1309 06 06 020306026ｧ8 BO06EIO08 6ﾑ8 A04 ﾌ6ｾ4, 18: 119-131, 2006 ﾞ03 ﾞ6ｾ4 ﾒ ﾌ09 ﾇ6ｾ4 ﾇ 01036ｧ80409 07020600060203086 506 020607 02 06 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 apple07000ｸ700080706fi02080202080ｸ7 X. ﾞ0702 04fiapple080ｸ703080ｹ0, 6ﾑ8. 060809036ｧ9 090ｹ0 縺00 09 06 06 020306026ｧ8 ﾒ03060706026ｧ8 ﾞ0905, ｦﾐappleapple0802030702000608 03080408020800006ｧ908, 05000404 0308076ｧ90209 0900036ｧ903096 709. ｦ 020003000ｸ702 6ｧ9 0403fi0706 apple 03 020903006ｧ902 06 06000307060ｹ0, 030307 02 06 040209 040603 00 0ｹ0, 040900 07020602086ｦ0 6 5 0300086ｦ0 6ｦ00109-0409 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 apple07000ｸ700080706fi02080202080ｸ7 (Streptococcus pneumoniae) 0402 6 5-03 0202 00060207, 00 020308036ｧ9 000ｹ0 02 06 070303 000ｸ703 閨0ｷ30ｹ0 0408030909086ｦ0000007 07020600060203086 506 0207, apple080ｸ7 040ｸ7040707 040ｸ707 閨0002 06 0000 apple08020ｸ7046ｧ9 02090ｹ0 030003 apple000ｸ70206026ｧ80ｹ0 090ｷ3096ｧ80ｹ0. ﾇ 0707- apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 040ｸ7076ｧ8030ｷ30ｹ0 0808006ｧ9030002 06 0400 000002 00fi03080ｷ30409 (transformation), 0903 6ｧ8 apple03fi0403096 709 09000700020602086ｦ0 0ｸ7030602086ｦ0 applefi 070303, 0703000202060207 04020003 閨0409 02 06 04apple070706 0400 0409000006 026ｧ8 000002070303 0109 6ｧ8 000002 08080307 apple03 040006 6ｧ9-080ｸ7. ﾇ 026ｦ00306 0001 0000076ｧ8 0906 0209 0607 080409 020ｷ307 070300020206020607 0402000300040607 00 閨04 04020907 02080607fi020902 006ｧ907 06 08 030607080807030ｸ70909 0ｹ0 040ｸ700apple020ｷ300 0206020607 080803 閨0ｷ307 020ｷ307 0402000300040607 0ｸ7020607. ﾞapplefi 00apple06 0900060803080906026ｧ80ｹ0 apple03000ｸ703070ｹ0, 08 040900 07020602fi020003080ｹ0 apple 03070908-0702 0ｹ0 020607 6ｦ007080ｸ7 0906 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 006ｧ907 06 09 0408036ｧ809090409 07020600060203086 506 020607, apple080ｸ7 apple030802 03006ｧ9 00 apple080207030ｸ76 70903 02 06 0402 06 026ｧ8 00apple0602030702090409 070300020206020607 020306070ｷ307, apple080ｸ7 apple030800apple6ｧ80304 07 0400 00060203fi 03060300fi 040208 030607080807030ｸ70909, 6ｧ8 07020602-02070402 0409 02090ｹ0 000ｸ7 6ｧ904030902090ｹ0 04030ｷ3036ｧ9 0ｹ0 applefi 0703000202060207 04020003 閨0409 02090ｹ0 02080607fi020902 0ｹ0. ﾌ06 apple030804apple07030006000ｹ0 apple0003060803060400086ｦ0 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae apple03 鐶pple0006 07 00040206 0403086ｦ007 020ｸ7036ｧ90ｷ30ｹ0 04020907 00030702020ｷ30409 02090ｹ0 04036ｧ804090ｹ0 07020600060203086 506 020607 04020807 apple0309030ｸ70400fi, 0000 00apple0600fi03080ｷ30409 020ｷ307 03000602080ｸ703090607 0ｸ709006ｧ9 0ｹ0 02 06 00070900 閨030ｷ30409 02080ｸ7 02080607086ｦ0. 090303000ｹ0 040203 0209090602 閨0ｹ0 apple080ｸ7 閨04080ｸ707 apple030802 03006ｧ9 apple00030603 006 50707080ｸ707 0209 04036ｧ80409 07020600060203086 506 020607 apple080ｸ7 0003 0406040208apple0806086ｦ007 020907 00apple060308096ｧ8 070300020206020607 0402000300040607, 02 03060ｹ0 02 06 0209 0408036ｧ809090409 0ｸ7020607 0400 0ｸ76 70903 閨0ｹ0 fi0400060ｹ0, 0ｷ30402fi0408 0806 apple030802070400060ｹ0 0ｸ702 閨0ｹ0 0403000607ｨB080702 06 apple0003060404fi02000309 0600-03006ｦ007090409. ﾇ 0408036ｧ809090409 02080ｸ7 040ｸ7ｨB000ｸ70900 閨07080ｸ7 00apple02 6ｦ007 00080ｸ7 apple07000ｸ70008070608020802020602086ｦ0 00006 508036ｧ9080ｸ7 006ｧ907 06 0ｸ707 02fi 07 040ｸ7006 507-030006 04020807 apple0003060803060400fi 020ｷ307 070300020206020607 0402000300040607 04020807 apple0309030ｸ70400fi. 6ﾑ86ｧ907 06 0709070ｷ3040208 fi000ｷ30ｹ0 07 00000303080702060207 00apple060203-026ｧ804080ｸ707 0803fi020ｸ7apple0806 02080ｸ7 00060203086 56ｧ9080ｸ7 apple080ｸ7 0007 apple00030603 006 50707080702 06 040208 00006 5fi030608. 閨0100060ｹ0-02030006 0607: Streptococcus pneumoniae, 070208046ｧ8, 07020600060203086 506 0207, 6 5-03 02020700000ｹ0, 00 020308036ｧ9 000ｹ0. Antachopoulos C, Roilides E. Use of antimicrobials and development of pneumococcal resistance. 