Increase in the rate of azithromycin-resistant Streptococcus pneumoniae isolates carrying the erm(b) and mef(a) genes in Taiwan,

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1 BMC u D hp//wwwbmdnm/ /14/74 REEARCH ARICE O A n h hmn-n pu umn ng h m(b nd m(a gn n wn Dd 1 u-ng Ku 2 Yu-ung Hung 3 un-hng 3 Wng-Hu hng 2 nd P-Rn Huh 24* Ab Bgund h ud ngd h mu h hmn-n pu umn n wn Mhd A 486 nn-dup hmn-n umn d m u n u d 22 dn hp n wn m h m(b nd m(a gn ung dupx PCR muu qun g (M nd pud-d g ph h w udd Ru O h d 59% d h m(b gn 22% d h m(a gn nd 19% d bh gn h ng h m(b nd m(a gn nd m 1% (11/11 n 26 25% (15/6 n 21 (p-u = 136 h mj ng bh m(b nd m(a gn bngd p 19 F (64% wd b 19 F A (24% O h 33% w qun p 32 (32 32% w 236 nd 12% w 271 Cnun h n n ndn m(a/m(b-p hmn-n umn dung h ud pd w pm du p 19 F nd 19A nd 236 nd 32 Kwd pu umn Ahmn-n gn V un n wn (I ud Bgund pu umn dng u b umn mnng nd p wdwd n 1965 mn nn du dug-n umn h bn pd [1] h mgn nmb n d wh pu m h u n nppp nmb gn nd u n nd m mbd nd hh [2] Anb n n umn nng ng p β-m nd md (hmn hmn hmn wh ngng bwn 1% nd 9% ddng n h ggph [3] Fuqunn n h bn pd n * Cdn h@nuduw 2 Dpmn n Mdn Nn wn Un Hp Nn wn Un Cg Mdn p wn 4 Dpmn b Mdn Nn wn Un Hp Nn wn Un Cg Mdn p wn Fu uh nmn b h nd h un wh hgh nb n nd num [3] Md n n umn m n mdd b w mhnm g- mdn ndd b h m(b gn nd dug ux mdd b mmbn ux pump ndd b m- gn [4] ng pd h m(b gn w und n >5% um h n n mbnn wh m(a mng umn m 1 An un dung [5] Fnnd nd Gmn h m qun md n dmnn d w h m gn [67] Md n mng um n A d m w pd b pdmnn mdd b m gn nd h h n hngd gnn m [8] Hw h uh h ud pd gnn n n h p h p bh m(b nd m(a pm mng p 19A 214 ; n BMd Cn h n O A dbud und h m h C Cmmn Abun n (hp//mmng/n/b/4 whh pm und u dbun nd pdun n n mdum pdd h gn w pp dd h C Cmmn Pub Dmn Ddn w (hp//mmng/pubdmn//1/ pp h d md b n h un hw d

2 BMC u D Pg 2 6 hp//wwwbmdnm/ /14/74 Bw pd h 592 n um d n An m ng h hmn-n gn m(e nd m(b w mudug-n n ng wn 19 F-14 nd m w muu qun p ( 32 [9] n n ud h hwn h hmn-n mmn bh gn nd h h mj bng wh n mpx 271 (CC271 bng h m qun d CC [1-12] 25 w pdmnn md-n umn CC nm CC271 nd CC15 w dnd n Nw uh W Au [13] Rn pd h p 19A um nd gnn n wn m nd h m hn 9% h w nn-upb hmn [14] h un ud w ngd h mu h hmn-n umn d m u n u wh w d 22 dn hp n wn m Mhd B A 53 nu nd nn-dup um w d m u n pmn d 22 dn hp n wn dung 3-mnh pd p wh mxmum numb p 1 dung nd 5 dung [14] Amng h 486 w n upb hmn [14] h um w d p h gn V un n wn (I ud nnwd mun pp un ud ndud n 12 gn hp (5 1 bd nd 1 md n (12 3 bd (gh n nhn u n n x n uhn nd w n n wn m nu 26 Dmb 21 [15] Pnum w dnd h hp nd h dnn w nmd b h n b h Nn wn Un Hp [15] p dmnn b x ggunn mhd nd nmb upb ng b h bh mdun mhd w pmd dbd pu [14] I w d p ndd nd n h pp qud u u Dn m(b nd m(a gn h dn m(b nd m(a w pmd b dupx PCR pu dbd [516] Pud-d g ph (PFGE n PFGE n w pmd dbd pu [1718] h D n m w ud nd h unwghd p gup mhd