bacteriostat bacteriosid 24ab c.jejuni.full

7/29/2019 Bacteriostat Bacteriosid 24Ab C.jejuni.full

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DOI: 10.1128/AAC.18.1.118.

1980, 18(1):118.Antimicrob. Agents Chemother.P ButzlerR Vanhoof, B Gordts, R Dierickx, H Coignau and Jjejuni.

against Campylobacter fetus subsp.activities of 24 antimicrobial agentsBacteriostatic and bactericidal

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A N T I M I C R O B I A L AGENTS A N D C H E M O T H E R A P Y , J U l Y 1 9 8 0 , p . 1 1 8 - 1 2 10 0 6 6 - 4 8 0 4 / 8 0 / 0 7 - 0 1 1 8 / 0 4 $ 0 2 . 0 0 / 0 V o l . 1 8 , N o . 1

B a c t e r i o s t a t i c a n d B a c t e r i c i d a l A c t i v i t i e s o f 2 4 A n t i m i c r o b i a lA g e n t s A g a i n s t C a m p y l o b a c t e r f e t u s s u b s p . jejuniR . VANHOOF,* B . GORDTS, R . DIERICKX, H . COIGNAU, AND J . P . BUTZLER

D e p a r t m e n t o f M i c r o b i o l o g y , S t . P i e t e r s H o s p i t a l , F r e e U n i v e r s i t y o f B r u s s e l s , 1 0 0 0 B r u s s e l s , B e l g i u mThe b a c t e r i o s t a t i c a n d b a c t e r i c i d a l a c t i v i t i e s o f 2 4 a n t i m i c r o b i a l a g e n t s weret e s t e d w i t h t h e D y n a t e c h MIC 2 0 0 0 s y s t e m a g a i n s t 8 6 s t r a i n s o f C a m p y l o b a c t e rf e t u s s u b s p . j e j u n i f r o m human sources. The p e n i c i l l i n s ( p e n i c i l l i n G , a m p i c i l l i n ,a m o x y c i l l i n , c a r b e n i c i l l i n ) h a d poor a c t i v i t y . A m p i c i l l i n a n d a m o x y c i l l i n weree q u a l l y a c t i v e . C e f o t a x i m e r e v e a l e d a r a t h e r g o o d a c t i v i t y . E r y t h r o m y c i n , g e n t a -m i c i n , t o b r a m y c i n , a m i k a c i n , a n d f u r a z o l i d o n e were t h e most a c t i v e c o m p o u n d s .T wo s t r a i n s ( 2 . 3 % ) were r e s i s t a n t t o e r y t h r o m y c i n . One s t r a i n ( 1 . 2 % ) was com-p l e t e l y r e s i s t a n t t o t o b r a m y c i n . The t e t r a c y c l i n e s ( t e t r a c y l i n e , d o x y c y c l i n e , m i -n o c y c l i n e ) were g e n e r a l l y e f f e c t i v e , b u t 8% o f t h e s t r a i n s were t o t a l l y r e s i s t a n t t ot h e m . M i n o c y c l i n e was t h e most a c t i v e . C h l o r a m p h e n i c o l , t h i a m p h e n i c o l , a n dc l i n d a m y c i n h a d g o o d a c t i v i t y . T he b a c t e r i o s t a t i c a n d b a c t e r i c i d a l d i s t r i b u t i o n sf o r c o l i s t i n , n a l i d i x i c a c i d , a n d m e t r o n i d a z o l e were b r o a d .

S i n c e K i n g ( 8 ) i d e n t i f i e d c a m p y l o b a c t e r s a s ap o s s i b l e c a u s e o f e n t e r i t i s i n h u m a n s , t h e s e m i -c r o o r g a n i s m s h a v e become i m p o r t a n t p a t h o -g e n s , e s p e c i a l l y s i n c e 1 9 7 2 when w o r k e r s i nB r u s s e l s ( 5 ) f a c i l i t a t e d t h e i s o l a t i o n o f t h e o r g a -n i s m s b y u s e o f a s e l e c t i v e t e c h n i q u e . S i n c e t h a tt i m e C a m p y l o b a c t e r f e t u s s u b s p . j e j u n i ( C . j e -j u n i ) b e c a m e a f r e q u e n t l y i s o l a t e d e n t e r o p a t h -o g e n i c m i c r o o r g a n i s m ( 2 , 7 , 1 3 ) w i t h a w o r l d w i d ed i s t r i b u t i o n ( 6 , 9 , 1 2 ) . I t h a s a l s o b e e n a s s o c i a t e dw i t h o t h e r p a t h o l o g i e s ( 4 , 1 1 , 1 9 ) .The s e r i o u s l y i l l a n d s e p t i c e m i c p a t i e n t s h o u l db e t r e a t e d , b u t u n t i l no w t h e r e h a s b e e n l i t t l ei n f o r m a t i o n t o g u i d e t h e t h e r a p y . T h e a i m o ft h i s s t u d y w a s t o d e t e r m i n e t h e i n v i t r o a c t i v i t yo f v a r i o u s a n t i b i o t i c s , a s w e l l a s t h e i r d e g r e e o fb a c t e r i c i d a l a c t i o n on c a m p y l o b a c t e r s .

