to it are streaks of (1) Enterococcus faecalis, (2) Streptococcus salivarius, (3) S. agalactiae, and (4) E. durans. The large area of complete lysis where the extracellular compound of S. agalactiae encounters the beta-lysin of S. Aureus.
7
Definitive
Id e n t i f i c a t i o n
of
gr o u p
B
streptococci
is
based
on
d e t e c t i o n o f t h e gr o u p B s p e c i f i c c e l l w a l l a n t i ge n c o m m o n t o al l s t r a i n s . A n u m b e r o f m e t h o d s , e a c h o f w h i c h u s e s h yp e r i m m u n e gr o u p - s p e c i f i c a n t i s e r a , h a v e b e e n d e v e l o p e d f o r t h e d e t e c t i o n o f t h e gr o u p
B
antigen:
countercurrent
i m m u n o e l e c t r op h o r e s i s
e nz ym e -
l i n k e d i m m u n o so r be n t a s s a y ( E L IS A ) , i n di r e c t i m m u n o fl u o r e s c e n c e , s t a p h yl o c o c c a l a g gl u t i n a t i o n i s
c o a g gl u t i n a t i on the
most
,
and
l a t ex
w i d e l y e m p l o ye d
a ggl u t i n a t i o n . due
to
La t e x
commercial
a v a i l a b i l i t y a n d s i m p l i c i t y. W h e n t h e m a n u f a c t u r e ’ s i n s t r u c t i o n s a r e f o l l o w e d , t h e s e p r od u c t s f o r s e r o gr o u p i n g β - h e m o l yt i c s t r e p t o c o c c i . N o n s e r o l o gi c m e t ho d s t h a t p e r m i t t h e p r e s u m p t i v e i d e nt i f i c a t i o n o f gr o u p
B
streptococci
include
resistance
to
bacitracin
or
t r i m e t h op r i m - su l f am e t h ox az l e , po s i t i ve s o d i um h i p p u r a t e h yd r o l ys i s , a n d p r o d u c t i o n o f a n o r a n ge p i gm e n t d u r i n g a n a e r o b i c gr o w t h o n certain media.
β - h e m o l yt i c s t r e p t o c o c c i t h a t h yd r o l yz e s o d i um
h i p p u r a t e b e l o n g t o e i t h e r gr o u p s B o r D ; t h e s e m a y b e d i s t i n gu i s h ed o n t h e b a s i s o f h yd r o l ys i s o f b i l e e s c u l i n a ga r . A m o n g gr o u p D s t r a i n s , 99 p e r c e n t h yd r o l yz e b i l e e s c u l i n , w h e r e a s 9 9 - 1 0 0 p e r c e n t o f gr o u p B s t r a i n s f a i l t o r e a c t ( 1 4 ) . P r o d u c t i o n o f C A M P f a c t o r , w h i c h i s a t h e r m o s t a bl e e x t r a c e l l ul a r p r o t ei n t h a t r e s u l t s i n s yn e r gi s t i c h e m o l ys i s o n s h e e p b l o o d a ga r w i t h t h e β - l ys i n o f s t a p h yl o c o c c u s a u r e u s , i s o b s e r v e d i n 9 8 - 1 0 0 p e r c e n t of gr o u p B s t r e p t o c o c c i . A s p ot C A M P t e st , a v a i l a bl e c o m m e r c i a l l y , a l l o w s r a p i d i d e n t i f i c a t i o n o f gr o u p B s t r e p t o c o c c i f r o m a s i n gl e c ol o n y o f t h e p r i m a r y i s o l a t i o n p l a t e . T h e c o m bi n at i o n o f t h e C A MP t e s t w i t h b a c i t r a c i n s e n s i t i v i t y a n d t h e b i l e e s c ul i n r e a c t i o n h a s b ee n s u gg e s t e d a s a n a d e q u a t e m e t h o d f o r t h e p r e s u m p t i v e d i f f e r e n t i a t i o n o f gr o u p B f r o m o t h e r s e o gr o u p o f β - h e m ol yt i c s t r e p t o c o c c i ( 1 6 ) .
8
Serologic classification
1. 3
La n c e f i e l d d e f i n e d t w o c e l l w a l l c ar b o h yd r a t e a n t i ge n s f o r gr o u p B s t r e p t o c o c c i , t h e gr o u p B s p e c i f i c o r ― C ‖ s u b st a n c e c o m m o n t o a l l s t r a i n s o f t hi s s e r ogr o u p a n d t h e t yp e - s p e c i f i c o r
― S ‖ substance
t h a t a l l o w s c l a s si f i c a t i o n i n t o f o u r s e r o t yp e s : Ia . Ib . I I, a n d I I I (Table.1)
(17).
The
fifth
s e r o t yp e
of
gr o u p
B
streptococcus,
h i s t o ri c a l l y d e s i gn a t e d t yp e Ic , w a s c h a r a c t e r i z e d b y W i l k i n s o n a nd E a go n ( 1 8 ) . T h e s e s t r a i n s p os s e s s a c ap s u l a r p o l ys a c c h a r i d e a n t i ge n , Ia t h a t i s i m m u n o ch e m i c a l l y i d e n t i c a l t o t h a t c o m m o n t o a l l t yp e Ia s t r a i n s a n d a s u r f ac e p r o t e i n a n t i ge n t h a t i s c o m m o n t o a l l t yp e Ib s t r a i n s , a p p rox i m at e l y 6 0 p e r c e n t o f t yp e I I s t r a i n s , a n d i n a n o c c a s i o n a l t yp e II I s t r a i n . H o w e v e r , t h i s p r o t e i n a n t i ge n , h i s t o r i c a l l y c a l l e d t h e Ib c p r o t e i n a n t i ge n , i s n ot f o u n d i n t yp e Ia s t r a i n s . A minor
a n t i ge n i c
determinant, the
t yp e
Ia b c
p o l ys a c c h a r i d e
was
d e m o n s t r a t e d b y La n c e f i e l d t o b e c o m m o n t o m a n y t yp e I s t r a i n s . T h e n o m e n c l a t u r e o f gr o u p B s t r e p t o c o c c i h a s b e e n r e v i s e d t o d e s i gn a t e t h e c a p s u l a r p o l ys a c c h a r i d e s a s t yp e - s p e c i f i c a n t i ge n s a n d t h e s u r f a c e proteins
as
a d di t i o n a l
a n t i ge n i c
markers
(19).
The
s i m pl i f i e d
d e s i gn a t i o n f o r t h e p r o t e i n a n t i ge n Ib c i s c , s o t h e f o r m e r t yp e Ic i s p r e s e n t l y d e s i gn a t e d t yp e Ia / c ( T a b l e . 1 ) , a n d t h e f o r m e r t yp e Ic i s t yp e Ib i s t yp e Ib / c . S e v e r a l s e r o t yp e s , t yp e s IV , V , a n d V I, e a c h w i t h u n i q u e p ol ys a c c h a r i d e s a l o n e o r w i t h p r o t e i n a n t i ge n s h a v e b e e n d e f i n e d r e c e n t l y, ( 2 0 - 2 1 ) a n d a d d i t i on a l c a n d i d a t e s e r ot yp e s a r e being
evaluated.
Antibodies
a ga i n s t
the
major
and
minor
p o l ys a c c h a r i d e a n t i ge n , w i t h t h e ex c e p t i o n o f t h e t yp e I I I a n t i g e n , w e r e s h o w n b y La n c e f i e l d t o p r ov i d e p a s s i v e p r ot e c t i o n f o r m i c e c h a l l e n ge d
with
h o m o l o go u s ― b ut
not
h e t e r o l o go u s ― a n t i ge n -
c o n t a i n i n g s t ai n s ( 22 ) . A l t ho u gh m o u s e v i r u l e n c e f o r t yp e I I I s t r a i n s c o u l d n o t b e a c h i ev e d i n t h e o r i gi n a l m o u s e - p r o t e c t i v e a s s a y, ( 2 2 ) o t h e r s s u b s e qu e n t l y h a v e m o d i f i e d t h i s e x p e r i m e n t a l m od e l s o t h at a n t i b o d y t o t h e t yp e I I I c a p s u l a r p o l ys a c c h a r i d e a n t i ge n a l s o h a s b e e n s h o w n t o p r o t e c t a ga i n s t c h a l l e n ge w i t h s t r a i n s c o nt a i n i n g t h e
9
h o m o l o go u s b u t no t t h e h e t e r o l o go u s a n t i ge n s ( 2 3 ) . B y c o n t r a s t , r a b b i t a n t i b o d i e s wi t h gr o u p B s p e c i f i c i t y d o n o t p r o t e c t m i c e f r o m a l e t h a l c h a l l e n ge ( 2 2) .
( T a b l e 1 ) A n t i g en i c D e t e r mi n a n t s of g r o u p B s t r e p t o c o cc i Antigens Sorotype Designation Present
Historical
Proteins Major
Present
Historical
Polysaccharide
Ia
Ia
Ia
―
―
Ib/c
Ib
Ib
c
Ibc
Ia/c
Ic
Ia
c
Ibc
II
II
II
cª
Ibcª
III
III
III
—b
—b
IV
―
IV
NDc
―
V
―
V
ND
―
VI
―
VI
ND
―
ª Sixty percent of type II isolates possess the protein antigen c. b Serotype III strains occasionally may possess the protein antigen c or the proteins X
or R. c ND , not determined.