3rd Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece. Paediatr N Gr 2006, 18: 119-131. Over the last years, an increase in the rates of resistance of Streptococcus pneumoniae to 6 5-lactam antibiotics, macrolides and other commonly used antibacterial agents has been observed, both worldwide and in our country, and is often associated with treatment failures. The development of resistance among S. pneumoniae isolates is usually due to transformation, i.e. acquisition of genetic material from other, resistant isolates, and rarely to a single mutation or plasmid transfer. The main reservoir for the spreading of resistant strains in the community is the nasopharynx of asymptomatic carriers. From an epidemiological perspective, the most significant risk factor for development of resistance is the administration of antibacterial drugs, which causes ｰunmasking ｱ of resistant clones that were present at low density in the nasopharynx or replacement of sensitive flora with resistant strains from the community. Efforts to limit resistance of S. pneumoniae should mainly focus on the reduction of antimicrobial consumption in the population, through education of health professionals and the public. Other strategies include use of antimicrobials that minimize selection of resistant strains and their administration at high doses; however, these approaches need to be further investigated. Finally, the use of the conjugated 7-valent pneumococcal vaccine may contribute to the reduction of resistant strains in the population. It is, however, uncertain whether serotypes of S. pneumoniae not included in the vaccine emerge in the future. Key words: Streptococcus pneumoniae, resistance, antimicrobials, 6 5-lactams, macrolides.
13120 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 6ﾑ80604 090ｷ3096ｧ8 O apple07000ｸ700080706fi02080202080ｹ0 (Streptococcus pneumoniae) apple08020003006ｧ9 閨07 applefi 02 040900 07020602fi020003 6ｧ90206 0006-0203086 506 020607 030806000601000ｷ307 02090ｹ0 apple 06 06026ｧ80ｹ0 090306026ｧ9 0ｹ0. O06 03080600060100060ｹ0 apple080ｸ7 apple030802 03006ｧ9 040ｸ70407fi020003 02 036ｦ0apple02080ｸ707 閨07 000ｸ7036ｦ0 08070400 070804090007020ｷ307, applefi 0801006ｧ9 00 閨0409 0ｷ3026ｧ9-0206 02 06 apple 03 0303060708020803apple6ｧ90206 00 閨040306 apple07000ｸ70008076ｧ9, 6 5 0202090306 06006ｧ9 02 06 0009070609096ｧ90206 1,2. ﾞ07020600060203086 506 02086ｧ9 apple 030709080702000ｹ0 fiapple0ｷ30ｹ0 0806 apple000706020603036ｧ907000ｹ0, 0806 020008 030804apple08-036ｧ907000ｹ0, 0806 00 020308036ｧ9 000ｹ0, 0806 02000203 020ｸ702036ｧ907000ｹ0 02 06 09 0208-020306000801 ｨBfi0309 6ｧ802 07 040208 apple 03000303fi07 apple08020003000400 020602086ｧ9 04020907 07020600000206apple060409 020ｷ307 apple07000ｸ700080706080208020206020607 0308060006-01000ｷ307. 6ｾ40209 060703020006 020ｷ307 020003000ｸ702 6ｧ90ｷ307 0002 0002060607, 09 0402 06 026ｧ8 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7 0402080ｸ70ｹ0 apple 030709080702000ｹ0 0ｸ702086ｦ00ｹ0 閨040006 040ｸ707 0003006ｧ9 0000 030003 apple000ｸ70206026ｧ8 apple08020ｸ7046ｧ9 02 06 閨040006 08 09096ｧ8040006 040209 04036ｧ80409 0700fi0200030ｷ307 07020600060203086 506 020607, fiapple0ｷ30ｹ0 006ｧ907 06 02 09030ｸ70208apple00apple026ｧ9 06 (6 5 070208000ｸ7026ｧ90709 02 06 02000ｸ80408apple03 076ｧ90709), 0906 020907 07020600000206apple060409 04086 5 030607 apple07000ｸ700080706080208020206020607 030806000601000ｷ307 1,3,4. 6ｾ4020907 apple 03086ｦ004 07 0402fiapple090409, 0304060207 040ｸ7ｨB0902006ｧ9-02 06 09 0404 閨0409 000002 016ｦ0 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 07020600060203086 506 0207 02 06 02080ｸ7 030003 apple000ｸ7020602086ｦ0 apple080200-03 閨0400 02080ｹ0, apple 03080ｸ7040607ｨB080702 06 00apple06 09000608030809060207 04020806-04006ｧ9 04040002060207 0000 0209 0ｸ707 0006026ｧ8 02090ｹ0 000107apple030ｷ304090ｹ0 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7 04020907 02080607fi020902, 02 06 040ｸ70708-6 76ｧ9ｨB080702 06 apple03fi0408 02 00 0800 閨07 04040002060207 0000 02 apple080408-040207 070208046ｧ80ｹ0 04020807 6ﾑ80303 0602fi 04060308. 6ｾ40209 040ｸ707 閨040006 apple00030609030708080702 06 0806 000904 07060400086ｧ9 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402060ｹ0 020ｸ70306fi020003000ｹ0 080007 000ｹ0 07020600060203086 506-020607 02 06 07 apple026ｦ004040002 06 09 0404 閨0409 000002 016ｦ0 0408036ｧ8090904090ｹ0 07020600060203086 506 020607 02 06 00000807070604090ｹ0 070300020206020607 040200-0300040607. ｦ 閨03080ｹ0, 040ｸ7ｨB0902086ｦ00702 06 06000108 060207 0806 apple030802000607fi- 000007000ｹ0 040203 0209090602 閨0ｹ0 0906 020807 apple0003060803060400fi 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020907 02080607fi020902. 