MATERIALS A N D METHODSB a c t e r i a l s t r a i n s . E i g h t y - s i x s t r a i n s o f C . j e j u n ii s o l a t e d f r o m human s t o o l s ( 5 ) w e r e u s e d i n t h i s s t u d y .T h e s t r a i n s w e r e p r e s e r v e d i n f l u i d t h i o g l y c o l a t e a g a rm e d i u m ( n o . 0 2 5 6 - 0 1 , D i f c o L a b o r a t o r i e s , D e t r o i t ,

M i c h . ) a n d s t o r e d i n l i q u i d n i t r o g e n o r k e p t i n a f r e e z e ra t - 7 0 C . When r e q u i r e d , t h e s u s p e n s i o n s w e r et h a w e d a n d i n o c u l a t e d o n t o p e t r i d i s h e s c o n t a i n i n gf l u i d t h i o g l y c o l a t e a g a r medium w i t h 1 . 5 % a g a r a n d1 0 % d e f i b r i n a t e d s h e e p b l o o d ( I n s t i t u t e P a s t e u r , B r u s -s e l s ) a n d ( p e r m i l l i l i t e r ) 2 5 I U o f b a c i t r a c i n ( N u t r i -t i o n a l B i o c h e m i c a l s C o r p . , C l e v e l a n d , O h i o ) , 0 . 0 0 5 mgo f n o v o b i o c i n ( T h e U p j o h n C o . , K a l a m a z o o , M i c h . ) ,a n d 0 . 0 5 mg o f c y c l o h e x i m i d e ( T h e U p j o h n C o . ) .I n o c u l u m . The i n o c u l a t e d p l a t e s w e r e i n c u b a t e d a t3 7 0 C i n a 1 0 % C 0 2 a t m o s p h e r e f o r 2 d a y s . The c o l o n i e sf r o m t h e p l a t e s w e r e t h e n s u s p e n d e d i n 1 0 m l o f f l u i dt h i o g l y c o l a t e medium a n d i n c u b a t e d f o r 2 4 h i n 1 0 %C O 2 . The t u r b i d i t y o f t h e s e o v e r n i g h t c u l t u r e s w a s