10
1. 4. Epidemiology and Transmission Asymptomatic Colonization G r o u p B s t r e p t oc o c c i h a v e b e e n i s o l a t e d f r o m ge n i a l a n d / o r l o w e r ga s t r o i n t e s t i n al t r a c t c u l t u r e s o f p r e gn a n t w o m e n a t a r a t e r a n gi n g 5 t o 4 0 % ( 2 4 , 2 5 ) . T h e s e v a r i a t i o n s i n t h e r e p o r t e d p re v a l e n c e o f a s ym p t o m a t i c c o l on i z a t i o n r e l a t e n ot o n l y t o d i f f e r e n c e s i n t h e c u l t u r e m e t h od e m p l o ye d b u t a l s o t o i n t r i ns i c d i f f e r e nc e s i n t h e p o p u l a t i o n s s t u di e d ( T a b l e 2 ) . W h e n t he c u l t u r e m et h o d i s s e l e c t e d t o optimize the sensitivity of detection and when more then one a p p r o p r i a t e s i t e s uc h a s t h e l o w e r va gi n a o r t h e p e r i ur e t h r a l o r a n o r e c t a l a r e a i s c u l t u r e d o n m o r e t ha n o n e o c c a s i o n , t h e r a t e o f c o l o n i z a t i on d e t e c t ed u s u a l l y e x c e e d s 20 % . G r o u p B s t r e p t o c o c c i m a y b e h a r b o r e d i n t h e u r i n a r y t r a c t d u r i n g p r e gn a n c y i n a s s o c i a t i o n w i t h a s ym p t o m a t i c b a c t e r i u r i a ( 2 6 ) . B a c t e r i u r i a a l s o i s a m a r k e r f o r a h i gh i n o c u l um i n t h e ge n i t a l t r a c t . E v e n w h en o p t i m a l c u l t u r e m e t h o d s a r e u s e d , a s i gn i f i c a n t l y l o w e r p r e v a l e n c e o f ge n i t a l c o l o n i z a t i o n o c c u r s a m o n g w o m e n w h o a r e v i r gi n s , o l d e r t h a n 2 0 ye a r s o f a ge , o r o f M e x i c a n - A m e r i c a n o r i gi n ( 2 7 ) . R e p o r t s f r o m 1 9 7 3 t o 198 1 i n di c a t e t h a t t h e s e r o t yp e d i s t r i b u t i o n o f i sol a t e s f r o m a s ym p t o m a t i c a l l y c o l o n i z e d p a t i e n t s , i r r e s p e c t i v e o f a ge o r s e x , i s d i v i d e d e v e n l y a m o n g t h e t h r e e m aj o r s e r o t yp e s : I, I I, a n d II I. P r e gn a n c y i t s e l f a n d t h e t i m i n g o f c u l t u r e s d u r i n g p r e gn a n c y d o n o t i n f l u e n c e t h e p r e v al e n c e o f c o l o n i z a t i on w i t h gr o u p B s t r ep t o c o c c u s . B o ye r a n d a s s o c i a t es ( 2 8 ) f o un d t h a t t he o v e r a l l p r e di c t i v e v a l u e o f a positive
second-trimester
culture
of
the
v a gi n a
or
rectum
for
c o l o n i z a t i on a t d e l i v e r y w a s 6 7 % w h e r e a s a n e ga t i v e p r e n a t a l c u l t u r e h a d a p r e d i c t i v e v al u e o f 9 2 % . A l t h o ugh s o m e l o n gi t ud i na l s t u di e s ( 2 7 . 2 9 ) r e p o r t t h e l i m i t a t i o n s o f a si n gl e g e n i t a l c u l t u re o b t a i n e d d u r i n g p r e gn a n c y a s a n a c c u r a t e p r e d i c t o r o f c o l o n i z a t i on s t a t u s a t d e l i v e r y, a r e c e n t r e p o r t i n d i c a t e s t h a t 9 4 % o f c u l t ur e - p o s i t i v e w o m e n w i l l b e d e t ec t e d i f c u l t u r e s o f t h e l o w e r v a gi n a a n d a n o r e c t u m a r e o b t a i n e d a t si n g l e a n t e p a r t u m vi s i t ( 2 5 , 3 0 ) .
11
A gr o w i n g b o d y o f c o m p e l l i n g b u t n o t c o n c l u s i v e e v i d e n c e s u p p o r t s t h e c o n c e p t t h at t h e p r i n c i p a l r e s e r v oi r f o r gr o u p B s t r e p t o c o c c i m a y b e t h e l o w e r ga s t r o i n t e s t i n a l t r a c t r at h e r t h a n t h e f e m a l e ge n i t a l t r a c t . S t u d i e s d o c um e n t i n g r e c t a l - t o - va gi n a l i s o l a t i o n r a t i o e x c e e d i n g 1
and
the
anorectum
as
the
site
most
accurately
predicting
p e r s i s t e n c e o f c h ro n i c i t y o f c a r r i a g e s u p p o r t t h e p o s si b i l i t y t h a t ge n i t a l c o l o n i z a t i on m a y r e f l e c t c o n t a m i n a t i o n f r o m t h e r e c t u m ( 2 8 . 3 1 ) . F u r t h e r , gr o u p B s t r e p t o c o c c i h a v e b e e n i s ol a t e d f r o m t he p r o x i m a l p a r t o f t h e s m a l l i n t e st i n e o f a d u l t s . T h e p r e v a l e n c e o f o r o p h a r yn g e a l c o l o n i z a t i o n i s l o w i n pr e gn a n t w o m e n ( a p p r o x i m a t e l y 5 % ) , b u t i t a p p r o a ch e s 2 0 % i n h o m os e x u a l m e n .
Transmission to Neonates M u c o u s m e m b r a n e c o l o n i z a t i on o f ne w b o r n s r e s u l t s f ro m v e r t i c a l t r a n s m i ss i o n o f t h e o r ga n i s m f r o m t h e m o t h e r , e i t h e r i n ut e r o b y t h e a s c e n d i n g r o u t e o r a t t h e t i m e o f d e l i v e r y. T h e r a t e o f v e r t i c a l t r a n s m i ss i o n i n n eo n a t e s b o r n t o w om e n c o l o ni z e d w i t h gr o u p B s t r e p t o c o c c i a t t h e t i m e o f d e l i v e r y r a n ge s f r o m 2 9 t o 7 2 p e r c e nt ( m e a n , 5 0 % ) ( 3 2 - 3 4) . P a i r e d i s o l a t e s f r o m m ot h e r s a n d t h ei r n e o n a t e s a r e o f c o n c o r d a n t s e r o t yp e s ( 3 2 ) . T h e o n l y m a t e r n a l f a c t o r t h a t h as b e e n s h o w n t o s i gn i f i c a n t l y i n f l u e n c e t h e l i k e l i h o o d o f v e r t i c a l t r a n s m i ss i o n i s t h e p r e s e n c e o f a h i gh ge n i t a l i n o c u l u m at d e l i v e r y, as
detected
by
semiquantitative
culture
m e t h o ds
( 2 8 , 2 9 , 3 4 , 3 5 ).
In f a n t s b o r n t o h e a v i l y c o l o n i z e d w o m e n a r e m o r e l i k e l y t o d e v e l o p invasive
e a r l y- o n s e t
disease,
(28)
and
infants
acquiring
heavy
c o l o n i z a t i on h a v e s i gn i f i c a n t l y i n c r e a s e d r a t e s o f e a r l y - a n d l a t e - o n s e t disease. In a d d i t i o n t o ex p os u r e a t bi r t h , h o r i z o n t a l l y a c q u i r e d ( n o s o c o m i a l ) c o l o n i z a t i on o f t h e n e o n a t e h a s b e e n f o u n d t o c o nt r i b ut e t o t h e r a t e o f c o l o n i z a t i on i n s o m e n u r s e r y s e t t i ngs . A c q u i s i t i on i s m o r e l i k e l y w h e n t h e m a t e r n a l p o p u l a t i o n h a s a h i gh e n d o ge n o u s c o l o n i z a t i on r a t e ( a s i n f l u e n c e d b y s u c h f a c t o r s a s a ge , p a r i t y, e t h n i c c o m p o s i t i o n, a n d s o c i o e c o n o m i c s t a t u s ) a nd w h e n c r o w d e d c o n d i t i on s i n t h e
12
n u r s e r y p r o m o t e p o o r h a n d - w a s h i n g t e c h n i q u e s a n d t r a n sm i s si o n t o i n f a n t s v i a h a n ds o f p e r s o n n e l . A l t h o u gh n o s o c o m i a l l y a c q u i r e d r a t e s o f c o l o n i z a t i on i n ex c e s s o f 4 0 % h a v e b e e n r e p o r t e d , ( 3 6 ) n o s o c o m i al t r a n s m i ss i o n i s n e gl i gi b l e i n s m al l e r , l e s s c r o w d e d n u r s e r i e s ( 3 7 ) . N o ya a n d a s s o c i a t e s ( 3 8 ) d e s c r i b e d a c u l t u r e o f l a t e - o n s et i n f e c t i o ns t h a t b y p h a ge t yp i n g a p p e a r e d t o r e s u l t f r o m a s i n gl e e p i d e m i c s t r a i n o f t yp e Ib / c gr o u p B s t r e p t o c o c c u s . E pi d e m i ol o gi c a n a l ys i s s u gge s t e d t h a t i n f a n t - t o - i n f a nt s p r e a d v i a t h e h a n d s o f p e r s o n n e l w a s t h e m o s t l i k e l y m o d e b y w h i c h f i v e v e r y l o w b i r t h w e i gh t i n f a n t s d e v e l o p e d bacteremic
infection.
A
few
smaller
case
clusters
have
been
a t t r i b u t e d t o n o s o co m i a l a c q u i si t i o n of t yp e I I I s t r a i n s . C o m m u n i t y acquisition
of
gr o u p
B
streptococci
in
yo u n g
infants
occurs
i n f r e q u e n t l y. T h i s m o d e o f a c q u i s i t i on o c c u r r e d i n o nl y 4 . 3 % o f p a t i e n t s d u ri n g t h e f i r s t 2 m o n t h s o f l i f e ( 3 9 ) . N o n e o f t h e s e i n f a n t s w a s c o l o n i z e d a t t he t i m e o f ho s p i t a l di s c h a r ge . The importance of defining the modes of transmi ssion by which neonates
acquire
a s ym p t o m a t i c
c o l o n i z a t i on
with
gr o u p
B
s t r e p t o c o c c i i s e vi d e n c e d b y t h e f a c t t h a t v e r t i c a l t r a n sm i s si o n i s r e q u i r e d f o r t h e d e v e l o p m e n t o f i n v a si v e e a r l y - o n s e t i n f e c t i o n ( 3 2 34) several factors have been noted that increase the incidence of i n v a s i v e e a r l y- o n s e t i n f e c t i o n a m o n g n e o n a t e s b o r n t o c o l o n i z e d mothers. They include rupture of membranes for more than 18 hours b e f o r e d e l i v e r y, m u l t i pl e b i r t h s, p r e m a t u r e r u p t u r e o f m e m b r a n e s a t l e s s t h a n 3 7 w e e k s , ge s t a t i o n , a n d m a t e r n a l f e v e r a n d / o r a m n i o n i t i s ( 2 8 ) . M o r e r e c e n t s t u d i e s o f m a t e r n a l fe a t u r e s a s s o c i a t e d w i t h h i gh e r a t t a c k r a t e s f o r e a r l y o n s e t n e o n a t a l d i se a s e h a v e r e p o r t e d b l a c k r a c e , a ge l e s s t h a n 2 0 ye a r s , h i s t o r y o f p r e v i o u s m i s c a r r i a ge , a n d p r e t e r m d e l i v e r y a s r i s k f a c t o r s ( 4 0 ) . A l t h o u gh i t i s c l e a r t h a t s o m e i n f a n t s who
develop
late-onset
infection
acquire
the
o r ga n i s m
f r om
n o n m a t e r n a l so u r c e s ( 3 4 ) t h e c o n c or d a n c e o f s e r o t yp e s b e t w e e n n e o n a t a l a n d m a t e r n a l ge n i t a l i s o l a t e s a t t h e t i m e o f d i a gn o s i s i n o n e h a l f t o t w o - t h i r ds o f c a s e s s u g ge s t s t h a t t h e v e r t i c al r o u t e o f acquisition
also is
a
major
determinant
13
of
risk
for late -onset
i n f e c t i o n s ( 41 ) . A dd i t i on a l r i sk f a c t o rs a r e b l a c k r a c e a n d ge s t a t i o n l e s s t h a n 3 4 w e e k s (6 ) .