6ｾ404 閨0409 000002 016ｦ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 02 06 030003 apple000ｸ7020602086ｦ0 apple08020003 閨0400 02080ｹ0 O 6 5 0300fi0ｹ0 000ｸ7 06040309046ｧ9 0ｹ0 0007fi0ｹ0 04020003 閨04080ｸ70ｹ0 S. pneumoniae 0400 0207apple080608 07020600060203086 506 02fi apple 030709080702 08036ｧ9ｨB0002 06, fiapple0ｷ30ｹ0 02 06 0906 070303080ｸ70ｹ0 0006020308080309 07060400086ｦ00ｹ0, 0000 020907 0003070406040209 07 0402 030206026ｧ8 040ｸ70902 閨0702030ｷ30409 (Minimal Inhibitory Concentration, MIC) 02080ｸ7 08 03000702080ｸ7 0906 0208 0402 閨030004080ｹ0 0ｸ702fi. ﾇ MIC 006ｧ907 06 09 0003070406040209 040ｸ7-0902 閨0702030ｷ30409 02080ｸ7 08 03000702080ｸ7 apple080ｸ7 apple030802 03006ｧ9 07 040208036ｧ8 02090ｹ0 0707apple020ｸ701090ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7 in vitro, 0ｸ7applefi 02 03080306-0400 閨07000ｹ0 040ｸ707036ｧ802000ｹ0. 086 709036ｧ8 MIC 040900 6ｧ9070006 070208046ｧ8 02080ｸ7 04020003 閨04080ｸ70ｹ0 040208 040ｸ709020002030600 閨0708 07020600060203086 506 02fi 08070300 0208, 000706 04 0009036ｧ8 MIC 040900 6ｧ9070006 000ｸ7 06040309046ｧ9 02080ｸ7 04020003 閨04080ｸ70ｹ0. ﾇ 0206006ｧ8 02090ｹ0 09ｦﾐC apple07070ｷ3 applefi 020907 08apple086ｧ9 000603070000 0906 070208046ｧ8 006ｧ907 06 06 080803000206026ｧ8 0906 02070300 08070300 0208 02 06 apple030804 0608036ｧ9ｨB0002 06 0000 6 5070409 08 03-00 0208 0ｸ707 00060207 02 06 08 0300 02080206070902060207 020306026ｧ80306. 縺06 02 apple0003060404fi020003 07020600060203086 506 0207 08036ｧ9ｨB0002 06 02 06 0006 apple00030608046ｧ8 0206000607 02090ｹ0 MIC 000002 016ｦ0 000ｸ7 06040309046ｧ9 0ｹ0 02 06 apple036ｧ803080ｸ70ｹ0 070208046ｧ80ｹ0, apple080ｸ7 04 03 020209036ｧ9ｨB0006 020907 000007 060700000409 070208046ｧ803 5. 0903 0202060207 030806applefi07, 070208046ｧ8 0007fi0ｹ0 04020003 閨04080ｸ70ｹ0 S. pneumoniae 0400 閨07 040ｸ709020002030600 閨0708 07020600060203086 506-02fi apple 030709080702 040900 6ｧ9070006 fi0206 0906 07 07 0402 03006ｧ9 08 apple0803-03 apple03 0406 0400fi0ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7 apple 0602086ｦ00702 06 000009 036ｦ0-020003000ｹ0 040ｸ7090200070203060400060ｹ0 02080ｸ7 08 03000702080ｸ7 applefi 0ｸ702 閨0ｹ0 apple080ｸ7 apple 0602086ｦ00702 06 0906 閨07 000ｸ7 6ｧ90403090208 0402 閨030004080ｹ03,6. 6ﾑ806 060207 0906 020907 apple000706020603036ｧ90709, 0806 020600 閨0ｹ0 MIC apple080ｸ7 08036ｧ9ｨB080ｸ707 020907 000ｸ7 06040309046ｧ9, 0007 060700000409 070208046ｧ8 02 06 070208046ｧ8 02080ｸ7 S. pneumoniae 006ｧ907 06 ﾜ0.06, 0.12-1 02 06 ﾝ2 00g/ml 07026ｧ9-0402080604 5. 縺06 02060ｹ0 020008 030804apple08036ｧ907000ｹ0 3 090ｹ0 09000706070ｹ0 (02000808-02 016ｧ90009, 020008020306 01fi0709) 09 0003000907006ｧ9 020ｷ307 0206000607 MIC 0001 03020702 06 02 06 applefi 020907 000702fiapple060409 02090ｹ0 03086ｧ9000ｷ301090ｹ0 applefi S. pneumoniae: 07 apple03fi02000602 06 0906 0009070609096ｧ90206 0806 0206-00 閨0ｹ0 MIC apple080ｸ7 08036ｧ9ｨB080ｸ707 020907 070208046ｧ8 02080ｸ7 00060203086 56ｧ9080ｸ7 006ｧ9-07 06 apple0608 04 000903 閨0ｹ0 ( ﾝ2 00g/ml) apple ｯ fi,0206 07 09 03086ｧ9000ｷ30109 0007 00070208apple6ｧ9ｨB0002 06 0402060ｹ0 006ｧ807060909000ｹ0 ( ﾝ4 00g/ml) 5. 0900 6 5070409 02 apple 03 apple07070ｷ3, 09 040ｸ707 鐶pple0006 apple080ｸ7 閨040006 040208 030003 apple000ｸ7020602fi apple0802 閨03000400 09 6ｦ0apple 030109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 040209 0408030909086ｦ000000709 04020807 040300076ｧ8 07020600060203086 506 026ｧ8 090ｷ3096ｧ8, 0001 03020702 06 0400 000009070308 6 5 03-00fi applefi 020907 000702fiapple060409 02090ｹ0 03086ｧ9000ｷ301090ｹ0 02 03060ｹ0 02 06 applefi 0209 08 0300 0208020607090206026ｧ8 02 06 08 0300 0208 0ｸ707 0006026ｧ8 02080ｸ7 07020600060203086 506 02086ｦ0 apple080ｸ7 0408030909006ｧ902 06. 6ｾ40ｸ709020002030600 閨07 0001 03020702 06 applefi 020907 0602 07fi020902 02080ｸ7 08 03000702080ｸ7 07 00apple06020ｸ7090407070006 0ｸ76 70903 閨0ｹ0 040ｸ7090200070203060400060ｹ0 040208 040900006ｧ908 02080ｸ7 080309 07060400086ｦ0 fiapple080ｸ7 閨040006 07 apple020ｸ70403006ｧ9 09 03086ｧ9000ｷ30109 6,7. 03020406, 09 apple0608 0402 0300036ｧ8 0404 閨0409 000002 016ｦ0 0707apple020ｸ701090ｹ0-070208046ｧ80ｹ0 02 06 030003 apple000ｸ70206026ｧ80ｹ0 apple08020ｸ7046ｧ9 0ｹ0 閨040006 02 02 0006-0403006ｧ9 0906 03080600060100060ｹ0 fiapple0ｷ30ｹ0 09 0009070609096ｧ90206 02 06 09 0801006ｧ9 00 閨0409 0ｷ3026ｧ90206, 00apple0006 6ｧ8 09 06006ｧ904 0ｸ70409 020ｷ307 0702060006020308-6 506 020607 040208 0009020008 0308070ｷ30206 6ｧ908 0ｸ70903fi 6ｧ8 0208 00 閨0408 080ｸ70ｹ0, 07026ｧ90402080604, 006ｧ907 06 apple0003060803060400 閨0709, 000706 0906 020907 apple07000ｸ7-0008076ｧ9 09 0404 閨0409 0ｸ7026ｧ8 006ｧ907 06 030609fi02000308 04 086ｧ80ｹ0, 08086ｦ0 apple08030307 07020600060203086 506 0207, fiapple0ｷ30ｹ0 0806 