a d j u s t e d t o m a t c h a M c F a r l a n d n o . 1 s t a n d a r d . T h e s ec u l t u r e s w e r e t h e n i n o c u l a t e d i n t o m i c r o t i t e r p l a t e sc o n t a i n i n g 0 . 1 m l o f b r o t h s o t h a t t h e f i n a l i n o c u l u mc o n t a i n e d a p p r o x i m a t e l y 3 x 1 0 6 c o l o n y - f o r m i n g u n i t sp e r m l . The C 0 2 w a s c o n t r o l l e d w i t h a P o r t o m a t i c C 0 2c o n t r o l l e r ( 3 0 5 6 / 3 0 6 2 , F o r m a S c i e n t i f i c I n c . ) .A n t i b i o t i c s u s c e p t i b i l i t y t e s t s . A C o o k e D y n a -t e c h 2 0 0 0 d i s p e n s o r a n d i n o c u l a t o r , w i t h a 1 - p I a m o u n to f i n o c u l u m , w e r e u s e d f o r t h e d e t e r m i n a t i o n o f t h em i n i m a l i n h i b i t o r y c o n c e n t r a t i o n ( M I C ) i n f l u i d m e -d i u m .The m i c r o t i t e r p l a t e s ( D y n a t e c h MIC p l a t e s MA1 5 0 1 / N ) w e r e f i l l e d w i t h 0 . 1 - m l s a m p l e s o f t h e a n t i b i -o t i c s o l u t i o n s p r e p a r e d i n M u e l l e r - H i n t o n b r o t h(MHB) ( 4 0 7 0 2 , B i o - M e r i e u x ) , e x c e p t t h a t f o r s u l f a -m e t h o x a z o l e , t r i m e t h o p r i m , a n d c o - t r i m o x a z o l e , t h emedium w a s MHB w i t h 5 % h e m o l y z e d h o r s e b l o o d( I n s t i t u t e P a s t e u r , B r u s s e l s ) . The m i c r o t i t e r p l a t e sw e r e i n c u b a t e d i n a 1 0 % C 0 2 a t m o s p h e r e a t 3 7 0 C f o r4 8 h . I n e v e r y m i c r o t i t e r p l a t e , o n e row w i t h o u t a n t i -b i o t i c s s e r v e d a s a c o n t r o l . F o r e a c h a n t i b i o t i c , S t a p h -y l o c o c c u s a u r e u s ( A T C C 2 5 9 2 3 ) a n d E s c h e r i c h i a c o l i(ATCC 2 5 9 2 2 ) w i t h k n o w n a n t i b i o t i c s u s c e p t i b i l i t yp a t t e r n s w e r e t e s t e d a t t h e same t i m e . T h e t r a y s w e r ee x a m i n e d o n a C o o k e - D y n a t e c h v i e w i n g b o x . MICsw e r e r e c o r d e d a s t h e l o w e s t c o n c e n t r a t i o n s i n h i b i t i n gv i s i b l e g r o w t h .To m e a s u r e t h e m i n i m a l b a c t e r i c i d a l c o n c e n t r a t i o n s( M B C ) , we p l a t e d t h e MIC c u l t u r e s o n M u e l l e r - H i n -t o n a g a r ( B B L M i c r o b i o l o g y S y s t e m s , C o c k e y s v i l l e ,M d . ; 1 1 4 3 8 ) w i t h 5% l y s e d h o r s e b l o o d a n d i n c u b a t e dt h e m f o r 2 4 h a t 3 7 0 C i n a 1 0 % C 0 2 a t m o s p h e r e . Ar e d u c t i o n o f a t l e a s t 9 0 % o f t h e c o l o n i e s , c o m p a r e dw i t h t h e c u l t u r e o f t h e i n i t i a l i n o c u l u m o f t h e s t r a i n ,w a s r e g a r d e d a s e v i d e n c e o f b a c t e r i c i d a l a c t i v i t y .A n t i b i o t i c s . The f o l l o w i n g a n t i m i c r o b i a l a g e n t sw e r e t e s t e d : a m p i c i l h i n , a m o x y c i l l i n , a n d c a r b e n i c i l l i n( B e e c h a m L a b o r a t o r y ) , b e n z y l p e n i c i l l i n ( C o n t i n e n t a lP h a r m a ) , c e f a z o l i n , m o x a l a c t a m , a n d t o b r a m y c i n ( E l i

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MIC AND MBC ACTIVITIES A G A I N S T C . JEJUNI 119L i l l y & C o . ) , c e f o t a x i m e ( H o e c h s t ) , e r y t h r o m y c i n ( A b -b o t t L a b o r a t o r i e s ) , t h i a m p h e n i c o l ( Z a m b o n ) , c h l o r -a m p h e n i c o l ( L e p e t i t ) , c l i n d a m y c i n ( U p j o h n ) , g e n t a -m i c i n ( S c h e r i n g C o r p . ) , a m i k a c i n ( B r i s t o l L a b o r a t o -r i e s ) , t e t r a c y c l i n e ( C E R T A ) , d o x y c y c l i n e ( P f i z e r , I n c . ) ,m i n o c y c l i n e ( L e d e r l e L a b o r a t o r i e s ) , c o l i s t i n ( B e l l o nL a b o r a t o r i e s ) , n a l i d i x i c a c i d ( W i n t h r o p ) , f u r a z o l i d o n e( N o r w i c h , B e n e l u x ) , m e t r o n i d a z o l e ( S p e c i a ) , s u l f a m e -t h o x a z o l e , t r i m e t h o p r i m ( R o c h e S . A . ) , a n d c o - t r i m o x -a z o l e , t h e 2 0 : 1 c o m b i n a t i o n o f s u l f a m e t h o x a z o l e a n dt r i m e t h o p r i m .S t a t i s t i c a l a n a l y s i s . We c a l c u l a t e d t h e g e o m e t r i cmean MIC a n d MBC f o r e v e r y a n t i m i c r o b i a l a g e n t .F o r c o m p a r i s o n o f t h e d i f f e r e n c e b e t w e e n MIC a n dMBC, we u s e d a o n e - s i d e d t - t e s t f o r r e l a t e d s a m p l e s .The p a i r e d c o m p a r i s o n o f MIC o r MBC v a l u e s w a sd o n e b y a t w o - s i d e d t - t e s t f o r r e l a t e d s a m p l e s .