wh hm g (UPGMA w ud u n I wh n m 8% w ndd b h m u [18] Muu qun g (M M w pmd dbd pu [19] A p nd qun p w dmnd ung h M db (hp//umnmn/ n n w ndud ung GphPd Pm V5 (GphPd w n Dg CA UA Ru Pn ng h m(b nd m(a gn Amng h % d h m(b gn 22% d h m(a gn nd 19% d bh gn (b 1 h ng h m(b gn dd n d gnn m (p-u = 2436 (b 1; h ng h m(a gn dnd gnn m 3% n 26 5% n 21 (p-u = 1; nd h ng bh gn nd gnn m 1% n 26 25% n 21 (p-u = 136 (b 1 h w n bu ggph dn wh p h dbun ng m(b m(a bh gn (d n hwn b 1 Pn m(b nd m(a gn mng hmn-n pu umn m 22 hp n wn m Rn gn N (% b ud pd (n = (n = 11 (n = 11 (n = 153 (n = 53 (n = 6 m(b-p 66 (6 65 (59 92 (6 24 (45 42 (7 289 (59 m(a-p 33 (3 26 (24 33 (22 11 (21 3 (5 16 (22 m(a/m(b-p 11 (1 19 (17 28 (18 18 (34 15 (25 91 (19 P-u* *P-u mp hng m(a/m(b-p b ud pd

3 BMC u D Pg 3 6 hp//wwwbmdnm/ /14/74 p nd qun p ng bh m(b nd m(a gn A p 3 nd 15B d n m(b (b 2 h mj h h mn p d n h m(b gn nm p 23 F (73% 14 (87% 23A (86% nd 6B (54% (b 2 Amng p 19 F 13% d h m(b gn 36% d h m(a gn nd 52% d bh gn h mj p 19A d bh m(b nd m(a gn (61% (b 2 O 91 h d bh gn 58 (64% w bng p 19 F wd b 19A (22/91; 24% h dbun hbng m(b nd m(a gn b qun p w 33% 32 32% % 271 8% 81 2% 283 nd 8525 nd 11% h qun p (b 3 h mj 236 (28/29 nd 271 (1/11 n bngd p 19 F I n 32 mn bngd p 19 F (16/3 nd p 19A (13/3 (b 3 n n 81 w dnd bngng p 23 F (n = 2 23A (n = 1 nd 6A (n = 4 Bd n h u M g h 236 nd 81 n w dnd n n PMEN gb n wn 19F -14 nd n n PMEN gb n 23F -1 p (b 3 32 nd 271 n w dnd dubu n (DV nd ng-u n (V h wdwd-bhd wn 19F -14 (236 n p Cu ng bh m(b nd m(a gn W nud phgn bd n PFGE p nd und n p ung h n b 2 Cn bwn h mn p hmn-n pu umn nd md-n gn p* N N (% b n gn m(b- p m(a- p m(a/m(b- p 19F (13 4 (36 58 (52 23 F 9 66 (73 21 (23 3 ( (87 8 (11 1 (1 6B (53 29 (44 2 (3 19A 36 1 (28 4 (11 22 ( (1 ( ( 15B (1 ( ( 23A (88 1 (6 1 (6 N (89 3 (11 ( Oh** (86 ( 4 (14 N nnpb *D p w ud n h ud pd b HY [14] **ud 9 V (n = 9 6A (n = 9 1A (n = 2 2 (n = 1 11A (n = 1 15A (n = 5 22 F (n = 2 b 3 qun p nd p hmnn pu umn wh PCR p m(b/m(a gn N (% p (n Rd PMEN n [2] ** (32 19 F (28 19A (1 wn 19F -14/ (33 19F (16 19A (13 14 (1 DV wn 19F -14/ (12 19 F (1 19A (1 V wn 19F -14/ (8 23 F (2 23A (1 23F -1/81 6A ( (2 19 F ( (2 19 F (2 - Oh * 1 (11 19 F (4 19A (3 23 F (1 6B (2 qun p; PMEN Pnum mu pdmg nw * Oh (n 3111 ( ( ( (1 237 (1 257 ( ( (1 76 (1 nw (1; DV dub u n; V ng-u n; ** PMEN wb Ab hp//wb1phmdu/pmen/pmn_b2hm p 19 F nd 19A h h mj qun p ( nd 236 (Fgu 1 h ud h ng bh m(b nd m(a w d n gh u (Cu I VIII b PFGE (Fgu 1 nd b 4 Cu III IV V nd VII dd h wh p 19 F (b 4 I bngng h m u n h dn p nd Fuhm wh h m xhbd dn p nd pup h mj p 19A w n u VI (13/24 54% 32 n bngd u VI (13/24 54% u II (9/16 56% nd u I (2/4 5% Mnwh n 236 w qun ud n u V (9/9 1% nd III (6/7 86% (b 4 h mj 81 n w ud n u VIII (4/5 8% Dun Ahmn h m mmn ud md n h mn mmun-qud umn nd h p nn n wn h upb hmn mnd n m n wn hugh h numb ndm d n 29 nd 21 w w hn n [14] wn PCV-7 nn w ndud n Ob 25 nd PCV-13 w ndud n u 21 Nh m ud h hwn h hng n nmb upb b nd mpmnn h PCV-7 n w n d wh p [14] Ou ndng n n h hmn-n umn ng h m(b nd m(a gn m m 1% n 26 25% n 21 h ndun h -