6 5-03 02020700000ｹ0, 00apple06-020ｸ709040707080ｸ707 04040002060207 0ｸ76 70903 閨0ｹ0 040ｸ7090200070203060400060ｹ0 0402080ｸ70ｹ0 apple07006ｦ0000807000ｹ07-10. ﾞ02fi00 fi000ｷ30ｹ0 02 06 07, 0906 0803060400 閨07000ｹ0 applefi 02060ｹ0 apple07000ｸ70008070608020802020602 閨0ｹ0 03080600060100060ｹ0, 09 0408036ｧ809090409 0ｸ7010900 閨070ｷ307 fi04000ｷ307 07020600060203086 506 020607 00apple0803006ｧ9 apple03080ｹ0 0208 apple 03fi07 07 006ｧ907 06 apple08020003000400 0206026ｧ8 0906 02 070300020206-0207 04020003 閨0409 11,12, 09 apple0003 0602 閨030ｷ3 6ｦ001090409 02090ｹ0 070208046ｧ80ｹ0, 0000 apple 03080ｸ7046ｧ9 0402000300040607 apple080ｸ7 閨04080ｸ707 apple08036ｦ0 0ｸ76 70903 閨0ｹ0 MIC, 00apple0803006ｧ9 apple070306 07 08 09096ｧ8040006 0400 0ｸ707 006ｧ9 0002036ｧ9- ｨB0ｷ304090ｹ0 02080ｸ7 0006020308080309 07060400086ｦ0. 6ｾ4020003 閨0409 S. pneumoniae 0000 0ｸ76 709036ｧ8 070208046ｧ8 04020907 apple000706020603036ｧ90709 (MIC ﾝ8 00g/ml) 02 06 0400 070303000ｹ0 6 5-03 02020700000ｹ0 閨04080ｸ707 apple080008070ｷ303006ｧ9 04020907 6ﾑ80ｸ70306apple09 02 06 0402060ｹ0 ﾇ070ｷ300 閨07000ｹ0 0908030602006ｧ9000ｹ013,14.
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 121 6ﾑ8apple06 090006080308096ｧ9 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae O 030607080807030ｸ70909 0ｹ0 apple08020003006ｧ9 04020807 070703030ｷ3apple08 020907 026ｦ00306 0001 0000076ｧ8 apple080ｸ7 apple0806026ｧ9ｨb0002 06 applefi S. pneumoniae 02 06 apple08020003006ｧ9 040209 040ｸ707 閨040006 020907 apple09096ｧ8 00000207-0804090ｹ0 020ｷ307 0402000300040607 02080ｸ7 00060203086 56ｧ9080ｸ7 applefi 070703030ｷ3apple08 0400 070703030ｷ3apple08, 030307 02 06 0208 040900006ｧ908 06006ｧ904 0ｸ704090ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7 04020807 080309 07060400fi, apple080ｸ7 08 0909006ｧ9 0400 03086ｧ9000ｷ3-0109 15-17. ｦ 08 apple0804080402fi 080803006ｧ9 0ｹ0 02080ｸ7 S. pneumoniae 006ｧ9-07 06 apple08036ｦ0 000009 036ｦ002000308 0402 0006020307 apple 06 0607 apple ｯ fi,0206 0402080ｸ70ｹ0 00076ｧ8030602000ｹ0, 00apple0803006ｧ9 07 apple0806026ｧ9030006 applefi apple00030608046ｧ8 0400 apple00030608046ｧ8 02 06 00apple09030007ｨB0002 06 applefi 020806070ｷ3070602080806020807080006-02086ｦ00ｹ0 apple 030709080702000ｹ0, fiapple0ｷ30ｹ0 08 040ｸ70904030ｷ302060400fi0ｹ0 0000 070303 07020800, 0208 00 閨090003080ｹ0 02090ｹ0 0806020809 閨070006 0ｹ0 02 06 09 08086ｧ902090409 0400 6 5030008080709apple06 02fi 0402 0300fi, 02 03060ｹ0 02 06 applefi 090007000206-02086ｦ00ｹ0 apple 030709080702000ｹ0 apple080ｸ7 080803086ｦ007 020807 0100070604026ｧ8 7,16,17. O06 040ｸ700apple020ｷ300 020602086ｧ9 080803006ｧ90ｹ0 00apple0803006ｧ9 07 006ｧ907 06 apple0806-02060400 閨070806 006ｧ90200 applefi 000ｸ7 6ｧ904030902 006ｧ90200 applefi 0703000202060207, 0400 0607080803 07020600060203086 506 0207, 04020003 閨0409 S. pneumoniae, 02 06 006ｧ907 06 0ｸ702086ｧ9 apple080ｸ7 040ｸ7006 5070303080ｸ707 040209 00000207 08-0409 020ｷ307 070300020206020607 0402000300040607 00 閨04 04020907 02080607fi020902 apple08036ｦ0 apple0003060404fi02000308 applefi 02 07020800 apple080ｸ7 閨04080ｸ707 0002 09-0306040006 03086ｧ9000ｷ30109 applefi S. pneumoniae 7,15. 0900 6 5070409 0702060908070602 閨0ｹ0 06 080803 閨0ｹ0 020ｷ307 apple08030ｸ704 02-04 0306020607 02080ｸ7 00036ｦ00203080ｸ7 02080ｸ7 S. pneumoniae 閨04080ｸ707-07 09070ｷ303060403006ｧ9 046ｧ8000003 apple0003060404fi0200030806 applefi 90 0803fi020ｸ7apple0806. 03040006 6 5030003006ｧ9 fi0206 09 apple030006086 709086ｧ9 020ｷ307 0402000300040607 apple080ｸ7 000008 076ｧ9ｨB080ｸ707 070208046ｧ8 0402060ｹ0 6 5-03 02020700000ｹ0 076ｧ802080ｸ707 0400 0803060400 閨07080ｸ70ｹ0 080308026ｦ0apple080ｸ70ｹ0, fiapple0ｷ30ｹ0 006ｧ907 06 0806 6B, 9V, 9A, 14, 19F 02 06 23F 18-20. 040007 006ｧ907 06 02fi0009 02 02 070809-02fi 0906 026ｧ9 0806 040ｸ709020002030600 閨070806 0803fi020ｸ7apple0806 040400026ｧ9ｨB080702 06 0000 000009 036ｦ002000309 apple0603 07fi020902 00000807070604090ｹ0 070208046ｧ80ｹ0. 0906 apple0603 07fi020902 006ｧ907 06 fi0206 04020003 閨0409 0ｸ7020607 020ｷ307 080308026ｦ0apple0ｷ307 apple0806026ｧ9ｨb080ｸ707 0208 030607080807030ｸ70909 0906 000009 036ｦ002000308 0403080706-02fi 060704020900 040ｸ70902030602060207 0000 070303080ｸ70ｹ0 0803fi020ｸ7apple080ｸ70ｹ0 02 06 02 0207 040ｸ707 鐶pple0006 0ｸ7086ｧ90402 0702 06 000009 036ｦ002000309 閨0203000409 0400 07020600060203086 506 02086ｦ00ｹ0 apple 030709080702000ｹ0. 