RESULT SM I C s . Th e r a n g e o f M I C s , t h e g e o m e t r i cmean M I C , a n d t h e c o n c e n t r at i o n s o f t h e v a r i o u sd r u g s n e e d e d f o r i n h i b i t i o n o f 5 0 a n d 9 0 % o f t h es t r a i n s ( M I C 5 0 a n d M I C 9 o , r e s p e c t i v e l y ) a r el i s t e d i n T a b l e 1 .I n g e n e r a l , t h e p e n i c i l l i n s s h o w e d l o w a c t i v i t yt o w a r d s c a m p y l o b a c t e r s t r a i n s . A l t h o u g h a m p i -c i l l i n a n d a m o x y c i l l i n h a d a r a t h e r l o w g e o m e t r i cmean M I C , t h e M I C 9 o s o f t h es e p e n i c i l l i n s w e r e1 2 . 5 , t g o r more p e r m l . I n t h e g r o u p o f c e p h a -l o s p o r i n s , o n l y c e f o t a x i m e s h o w e d a c t i v i t ya g a i n s t t h e s t r a i n s t e s t e d . The M I C 9 o o f 6 . 2 5 , u g /m l i s a c h i e v a b l e i n s e r u m . E r y t h r o m y c i n , c i n -d a m y c i n , t h e a m i n o g l y c o s i d e s , t h e t e t r a c y c l i n e s ,

D r u gP e n i c i l l i n GA m p i c i l l i nA m o x y c i l l i nC a r b e n i c i l l i nC e f a z o l i nC e f o t a x i m eM o x a l a c t a mE r y t h r o m y c i nT h i a m p h e n i c o lC h l o r a m p h e n i c o lC l i n d a m y c i nG e n t a m i c i nT o b r a m y c i nA m i k a c i nT e t r a c y c l i n eD o x y c y c l i n eM i n o c y c l i n eC o l i s t i nN a l i d i x i c a c i dF u r a z o l i d o n eM e t r o n i d a z o l eS u l f a m e t h o x a z o l eT r i m n e t h o p r i mC o - t r i m o x a z o l e

a n d f u r a z o l i d o n e w e r e t h e m o s t a c t i v e c o m -p o u n d s o f t h e 2 4 a n t i m i c r o b i a l a g e n t s .O n l y t w o s t r a i n s s h o w e d a h i g h r e s i s t a n c e t oe r y t h r o m y c i n . C l i n d a m y c i n , w i t h a g e o m e t r i cmean MIC o f 0 . 1 3 , u g / m l a n d a n M I C 9 o o f 0 . 3 9A g / m l , i s o n e o f t h e m o s t a c t i v e c o m p o u n d s .G e n t a m i c i n i s t h e m o s t p o t e n t a m i n o g l y c o s i d i ca n t i b i o t i c . A l l s t r a i n s w e r e f u l l y s u s c e p t i b l e t og e n t a m i c i n , a n d i t d i f f e r e d s i g n i f i c a n t l y f r o mt o b r a m y c i n a n d a m i k a c i n ( P < 0 . 0 0 1 ) . O n e s t r a i nw a s c o m p l e t e l y r e s i s t a n t t o t o b r a m y c i n ( M I C= 2 5 , u g / m l ) .The t e t r a c y c l i n e s h a d r a t h e r g o o d a c t i v i t y ,b u t 8 . 1 % o f t h e s t r a i n s w e r e c o m p l e t e l y r e s i s t a n t( M I C > 6 . 2 5 , g / m l ) . M i n o c y c l i n e w a s t h e m o s ta c t i v e t e t r a c y c l i n e c o m p o u n d . The g e o m e t r i cmean MIC v a l u e f o r f u r a z o l i d o n e w a s 0 . 0 9 j u g /m l .A l t h o u g h a l l t h e s t r a i n s h a d t h e b i o c h e m i c a lc h a r a c t e r i s t i c s o f C . j e j u n i , t h e MIC f o r 2 8s t r a i n s ( 3 2 . 6 % ) w a s > 6 . 2 5 , t g o f n a l i d i x i c a c i d p e rm l . M e t r o n i d a z o l e h a d n o g o o d a c t i v i t y .C h l o r a m p h e n i c o l a n d t h i a m p h e n i c o l h a dM I C g o s o f 3 . 1 2 a n d 6 . 2 5 , u g / m l , r e s p e c t i v e l y ( 0 . 7< P < 0 . 8 ) . We f o u n d t h e a c t i v i t y o f c o l i s t i nc o n t r o v e r s i a l b e c a u s e t h e s t r a i n s w e r e i n i t i a l l yi s o l a t e d o n a s e l e c t i v e medium c o n t a i n i n g c o l i s -t i n .A l l t h e s t r a i n s w e r e r e s i s t a n t t o t r i m e t h o p r i m .S u l f a m e t h o x a z o l e a n d c o - t r i m o x a z o l e w e r e o n l ym o d e r a t e l y a c t i v e : 3 8 a n d 5 8 % o f t h e s t r a i n s

TABLE 1 . S u s c e p t i b i l i t y o f C . f e t u s s u b s p . j e j u n i t o a n t i m i c r o b i a l a g e n t sMI C ( J u g / m l o f m e d i u m )