Incidence and Serotype Distribution of Infecti on. The
reported
incidence
of
early-onset
neonatal
gr o u p
B
s t r e p t o c o c c a l i n f e c t i o n , d e f i n e d a s t h e o n s e t o f s ym p t o m s d u r i n g t h e f i r s t 5 d a ys o f l i f e , r a n ge s f r o m 0 . 7 t o 3 . 7 p e r 1 0 0 0 l i v e bi r t h s . T h e i n c i d e n c e h a s b e e n s t a b l e f o r 2 de c a d e s . T h e a t t a c k r a t e u p t o 1 9 9 3 r e m a i n s a p p r o x i m a t e l y 2 . 0 p e r 1 0 0 0 l i v e b i r t h s. A t t ac k r a t e s f o r e a r l y- o n s e t gr o u p B s t r e p t o c o c c a l d i s e a s e a r e i n v e r s e l y r e l a t e d t o b i r t h w e i gh t a n d m a y e x c e e d 2 0 p e r 1 0 0 0 l i v e b i r t h s a m o n g i n f a n t s w i t h b i r t h w e i gh t s l e s s t h a n 1 0 0 0 g ( 4 2 ) . H o w e v e r , a p p r o x i m a t e l y 6 0 8 0 % o f e a r l y- o n s e t i n f e c t i o ns o c c u r i n t e r m i n f a n t s ( 41 - 4 3 ) . T h e a t t a c k r a t e f o r l a t e - o n s e t n e o n a t a l i n fe c t i o n , w h i c h i s c ha r a c t e r i z e d b y t h e o n s e t o f s ym p t o m s f r o m 6 d a ys t o 3 m o n t h s o f a ge , i s a p p r o x i m a t e l y 0 . 5 - 1 . 0 p e r 1 0 0 l i v e bi r t hs ( 4 1 ) . B e yo n d e a r l y i n f a n c y, p o s t p a r t u m wo m e n a r e t h e o n l y gr o u p o f patients
in
wh o m
gr o u p
B
s t r e p t oc o c c a l
disease
is
d i a gn o s e d
f r e q u e n t l y. T h e s e o r ga n i s m s h a v e b e e n e s t i m a t e d t o c a u s e 1 5 - 2 5 % o f t h e c a s e s o f p o s t p a rt u m f e b r i l e m o r bi d i t y w i t h o r w i t h o ut ba c t e r e m i a , o r a n e s t i m a t e d 5 0, 0 0 0 c a s e s a n n u a l l y ( 4 4 - 4 6 ) . In o n e p o p u l a t i o n w i t h a k n o w h i gh i nc i d e n c e o f c a r r i a ge , p u e r p e r a l s e p s i s d ue t o gr o u p B streptococci occurred with an attack rate of 2 per 1000 deliveries ( 4 7 ) . A d u l t s w i t h a l t e r e d i m m u n e st a t u s d u e t o d i a b e t es m e l l i t u s , c h r o n i c h e p a t i c d ys f u n c t i o n , h um a n i m m u n o d e f i ci e n c y v i r u s ( H IV ) i n f e c t i o n , ( 4 8 ) o r m a l i gn a n c i e s r e q u i r i n g i m m u n o s u p p r e s si v e t h e r a p y a l s o a r e s u s c e p t i b l e t o gr o u p B s t r e p t o c o c c a l i n f e c t i o n s . H o w e v e r , i t s i n c i d e n c e i n t h e s e h o s t s a p p e a r s t o be l o w e r t h a n t h a t i n p r e gn a n t women. F o r n e o n a t e s w i t h e a r l y - o n s e t i n f e c t i o n w i t h o u t m e ni n gi t i s , t h e s e r o t yp e d i s t r i b u t i on o f i so l a t e s p a r a l l e l s t h a t o f a s ym p t o m a t i c a l l y c o l o n i z e d m ot h e r s o r i n f a n t s a n d i s d i v i d e d e q u a l l y a m o n g t yp e I, I I, a n d II I s t r a i n s . H o w e v e r , t yp e I I I s t r a i n s o f gr o u p B s t r e p t o c o c c i
14
h a v e b e e n i so l a t e d f r o m m o s t n e w b or n s ( 8 0 % ) w i t h ea r l y - o n s e t i n f e c t i o n i n w h om m e n i n ge a l i n v ol v e m e n t o c c u r s . T h i s s e r o t yp e i s r e s p o n s i bl e f o r 9 3 % o f l a t e - o n s e t i n f e c t i o n r e ga r d l e s s o f c l i n i c a l e x p r e s si o n ( 4 9 ) . T he e x p r e s s i o n f o r t he a p p a r e n t t r o p i s m o f t yp e I I I s t r a i n s f o r t h e m e ni n ge s o f n e o n a t e s i s p o o r l y u n d e r s t o o d . A l t h o u gh each
of
the
s e r o t yp e s
has
been
reported
to
cause
disease
in
i m m u no c o m p r o m i s ed a d u l t s , t yp e I I s t r a i n s h a v e b e e n i s o l a t e d f r o m m o s t a d u l t s w i t h m e n i n gi t i s; i n c o n t r a s t , t h e y r a r e l y p e n e t r a t e t h e m e n i n ge s o f n e o n a t e s ( 5 0 , 5 1 ) . Th e m ec h a n i s m s f o r t hi s ―d i f f e r e n t i a l t r o p i sm ‖ a m o n g d i f f e r e n t s e r o t yp e s o f g r o u p B s t r e p t o c o c c i i n d i s t i n c t p op u l a t i o n s o f p a t i e n t s h a v e n ot b e e n d e f i n e d .
15
( Table 2 )
Effect on Isolation Rate Feature
Increased
Decreased
Non
Method employed Culture media
Site(s) Interval
Broth media Agar media Antibiotic-containing Nonselective media broth media Lower vagina Cervical os Multiple sites Single sites ≤20 cultures in 6-8 Single sampling Wk interval time
Genital carriage in women Pregnancy
+
Timing during pregnancy
+
Day of menstrual cycle
First half
Age
≤20 yr
Sexual activity
Active
Birth control method
Intrauterine device
Parity
≤3 pregnancies
Virgin
Ethnic origin
Oral contraceptives ≤3 pregnancies Mexican American
Marital status
+
Frequency of sexual Intercourse/total number of partners
+
Vaginal discharge
+
Socioeconomic group
Lower income
16
1. 5. Clinical manifestations of main representatives
Early -Onset Neonatal Infection A s t h e i n c i d e nc e o f n e o n a t a l gr o u p B s t r e p t o c o c c a l i n f e c t i o n s r o s e d u r i n g t h e 1 9 70 s , a b i m o d a l d i st r i b u t i o n o f c a s e s b y a ge a t o n s e t of
s ym p t o m s
became
apparent.
T hu s ,
two
d i st i n c t i ve
clinical
s yn d r o m e s r e l a t e d t o a ge w e r e d e s c r i b e d b y F r a n c i o s i e t a l . ( 5 9 ) ( a c u t e a n d d e l a ye d ) a n d b y B a k e r e t a l ( 6 0 ) . ( e a r l y a n d l a t e o n s e t ) . E a r l y- o n s e t i n f e c t i o n , d e f i n e d a s t he d e v e l o p m e n t o f s ym p t o m s d u r i n g t h e f i r s t 5 d a ys o f l i f e , h a s m e a n a g e a t o n s e t o f 2 0 h o u r s (57.59). Maternal obstetric complications are observed frequently ( 6 0 % ) ; p r e m a t u r e i n f a n t s a r e a f f e c t e d s i gn i f i c a n t l y m o r e o f t e n t h an a r e i n f a n t s b o r n a t t e r m . T h e t h r e e m a j o r c l i ni c a l ex p re s s i o n s o f e a r l y- o n s e t i n f e c t i o n a r e b a c t e r e m i a w i t h n o i d e n t i f i a b l e f o c u s o f infection,
p n e u m on i a ,
and
m e n i n gi t i s ,
and
their
d i st r i b u t i on
is
a p p r o x i m a t e l y 5 0 , 3 5 a n d 1 5 % , r e s p e c t i v e l y. T h e p r e s e n t i n g s i gn s a n d s y m p t o m s o f e a r l y - o n s e t g r o u p B s t r e p t o c o c c a l i n f e c t i o n — l e t h a r g y, p o o r f e e d i n g, j a u n d i c e , a b n o r m a l t e m p e r a t u r e , gr u n t i n g r e s p i r a t i o n s , p a l l o r , a n d h yp o t e n s i o n — a r e n o t d i s t i n gu i s h a b l e f r om t h o s e o f n e o n a t es w i t h o t h e r t yp e s o f b a c t e r i a l i n f e c t i o n . R e ga r d l e s s o f t h e f o c u s o f i n f e c t i o n , r e s p i r a t o r y s ym p t o m s are observed in the majority (59.60). Among infants with early-onset infection who have bacteremia w i t h p n e u m on i a , s i gn s o f r e s p i r a t o r y d i s t r e s s s u c h a s a p n e a , gr u n t i n g, t a c h yp n e a , a n d c ya n o s i s a r e vi r t u a l l y a l w a ys p r e s e n t . A l t h o u gh p u l m o n a r y i n f i l t r a t es o n c h e s t x - r a y f i l m s m a y s u g ge s t t h e d i a gn o s i s , at
least
one-half
o f t h e s e i n f a n t s h a v e a r a d i o gr a p h i c p a t t e r n
c o n s i s t e nt w i t h a nd i n di s t i n gu i s h a b l e fr o m t h at o f h ya l i n e m e m b r a n e d i s e a s e . In m o s t ( ~8 0 % ) o f t h e s e i n fa n t s , s ym p t o m s o f r e s p i r a t o r y d i s t r e s s a r e p r e s en t a t o r w i t h i n a f e w h o u r s a f t e r b i r t h . A t p o s t m o rt e m
e x a m i n a t i o n , a t yp i c a l
17
h ya l i n e m e m b r a n e s c o n t a i n i n g
gr o u p B s t r e p t o c o c c i a r e f o u n d i n t h e l u n gs . T h i s f i n di n g p r o v i d e s a p a r t i a l Ex p l a n a t i o n f o r t h e d i f f i c ul t i e s e n c o u n t e r e d i n c l i ni c a l l y d i s t i n gu i s h i n g
between
infectious
and
n o n i n f e c t i ou s
forms
of
i m p r o v e m e nt s
in
respiratory tract disease (62). In c r e a s e d
awareness
of
the
disease
and
supportive therapy have resulted in decreased mortality among i n f a n t s wi t h e a r l y - o n s e t gr o u p B s t r e p t o c o c c a l i n f e c t i o n , an d p r e s e n t rate range from 10 to 15 % (54,63). Mortality rates are inversely p r o p o r t i o n al t o b i r t h w e i gh t a n d m a y e x c e e d 5 0 % i n v e r y l o w b i r t h w e i gh t ( < 1 5 0 0 g) n e o n a t e s . In t e r m i n f a n t s , m o r t a l i t y r a n ge s f r o m 2 t o 8 % ( 5 8 , 63 ) .