0908030807fi0206 02 03 閨07 0ｹ0 applefi 02080ｸ70ｹ0 apple 03 apple07070ｷ3 0803fi020ｸ7apple080ｸ70ｹ0 apple 03080ｸ7040607ｨB0006 09000700-0206026ｧ8 000200030809 閨070006, 02 0703000202060207 04020003 閨0409 076ｧ802080ｸ707 040ｸ7040707 0400 02 0307 04 03 02020903060400 閨07080ｸ70ｹ0 02030607080ｸ70ｹ0, 0000 000ｸ7-03006ｧ9 0607 080409 04020907 02080607fi020902 7,19. 縺06 03fi09080ｸ70ｹ0 fi0406 applefi030ｸ702 02 02 07080902086ｦ00ｹ0, 03020002086ｧ9 applefi 0ｸ702086ｦ00ｹ0 02080ｸ70ｹ0 02030607080ｸ70ｹ0 閨04080ｸ707 apple0802026ｧ8040006 070208046ｧ8 02 06 0400 070303 07020600060203086 506 0207, fiapple0ｷ30ｹ0 0806 00 020308036ｧ9 000ｹ0, 09 02080203060008-01 ｨBfi0309 02 06 09 02000203 020ｸ702036ｧ90709 7,20. 6ﾑ8apple06 090006080308090602 閨0ｹ0 000003 閨02000ｹ0 04020807 6ﾑ80303 0602fi 0406-0308 閨04080ｸ707 006ｧ9010006 fi0206, fiapple0ｷ30ｹ0 02 06 0400 070303000ｹ0 6ﾑ80ｸ7030ｷ3apple 0ｸ8-02 閨0ｹ0 040603000ｹ0 02 06 0402060ｹ0 ﾇ070ｷ300 閨07000ｹ0 0908030602006ｧ9000ｹ0, 09 apple03000608-6 709086ｧ9 020ｷ307 0402000300040607 apple080ｸ7 apple080008070607080702 06 applefi 0ｸ70906-006ｧ90ｹ0 080803006ｧ90ｹ0 6ｧ8 04030007006ｧ90ｹ0 0000 apple07000ｸ700080706080208020206026ｧ8 03086ｧ9000ｷ3-0109 076ｧ802080ｸ707 0402080ｸ70ｹ0 apple 03 apple07070ｷ3 080308026ｦ0apple080ｸ70ｹ0. O06 0803fi020ｸ7apple0806 0ｸ702086ｧ9 apple00030603 006 50707080702 06 040208 00apple02 6ｦ007 0008 040ｸ7ｨB000ｸ7-0900 閨0708 00006 5fi030608 02 0207 02080ｸ7 S. pneumoniae, apple080ｸ7 02 0200-03000ｸ702 6ｧ9 0403fi0706 020ｸ7020308080803006ｧ9 02 06 040209 040603 00 0ｹ021-23. 6ｾ400 fi,0206 08080307 020807 00apple06apple0803 0400fi 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020907 6ﾑ8030307, 0806 apple0003060404fi020003000ｹ0 applefi 02060ｹ0 000003 閨02000ｹ0 apple080ｸ7 閨04080ｸ707 0900080406000ｸ703006ｧ9 applefi 0208 2000 02 06 00000207 apple 03 閨04080ｸ707 0402080604006ｧ9 0906 040ｸ709020002030600-07000ｹ0 apple0003060804 閨0ｹ0 02090ｹ0 040603 0ｹ0, fiapple0ｷ30ｹ0 09 ﾞ020206026ｧ8 24-26 02 06 09 ﾒ036ｧ80209 27. 6ｾ402060ｹ0 000003 閨02000ｹ0 0ｸ702 閨0ｹ0 02 apple080408040207 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020907 apple000706020603036ｧ90709 020ｸ700 6ｧ907080702 07 applefi 13.1%-22% (0007 060700000409 070208046ｧ8) 02 06 applefi 3.8%-12% (apple036ｧ803090ｹ0 070208046ｧ8), 000706 04020907 00030ｸ7030308000ｸ7026ｧ9-0709 applefi 16.8%-42.8% 24-27. 09 03 020903006ｧ902 06 00 040900-070206026ｧ8 6ｦ001090409 0400 0404 閨0409 0000 02 07026ｧ90402080604 apple080408040207 070208046ｧ80ｹ0 apple080ｸ7 006ｧ904 07 02 02 0903 08006ｧ9 0402060ｹ0 0304 閨0ｹ0 02090ｹ0 00-02 00026ｧ9 0ｹ0 02080ｸ7 1990 24-28. ｦ 04020003 閨0409 apple080ｸ7 006ｧ904 07 0003 02-020ｷ300 閨0709 000ｸ7 06040309046ｧ9 04020907 apple000706020603036ｧ90709 apple 03080ｸ7046ｧ9 ｨB 07 070208046ｧ8 02 06 0400 070303 07020600060203086 506 0207, fiapple0ｷ30ｹ0 09 00030ｸ7030308000ｸ7026ｧ90709, 09 02000203 020ｸ702036ｧ90709 02 06 09 0208020306000801 ｨBfi0309, 0400 040900 0702060207 000009 036ｦ002000308 apple0804080402fi applefi 02 04020003 閨0409 apple080ｸ7 6ｧ802 07 000ｸ7 6ｧ904030902 04020907 apple000706020603036ｧ90709 25. 0900 040208applefi 0209 040ｸ7030308096ｧ8 070206apple0308040ｷ3apple000ｸ70206020607 0402080604006ｧ90ｷ307 applefi fi0309 020907 6ﾑ8030307, 0208 2004 apple03 0900 0208apple08066ｧ803090200 apple 07000303 06026ｧ8 閨03000ｸ707 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae, 0000 apple030ｷ302086 5080ｸ7036ｧ9 02090ｹ0 04 09 030803080906026ｧ80ｹ0 ﾒ03060706026ｧ80ｹ0 02080ｸ7 09 0700apple06040209006ｧ9080ｸ7 ﾞ0309070607 02 06 040ｸ70000000208-046ｧ8 ﾒ03060706020607 applefi apple080303 閨0ｹ0 apple0003060804 閨0ｹ0 02090ｹ0 040603 0ｹ029,30. ﾇ 閨03000ｸ707 apple000306000307006 5 0700 02 0ｸ70208apple086ｧ9090409 02 06 閨0300090408 000ｸ7 06040309046ｧ9 0ｹ0 02080ｸ7 S. pneumoniae applefi 0306070808 030ｸ7090906-0207 006ｧ90900 02 0ｸ709060607 apple 06 060607 090306026ｧ9 0ｹ0 2-6 00020607, 02-03060ｹ0 02 06 applefi 02030607060207 006ｧ90900 02 040300070607 0000 apple07000ｸ7-00080706080208020206026ｧ8 03086ｧ9000ｷ30109. 09 03 0209036ｧ8030902 07 06 080803 閨0ｹ0 0402 apple080408040207 070208046ｧ80ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7 000002 016ｦ0 020ｷ307 06 08fi030ｷ307 06 00000306040007020ｷ307 02090ｹ0 040603 0ｹ0. 6ｾ4020807 apple6ｧ907 02 1 apple 03080ｸ7040607ｨB080702 06 040ｸ70708apple02060207 02 apple08020003 閨0400 02, 0906 fi0309 0209 040603 02 03060ｹ0 02 06 0906 020907 apple00030608046ｧ8 02090ｹ0 05000404 0308076ｧ902090ｹ0. 