R a n g e< 0 . 0 4 8 - 5 0S 0 . 0 4 8 - 5 0' < 0 . 0 4 8 - > 5 0< 0 . 0 4 8 - > 5 00 . 0 9 7 - > 5 0, < 0 . 0 4 8 - 5 00 . 1 9 5 - > 5 0: 0 . 0 4 8 - > 5 0< 0 . 0 4 8 - > 5 0< 0 . 0 4 8 - 1 2 . 5, 0 . 0 4 8 - 1 2 . 5- 0 . 0 4 8 - 0 . 7 8< 0 . 0 4 8 - 2 5, < 0 . 0 4 8 - 3 . 1 20 . 0 9 7 - > 5 0- 0 . 0 4 8 - > 5 0- 0 . 0 4 8 - > 5 0S 0 . 0 4 8 - 5 00 . 1 9 5 - > 5 0< 0 . 0 4 8 - 0 . 7 80 . 0 9 7 - > 5 02 0 . 9 7 - > 1 , 0 0 01 2 . 5 - > 2 0 0- < 0 . 9 7 - > 1 , 0 0 0

M I C 56 . 2 53 . 1 23 . 1 26 . 2 52 53 . 1 21 2 . 50 . 1 9 51 . 5 61 . 5 60 . 0 9 70 . 0 9 70 . 3 90 . 3 90 . 1 9 50 . 0 9 7< 0 . 0 4 80 . 7 86 . 2 50 . 0 9 71 2 . 51 5 . 62 0 03 1 . 2

M I C 91 2 . 51 2 . 51 2 . 52 55 06 . 2 55 00 . 7 86 . 2 53 . 1 20 . 3 90 . 1 9 51 . 5 60 . 7 81 . 5 61 . 5 60 . 3 93 . 1 25 00 . 1 9 5

5 01 2 5>2001 2 5

G e o m e t r i c mean4 . 6 02 . 1 52 . 5 36 . 3 5

1 2 . 9 02 . 0 01 0 . 5 50 . 2 41 . 2 11 . 2 60 . 1 30 . 1 40 . 4 80 . 3 90 . 3 60 . 2 20 . 1 20 . 9 66 . 6 10 . 0 97 . 5 81 8 . 9 41 9 8 . 3 63 1 . 4 7

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TABLE 2 . S u s c e p t i b i l i t y o f C . f e t u s s u b s p . j e j u n i t o a nt i m i c r o b i a l a g e nt sMBC ( p g / m l o f m e d i u m )D r u g R a n g e M B C 5 o M B C 9 o G e o m e t r i c m e a n

