Depar t ment of I nf ect i on Cont r ol
Shoichi Onodera,Professor Masaki Yoshida,Assistant Professor
Res ear ch Act i v i t i es
Ep i de mi o l o g i c al r e s e ar c h o n s e xual l y t r ans mi t t e d di s e as e s
The Mi ni s t r y of He a l t h,La bour a nd We l f a r e ʼ s“ Spe c i f i c STD I nj e c t i on Pr e v e nt i on Pol i c y Pr omot i on St udy ”Gr oup ha s be e n ope r a t i ng , s i nc e 2 0 0 6 , wi t h Pr of e s s or Onode r a a s t he l e a d r e s e a r c he r . Thi s s t udy g r oup wa s f or me d t o r e s e a r c h,de v e l op,a nd pr omot e pol i c i e s f or pr e v e nt i ng t he e me r g e nc e a nd s pr e a d of s e x ua l l y t r a ns mi t t e d di s e a s e s( STDs ) , a c c or di ng t o t he“ STD Spe c i f i c I nf e c t i on Pr e v e nt i on Gui de l i ne s ”t ha t we r e r e v i s e d i n 2 0 0 6 . The s t udy g r oupʼ s a c t i v i t i e s ha v e i nc l ude d:1 )a n e pi de mi ol og i c a l s ur v e y of STD e me r g e nc e pa t t e r ns ;2 )e x pe r i me nt a l r e s e a r c h f or t he e a r l y di s c ov e r y a nd t r e a t me nt of STDs i n y oung a dul t s ;3 )t he de v e l opme nt of f a s t a nd a c c ur a t e t e s t me t hods f or g e ni t a l he r pe s a nd g e ni t a l wa r t s ;a nd 4 )dr ug - r e s i s t a nt g onoc oc c us s ur v e i l l a nc e a nd t he de v e l - opme nt of me t hods f or di a g nos i ng a nd t r e a t i ng g onoc oc c a l pha r y ng i t i s .
I n J a pa n,t he pa t t e r ns of e me r g e nc e of g e ni t a l c hl a my di a l i nf e c t i ons ,g onoc oc c a l i nf e c - t i ons ,g e ni t a l he r pe s i nf e c t i ons ,a nd g e ni t a l wa r t s( c ondy l oma a c umi na t a )a r e be i ng i nv e s t i g a t e d by me a ns of a f i x e d- poi nt s ur v e y . The s e l e c t i on of t he de s i g na t e d r e por t i ng i ns t i t ut i ons i n t hi s f i x e d- poi nt s ur v e y wa s l e f t up t o t he i ndi v i dua l l oc a l g ov e r nme nt s , a nd pr obl e ms wi t h t hi s s e l e c t i on me t hod ha v e a l r e a dy be e n not e d. The c ur r e nt s t udy g r oup i nv e s t i g a t e d a l l c a s e s of STDs i n a l i mi t e d g e og r a phi c a l a r e a t o a s s e s s t he v a l i di t y of t hi s f i x e d- poi nt s ur v e y . I n 2 0 0 6 ,t he 4 pr e f e c t ur e s of Chi ba ,I s hi ka wa ,Gi f u,a nd Hy og o we r e de s i g na t e d a s r e pr e s e nt a t i v e pr e f e c t ur e s ,a nd,i n 2 0 0 7 ,t he 3 pr e f e c t ur e s of I wa t e ,I ba r a ki ,a nd Tokus hi ma we r e a dde d;t he c oope r a t i on of t he s e 7 r e pr e s e nt a t i v e pr e f e c t ur e s wa s r e que s t e d i n c onduc t i ng a s ur v e y of a l l c a s e s of STDs i n e a c h of t he s e r e g i ons ,i n c oope r a t i on wi t h t he J a pa n Me di c a l As s oc i a t i on,t he pr e f e c t ur a l me di c a l a s s oc i a t i ons ,phy s i c i a nʼ s a s s oc i a t i ons ,a nd ot he r bodi e s i n e a c h of t he r e g i ons ,t o v e r i f y t he v a l i di t y of t he f i x e d- poi nt s ur v e y . Compa r i s on of t he f i x e d- poi nt s ur v e y wi t h t hi s s ur v e y of a l l c a s e s r e v e a l e d a c l e a r di s c r e pa nc y be t we e n t he 2 s ur v e y s i n t e r ms of t he numbe r of r e por t e d pa t i e nt s wi t h STDs ,pa r t i c ul a r l y a mong y oung a dul t s . I n l i g ht of t he s e r e s ul t s ,we i nt e nd t o pr opos e t ha t t he s t udy g r oup r e c ons i de r t he e x i s t i ng f i x e d- poi nt ［me t hod ］a nd e s t a bl i s h s pe c i f i c c r i t e r i a r e g a r di ng how t he f i x e d poi nt s a r e s e l e c t e d.