4 BMC u D Pg 4 6 hp//wwwbmdnm/ /14/74 Fgu 1 A phgn n bd n pud-d g ph p wh mi mng hmn-n pu umn ng bh m(b/m(a gn

5 BMC u D Pg 5 6 hp//wwwbmdnm/ /14/74 b 4 Pud-d g ph (PFGE u p nd qun p hmn-n pu umn wh PCR p m(b/m(a-p gn PFGE u* N (n = 87** p (n qun p (n I 4 19 F (3 19A (1 32 (2 236 (2 II F (12 19A (4 32 (9 236 (2 271 (5 III 7 19 F (7 236 (6 271 (1 IV 3 19 F (3 32 (1 236 (1 237 (1 V 9 19 F (9 236 (9 VI F (11 19A (13 32 ( (3 271 ( ( ( ( (1 283 (1 VII 4 19 F (4 32 (1 236 (1 271 (1 283 (1 VIII 5 19 F (1 6A (2 23 F (1 23A (1 236 (1 81 (4 Un-ud F (7 19A (3 23 F (2 6B (1 6A (1 14 (1 32 (3 236 (4 271 (1 81 (2 76 (1 275 ( ( ( (1 * PFGE-bd u w dnd gup 3 m wh 8% m n h dndgm **PFGE d w n b u (H H H H um njug n n wn h ndng n n wh pu pubhd p n h PROEK U un ud m 1% n % n 23 [21] h ud n A m % n % n 21 [8] nd h ud n Cnd m 3% n % n 28 [22] h ud h mj hmn-n ng bh m(a nd m(b gn w p 19 F (58/91; 64% wd b19a (22/91; 24% nd m pu pubhd p n K 57% d bh gn w p 19 F (44/77 57% wd b 19A (21/77 3%75% [23] Hw h ud n A hwd 79% ng bh gn w p 19A (15/19 wd b 19 F (3/19; 16% [8] W ngd uh M nd PFGE d bh h m(b nd m(a nd dnd 33% h b 32 wd b 236 (32% 271 (12% nd h (23% Pu w pd n wn h h CC d 23F -1 wn 19F -14 nd wn 23F -15 w b h pd wh hgh-b-m n [2425] Rn h umn p 19A 32 n dd m n nnn wn 19F -14 (236 n h bm n mn un nudng wn [25] An h ng bh m(e/m(b-p gn mudug-n n ng wn 19F -14 [9] h w dd PFGE nd M h bm h mn gng mhd ng h gn d [26] Ahugh bh mhd mnd b-numng h uu udng h nd gb pdmg umn h ud d g u b h w mhd ud n um pb undgng pu whng nd gnd n h m mbngn b ddn g mhd mup-u b numb ndm p n nd MI h bn dpd n bdmnnn umn [26] Cnun h n n ndn m(a- nd m(b-p hmn-n umn dung h ud pd w pm du p 19 F nd 19A nd 236 nd 32 Abbn M Muu qun g; I gn V un n wn; PCR Pm hn n; qun p; CC Cn mpx; PFGE Pud-d g ph; UPGMA Unwghd p gup mhd wh hm g; PMEN Pnum mu pdmg nw; DV Dub-u n; V ng-u n Cmg n h uh d h h h n mg n h h w uppd b whp gn m h nn mhp n nd Cn (IC Auh nbun D d h mnup; D YH nd PRH n h d; CH nd WH h d; PRH mp h mnup A uh d nd pp h n mnup b ubmn Anwdgmn h I ud m nudd Hh-Yh Yn-Hu n un-hng P-ng u ng-hu Hung n- u Yn-ng ung hh-mng Y-hn n Yung-ng u W-Yu n ng-nng ng Hu-n n h-mng n Zh-Yun h ung-ng Pn -ng Yng Hng- Kung un-eng u Yu-n ng n-w u Wu un h-hnn Wng Wn-n K Kw-Wn Yu Png-ng ng Mng-Hun un-mng Gw-ng Hu nd P-Rn Huh Auh d 1 Ejmn u Mu Bg dn 2 Dpmn n Mdn Nn wn Un Hp Nn wn Un Cg Mdn p wn 3 Dpmn n Mdn F En Mm Hp p wn 4 Dpmn b Mdn Nn wn Un Hp Nn wn Un Cg Mdn p wn