P e n i c i l l i n G 0 . 0 9 7 - > 5 0 1 2 . 5 5 0 8 . 5 6A m p i c i l i n 0 . 0 9 7 - > 5 0 3 . 1 2 2 5 3 . 7 9A m o x y c i l i n 0 . 0 9 7 - > 5 0 3 . 1 2 2 5 3 . 5 8C a r b e n i c i l i n r 0 . 0 4 8 - > 5 0 1 2 . 5 5 0 1 0 . 8 1C e f a z o l i n 0 . 0 9 7 - > 5 0 5 0 5 0 2 7 . 4 4C e f o t a x i m e 0 . 0 9 7 - > 5 0 3 . 1 2 2 5 3 . 7 9M o x a l a c t a m 0 . 7 8 - > 5 0 2 5 > 5 0 1 8 . 4 0E r y t h r o m y c i n 4 0 . 0 4 8 - > 5 0 0 . 3 9 1 . 5 6 0 . 4 8T h i a m p h e n i c o l 4 0 . 0 4 8 - > 5 0 1 . 5 6 2 5 2 . 4 1C h l o r a m p h e n i c o l e % 0 . 0 4 8 - > 5 0 1 . 5 6 2 5 2 . 6 1C l i n d a m y c i n 4 0 . 0 4 8 - > 5 0 0 . 1 9 5 1 2 . 5 0 . 3 2G e n t a m i c i n 4 0 . 0 4 8 - > 5 0 0 . 1 9 5 3 . 1 2 0 . 2 9T o b r a m y c i n 4 0 . 0 4 8 - > 5 0 0 . 7 8 6 . 2 5 0 . 9 2A m i k a c i n 4 0 . 0 4 8 - > 5 0 0 . 7 8 3 . 1 2 0 . 8 7T e t r a c y c H n e 0 . 0 9 7 - > 5 0 0 . 3 9 6 . 2 5 0 . 6 1D o x y c y c l i n e 4 0 . 0 4 8 - > 5 0 0 . 1 9 5 6 . 2 5 0 . 4 9M i n o c y c i n e 4 0 . 0 4 8 - > 5 0 0 . 1 9 5 1 . 5 6 0 . 2 8C o l i s t i n 0 . 0 9 7 - > 5 0 1 . 5 6 1 2 . 5 2 . 1 2N a l i d i a i c a c i d 0 . 3 9 - > 5 0 6 . 2 5 > 5 0 9 . 4 2F u r a z o l i d o n e s . 0 . 0 4 8 - 1 2 . 5 0 . 0 9 7 1 . 5 6 0 . 1 6M e t r o n i d a z o l e 0 . 3 9 - > 5 0 2 5 5 0 1 3 . 2 2S u l f a m e t h o x a z o l e 1 . 9 5 - > 1 , 0 0 0 6 2 . 5 > 1 , 0 0 0 7 3 . 9 7T r i m e t h o p r i m 2 5 - > 2 0 0 > 2 0 0 > 2 0 0 2 6 9 . 4 7C o - t r i m o x a z o l e 1 . 9 5 - > 1 , 0 0 0 1 2 5 > 1 , 0 0 0 1 1 0 . 7 4s h o w e d r e s i s t a n c e t o t h e t w o c o m p o u n d s , r e -s p e c t i v e l y .MBCs. T h e r a n g e o f M B C s , t h e g e o m e t r i cmean MBC, a n d t h e c o n c e n t r a t i o n s o f t h e v a r -i o u s d r u g s n e e d e d t o k i l l 5 0 a n d 9 0 % ( M B C 5 0 a n dM B C e o ) o f s t r a i n s a r e l i s t e d i n T a b l e 2 . I n g e n -e r a l , t h e MBCs d i f f e r e d s i g n i f i c a n t l y f r o m t h eMICs ( P < 0 . 0 0 1 ) ; t h i s means t h a t t h e a n t i b i o t i c se x h i b i t e d a b a c t e r i o s t a t i c a c t i v i t y t o w a r d s t h ec a m p y l o b a c t e r s . T h e amount o f d r u g n e c e s s a r yt o i n c r e a s e t h e i n h i b i t o r y c o n c e n t r a t i o n t o ab a c t e r i c i d a l o n e v a r i e d f r o m 3 6 % ( t r i m e t h o p r i m )t o 2 5 2 % ( c o - t r i m o x a z o l e ) .I n t h e g r o u p o f t h e b e t a - l a c t a m s , a m p i c i l l i n ,a m o x y c i l l i n , a n d c e f o t a x i m e s e e m e d t o h a v e a l -m o s t t h e s a m e k i l l i n g p r o p e r t i e s . T h e g e o m e t r i cmean MBCs o f t h e s e t h r e e c o m p o u n d s w e r e ,r e s p e c t i v e l y , 3 . 7 9 , 3 . 5 8 , a n d 3 . 7 9 A g / m l . T h et h r e e a n t i b i o t i c s d i d n o t d i f f e r s i g n i f i c a n t l y ( P> 0 . 3 ) . M o r e t h a n 5 0 % o f t h e s t r a i n s w e r e k i l l e db y c o n c e n t r a t i o n s o f t h e s e a n t i b i o t i c s e a s i l ya c h i e v a b l e i n t h e b l o o d . F o r e r y t h r o m y c i n , g e n -t a m i c i n , a m i k a c i n , m i n o c y c H i n e , a n d f u r a z o l i -d o n e , t h e M B C g o s m i g h t h a v e a c l i n i c a l i m p o r -t a n c e . W i t h t h e e x c e p t i o n o f f u r a z o l i d o n e , t h eM B C g o s a r e a t t a i n a b l e i n t h e b l o o d .

DISCUSSIONThe r e s u l t s o f o u r i n v i t r o s t u d y o n t h e b a c -t e r i o s t a t i c a n d b a c t e r i c i d a l a c t i v i t i e s o f 2 4 a n t i -m i c r o b i a l a g e n t s on 8 6 s t r a i n s o f C . j e j u n i w e r e