Ef f e c t o f s i l v e r - b as e d ant i mi c r o b i al ag e nt s f o r mul t i dr ug - r e s i s t ant Ps e udo mo nas ae r - ug i no s a
Nos oc omi a l i nf e c t i ons c a us e d by mul t i dr ug - r e s i s t a nt P.ae r ug i no s a ha v e be c ome a pr obl e m i n r e c e nt y e a r s . I n our da i l y l i v e s ,we c ome a c r os s ma ny di f f e r e nt ki nds of a nt i mi c r obi a l pr oduc t s ,i nc l udi ng s i l v e r - ba s e d a nt i mi c r obi a l s ,whi c h ha v e e x c e l l e nt s a f e t y ,dur a bi l i t y ,a nd pr a c t i c a l i t y . We ,t he r e f or e ,i nv e s t i g a t e d t he a nt i mi c r obi a l e f f e c t s of s i l v e r - ba s e d a nt i mi c r obi a l a g e nt s . P.ae r ug i no s a( 1 , 3 5 9 s t r a i ns )wa s de t e c t e d i n 4 7 2
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Research Activities 2007 The Jikei University School of Medicine
pa t i e nt s a t The J i ke i Uni v e r s i t y Hos pi t a l f r om Ma y 1 , 2 0 0 6 , t hr oug h Ma r c h 3 1 , 2 0 0 7 . P.
ae r ug i no s a e x hi bi t i ng r e s i s t a nc e t o 2 of t he 3 dr ug s i mi pe ne m,a mi ka c i n,a nd c i pr of l ox - a c i n a c c ount e d f or 1 3 7 of t he s e i s ol a t e s( 1 0 . 1 %)i n 3 6 of t he s e pa t i e nt s( 7 . 6 %) . We t he n i nv e s t i g a t e d 5 0 of t he s e i s ol a t e s( e x c l udi ng t hos e de t e c t e d i n t he s a me s a mpl e s or f r om t he s a me pa t i e nt s ) . Mul l e r - Hi nt on br ot h c ont a i ni ng s i l v e r i ons or na noc ol l oi da l s i l v e r a t v a r i ous c onc e nt r a t i ons( 0 . 5 t o 6 4 ppm ［mg / L ］)wa s pr e pa r e d a nd i noc ul a t e d wi t h 5 × 1 0 ba c t e r i a( 5 0 s t r a i ns )a nd,a f t e r 2 4 hour s ,wa s c he c ke d f or t he pr e s e nc e or a bs e nc e of g r owt h,a nd t he mi ni mum i nhi bi t or y c onc e nt r a t i ons( MI Cs )we r e me a s ur e d. Of t he P.ae r ug i no s a i s ol a t e s s t udi e d,1 3 7( 1 0 . 1 %)we r e obs e r v e d t o e x hi bi t r e s i s t a nc e t o 2 of t he 3 dr ug s i mi pe ne m,a mi ka c i n,a nd c i pr of l ox a c i n;t he s i l v e r i on MI Cs wi t h r e s pe c t t o 5 0 of t he s e s t r a i ns r a ng e d f r om 1 t o 8 ppm,a nd t he na noc ol l oi da l s i l v e r MI Cs f r om 1 t o 4 ppm. Si l v e r - c oa t e d f i l t e r s i nhi bi t e d ba c t e r i a l g r owt h a nd pos s e s s e d a n a nt i mi c r obi a l e f f e c t . The ba c t e r i a c ount s de c r e a s e d ov e r t i me i n Mul l e r - Hi nt on br ot h c ont a i ni ng 4 t o 2 0 ppm of na noc ol l oi da l s i l v e r . The y a r e e x pe c t e d t o be us e f ul f or c omba t i ng nos oc omi a l i nf e c t i ons c a us e d by mul t i dr ug - r e s i s t a nt P.ae r ug i no s a.