00apple0ｷ30ｹ0 08 6ｧ9070002 06, 006ｧ907 06 040900 0702060207 02 apple080408040207 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020907 apple000706-020603036ｧ90709 (020ｸ7036ｧ90ｷ30ｹ0 0007 060700000409 070208046ｧ8), 020907 020008080ｸ70308-016ｧ90009, 020907 00030ｸ7030308000ｸ7026ｧ90709, 020907 02000203 020ｸ702036ｧ90709 02 06 020907 0208020306000801 ｨBfi0309. ﾇ 070208046ｧ8 02080ｸ7 S. pneumoniae 0402060ｹ0 0700fi020003000ｹ0 0206070803fi07000ｹ0 03006 50808030801 046ｧ90709 02 06 00080106080308-01 046ｧ90709, 02 03060ｹ0 02 06 04020907 02000306030308000ｸ7026ｧ90709, 006ｧ907 06 apple03080ｹ0 0208 apple 03fi07 0009 000706026ｧ8 29-31. 090904 07060400086ｧ9 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 07020600060203086 506 0207 08070300 02 ｦ 07020600060203086 506 0207 08070300 02 03080ｸ707 0400 06 0808-0300020602086ｦ00ｹ0 0402fi04080ｸ70ｹ0 040208 026ｦ00202 0308 02080ｸ7 S. pneumoniae. O06 06 08080300020602086ｧ9 0ｸ702086ｧ9 0402fi040806 02 03060ｹ0 02 06 0806 07026ｧ9-
13122 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 096ｧ907 02 0ｹ0 1. 09080408040207 (%) 0007 0607000004090ｹ0 (IR) 02 06 apple036ｧ803080ｸ70ｹ0 (R ) 070208046ｧ80ｹ0 0400 0607080803 07020600060203086 506 0207 0402000300040607 S. pneumoniae apple080ｸ7 apple0800080706030902 07 applefi 0208 030607080807030ｸ70909 0ｸ709060607 apple 06 060607 2-6 00020607 04020907 6ﾑ8030307 0208 2004. 6ﾑ8030307 040ｸ70902000702030ｷ302060207 09000706020603036ｧ90709 ﾒ0008080ｸ70308016ｧ90009 ﾒ0008020306 01fi0709 6ﾑ8030ｸ7030308000ｸ7026ｧ90709 ｦ 000203 020ｸ702036ｧ90709 ﾒ08020306000801 ｨBfi0309 IR 20,3 1,8 0,8 0,8 1,6 18,7 R 14,8 24 0,1 33 24,8 25,6 0900030608046ｧ8 05000404 0308076ｧ902090ｹ06 5 IR 23,6 3,3 0,8 0 0,8 8,1 R 7,3 12,2 0 27,6 20,3 30,9 ﾞapple08020003 閨0400 02 0003 閨0904080ｸ7 762 0306070808 030ｸ7090906020607 02 06 35 0203060706020607 0402000300040607 S. pneumoniae 29 6 5 ﾞapple08020003 閨0400 02 0003 閨0904080ｸ7 161 0306070808 030ｸ7090906020607 0402000300040607 S. pneumoniae 30 04020806040806 000904 07060400086ｧ9 00 閨040ｷ3 020ｷ307 08apple086ｧ90ｷ307 0208 00060203fi6 50608 07 apple026ｦ004040006 070208046ｧ8 7,32 040ｸ707086 76ｧ9ｨB080702 06 04020807 apple6ｧ907 02 2. O 000904 07060400fi0ｹ0 030704090ｹ0 020ｷ307 6 5-03 0202 000607 6 5 046ｧ9- ｨB0002 06 040209 046ｦ007 00046ｧ8 02080ｸ70ｹ0 0000 閨07ｨB0ｸ700 apple080ｸ7 000002 閨04080ｸ707 040209 046ｦ00703000409 02080ｸ7 020ｸ70202 030602086ｦ0 020806040600 02080ｹ0 02080ｸ7 S. pneumoniae, 02060ｹ0 030009fi000007000ｹ0 apple00070602060303060708-000400000ｸ70206-02 閨0ｹ0 apple030ｷ302000ｹ107000ｹ0 (PBPs) 32,33. ﾇ 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402060ｹ0 6 5-03 02020700000ｹ0 0808006ｧ9030002 06 0400 000002 0303070100060ｹ0 020ｷ307 09080706 6ｧ90ｷ307 apple080ｸ7 020ｷ3 060208apple0806086ｦ007 02060ｹ0 PBPs 02 06 00apple09030007ｨB080ｸ707 020907 0602 07fi020902 046ｦ007 0004090ｹ0 020ｷ307 apple030ｷ302000ｸ8070607 0ｸ7020607 0000 02 040ｸ709020002030600 閨07 0702060006020308-6 506 0207 08070300 02. 030ｷ30ｹ0 020603 閨04080ｸ707 apple0003060903 08006ｧ9 apple - 070200 PBPs 0ｸ76 70903086ｦ0 00080306 02086ｦ0 6 50703080ｸ70ｹ0 (PBPs 1a, 1b, 2x, 2a, 02 06 2b) 02 06 006ｧ9 04 000903086ｦ0 00080306 02086ｦ0 6 507-03080ｸ70ｹ032. 縺06 020907 0707apple020ｸ70109 apple036ｧ803080ｸ70ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae, 03 apple03 鐶pple0006 07 040ｸ7006 5086ｦ007 000002 0303070100060ｹ0 0400 apple0003060404fi020003000ｹ0 applefi 006ｧ9 PBPs. 6ｾ40ｸ7076ｧ8030ｷ30ｹ0, 000002 03-03070100060ｹ0 0402060ｹ0 apple030ｷ302000ｹ107000ｹ0 PBP2x 02 06 PBP2b 08 0909086ｦ007 0400 0007 060700000409 070208046ｧ8 0402060ｹ0 6 5-03 02020700000ｹ0 02 06 006ｧ907 06 apple030800applefi03000409 0906 020907 0707apple020ｸ70109 apple036ｧ803080ｸ70ｹ0 070208046ｧ80ｹ0, apple080ｸ7 apple00030603 006 507070006 000002 0303070100060ｹ0 02 06 0400 070303000ｹ0 PBPs, fiapple0ｷ30ｹ0 09 PBP1a 32-34. 046ｦ008 006ｧ907 06 0806 026ｦ003060806 000904 07060400086ｧ9 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402060ｹ0 00 020308036ｧ9 000ｹ0. O apple030602080ｹ0 040400026ｧ9ｨB0002 06 0000 020907 000203086ｧ8 (efflux) 02080ｸ7 08 03-000702080ｸ7 閨010ｷ3 applefi 0208 026ｦ00202 0308, 00 閨040ｷ3 0702036ｧ9 0ｹ0 apple080ｸ7 020ｷ3-060208apple0806006ｧ902 06 applefi 0208 0908076ｧ9 0608 mef(a). ｦ 04020003 閨0409 02080ｸ7 S. pneumoniae 0000 000700030908apple08060900 閨0708 0ｸ702fi 0208 0009-04 07060400fi 076ｧ802080ｸ707 040208 08 0607fi020ｸ7apple08 09, 07000ｸ7036ｧ9040208-0702 06 040ｸ70407fi020003 040209 ｦﾌfi03000608 ﾞ00000306026ｧ8, 02 06 閨04080ｸ707 0007-060700000409 070208046ｧ8 0402060ｹ0 14-000003006ｧ90ｹ0 02 06 15-000003006ｧ90ｹ0 00-020308036ｧ9 000ｹ0, fiapple0ｷ30ｹ0 006ｧ907 06 09 00030ｸ7030308000ｸ7026ｧ90709, 09 0203 0306030308-000ｸ7026ｧ90709 02 06 09 ｨB06030308000ｸ7026ｧ90709. 