i n g e n e r a l a g r e e m e n t w i t h t h o s e o b t a i n e d b y

o t h e r i n v e s t i g a t o r s ( 1 , 3 , 1 6 , 1 7 ) . I t i s a c c e p t e dt h a t b e t a - l a c t a m a n t i b i o t i c s a r e n o t v e r y a c t i v eo n c a m p y l o b a c t e r s . I n t h i s s t u d y , we h a v e f o u n da r a t h e r g o o d a c t i v i t y o f c e f o t a x i m e , a new s e m i -s y n t h e t i c p a r e n t e r a l c e p h a l o s p o r i n . T h i s h a sa l s o b e e n r e p o r t e d p r e v i o u s l y ( 1 5 ) . A t o t a l o f9 0 % o f t h e s t r a i n s w e r e i n h i b i t e d b y 6 . 2 5 , L g / m l ,a n d t h i s c o n c e n t r a t i o n k i l l e d 8 0 % o f t h e s t r a i n s .A c o n c e n t r a t i o n o f 6 . 2 5 , u g / m l i s e a s i l y a c h i e v a -b l e i n t h e b l o o d w i t h a n o r m a l d o s e ( 1 0 ) . C l i n i c a lr e s u l t s o b t a i n e d w i t h a m p i c i l l i n a r e v e r y v a r i -a b l e , a n d t h i s i s r e f l e c t e d b y o u r i n v i t r o r e s u l t s .G o o d c l i n i c a l r e s u l t s h a v e b e e n o b t a i n e d w i t he r y t h r o m y c i n . N e v e r t h e l e s s , e r y t h r o m y c i n - r e -s i s t a n t s t r a i n s h a v e b e e n r e p o r t e d . V a n h o o f e ta l . ( 1 6 ) j u d g e d 8 . 4 % o f t h e i r s t r a i n s t o b e r e s i s t -a n t , a n d W a l d e r a n d F o r s g r e n ( 1 7 , 1 8 ) r e p o r t e dt h e s a m e p r o p o r t i o n . H o w e v e r , T e l f e r - B r u n t o ne t a l . ( 1 4 ) i n B r i t a i n r e p o r t e d a f i g u r e o f 0 . 5 % . I no u r s t u d y e r y t h r o m y c i n e x h i b i t e d g o o d b a c t e r i -o s t a t i c a n d b a c t e r i c i d a l a c t i v i t i e s , a n d o n l y t w os t r a i n s ( 2 . 3 % ) w e r e j u d g e d a s r e s i s t a n t . The r e a -s o n s f o r t h e d i f f e r e n c e i n f r e q u e n c y o f e r y t h r o -m y c i n r e s i s t a n c e a r e n o t k n o w n .The s a m e p r o b l e m o f r e s i s t a n c e i s e n c o u n -t e r e d i n t h e g r o u p o f t h e t e t r a c y c l i n e s . T h e s ec o m p o u n d s h a v e g o o d i n v i t r o b a c t e r i o s t a t i c a c -t i v i t i e s , b u t s e v e n s t r a i n s ( 8 . 1 % ) s h o w e d a h i g h -l e v e l r e s i s t a n c e t o t h e t h r e e c o m p o u n d s t e s t e d .I n a p r e v i o u s s t u d y , we f o u n d a p r o p o r t i o n o f 5%( 1 6 ) . C l i n d a m y c i n a n d t h e a m i n o g l y c o s i d i c a n t i -b i o t i c s w e r e t h e m o s t a c t i v e p a r e n t e r a l a n t i b i -

1 2 0 VANHOOF E T A L . A N T I M I C R O B . AGENTS C H E M O T H E R .

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MIC AND MBC ACTIVITIES A G A I N S T C . JEJUNI 1 2 1o t i c s . F u r t h e r m o r e , g e n t a m i c i n was t h e mosta c t i v e a m i n o g l y c o s i d e . F u r a z o l i d o n e e x h i b i t svery g o o d b a c t e r i o s t a t i c a n d b a c t e r i c i d a l a c t i v i -t i e s , b u t t h e c l i n i c a l us e o f t h i s c o m p o u n d i sl i m i t e d s i n c e i t e x e r t s o n l y a c o n t a c t e f f e c t i n t h eg u t .

ACKNOWLEDGMENTWe ar e very i n d e b t e d t o L . K a u f m a n , D e p a r t m e n t o f S t a -t i s t i c s a n d O p e r a t i o n s R e s e a r c h , F r e e U n i v e r s i t y , B r u s s e l s , f o rh i s s t a t i s t i c a l a d v i c e a n d f o r c a r r y i n g o u t t h e s t a t i s t i c a l a n a l -y s i s .

LITERATURE CITED1 . B u t z l e r , J . P . , P . De K e y z e r , and T . L a f o n t a i n e . 1 9 7 4 .S u s c e p t i b i l i t y o f r e l a t e d v i b r i o s a n d V i b r i o f e t u s t ot w e l v e a n t i b i o t i c s . A n t i m i c r o b . A g e n t s C h e m o t h e r . 5 :8 6 - 8 9 .2 . B u t z l e r , J . P . , and M. B . S k i r r o w . 1 9 7 9 . C a m p y l o b a c t e re n t e r i t i s . A c t a P a e d i a t r . B e l g . 3 2 : 8 9 - 9 4 .3 . Chow, A . W . , V . P a t t e n , and D . B e d n o r z . 1 9 7 8 . S u s -c e p t i b i l i t y o f C a m p y l o b a c t e r f e t u s t o t w e n t y - t w o a n t i -