Cl i ni c al i nv e s t i g at i o n o f P.ae r ug i no s a s e p t i c e mi a
Cl i ni c a l a nd de mog r a phi c f a c t or s ,i nc l udi ng a g e ,s e x ,unde r l y i ng di s e a s e s ,a nd por t a l s of e nt r y , we r e i nv e s t i g a t e d i n 8 9 pa t i e nt s a t The J i ke i Uni v e r s i t y Hos pi t a l f r om whos e bl ood P.ae r ug i no s a wa s i s ol a t e d f r om Apr i l 2 0 0 3 t hr oug h De c e mbe r 2 0 0 7 ,t o i nv e s t i g a t e poor - pr og nos i s f a c t or s f or P.ae r ug i no s a s e pt i c e mi a . Le uke mi a ,pr e s e nt i n 2 8( 3 1 . 5 %) pa t i e nt s ,wa s t he mos t c ommon unde r l y i ng di s e a s e i n t he pa t i e nt s wi t h P.ae r ug i no s a s e pt i c e mi a ,a nd t he mos t c ommon por t a l of e nt r y wa s ur og e ni t a l ,i n 2 0( 2 2 . 5 %)of t he pa t i e nt s . Of t he 8 9 pa t i e nt s ,2 2 di e d wi t hi n 3 0 da y s of t he e me r g e nc e of P.ae r ug i no s a s e pt i c e mi a ,f or a mor t a l i t y r a t e of 2 4 . 7 %. Al t houg h no s i g ni f i c a nt di f f e r e nc e s we r e s e e n i n a g e , unde r l y i ng di s e a s e , por t a l of e nt r y , or ot he r f a c t or s be t we e n pa t i e nt s who di e d a nd pa t i e nt s who s ur v i v e d,pa t i e nt s who di e d ha d s i g ni f i c a nt l y l owe r pl a t e l e t c ount s a nd s e r um a l bumi n l e v e l s t ha n di d s ur v i v i ng pa t i e nt s a nd we r e mor e l i ke l y t o ha v e bl ood c ul t ur e s pos i t i v e f or ba c t e r i a ot he r t ha n P.ae r ug i no s a. We a l s o i nv e s t i g a t e d t he us e of a ppr opr i a t e a nt i mi c r obi a l a g e nt s i n t he e a r l y s t a g e s of P.ae r ug i no s a s e pt i c e mi a but obt a i ne d no e v i de nc e t ha t s uc h us e i mpr ov e d t he s ur v i v a l r a t e .
St udy o f p at i e nt s r e c e i v i ng l i ne z o l i d
We i nv e s t i g a t e d pa t i e nt c ha r a c t e r i s t i c s a nd t he c l i ni c a l e f f i c a c y of l i ne z ol i d a t The J i ke i Uni v e r s i t y Hos pi t a l . The pa t i e nt s r a ng e d i n a g e f r om 0 t o 8 0 y e a r s( me a n:6 6 y e a r s ) , a nd t he r e a s ons t he y r e c e i v e d l i ne z ol i d ( mul t i pl e a ns we r s pos s i bl e )we r e :pr e v i ous t r e a t me nt i ne f f e c t i v e( 1 0 pa t i e nt s ) ;r e na l i mpa i r me nt( 5 pa t i e nt s ) ;a nd c ha ng e of me di c a - t i on r e qui r e d due t o a dv e r s e r e a c t i on( s )wi t h pr e v i ous t r e a t me nt( 4 pa t i e nt s ) . The c l i ni c a l e f f i c a c y of l i ne z ol i d wa s :e f f e c t i v e( 1 3 pa t i e nt s ) ;i ne f f e c t i v e( 1 pa t i e nt ) ;a nd i nde t e r mi na t e( 1 pa t i e nt ) . Al t houg h mi l d a ne mi a( i n 4 pa t i e nt s ) , t hr omboc y t ope ni a( i n 3 pa t i e nt s ) ,a nd he pa t i c i mpa i r me nt( i n 1 pa t i e nt )de v e l ope d dur i ng t r e a t me nt wi t h l i ne z ol i d,t he y r e s ol v e d wi t h c ons e r v a t i v e t r e a t me nt . Li ne z ol i d i s e f f e c t i v e a g a i ns t dr ug - r e s i s t a nt g r a m- pos i t i v e ba c t e r i a l i nf e c t i ons ,e v e n whe n e x i s t i ng dr ug s a r e i ne f f e c t i v e or poor l y t ol e r a t e d,a nd a l s o ha s a n a c c e pt a bl e r a t e of a dv e r s e r e a c t i ons . Howe v e r ,