Late-Onset Neonatal Infections La t e - o n s e t g r o u p B s t r e p t o c o c c a l i n f e c t i o n h a s a n o n s e t f ro m 7 d a ys t o 3 m o n t h s of a g e , a n d h a s a m e a n a ge o f o n s e t o f 2 4 d a ys . M a t e r n a l o b s t e t ri c c o m p l i c a t i o n s a r e u nc o m m o n , a n d t h e c a s e - f a t a l i t y ratio
is
s om e w h a t
lower
than
t h at
of
early-onset
infections
( 5 4 . 6 3 , 6 4 ) . B a c t e r e m i a w i t h c o n c o m i t an t m e ni n gi t i s ( 4 0 % o f c a s e s ) i s a c o m m o n c l i ni c a l m a n i f e s t a t i o n o f l a t e - o n s e t i n fe c t i o n . T h e n o n s p e c i f i c i ni t i a l s ym p t o m s o f l a t e - o n s e t d i s e a s e s u c h a s l e t h a r g y, p o o r f e e d i n g, a n d i r r i t a bi l i t y ge n e r a l l y o c c u r i n a s s o ci a t i o n w i t h f e v e r ( t e m p e r a t u r e ≥ 3 8 º C ) , a f i n d i n g t h a t m a n d a t e s h os pi t a l i z a t i o n , blood
a nd
cerebrospinal
fluid
(CSF)
cultures,
and
e m p i r i c al
a n t i m i c r o bi a l t h e r ap y p e n d i n g l a b o r a t o r y r e s u l t . A s i gn i f i ca n t n u m b e r ( 2 5 - 5 0 % ) o f s u r v i vo r s o f gr o u p B s t r ep t o c o c c a l m e n i n gi t i s , w h e t h e r e a r l y- o r l a t e - o n s e t t yp e , w i l l h a v e pe r m a n e n t n e u r o l o gi c s e q u e l a e (61,65,66).
Ap p r ox i m a t e l y
one-third
of
p a t i e nt s
with
these
c o m p l i c a t i o n s m a n i f e s t t h e m a s s e v e re b l i n dn e s s , d e a f n e s s , a n d / or gl o b a l d e v e l o p m e n t d e l a y; i n t h e r e m a i n d e r o f p a t i e n t s , t h e d e f i c i t s a r e m o r e s u b t l e a n d m a y b e d e t e c t a b l e o n l y w h e n l a n gu a ge a n d c o gn i t i v e f u n c t i on c a n b e t e s t e d a d e q u at e l y. B a c t e r e m i a w i t h o u t a n a p p a r e n t f o c u s a n d b o n e a n d j o i nt i n f e c t i o n s a r e t h e o t h e r c l i ni c a l f o r m s o f l a t e - o n s e t gr o u p B s t r e p t o c o c c a l
18
d i s e a s e t h a t o c c u r r e l a t i v e l y f r e q u e n t l y. T h e f o r m e r p a t i e n t s a r e yo u n g i n f a n t w i t h fe v e r ; r e c o v e r y a f t e r a p p r o p r i a t e t r e a t m e n t i s t h e rule. These infants should be evaluated carefully for the presence of a s s o c i a t e d f o c i o f i n f e c t i o n s u c h a s p r e a u r i c u l a r o r s u bm a n d i b ul a r c e l l u l i t e s a n d a d e n i t i s , ( 6 7 ) o t i t i s m e di a , c o n j u n c t i v i t i s , p e r i t o n i t i s , e n d o c a r d i t i s , o r d e e p a b s c e s s e s ( 6 8 ) . E a c h o f t h e s e f o c a l t yp e s o f infections has also occurred in a ssociation with early-onset disease. Group i n d o l e nt
B
s t r e pt o c o c c a l
o n s et
o s t e o m ye l i t i s
is
characterized
i n w h i c h di m i ni s h ed m o v e m e nt
by an
of the involved
e x t r e m i t y i s t h e m o s t c o m m o n s ym p t o m . In c o n t r a s t , s e p t i c a r t h r i t i s i s a s s o c i a t e d w i t h a n a c u t e o n s e t o f s ym p t o m s , a n d p a t i e n t s u s u a l l y have bacteremia documented at the time of admission. Both bone and j o i n t i n f e c t i o ns a r e a s s o c i a t e d w i t h m i n i m a l i n f l a m m a t o ry c h a n ge s , a n d f e v e r i s r e p o r t e d i n o nl y 2 0 % o f p a t i e n t s . Lo w e r e x t r e m i t y i n v o l v em e n t i s c om m o n l y o b s e r v e d i n i n f a n t s w i t h s e p t i c a r t h r i t i s , w h e r e a s o s t e o m ye l i t i s h a s a p r e d i l ec t i o n f o r i n v o l v em e n t o f t h e p r o x i m a l h um e r u s ( 6 0 % o f t h e c a s e s ) . In c o n t r a s t t o o t h e r b a c t e r i a l c a u s e s o f n e o n a t a l s e p t i c a r t h r i t i s a nd o s t e om ye l i t i s , m o s t i n f a n t s h a v e n o p e r m a n e n t f u n c t i o n a l i m p a i rm e n t o f t h e i n v ol v e d ex t r e m i t y.
Infection in Adults In v a s i v e gr o u p B s t r e p t o c o c c a l i n f e c t i o n c a u s e s s u b st a n t i a l m o r b i d i t y a n d m o r t a l i t y a m o n g a d u l t s . A b ou t 5 3 % of gr o u p B s t r e p t o c o c c a l b l o od c u l t u r e i s o l a t e s w e r e f r o m a d u l t s ( 6 9 ) . In a prospective,
p o pu l a t i o n - b a s e d
a s s e s sm e n t
of
i n v a si v e
gr o u p
B
s t r e p t o c o c c a l d i s e a se , m e n a n d n o n p r e g n a n t w o m e n a c c o u n t e d f o r 6 8 % ( 1 4 0 ) o f t h e t ot a l a d u l t c a s e s ( i n ci de n c e 4 . 4 / 1 0 0 ,0 0 0 no n p r e gn a n t a d u l t s / ye a r ) ( 7 0 ) . A d u l t s w i t h b a c t e r e m i a u n r e l a t e d t o p r e gn a n c y u s u a l l y a r e e l d e r l y w i t h a ge s r a n gi n g f r o m 1 8 t o 9 9 ye a r s ( 6 9 , 7 1 , 7 2 ) . T h e m e a n a ge i n o n e r e c e n t r e p o r t w a s 6 2 ye a r s a n d 5 7 % w e r e m a l e ( 7 0 ) . T h e i n c i d e n c e i n c r e a s e s w i t h a ge a n d h i gh e r i n b l a c k s t h an w h i t e s ( 7 0 ,7 3 ) .
19
T h e t w o f o l d h i gh e r r a t e i n b l a c k ad u l t s c o m p a r e d t o w h i t e s i s p a r t i c u l a r l y h i gh i n o l d e r b l a c k s ; h o we v e r , t h i s a s s o c i a t i o n m a y b e due
to
s o c i o e c o no m i c
factors
( 7 3 ).
One
or
more
conditions
p r e d i s p o si n g t o i n fe c t i o n c a n b e i d e nt i f i e d i n m o st b u t n ot a l l a d u l t s w i t h i nv a s i v e di s e a s e . D i a b e t e s m e l l i t u s i s t h e s i n gl e m os t c o m m on u n d e r l yi n g
condition.
N e u r o l o gi c
conditions
as
sociated
with
i n f e c t i o n i n c l u d e d e m e n t i a , c e r e b r o va s c u l a r d i s e a s e r es u l t i n g i n a l t e r a t i o n s o f m e n t a l s t a t u s , a n d p a r ap l e gi a o r q u a d r i pl e gi a ( 7 0 ) . Y o n g a d u l t s ( 2 0 - 40 ye a r s o f a ge ) w i t h d i a b et e s , c a n c e r , o r H IV i n f e c t i o n a r e a t s i gn i f i c a n t l y i n c r e a s e d r i s k ( 2 8 t o 3 0 - f o l d ) f o r i n v a s i v e gr o u p B s t r e p t o c o c c a l d i s e a s e ( 7 0 ) . M o r t a l i t y i s i n c r e a s e d i n o l d p a t i e n t s , i n t h o se w i t h p o l ym i c r o b i a l i n f e c t i o n s, a n d i n t h o s e w i t h d i a b e t e s m e l l i t u s , l i v e r d i s e a s e , o r m a l i gn a n c y. F a t a l i t y r a t e s i n r e c e n t ye a r s c a s e s h a v e r a n ge d f r o m 2 1 t o 3 2 % i n n o n p r e gn a n t a d u l t s ( 7 0 - 7 3 ) . A d u l t s c u r re n t l y a r e m o r e l i k e l y t o d i e a s a r e s u l t o f gr o u p B s t r e p t o c o c c a l i n f e c t i o n t h a n a r e i n f a n t s ( 5 2 ) . O f t h e 2 9 a d u l t s wi t h b a c t e r e m i a d e s c r i b e d b y O p a l a n d a s s o c i a t e s ( 6 9 ) , o nl y 3 4 % a c q u i r e d t h e i r i n f e c t i o ns i n t h e c o m m u n i t y. O t h e r s h a v e d e s c r i b e d r a t e s o f n o s o c o m i al i n f e c t i on f r o m 3 8 t o 7 0 % ( 72 ) , b u t c a s e c l u s t e r i n g h a s n o t been
observed.
ge n i t o u r i n a r y,
or
Th e
latter
su gge s t s
ga s t r o i n t e s t i n al
that
mucosal
chronic infection
re s p i r a t o r y, ra t h e r
than
a c q u i s i t i o n o f gr o u p B s t r e p t o c o c c i i n t h e h o s p i t a l i s s o u rc e f o r t h e s e bacteremias. P o s t p a rt u m b a c t e r e m i a d u e t o gr o u p B s t r e p t o c o c c i i n c r e a s e d d u r i n g t h e 1 9 7 0 s , a n i n c re a s e t h a t p a r a l l e l ed t h a t r e p o r t e d f or n e o n a t a l i n f e c t i o n . R e c e n t re p o r t s i n di c a t e t h a t gr o u p B s t r e p t o c o c c i a c c o u n t f o r 1 0 - 2 0 % o f bl o o d c ul t u r e i s ol a t e s f r o m w om e n ad m i t t e d t o o b s t e t r i c s e r v i c e s (5 3 , 5 5 ) . F a r o ( 5 5 ) r e p o r t e d a n i n ci d e n c e o f gr o u p B streptococcal
e n d om e t r i t i s
or
e n d o pa r a m e t r i t i s
of
1 .3 p e r
1000
d e l i v e r i e s ; o n e t hi r d o f t h e s e p a t i e n t s h a d c o n c o m i t a nt b ac t e r e m i a .