m i c r o b i a l a g e n t s . A n t i m i c r o b . A g e n t s C h e m o t h e r . 1 3 :4 1 6 - 4 1 8 .4 . D a v i e s , J . S . , and J . B . P e n f o l d . 1 9 7 9 . C a m p y l o b a c t e ru r i n a r y i n f e c t i o n . L a n c e t i : 1 0 9 1 - 1 0 9 2 .5 . De K e y s e r , P . , M. G o s s u i n - D e t r a i n , J . P . B u t z l e r , andJ . S t e r n o n . 1 9 7 2 . A c u t e e n t e r i t i s d u e t o r e l a t e d v i b r i o :f i r s t p o s i t i v e s t o o l c u l t u r e s . J . I n f e c t . D i s . 1 2 5 : 3 9 0 - 3 9 2 .6 . De M o l , P . , and E . Bosmans. 1 9 7 8 . C a m p y l o b a c t e r en-t e r i t i s i n C e n t r a l A f r i c a . L a n c e t i : 6 0 4 .

7 . K a r m a l i , M . A . , and P . C . F l e m i n g . 1 9 7 9 . C a m p y l o b a c -t e r e n t e r i t i s i n c h i l d r e n . J . P e d i a t r . 9 4 : 5 2 7 - 5 3 4 .8 . K i n g , E . 0 . 1 9 5 7 . Human i n f e c t i o n s w i t h V i b r i o f e t u s a n da c l o s e l y r e l a t e d v i b r i o . J . I n f e c t . D i s . 1 0 1 : 1 1 9 - 1 2 8 .9 . L a u w e r s , S . , M . De B o e c k , and J . P . B u t z l e r . 1 9 7 8 .C a m p y l o b a c t e r e n t e r i t i s i n B r u s s e l s . L a n c e t i : 6 0 4 - 6 0 5 .1 0 . L u t h y , R . , R . Munch, J . B la se r , H . B e n d , and W.S i e g e n t h a l e r . 1 9 7 9 . Human p h a r m a c o l o g y o f c e f o t a x -i m e (HR 7 5 6 ) , a new c a p h a l o s p o r i n . A n t i m i c r o b . A g e n t sC h e m o t h e r . 1 6 : 1 2 7 - 1 3 3 .1 1 . M e r t e n s , A . , and M. De S m e t . 1 9 7 9 . C a m p y l o b a c t e rc h o l e c y s t i t i s . L a n c e t i : l 0 9 2 - 1 0 9 3 .1 2 . S e v e r i n , W. P . J . 1 9 7 8 . C a m p y l o b a c t e r e n t e r i t i s . N e d .T i j d s c h r . G e n e e s k d . 1 2 2 : 4 9 9 - 5 0 4 .1 3 . S k i r r o w , M. B . 1 9 7 7 . C a m p y l o b a c t e r e n t e r i t i s - a " n e w "d i s e a s e . B r . M e d . J . 2 : 9 - 1 1 .1 4 . T e l f e r - B r u n t o n , W. A . , A . M . M . W i l s o n , a n d R . M .MacRae. 1 9 7 8 . E r y t h r o m y c i n - r e s i s t a n t C a m p y l o b a c -t e r s . L a n c e t i i : 1 3 8 5 .1 5 . V a n h o o f , R . , J . P . B u t z l e r , and E . Y o u r a s s o w s k y .1 9 7 8 . I n v i t r o a c t i v i t y o f a new c e p h a l o s p o r i n ( H R 7 5 6 )a n d c e f a z o l i n . L a n c e t i i : 2 0 9 - 2 1 0 .1 6 . V a n h o o f , R . , M. P . V a n d e r l i n d e n , R . D i e r i c k x , S .L a u w e r s , E . Y o u r a s s o w s k y , and J . P . B u t z l e r .1 9 7 8 . S u s c e p t i b i l i t y o f C a m p y l o b a c t e r f e t u s s u b s p . j e -j u n i t o t w e n t y - n i n e a n t i m i c r o b i a l a g e n t s . A n t i m i c r o b .A g e n t s C h e m o t h e r . 1 4 : 5 5 3 - 5 5 6 .1 7 . W a l d e r , M . 1 9 7 9 . S u s c e p t i b i l i t y o f C a m p y l o b a c t e r f e t u ss u b s p . j e j u n i t o t w e n t y a n t i m i c r o b i a l a g e n t s . A n t i m i -c r o b . A g e n t s C h e m o t h e r . 1 6 : 3 7 - 3 9 .1 8 . W a l d e r , M . , and A . F o r s g r e n . 1 9 7 8 . E r y t h r o m y c i n r e -s i s t a n t c a m p y l o b a c t e r s . L a n c e t i i : 1 2 0 1 .1 9 . W r i g h t , E . P . 1 9 7 9 . M e n i n g i s m a s s o c i a t e d w i t h C a m p y -l o b a c t e r j e j u n i e n t e r i t i s . L a n c e t i : 1 0 9 2 .

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