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be c a us e of c onc e r ns t ha t t he l i be r a l us e of l i ne z ol i d c oul d i nc r e a s e ba c t e r i a r e s i s t a nc e , e a c h pa t i e nt s houl d be e x a mi ne d c a r e f ul l y t o e ns ur e t ha t l i ne z ol i d i s us e d a ppr opr i a t e l y . Pr e v e nt i ng o ut b r e aks o f no r o v i r us g as t r o e nt e r i t i s at me di c al i ns t i t ut i o ns
We a dopt e d t he t r a ns c r i pt i on- r e v e r s e t r a ns c r i pt i on c onc e r t e d( TRC)me t hod,a ne w g e ne t i c a mpl i f i c a t i on / de t e c t i on me t hod f or nos oc omi a l nor ov i r us ,a nd a na l y z e d t he r e s ul t s . I nv e s t i g a t i on of nos oc omi a l out br e a ks s ug g e s t e d t ha t t he TRC me t hod i s f a s t a nd i s a s s e ns i t i v e a s t he r e v e r s e t r a ns c r i pt a s e - pol y me r a s e c ha i n r e a c t i on. I n a ddi t i on, pe di a t r i c pa t i e nt s we r e obs e r v e d i n whom t he v i r us wa s e x c r e t e d ov e r a l ong pe r i od of t i me . We c onc l ude d t ha t ,i n t he pe di a t r i c wa r d,c l os e a t t e nt i on s houl d be pa i d t o me a s ur e s f or c omba t i ng i nf e c t i on,e v e n i f s y mpt oms ha v e r e s ol v e d.
Ne x t ,we i nv e s t i g a t e d whe t he r or not nor ov i r us g e ne s we r e pr e s e nt i n t he f e c e s of me di c a l pr of e s s i ona l s c ompl a i ni ng of s y mpt oms of g a s t r oe nt e r i t i s who we r e e x a mi ne d a t The J i ke i Uni v e r s i t y Hos pi t a l . Of 1 2 3 me di c a l pr of e s s i ona l s e x a mi ne d,5 4( 4 3 . 9 %)ha d pos i t i v e r e s ul t s on t he TRC NORO2 t e s t a nd we r e ,t he r e f or e ,g i v e n a di a g nos i s of nor ov i r us g a s t r oe nt e r i t i s . Of t he 3 2 4 pa t i e nt s who we r e a dmi t t e d dur i ng t hi s s a me pe r i od,9 0( 2 7 . 8 %)ha d pos i t i v e r e s ul t s ,me a ni ng t ha t t he r a t e of pos i t i v e r e s ul t s on t he nor ov i r us t e s t wa s s i g ni f i c a nt l y hi g he r a mong me di c a l pr of e s s i ona l s . Our r e s ul t s de mons t r a t e t he i mpor t a nc e of moni t or i ng t he he a l t h of me di c a l pr of e s s i ona l s .
Publications
Osaka K,Takakura T,Narukawa K,Takahata M, Endo K,Kiyota H,Onodera S.Analysis of amino acid sequences of penicillin-binding protein 2 in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime and ceftriax- one.J Infect Chemother 2008;14:195‑203.
Kato T,Sato F,Horino T,Nakaz awa Y,Sakamoto M,Yoshida M,Onodera S,Kiyota H.Clinical features of 15 cases treated with linezolid.Jpn J Chemother 2008;56:202‑5.
Kato T,Ieki R,Saito E,Ota T,Yuasa K,Iguchi M, Okamura T,Shibuya M,Ajisawa A.Clinical features of lung cancer HIV-infected patients.
Nihon Kokyuki Gakkai Zasshi 2007;45:661‑6.
Books
Onodera S.Studies on monitoring of HIV infec- tion and behavior among STD pat ients (in Japanese). Socio‑Epidemiology studies on monitoring and prevention of HIV/AIDS. Kyoto:
The Ministry of Health,Labour and Welfare;
2007.p.153‑62.
Yoshida M.Anisakiasis(in Japanese). Todayʼs therapy. Tokyo:Igakushoin;2007.p.187‑8.
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