030402fi0408, 02 04020003 閨0409 0ｸ70207 006ｧ907 06 000ｸ7 6ｧ904030902 0400 070303 07020600060203086 506 0207 0000 040ｸ7090900076ｧ8 08006ｧ8, fiapple0ｷ30ｹ0 006ｧ907 06 0806 16-000003006ｧ90ｹ0 00 020308036ｧ9 000ｹ0, 0806 030607020804 006ｧ9 000ｹ0 (02030607 000ｸ7026ｧ90709), 0806 04020300apple02080903 006ｧ9-07000ｹ0 ｦﾌ (02080ｸ70ｸ80708apple030604026ｧ90709/ 030808apple030604026ｧ90709) 02 06 0806 0200-0208036ｧ9 000ｹ0 (02000306030308000ｸ7026ｧ90709) 32,35. O 006ｦ0020003080ｹ0 000904 0706-0400fi0ｹ0 070208046ｧ80ｹ0 apple00030603 006 507070006 020907 020ｷ3 060208apple086ｧ9090409 00-040ｷ3 02080ｸ7 09080706 6ｧ9080ｸ7 erm(b) 0006 0ｹ0 0000030ｸ7030704090ｹ0, apple080ｸ7 0000030ｸ7030606070006 006ｧ9 6 5070409 00076ｧ907090ｹ0 040208 23S 03066 508040ｷ3000602fi RNA 02080ｸ7 00060203086 56ｧ9080ｸ7, 0000 apple0802 閨03000400 0209 000002 6 508036ｧ8 02090ｹ0 04020003000804090006026ｧ80ｹ0 08006ｧ80ｹ0 02080ｸ7 03066 508040600 02080ｹ0 02 06 06 02 03 046ｧ8 02090ｹ0 046ｦ007 00046ｧ80ｹ0 02080ｸ7 0000 0208 07020600060203086 506 02fi 08070300 0208. O 08 0607fi020ｸ7apple080ｹ0 apple080ｸ7 0702060402080604006ｧ9 040208 0009-04 07060400fi 0ｸ702fi apple000306090307080002 06 0ｷ30ｹ0 MLS B, apple 03080ｸ7040607- ｨB0006 apple036ｧ80309 070208046ｧ8 0400 fi03000ｹ0 02060ｹ0 00 020308036ｧ9 000ｹ0, 030607020804-006ｧ9 000ｹ0 02 06 04020300apple02080903 006ｧ907000ｹ0, 02 06 apple 03 020903006ｧ902 06 040ｸ7-0407fi020003 04020907 6ﾑ80ｸ70306apple09 32,35,36. 6ｾ40209 040603 00 0ｹ0 07000ｸ7-036ｧ90402080702 06 02 06 0806 6ｦ008 08 0607fi020ｸ7apple0806 09 02 06 MLS B, 03-0307 09 0404000206026ｧ8 040ｸ70407fi020902 0000 020907 08apple086ｧ9 apple 03 020903086ｦ0-0702 06 apple 03080ｸ7040607ｨB0006 06 020ｸ70007070400060ｹ0 0402060ｹ0 0607080803000ｹ0 0000-096ｧ907 02 0ｹ0 2. 090904 07060400086ｧ9 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 07020600060203086 506 0207 08070300 02 ﾞ07020600060203086 506 02fi0ｹ0 apple 0307090ｷ307 6ｾ402fi04080ｹ0 090904 07060400fi0ｹ0 070208046ｧ80ｹ0 6 5-02020700000ｹ0 (apple000706020603036ｧ907000ｹ0, 0900070602060303060708-000400000ｸ7020602 閨0ｹ0 020008 030804apple08036ｧ907000ｹ0) apple030ｷ302000ｹ107000ｹ0 (PBPs) 09 03 0303 096ｧ8 0402fi04080ｸ7 09 020308036ｧ9 000ｹ0 23S 03066 508040ｷ3000602fi RNA 09 03 0303 096ｧ8 0402fi04080ｸ7, 000203086ｧ8 (efflux) ﾒ06070803fi07000ｹ0 DNA 090ｸ703070409 02 06 0208apple080ｸ80408000003070409 IV 09 03 0303 096ｧ8 0402fi04080ｸ7, 000203086ｧ8 (efflux) ｦ 000203 020ｸ702036ｧ90709 30S 03066 508040ｷ30006026ｧ8 0ｸ7apple08080007 09 03 0303 096ｧ8 0402fi04080ｸ7 01030ｷ303 000800070602fi0309 50S 03066 508040ｷ30006026ｧ8 0ｸ7apple08080007 6ﾑ807ｨB0ｸ70006026ｧ8 020308apple08apple086ｧ9090409 02080ｸ7 08 03000702080ｸ7 ﾒ08020306000801 ｨBfi0309 04060ｸ7 0308080ｸ70306026ｧ8 0300 080ｸ70202070409 09 03 0303 096ｧ8 0402fi04080ｸ7
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 123 03 閨02000ｹ026,36-38. ﾇ 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 apple0003060404fi020003 applefi 02 0408030909086ｦ0000007 07020600060203086 506-0207, fiapple0ｷ30ｹ0 0806 6 5-03 02020700000ｹ0, 0806 00 020308036ｧ9 000ｹ0, 09 02000203 020ｸ7-02036ｧ90709 02 06 09 04030ｷ303 000800070602fi0309, 04apple070706 0808006ｧ9030002 06 0400 0409000006 026ｧ8 000002070303 0109 6ｧ8 000002 08080307 apple03 040006 6ｧ9080ｸ739. 6ｾ40ｸ7076ｧ8030ｷ30ｹ0 09 070208046ｧ8 apple0802020702 06 00 閨040ｷ3 000002 00fi03080ｷ304090ｹ0 (transformation), 0903 6ｧ8 apple03fi0403096 7090ｹ0 09000700020602086ｦ0 0ｸ7030602086ｦ0 applefi 070303 04020003 閨0409 00 閨040ｷ3 07 040ｸ707 0ｸ7 0400086ｦ0, 6ｧ8 0000 000002 080003fi000007 000203 0704apple08ｨBfi0706 03 (transposons), 0903 6ｧ8 0000090703 02006ｧ800 02 DNA apple080ｸ7 apple000306 閨04080ｸ707 0908-076ｧ9 06 apple080ｸ7 040400026ｧ9ｨB080702 06 0000 000904 07060400086ｦ00ｹ0 070208046ｧ80ｹ07,39. 