20
1.6 Therapy G r o u p B st r e p t o c o c c i a r e ge n e r a l l y s u s c e p t i b l e t o pe n i c i l l i n G w h i c h i s t h e d r u g o f c h o i c e . H o w e v e r , t h e m i ni m um i n h i bi t o r y c o n c e n t r a t i o n ( M IC ) n e e d e d t o i n h i b i t t h e o r ga n i s m i s a p pr o x i m a t e l y 1 0 t i m e s gr e a t e r t h a n t h a t n e e d e d t o i n h i b i t S . p y o g e n e s . In a d d i t i o n , t o l e r a n c e t o p e n i c i l l i n ( t h e a b i l i t y o f t h e a n t i b i ot i c t o i n hi b i t bu t n ot kill
the
o r ga n i s m )
has
been
r e p or t e d .
For
these
reasons,
a
c o m b i n a t i o n o f p e ni c i l l i n a n d a n a m i nogl yc o s i d e i s f r e q u e n t l y u s e d i n t h e m a n a ge m e n t o f s e r i o u s i n f e c t i on . V a n c o m yc i n i s a n a l t e r n a t i v e t h e r a p y f o r p a t i e n t s a l l e r gi c t o p e n i c i l l i n . A n t i b i o t i c r e s i s t a n c e t o e r yt h r o m yc i n a n d t e t r a c yc l i n e h a s b e e n o b s e r v e d . In a n e f f o r t t o p r e v e n t n e o n a t a l d i s e as e , i t i s r e c o m m e nd e d t h a t a l l p r e gn a n t w o m e n s h o u l d b e s c r e e n e d f o r c o l o n i z at i o n w i t h gr o u p B s t r e p t o c o c c i a t 3 5 t o 3 7 w e e k s o f ge s t a t i o n . C h e m o p r o p h yl a x i s s h o u l d b e u s e d f o r a l l w om e n w h o a r e e i t h e r c o l o n i z e d o r a t h i gh r i s k . A p r e gn a n t w o m a n i s c o n s i d e r e d t o b e a t h i gh r i s k t o gi v e b i r t h t o a b a b y w i t h i n v a s i v e gr o u p B d i s e a s e i f s h e h a s p r e v i o u sl y gi v e n b i r t h t o a n i n f a nt w i t h t he d i s e a s e o r r i s k f a ct o r s a r e : (1)
In t r a p a r t u m t e m p er a t u r e o f a t l e a s t 38° C
(2)
M e m b r a n e r u p t u r e at l e a s t 18 h o u r s b e f o r e d e l i v e r y
(3)
V a gi n a l o r r e c t a l c u l t u r e p os i t i v e f or o r ga n i s m s a t 3 5 t o 3 7
w e e k s o f ge s t a t i o n . In t r a v e n o u s p e n i c i l l i n G a d m i n i st e r e d a t l a s t 4 h o u r s b e f o r e d e l i v e r y is
recommended;
c l i n d a m yc i n
or
a
cephalosporin
is
used
for
p e n i c i l l i n - a l l e r gi c w o m e n . T h i s a p p r o a c h e n s u r e s h i gh p r o t e c t i v e a n t i b i ot i c l e v e l s i n t h e i n f a n t ’ s c i r c u l a t o r y s ys t e m a t t h e t i m e o f birth.
Because
n ew b o r n
disease
is
associated
wi t h
decreased
c i r c u l a t i n g a n t i bo d i e s i n t h e m ot h e r , e f f o r t s h a v e b e e n d i r e c t e d a t d e v e l o p i n g a p ol yv a l e n t v a c c i n e a ga i n s t s e r o t yp e s Ia , Ib , I I, I I I, a n d V . T h e c a p s u l a r po l ys a c c h a r i d e s a r e p o o r i m m u n o ge n s; h o w e v e r , c o m p l ex i n g
them
with
tetanus 21
t ox o i d
has
i m p ro v e d
the
i m m u no ge n i c i t y o f t h e v a c c i n e . C l i n i c a l t r i a l s w i t h t hi s p o l yv a l e n t vaccine are under way (75).
22
2 Praktical part of work 2. 1 Goals
The goal is to understand the evolutionary origin of this pathogen and to devise novel strategies for preventing infections with the pathogen.
Understanding
the
pathogenesis
of
neonatal
GBS
infections will also provide insights into the development of the neonatal immune system.
To determine the antimicrobial susceptibilit y pattern of a bac terial strain.
To identify the best preventive strategy.
23
2. 2 Methods.
HIPPURATE DIFFERENTIATION DISKS: (for Gram +) 1. Add one hippurate disk (Na hippurate) to a 0.4ml tube of sterile distilled water, and emulsify one loopful of your Beta Streptococcus sp. in the water. 2. Incubate the tube at 37 ° C for at least 2 hours. (You can incubate overnight if you cannot return to read the test in 2 hours). 3. Following incubation, add 0.2ml (5 drops) of ninhydrin reagent to the tubes and shake gentl y. Reincubate tubes for 10 -15 minutes and read color reaction. Do not incubate longer than 30 minutes because a false positive reading could result. 4. This test is used onl y to differentiate Group B -Strep from other Beta Strep. Results: a.
negative
=
b.
positive
=
no the
color
change
formation
to of
pale a
purple
deep
color
purple -blue
change color.
This indicates that the test bacteria is hydrol yzing hippurate and is a Group B-Beta Strep. Group B streptococci ( S. agalactiae) produce the enz yme hippurase that hydrol yzes sodium hippurate. A test for this enz yme can differentiate these organisms from other hemol ytic streptococci. This rapid method uses the end -product gl ycine, to detect the breakdown of sodium hippurate, rather than a nother end-product benzoic acid. This method employs a ninhydrin reagent to detect the presence of glycine. The ninhydrin and gl ycine reaction removes the amino group to produce water and ammonia. The ammonia is passed through sequential steps to produce a purple color (Figure 5).
24
(Figure 5). Hippurate test 3.5% Ninhydrin Reagent ninhydrin
0.35
1-butanol acetone
g
5 5
ml ml
Mix together the above reagents and store at room tempera ture in a brown glass bottle.
25
Antibiotic Disk Susceptibilities (Kirby-Bauer Disk-Diffusion Method) The disk-diffusion method (Kirby-Bauer) is more suitable for routine testing in a clinical laboratory where a large number of isolates are tested for susceptibilit y to numerous antibiotics. An agar plate is uniforml y
inoculated
with
the
test
organism
and
a
paper
disk
impregnated with a fixed concentration of an antibiotic is placed on the agar surface. Growth of the organism and diffusion of the antibiotic commence simultaneousl y resulting in a circular zone of inhibition in which the amount of antibiotic exceeds inhibitory concentrations. The diameter of the inhibition zone is a function of the amount of drug in the disk and susceptibility of th e microorganism ( Figure 6). This test must be rigorousl y standardized since zone size is also dependent on inoculum size, medium composition, temperature of incubation, excess moisture and thickness of the agar. If these conditions are uniform, reproducibl e tests can be obtained and zone diameter is onl y a function of the susceptibilit y of the test organism. Zone diameter can be correlated with susceptibilit y as measured by the dilution method. Further correlations using zone diameter allow the designation
of
an
organism
as
"susceptible",
"intermediate",
or
"resistant" to concentrations of an antibiotic which can be attained in the blood or other body fluids of patients requiring chemotherapy.
Figure 6
26
Procedure: 1. Make a suspension at an appropriate turbidit y of the bacterial culture to be tested. 2. Place a sterile cotton swab in the bacterial suspension and remove the excess fluid by pressing and rotating the cotton against the inside of the tube above the fluid level. The swab is streaked in at least three directions over the surface of the Mueller-Hinton agar to obtain uniform growth. A final sweep is made around the rim of the agar. Be sure to streak for confluency. 3. Allow the plates to dry for five minutes. 4. Using sterile forceps, place disks containing the following antibiotics on the plate : penicillin G, ampicillin, cephalothin, erythrom ycin, tetracycline, methicillin, streptom ycin or other appropriate antibiotic disks. 5. Incubate the plates within 15 minutes after appl ying the disks. The plates should be incubated soon after placing the disk s since the test is standardized under conditions where diffusion of
the
antibiotic
and
bacterial
growth
commence
at
approximatel y the same time. 6. Following overnight incubation, measure the diameter of the zone of growth inhibition around each disk to the nearest whole mm. Examine the plates carefull y for well -developed colonies within the zone of inhibition. 7. Using a standard table of antibiotic susceptibilities ( Table 3), determine if the strain is resistant, intermediate or susceptible to the antibiotics tested. 8. Discard the plates in the biohazard container.
27
Table 3. ZONE DIAMETER STANDARDS FOR ANTIBIOTIC SUSCEPTIBILITY Antimicrobial Agent Amikacin Ampicillin ---enterics ---staphyloccocci ---enterococci ---streptococci Cefoperazone Cephalothin Ciprofloxacin Clindamycin Erythromycin Gentamicin Imipenem Oxacillin ---staphylococci ---Pneumococci Penecillin G ---staphylococci ---enterococci ---streptococci
Disk Content 30 µg
10 µg
75 µg 30 µg 5 µg 2 µg 15 µg 10 µg 10 µg . 1 µg 1 µg 10 units
Zone diameter, nearest whole mm Moderately Resistant Intermediate Susceptible Susceptible 17 . . . . 14 29 17 30 21 18 21 21 23 15 16 . . . . 13 20 . . . . 29 15 28 18
100 µg 23.75 Sulfamethoxazole / µg 16 Trimethoprim 1.25 µg Tetracycline 30 µg 19 Vancomycin 30 µg 12 Obtained from National Committee of Clinical Standards (NCCS) Piperacillin
28
2. 3
Results
P e r h a p s t h e gr e a t e s t a r e a o f c o n c e r n t o m e d i c a l r e s e a r c h e r s , a s i t s ho u l d b e t o us al l , i s t h e al a r m i n g i n c r e a s e i n a n t i bi o t i c - r e s i s t a n t s t r a i n s o f b a c t e r i a . A n t i b i o t i c - r e s i st a n t b a c t e r i a c a n c a u s e i n f e c t i o ns in newborns that are very difficult to treat. Many large research s t u d i e s h a v e f o u nd n o t o n l y r e s i s t a n t st r a i n s o f G B S b u t al s o a n t i b i ot i c - r e s i st a n t s t r a i n s o f E . c o l i a nd o t h e r b a c t e r i a c a us e d b y t h e u s e o f a n t i bi o t i c s i n l a b o r i n g w o m e n . T h e i n c r e a s e i n o t h e r f o r m s o f b l o o d i n f e c t i o n a m o n g ne w b o r n s i s likely
due
a n t i b i ot i c s .