6 BMC u D h p / /www b md n m / /14 /74 P g6 6 R d 17un214A p d 11D mb KK ngh E u n h m n n p u ma nun h n n m (B nd m (A umn gn D H uhpr ng N Y ngpc HW uhk D m n n h gh n x ndd p umph p n nd p u umn n n wn h m n n C n M b C F u ng dam G AM DNA ng p n ng p u umn n bpu d dg ph C n M b En gh MC p BG A mu u qun p ng hm p u umn dn n n d w h u n d M b R deng (P M d A P I P ng A K ue dua A h n u d h p u umn P u p wn19f -14 nmngh d nn G C n M b F D n n G B wnd P M nb K ugm nkp Em gn p u umn w h m (B nd m (A ndp d n Em g D W bw AK K w A Ad mh N h KA Hb nd Zh n GG C n d nan m b R n A n (CARA E u nnd p u m u h n m d n umn ncndb wn1998nd28 An m b m h B K D bu n p u p nd m d n m hn m mng m d n p u umn nk D gn M b D A d nu C R D Fn A gd C ud Em gn mu d ug n n(32 mngn p19a um np n An m b m h x n 25 H hyc n ngky Hu ngyc nc ny W ng E nd u n p u umn p19a32 n D 213 mp d n n wn19f -14( E b K EM Nun R nd H d HG hu M Mu p u b numb ndmp n p u umn mp n w hpfgend M P On R n 1 H n m nd Bu n MM A n um u n C F u M F h ZY H uhpr CH ngn M KungHC H ug ngy nhc uyc u ngyc W ng ncm ng ng nd nn m b u p b p u n wn 2627 M b Immun umn V nb mb F R n RR App b umpc u n PM P m n W E Mu d ug n p u umn n n u n nd u u h pu p n D ug K ugm nkp n R H ddnp d m m d n um Em g D ngh nghh uhy KK ung I Oh W P KR NY Y ngy ng h nga A w p N uch h MK P Y Kum nghg m F K m u m na P h N V nph NgK AN OR P ud G up M d n ndgn p h n p u umn na nun ud ha nn w u n R n P hgn (ANORP An m b m h B C nd ndn M R n RR m (A hp dm nn m d n d m nn n p u umn nd p u p g n ng mn An m bag n R n M H nna Hu nnp K j nn nd n m b n nno V nna mp nd n n p u umn nf n nd 2226 An m bag n m h Rud phk Bu w B u M Zu R n A H n M Hu bu D u n m hn m m d n Hnn M n p u umn ma An m bag n m h Bw R D bem N b W j BR hd WngAH B PM Hub N Kn d A W nm W gn DM Fu d MR ub M Eng h DM K mp Dm nn mu d ug n CC271 n n m d n p u umn n b 212 A n BMC M Y m H Y u XuF ZhngB I Y M u h n m (B -nd m (E -md d h m n n p u nndmp DNAqun n21 App umn n M b Zh C Zh ngf uy uy C B n M YuY K Zh ng unz HuB HuZ Zh ngx W ng H Phn p ndgn p h n um mb hh d n nddu p n m mu n u n n n P ON E213 8 u 12 Zhu M X G W Y KH hnad Yu Y ngyh M h h m n n p u umn m pd p n ung hn nb j ng 21 BMC M b XuX C X M KngF O dh ZhuF G b G D bu n p gn p nd n d m nn mng m d n p u umn An m bag n m h HY nyh CH up Hu ngch uc u ngyc M ny uyc n WY ngn nhc ncm h ZY P nc Y ng KungHC uc E ngy uw un W W ng K WC YuKW ngpc MH CM H ug H uhpr nd nh n m b u p b nd p p u umn u mh g n V u n n w n( I ud 2621 An m bag n nyh up Hu ngch CH uc u ngyc M ny uyc n WY ngn nhc ncm h ZY P nc Y ng KungHC uc E ngy uw un W W ng K WC YuKW ngpc MH CM H ug H uhpr nd nh u p b n mp n n b g n u mh g nv u n n wn ud 2621 An m bag n m h d / C h nh h m n n p u umn ngh m ( B ndm (A g n n w n BMC u D ubm u nx mnu p B MdCn ndu dn g Cnn n n nubm n h ughp w Np n n gu h g Immd pub nn p n u nnpubmd CA pu ndgg h R h wh h b d bu n ubm u mnu p www b md n m / ubm