to
bacteria
E vi d en c e
made
shows
drug-resistant that
increased
by use
the of
overuse
of
a n t i b i ot i cs
frequently leads to increasing bacterial resistance. When a woman is gi v e n a n t i b i ot i c s du r i n g l a b o r t o t r e a t G B S , t h e a n t i b i ot i c s c r o s s t he p l a c e n t a a n d e n t e r t h e a m n i o t i c f l u i d . W h i l e t h e a n t i b i ot i cs m a y h a v e t h e d e s i r e d e f f e c t of k i l l i n g t h e G B S ba c t e r i a , s o m e G B S b a c t e r i a c a n s u r v i v e a n d b e c o m e d i f f i c u l t , i f i t n o t i m po s si b l e , t o k i l l w i t h t r a d i t i on a l l y u s e d a n t i b i o t i c s. S i m i l a r l y, o t h e r b a c t e r i a t h a t m a y b e p r e s e n t i n t h e m o t he r o f i n f a n t , s u c h a s E . c o l i , c a n b e c om e r e s i s t a nt t o a n t i b i ot i c t r e a t m e n t . T h e s e b a c t e r i a m a y n o t h a v e p r e s e n t e d a l a r ge risk
of
i n f e c t i on
to
the
newborn
a n t i b i ot i c s a n d m a de i n t o " s u p e r b u gs . "
29
until
they were
exposed
to
Table.4 Number of GBS isolated in NURCH Laaboratory of MicrobiologyPIESTANY
YEAR
2002
2003
2004
TOTAL
№ of
101
129
104
334
isolated races
Graph.1 Number of GBS isolated in NURCH Laaboratory of MicrobiologyPIESTANY 2002-2003-2004
140 120 100 80 60 40 20 0
2002
2003
2004
Number of GBS isolated
30
Table.5 Number of GBS isolated in NURCH during the year months 2002-2003-2004
Month
YEAR 2003 12 7 14 17 9 12 11 7 10 15 10 5 129
2002 1 10 7 6 9 9 6 14 4 18 12 5 101
January February March April May June July August September October November December together
2004 6 8 13 9 13 14 10 8 7 5 9 2 104
Graph.2 Number of GBS isolated in NURCH during the year months
2002 18
18 16 14
14
12
12 10
10 8
9 7
6
9
6
6
4 2 0
5
4 1 I.
II.
III.
IV.
V.
VI.
31
VII.
VIII.
IX.
X.
XI.
XII.
Graph.3 Number of GBS isolated in NURCH during the year months
2003 18
17
16 14 12
15
14 12
12
10
11
10
9
8
7
10
7
6
5
4 2 0
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.
G r a p h 4 Number of GBS isolated in NURCH during the year months
2004
14
13
13
14
12 10
6
9
8
8
10 8
6
9 7 5
4 2
2 0
I.
II.
III.
IV.
V.
VI.
32
VII.
VIII.
IX.
X.
XI.
XII.
Graph.5 Resisting of GBS isolated to Antibiotics in (NURCH) PIESTANY-2002
50
44
42
40 30
21
20 10 0
0 PEN
0 AMP
0 TET
0
NF
SXT
0
CXM
OFX
AMC
Graph.6 Resisting of GBS isolated to Antibiotics in (NURCH) PIESTANY- 2003
Resist 2003 70 60 50 40 30 20 10 0
65
60
57
24 0
0
PEN
AMP
0 TET
GEN
NF
33
0 SXT
CXM
0 OFX
AMC
Graph.7 Resisting of GBS isolated to Antibiotics in (NURCH) PIESTANY- 2004
Resist 2004 50
44
49
48
40 30 19
20 10 0
0
0
PEN
AMP
3 TET
GEN
NF
34
1 SXT
CXM
0 OFX
AMC
Table.6 N u m b e r o f G B S i s ol a t e d i n AN A LY T X . s . o . r L a b o r a t o r y o f M i c r o b i ol o g y - T R N A V A
YEAR
2002
2003
2004
№ of
1293
1631
1657
TOTAL 4581
isolated races
Graph.8 Number of GBS isolated in ANALYTX.s.o.r L aboratory of MicrobiologyTRNAVA
35
Table.7 Resisting of GBS isolated to Antibiotics 2002 in micro.lab-Trnava Tested Antibiotics
PEN
ERY
CLI
TET
AIB
№
1
90
70
543
0
℅
0%
8%
6%
72%
0%
Graph.9 Resisting of GBS isolated to Antibiotics 2002 in micro.lab-Trnava
GBS Resist to Antibiotics 2002 600
543
500 400 300 200 100 0
90
70
1 PEN
ERY
CLI
36
0 TET
AIB
Table.8 Sensitivity of GBS isolated to Antibiotics 2002 in micro.lab-Trnava Tested Antibiotics
PEN
ERY
CLI
TET
AIB
№
1284
1140
1140
263
1293
℅
100%
92%
94%
28%
100%
Graph.10 Sensitivity of GBS isolated to Antibiotics 2002 in micro.lab-Trnava GBS Sensitivity to Antibiotics 2002 AIB
100%
TET
28%
CLI
94% 92%
ERY
100%
PEN 0%
20%
40%
60%
37
80%
100%
120%
Table.9 Resisting of GBS isolated to Antibiotics 2003 in micro.lab-Trnava Tested Antibiotics
PEN
ERY
CLI
TET
AIB
№
5
152
152
928
0
℅
0%
10%
12%
79%
0%
Graph.11 Resisting of GBS isolated to Antibiotics 2003 in micro.lab-Trnava GBS Resist to Antibiotics 2003 928
1000 800 600 400 152
200 0
152
5
PEN
0
ERY
CLI
38
TET
AIB
Table.10 Sensitivity of GBS isolated to Antibiotics 2003 in micro.lab-Trnava Tested Antibiotics
PEN
ERY
CLI
TET
AIB
№
1617
1375
1231
286
1623
℅
100%
90%
88%
21%
100%
Graph.12 Sensitivity of GBS isolated to Antibiotics 2003 in micro.lab-Trnava
GBS Sensitivity to Antibiotics 2003 AIB
100%
TET
21%
CLI
88%
ERY
90%
PEN
100% 0%
20%
40%
60%
39
80%
100%
120%
Table.11 Resisting of GBS isolated to Antibiotics 2004 in micro.lab-Trnava Tested Antibiotics
PEN
ERY
CLI
TET
AIB
№
0
190
205
999
0
℅
0%
12%
13%
77%
0%
Graph.13 Resisting of GBS isolated to Antibiotics 2004 in micro.lab-Trnava
40
Table.12 Sensitivity of GBS isolated to Antibiotics 2004 in micro.lab-Trnava Tested Antibiotics
PEN
ERY
CLI
TET
AIB
№
1656
1385
1396
328
1657
℅
100%
88%
87%
23%
100%
Graph.14 Sensitivity of GBS isolated to Antibiotics 2004 in micro.lab-Trnava
GBS Sensitivity to Antibiotics 2004 100%
AIB 23%
TET CLI
87%
ERY
88%
PEN
100% 0%
20%
40%
60%
41
80%
100%
120%
2. 4 Discussion Lancefield group B beta streptococci, Streptococcus agalactiae, once were considered pathogens only of domestic animals, causing mastitis in cows. S agalactiae now is best known as a cause of postpartum infection and as the most common cause of neonatal sepsis. More recently, the role of this organism as a cause of infection in nonpregnant adults has been described in a number of series. These studies allow description of the clinical spectrum of disease, including clinical features, risk factors, therapy, and outcome of group B streptococci in the nonpregnant adult. Group B streptococci colonize the vaginal and gastrointestinal tract in healthy women. Neonates acquire the organism as a result of vertical transmission from the maternal genital tract to the infant in utero or at delivery. Carriage rates in women can range from 5-40%. While acquisition of the organism by the neonate is efficient, the rate of subsequent clinical disease is quite low, 1-2%. Neonatal sepsis from group B streptococci is a rare event, but it is more common in the setting of prematurity and prolonged rupture of the membranes. The large number of women who carry this organism and the fact that neonatal sepsis is a rare event make a prevention approach to this problem difficult. Many pregnant women will require treatment to prevent a single neonatal infection. Disease in the neonate is divided into early and late disease. Early neonatal sepsis with group B streptococci often is observed within 24 hours of delivery, but it can become apparent as late as 7 days after birth. Nothing specific regarding the clinical presentation in early disease differentiates group B streptococci as the etiology from other pathogens. Pneumonia with bacteremia is common and meningitis less likely. Late disease is defined as infection after 1 week and before 3 months after birth. Late disease commonly is serotype III, characterized by bacteremia and meningitis. Group B streptococcal infection in the infant is more common in the absence of antibody to group B streptococci. Because antibody to group B streptococci is protective for the disease in the animal model, interest in vaccination as an approach to reduce the incidence of group B streptococcal colonization in healthy women is ongoing. Vaccine development was promising at one time, but shifting serotypes of group B streptococci responsible for clinical disease have limited this approach. Problems related to access to vaccination for women of childbearing age and the
42
emotion and possible litigation associated with vaccination during pregnancy have made this approach less attractive. The current approach to the prevention of group B streptococcal infection in pregnancy has become a national standard. This approach requires intrapartum antimicrobial prophylaxis in term women with culture evidence of recent vaginal or rectal group B streptococcal infection. Women without a known group B streptococci status delivering before 37 weeks' gestation with premature rupture of the membranes or intrapartum fever also are candidates for intrapartum antimicrobial prophylaxis. Penicillin or ampicillin is the initial approach to this problem. Clindamycin and erythromycin are standard for the individual with penicillin allergy, but group B streptococci now are not always sensitive to these 2 drugs. Group B streptococci as a cause of infection in pregnant women can be manifest by chorioamnionitis, endometritis, or genitourinary infection with bacteremia. Rarely, endocarditis or meningitis can be observed. Only in the last 3 decades has the role of group B streptococci as a serious pathogen in the nonpregnant adult been well defined. A number of studies have allowed description of the clinical spectrum of disease, including clinical features, risk factors, therapy, and outcomes. This organism is an extremely rare cause of infection in a healthy individual. It almost always is associated with underlying abnormalities. Diabetes is associated most commonly with group B streptococci in some series.This association, which the authors have observed over the last 25 years, is unexplained. Malignancy was the most common association in a series from an institution with a large oncology population. Cardiovascular and genitourinary abnormalities have been observed as major factors for the acquisition of group B streptococci. Other conditions associated with group B streptococci in adults include neurologic deficits, cirrhosis, steroids, AIDS, renal dysfunction, and peripheral vascular disease. Group B streptococci in elderly people, aged 70 years or older, is strongly linked to congestive heart failure and being bedridden. Urinary tract infection, pneumonia, and soft tissue infection were the most common illnesses in this group. Neurologic illness is associated with pneumonia in elderly people, possibly as a result of aspiration of group B streptococci from the upper respiratory tract. Nosocomial infection with group B streptococci was common in this group and is described in other series. The source of this infection is not always clear, but the genitourinary tract and skin are thought to be the sources of some nosocomial infections. 43
Group B streptococci colonize not only the female genital tract but also are found commonly in the gastrointestinal tract and have been described as asymptomatic colonizers of the urethra in both men and women. Group B streptococci can colonize the upper respiratory tract. Colonization also is observed in wound and soft tissue cultures in the absence of obvious infection. Determining the acquisition and transmission of the organism can be puzzling. Group B streptococci are very invasive but produce little inflammation at the entry site. Primary bacteremia without an obvious source with group B streptococcal infection is a common presentation in adults. While one series suggests that group B streptococci bacteremia is low grade and easily controlled with little morbidity, other authors suggest that the clinical presentation may be that of classic sepsis with shock and may carry a high mortality. Sustained bacteremia raises the question of endocarditis or an infected catheter. Group B streptococci can be a cause of acute destructive endocarditis, which may require emergency valve replacement. Other sources of bacteremia include pneumonia in elderly people and genitourinary and soft tissue infection. Polymicrobial bacteremia with group B streptococci is observed in disease related to infected lines and also can reflect a genitourinary source. Urinary tract infections are a common manifestation of group B streptococcal disease. This is observed in pregnancy as well as in the nonpregnant adult. A variety of skin and soft tissue infections, including cellulitis, line-site infection, infected decubiti, diabetic feet, osteomyelitis, and arthritis, are described commonly and are the most common group B streptococcal infections in some reports. Necrotizing fasciitis caused by group B streptococci has been described recently. The soft tissue and bone infections may not be cured by a medical therapy alone, and surgical intervention may be necessary. For fasciitis or its possibility, surgery should be immediate. Other manifestations of group B streptococcal infection include meningitis, peritonitis, and endo-ophthalmitis. Group B streptococci at one time were sensitive to penicillin, ampicillin, cefazolin, erythromycin, and clindamycin. The organism remains sensitive to penicillin and ampicillin. While penicillin is the treatment of choice, that penicillin therapy produces a better outcome than other antibiotics is not clear. Because aminoglycoside may provide synergy in killing the organism, it often is added for serious infection. This 2-drug therapy is synergistic only if the organism is sensitive to aminoglycoside, making sensitivity testing important. Clinically, 2-drug therapy with penicillin and 44
aminoglycoside has not been shown to improve the outcome over penicillin alone. The efficacy of clindamycin and macrolides is good, but sensitivity testing must be performed before using these antibiotics because resistance is observed and appears to be increasing. Group B streptococci always are sensitive to vancomycin, and it would be the treatment of choice in the penicillin-allergic patient. Quinolones may have efficacy for group B streptococci, but little clinical experience exists. Linezolid may play a role in treating this infection, but, in the literature, no experience with treating group B streptococcal infection with linezolid exists.
Pathophysiology: S agalactiae is a gram-positive coccus that, when cultured on sheep blood agar, forms glistening gray-white colonies with a narrow zone of beta hemolysis. It is an invasive encapsulated organism capable of producing severe disease in hosts who are immunocompromised. Infection in the absence of associated comorbid medical conditions is rare. Virulence is related to the polysaccharide toxin produced by group B streptococci. Immunity is mediated by antibody to the capsular polysaccharide and is serotype-specific. Several serotypes are known—Ia, Ib, Ic, II, III, IV, V, VI, VII, and VIII. Group B streptococci colonize the vagina, gastrointestinal tract, and the upper respiratory tract of healthy humans. The portal of entry is not apparent, but possible areas include the skin, genital tract, urinary tract, and respiratory tract.
Internationally: The role of group B streptococci in the developing world is not well defined. Carriage rates and serotypes in women in less developed countries are similar to those observed in the industrial world. However, group B streptococci early disease in infants is not documented in less developed countries. A clear explanation for this has not been found.
Mortality/Morbidity: Group B streptococci has significant mortality in both neonates and adults. The mortality rate of group B streptococci bacteremia ranges from 9-47% in adults. The mortality rate is highest for elderly patients with comorbid medical conditions. The highest mortality rate is observed in patients with endocarditis, meningitis, and pneumonia. The high mortality rate in elderly people with group B streptococci may not reflect the organism but may reflect the predisposing condition or conditions that put the individual at risk for group B streptococcal infection.
45
The mortality rate of group B streptococcal infection in neonates is much less than that of nonpregnant adults. Increasing awareness of group B streptococcal infection in infants has led to improved outcome in recent years. Postpartum group B streptococcal infection is associated with a low mortality rate because the group at risk is comprised of healthy, young or middle-aged women. Race: The incidence of group B streptococcal infection is higher in African Americans than whites. The difference is even more striking in older African Americans. These differences probably are a result of socioeconomic differences rather than race.
Sex: Young and middle-aged women are at risk because of obstetrical and gynecological manipulation. With the exclusion of pregnant women, adult group B streptococcal infection occurs in equal numbers of men and women.
Age: The mean age for infection is 64 years. Bimodal distribution is well recognized, with young and middle-aged healthy women with infection secondary to obstetrical or gynecological manipulation as one group. The second group is an elderly population with group B streptococcal infection complicating preexisting illness.
Lab Studies: Gram stain of an appropriate specimen is a useful first test. It can be an early indicator of streptococcal infection. Isolation of group B streptococci from blood, cerebrospinal fluid (CSF), and/or a site of local suppuration is the only means by which the diagnosis of invasive infection can be documented. Group B streptococcal antigen also may be detected in blood, CSF, and/or urine and may aid in diagnosis in certain circumstances.
Medical Care: Group B streptococci are as sensitive to penicillin and ampicillin as they were 50 years ago. The organisms were never as exquisitely sensitive to penicillin as were group A beta-hemolytic streptococci. As a result, the initial therapy for group B streptococcal infection always has been high-dose parenteral penicillin or ampicillin.
46
Synergy can be demonstrated with penicillin or ampicillin plus an aminoglycoside, but this therapy is not associated with a better clinical outcome than penicillin or ampicillin alone. Testing for aminoglycoside sensitivity is important because synergy is not observed if the organism is not aminoglycoside sensitive. Also, a group B streptococcal isolate can be resistant to one aminoglycoside and sensitive to another. While clindamycin and erythromycin were at one time uniformly active against group B streptococci, resistance has been increasing in recent years. As a result, checking the sensitivity before using these agents against group B streptococci is important. Oral clindamycin remains an excellent agent to follow a course of parenteral therapy for bone, soft tissue, and lung infections. Because of possible resistance with clindamycin, vancomycin remains the initial treatment of choice for group B streptococcal infection in the penicillin-allergic individual. Penicillin, ampicillin, or vancomycin remains the treatment of choice for endocarditis. While vancomycin may be adequate in group B streptococcal meningitis in a penicillin-allergic individual, skin testing and desensitization for penicillin therapy might be considered. Penicillin has not been demonstrated to be superior to vancomycin for endocarditis with group B streptococcus infection. The efficacy of quinolones for group B streptococci has not been well studied, although the isolates often are sensitive. Similarly, linezolid, a new antibiotic with efficacy for aerobic gram-positive cocci, should have activity against group B streptococci. It is available in parenteral or oral form. However, no clinical data exist concerning the use of linezolid for group B streptococci at this time.
MEDICATION
Section
Drug Category: Antibiotics ( Table. 13) Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Therapy should begin immediately after blood cultures are obtained.
47
Drug Name
Penicillin G (Pfizerpen) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Penicillin remains the drug of choice for group B streptococcal infection.
Adult Dose
12-24 million U/d IV for 4 wks for endocarditis and osteomyelitis; 2-4 wks for bacteremia, pneumonia, and soft tissue infection
Pediatric Dose
Not established
Contraindications Documented hypersensitivity Interactions
Coadministration of tetracyclines can decrease effects of penicillin
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in impaired renal function Cefazolin (Ancef, Kefzol, Zolicef) -- First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus. Typically used Drug Name alone for skin and skin structure coverage. IV and IM dosing regimens are similar. Cefazolin is alternative therapy to penicillin for group B streptococcal infection. Cefazolin would not be effective for meningitis. 1 g IV q8h Adult Dose Pediatric Dose Not established Contraindications Documented hypersensitivity Coadministration with aminoglycosides may increase renal toxicity; may yield false-positive results on urine-dip test for Interactions glucose A - Safe in pregnancy Pregnancy Adjust dose in renal impairment; superinfections and promotion of nonsusceptible organisms may occur with Precautions prolonged use or repeated therapy
Drug Name
Vancomycin (Vancocin) -- Potent antibiotic directed against gram-positive organisms. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or who have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients diagnosed with renal impairment. May need to adjust dose in renal impairment. Vancomycin is the initial treatment of choice for group B streptococcal infection in the penicillin-allergic individual.
48
Adult Dose Pediatric Dose
1 g IV q12h Not established
Contraindications Documented hypersensitivity Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; when taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside Interactions monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in renal failure; red man syndrome is caused by too rapid IV infusion (dose administered over a few min), but it rarely happens when dose is administered as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction
Drug Name
Gentamicin (Gentacidin, Garamycin) -- Aminoglycosides show synergy when used with penicillin for group B streptococcus. In neonates, the ill patient with sepsis and in certain situations, such as endocarditis, adding an aminoglycoside as a second drug may be helpful. The possible benefit must be weighed against the toxicity of renal and eighth nerve dysfunction, particularly in elderly people. The benefit of 2-drug therapy for group B streptococci has not been proven in terms of a better clinical outcome compared to penicillin therapy alone. The aminoglycoside needs to be tested against the isolate because only sensitive isolates can provide synergy.
Adult Dose
60 mg IV q8h
Pediatric Dose Contraindications
Not established Documented hypersensitivity; non–dialysis-dependent renal insufficiency; preexisting eighth nerve dysfunction
Interactions
Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase the auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment
49
Drug Name
Clindamycin (Cleocin) -- Not for use as initial therapy because a small percent of group B streptococci will be resistant to clindamycin. Should not be used for endocarditis, bacteremia, or meningitis. If bacteria are sensitive, it can be used for pneumonia, osteomyelitis, and soft tissue infection. May also be useful as oral therapy to follow a course of parenteral therapy or if access becomes an issue.
Adult Dose
600 mg IV q6h; 900 mg IV q8h 300 mg PO q6h
Pediatric Dose Contraindications
Not established Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis
Table. 13 Drug Category: Antibiotics
50
Deterrence/Prevention:Both chemoprophylaxis and immunoprophylaxis have been studied in neonates. While vaccine therapy to prevent group B streptococcal infection in women of childbearing age has been studied, no Food and Drug Administration (FDA)–licensed vaccines are available. Investigational vaccine studies are in early stages. Chemoprophylaxis has been shown to be efficacious in neonates. A significant decline in neonatal infections over the past decade may be a result of this national standard. The only approach to prevent group B streptococcal infection in the nonpregnant adult is to adhere to infection control practices because a significant number of these infections are nosocomial. What percent of these infections are preventable remains to be determined because single nosocomial cases are common but a clustering of cases is rare.
Complications:Group B streptococcal infection in healthy women usually is amenable to therapy without major sequelae. Neonatal infection, which still has significant morbidity and mortality, has become less common and has a better outcome as a result of chemoprophylaxis and early recognition of the infected infant. Group B streptococcal infection in the nonpregnant adult carries a high morbidity and a high mortality rate even with early and appropriate therapy. Having a high clinical suspicion, starting early therapy after cultures are obtained, and having the patient receive an appropriate surgical opinion and adequate surgical intervention when necessary are important.
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2. 5. Conclusion and recommendations Group B streptococcus, or Streptococcus agalactiae, is a gram-positive coccus that causes invasive disease primarily in newborns, pregnant women and adults with underlying medical conditions. Since its emergence in the 1970s, group B streptococcal (GBS) disease has been the leading bacterial infection associated with illness and death in newborns in the United States. Disease in infants usually occurs as bacteremia, pneumonia or meningitis. GBS disease in infants is characterized as either early onset (occurring in infants under seven days of age) or late onset (occurring at seven days of age or more). Approximately 25 percent of the cases of neonatal disease occur in premature infants. Colonized women who experience either a long duration of membrane rupture, premature delivery or intrapartum fever are at particularly high risk for transmitting GBS infection to their infants during labor and delivery. Many perinatal GBS infections can be prevented through intrapartum antimicrobial prophylaxis. The Centers for Disease Control and Prevention has developed prevention guidelines for perinatal GBS disease. The report includes information about epidemiology and prevention strategies, the results of clinical trials, the limitations of different approaches to prevention and recommendations for the prevention of GBS infection. The recommendations are using of one of two prevention strategies for GBS. In the first strategy, intrapartum antibiotic prophylaxis is offered to women identified as GBS carriers through prenatal screening cultures collected at 35 to 37 weeks of gestation and to women who develop premature onset of labor or rupture of the membranes at less than 37 weeks of gestation. In the second strategy, intrapartum antibiotic prophylaxis is provided to women who develop one or more risk conditions at the time of labor or rupture of the membranes. The appropriate clinical and laboratory methods required for prenatal screening programs designed to identify GBS carriers; risk conditions that indicate the need for intrapartum antibiotics; management of newborns whose mothers receive intrapartum antibiotic prophylaxis for GBS disease, and education of prenatal patients regarding GBS disease and the available prevention policy.
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Colonization: The gastrointestinal tract is the most likely human reservoir of GBS, with the genitourinary tract the most common site of secondary spread. Colonization rates differ among ethnic groups, geographic locales and by age; however, rates are similar for pregnant and nonpregnant women. Results of studies indicate that 10 to 30 percent of pregnant women are colonized with GBS in the vaginal or rectal area. Of all infants born to these women, 1 to 2 percent will develop early-onset invasive disease. Cultures of specimens from both the anorectum and the vaginal introitus increase the likelihood of GBS isolation over vaginal cultures alone. The use of selective media is essential because they can increase the yield of screening cultures by as much as 50 percent.
Risk Factors:Results of studies indicate that several obstetric, maternal and neonatal factors increase the likelihood of early-onset GBS disease in a newborn. Infants born to women who were identified prenatally as GBS carriers have 29 times the risk of earlyonset disease than infants born to women with negative prenatal cultures. Deliveries in which prematurity, longer duration of membrane rupture or intrapartum fever occur are approximately seven times more likely to be complicated by early-onset GBS disease. The role of GBS colonization in maternal infections was recently investigated. Factors found to independently increase the risk for clinical amnionitis included GBS colonization, duration of membrane rupture (i.e., more than six hours), duration of internal monitoring (i.e., more than 12 hours) and the number of vaginal examinations (i.e., more than six).
Recommendations 1.
Physicians who provide obstetric care, along with supporting laboratories and
labor and delivery facilities, should adopt a strategy for the prevention of early-onset GBS disease. Patients should be informed regarding the prevention strategy.
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2.
Regardless of which preventive strategy is used, all women with symptomatic or
asymptomatic GBS bacteriuria detected during pregnancy should be treated at the time of diagnosis; because such women are usually heavily colonized with GBS, they should also receive intrapartum chemoprophylaxis. Women who previously have given birth to an infant with GBS disease should receive intrapartum chemoprophylaxis; prenatal screening is not necessary for these women.
3.
Until further data are available to define the most effective strategy, the
following two approaches are appropriate:
SCREENING-BASED APPROACH All pregnant women should be screened at 35 to 37 weeks of gestation for anogenital GBS colonization (see algorithm on prenatal screening). Patients should be informed of the screening results and of potential benefits and risks of intrapartum antimicrobial prophylaxis for GBS carriers. Information systems should be developed and monitored to ensure that prenatal culture results are available at the time and place of delivery. Intrapartum chemoprophylaxis should be offered to all pregnant women identified as GBS carriers by culture at 35 to 37 weeks of gestation.
* If the results of GBS culture are not known at the time of labor, intrapartum antimicrobial prophylaxis should be administered if one of the following risk factors is present: less than 37 weeks of gestation, duration of membrane rupture of 18 hours or more, or temperature of 100.4[degrees]F (38.0[degrees]C) or more. * Culture techniques that maximize the likelihood of GBS recovery should be used. Because lower vaginal and rectal cultures are recommended, cultures should not be collected by speculum examination. The optimal method for GBS screening is collection of a single standard culture swab or two separate swabs of the distal vagina and anorectum. Swabs may be placed in a transport medium if the microbiology laboratory is offsite. The sample should be identified as being specifically for GBS culture. Specimens should be inoculated into selective broth medium, followed by overnight incubation and then subcultured onto a solid blood agar medium. In this screening culture, there is no need for the laboratory to culture for other organisms.
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* Laboratories should report the results to the delivery site and to the physician who ordered the test. Ideally, laboratories that perform GBS cultures will ensure that clinicians have continuous access to culture results.
* Oral antimicrobial agents should not be used to treat women who are found to be colonized with GBS during prenatal screening. Such treatment is not effective in eliminating carriage or preventing neonatal disease.
RISK-FACTOR APPROACH A prophylaxis strategy based on the presence of intrapartum risk factors alone (e.g., less than 37 weeks of gestation, duration of membrane rupture of 18 hours or more, or temperature of 38.0[degrees]C] or more) is an acceptable alternative
* For intrapartum chemoprophylaxis, intravenous penicillin G (5 million units initially and then 2.5 million units every four hours) should be administered until delivery. Intravenous ampicillin (2 g initially and then 1 g every four hours until delivery) is an acceptable alternative to penicillin G, but penicillin G is preferred because it has a narrow spectrum and thus is less likely to select for antibiotic-resistant organisms. Clindamycin (900 mg intravenously every eight hours until delivery) or erythromycin (500 mg intravenously every six hours until delivery) may be used for women allergic to penicillin, although the efficacy of these drugs for GBS disease prevention has not been measured in controlled trials. (Penicillin G does not need to be administered to women who have a clinical diagnosis of amnionitis and who are receiving other treatment regimens that include agents active against streptococci.)
* Routine use of prophylactic antimicrobial agents for infants born to mothers who received intrapartum prophylaxis is not recommended. However, therapeutic use of these agents is appropriate for those infants suspected clinically of having sepsis. Additional research is needed to determine algorithms for the management of infants born to mothers who receive intrapartum antimicrobial prophylaxis.
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Local and state public health agencies, in conjunction with appropriate groups of hospitals, should consider establishing surveillance to monitor the incidence of neonatal GBS disease, the occurrence of adverse reactions to antimicrobial prophylaxis and the emergence of perinatal infections caused by penicillinresistant organisms.
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List of content
Introduction .....................................................................................................1
1 Theoretical part of work 1. 1
Classificatioin and Morphologic characteristics.........................................4
1. 2
Indentification..............................................................................................7
1. 3
Serologic classification...............................................................................9
1. 4
Epidemiology and Transmission .............................................................11
1. 5
Clinical manifestations of main representatives.......................................17
1. 6
Therapy......................................................................................................21
2 Praktical part of work 2. 1
Goals.........................................................................................................23
2. 2
Methods sensitivity test- disk method...................................................24
2. 3
Results.......................................................................................................29
2. 4
Discussion.................................................................................................42
2. 5. Conclusion and recommendations............................................................52
References ..................................................................................................56
63
List of Figures, Tables and Graphs Figure.1 Streptococci, Gram-positive cocci arranged in pairs or chains .......................3 Figure.2 Group B Streptococcus (GBS) growing on a 5% sheep blood agar plate........5 Figure.3 Agar plate with growth and hemolytic activity of GBS and GAS...................6 Figure.4 GAMP test........................................................................................................7 Figure.5 Hippurate test..................................................................................................25 Figure.6 The disk-diffusion method (Kirby-Bauer)......................................................26 Table.1 Antigenic Determinants of group B streptococci.............................................10 Table.2 GBS and intrinsic differences in the populations studied...............................16 Table.3 Zone Diameter Standards for Antibiotic Susceptibility.................................28 Table.4 Number of GBS isolated in (NURCH) PIESTANY.......................................30 Table.5 Number of GBS isolated in (NURCH) during year months............................31 Table.6 Number of GBS isolated in ANALYTX.s.o.r-TRNAVA...............................35 Table.7 Resisting of GBS isolated to Antibiotics 2002 in micro.lab-Trnava...............36 Table.8 Sensitivity of GBS isolated to Antibiotics 2002 in micro.lab-Trnava.............37 Table.9 Resisting of GBS isolated to Antibiotics 2003 in micro.lab-Trnava...............38 Table.10 Sensitivity of GBS isolated to Antibiotics 2003 in micro.lab-Trnava...........39 Table.11 Resisting of GBS isolated to Antibiotics 2004 in micro.lab-Trnava..............40 Table.12 Sensitivity of GBS isolated to Antibiotics 2004 in micro.lab-Trnava............41 Table. 13 Drug Category: Antibiotics.............................................................48 Graph.1 Number of GBS isolated in ( NURCH) .Piestany........................................30 Graph.2 Number of GBS isolated in NURCH during the year months 2002..........31 Graph.3 Number of GBS isolated in NURCH during the year months 2003..........32 Graph.4 Number of GBS isolated in NURCH during the year months 2004..........32
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Graph.5 Resisting of GBS isolated to Antibiotics in (NURCH) PIESTANY-2002...33 Graph.6 Resisting of GBS isolated to Antibiotics in (NURCH) PIESTANY-2003...33 Graph.7 Resisting of GBS isolated to Antibiotics in (NURCH) PIESTANY-2004...34 Graph.8 Number of GBS isolated in ANALYTX.s.o.r-TRNAVA............................35 Graph.9 Resisting of GBS isolated to Antibiotics 2002 in micro.lab-Trnava.............36 Graph.10 Sensitivity of GBS isolated to Antibiotics 2002 in micro.lab-Trnava...........37 Graph.11 Resisting of GBS isolated to Antibiotics 2003 in micro.lab-Trnava.............38 Graph.12 Sensitivity of GBS isolated to Antibiotics 2003 in micro.lab-Trnava...........39 Graph.13 Resisting of GBS isolated to Antibiotics 2004 in micro.lab-Trnava.............40 Graph.14 Sensitivity of GBS isolated to Antibiotics 2004 in micro.lab-Trnava...........41
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