6ﾑ801 6ｧ903000409 apple08020003086ｦ007 09 0707apple020ｸ70109 070208046ｧ80ｹ0 04020907 0208-020306000801 ｨBfi0309 02 06 0007 0607000004090ｹ0 070208046ｧ80ｹ0 0402060ｹ0 0206070803fi- 07000ｹ0, apple080ｸ7 040ｸ7040707 0808006ｧ903080702 06 0400 apple03 閨0ｹ0 0409000006 02 閨0ｹ0 0000-02 0303070100060ｹ0. ﾒ 06 apple070306 fi000ｷ30ｹ0, 09 0707apple020ｸ70109 apple036ｧ803080ｸ70ｹ0 070208046ｧ80ｹ0 0402060ｹ0 0206070803fi07000ｹ0 apple030800apple0803 閨020006 apple080303 apple03 閨0ｹ0 000002 0303070100060ｹ0 6ｧ8 000002 08080307 09000700020602086ｦ0 0ｸ7030602086ｦ0 00 閨040ｷ3 000002 00fi03080ｷ304090ｹ07,40. ﾇ 0907060409 020ｷ307 apple 03 apple07070ｷ3 090007000206020607 000904 0706-04000607 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 閨040006 040900 046ｧ9 0906 020907 02-02 07fi090409 02090ｹ0 0ｸ707 0006026ｧ80ｹ0 02090ｹ0 00000807070604090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020807 apple0309030ｸ70400fi 02 06 02 0207 040ｸ707 鐶pple0006 0906 020907 00apple060308096ｧ8 020ｷ307 02 0207030309030ｷ307 040203 02090906020607 apple00-03060803060400086ｦ0 02090ｹ0 070208046ｧ80ｹ0 0ｸ7026ｧ80ｹ0. 0900 6 5070409 030806applefi07 02 fi04 07 08 閨03030902 07, 0906 02 apple0003060404fi020003 applefi 02 07020600060203086 506 0207, 08 apple080602060400fi0ｹ0 6ｧ8 09 03086ｧ9000ｷ30109 02080ｸ7 07030306apple0607080ｸ7 080309 07060400086ｦ0 applefi 0703000202060207 04020003 閨0409 S. pneumoniae 0808006ｧ9030002 06 040209 000002 08080307 0ｸ7020607 applefi 0208 030607080807030ｸ70909 0703030ｷ307 080803 閨0ｷ307 00 閨04 04020907 02080607fi020902. ﾇ de novo 0707apple020ｸ70109 070208046ｧ80ｹ0 0400 04020003 閨0409 apple080ｸ7 6ｧ802 07 0304060207 000ｸ7 6ｧ904030902, 0ｷ30ｹ0 apple0802 閨03000400 02090ｹ0 0408030909086ｦ00000-07090ｹ0 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ0, 040ｸ7006 5 6ｧ9070006 04apple070706 39. 09fi0708 0906 08070300 02 fiapple0ｷ30ｹ0 0806 0206070803fi07000ｹ0, fiapple080ｸ7 02 06 006ｧ9 02fi0009 0409000006 026ｧ8 000002070303 0109 00apple0803006ｧ9 07 08 09096ｧ8-040006 0400 6ｦ001090409 02090ｹ0 MIC, 006ｧ907 06 0ｸ707 02fi 04020003 閨0409 S. pneumoniae 0000 0304060207 0007 060700000409 070208046ｧ8 07 000008-076ｧ904080ｸ707 0309fi020003 apple036ｧ80309 070208046ｧ8 40. ｦ fi0200 fi000ｷ30ｹ0, 0906-026ｧ9 09 0408036ｧ809090409 07020600060203086 506 020607 03000ｷ303006ｧ902 06 08 026ｦ0-0306080ｹ0 apple 030709080702 0ｹ0 0906 020907 0000080707060409 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae; ｦ 08 03 閨00 0ｸ702fi 07 apple026ｦ004040002 06 040209 040ｸ7-07 閨040006. 0108036ｧ809090409 07020600060203086 506 020607 02 06 070208046ｧ8 02080ｸ7 S. pneumoniae Eapple06 090006080308090602 閨0ｹ0 000003 閨02000ｹ0 applefi 070303000ｹ0 040603000ｹ012, 41-47 02 06 applefi 020907 6ﾑ8030307 22 閨04080ｸ707 006ｧ9010006 fi0206 09 apple03fi- 0408 0209 030003 apple006ｧ9 0000 07020600060203086 506 0207 08070300 02 apple08020003006ｧ9 0208 040900 07020602fi02000308 apple 030709080702 020607 6ｦ007080ｸ7 0906 020807 apple080602060400fi 0000 0703000202060207 04020003 閨0409 S. pneumoniae. 090608 040ｸ709020002030600 閨07, 0806 6ｾ40ｸ703080906 0707fiapple080ｸ703080ｹ0 02 06 040ｸ707. 陦000601 07 fi0206 09 apple 03080ｸ7046ｧ9 070300020206020607 040200-0300040607 S. pneumoniae 040208 030607080807030ｸ70909 apple 06 060607 090306026ｧ9 0ｹ0 2-23 0009070607 040ｸ70404000206ｨBfi02 07 0000 0209 036ｧ86 709 070206-00060203086 506 020607 00 閨040306 02 06 60 00 閨03000ｹ0 apple0308 02090ｹ0 036ｧ86 7090ｹ0 02080ｸ7 006ｧ90900 02080ｹ022. O00086ｧ90ｷ30ｹ0 0806 Arason 02 06 040ｸ707., 04030904060008apple0806060702 0ｹ0 apple08030ｸ7apple 03 0908070206026ｧ8 0707030ｸ70409 06070808030ｷ307 apple 03 09fi07020ｷ307 020607 6ｦ007080ｸ7, 陦000601 07 fi0206 0400 apple 06 0607 090306-026ｧ9 0ｹ0 00 閨040306 7 00020607 09 apple03080909086ｦ000000709 036ｧ86 709 0702060006020308-6 506 020607 040ｸ70404000206ｨBfi02 07 0000 020907 apple 03080ｸ7046ｧ9 040208 03060708-0807030ｸ70909 070300020206020607 04020907 apple000706020603036ｧ90709 0402000300040607 S. pneumoniae 41. 0900030002060702 0ｹ0 0208 08 0607fi00000708 040ｸ7070803060207 04020907 020806-07fi020902, 0806 Granizo 02 06 040ｸ707. 陦000601 07 fi0206 09 6ｦ001090409 02090ｹ0 02 02 0707030ｷ304090ｹ0 6 5-03 0202 000607 02 06 00 0203080306 0607 04020907 ｦﾐ04apple 076ｧ9, 02 0207 020907 apple00036ｧ908 08 1979-1997, 040ｸ7040400-0206ｨBfi02 07 030002060207 0000 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402060ｹ0 07026ｧ90402080604000ｹ0 02 02090908036ｧ9000ｹ0 0702060006-0203086 506 020607. O06 Garcia-Rey 02 06 040ｸ707., 0400 0006 0007 06-08 閨03080ｸ704 000003 閨0209 02 02 0707030ｷ304090ｹ0 07020600060203086 506 020607 02 06 apple08040804020607 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0400 0607-080803000ｹ0 apple0003060804 閨0ｹ0 02090ｹ0 ｦﾐ04apple 076ｧ9 0ｹ0, 陦000601 07 fi0206 09 02 02-0707030ｷ30409 02 0300006ｧ9 0ｹ0 applefi 02060ｹ0 6ｦ008 06 08080300020602 閨0ｹ0 02 0209-0908036ｧ9000ｹ0 07020600060203086 506 020607, 020ｷ307 6 5-03 0202 000607 02 06 020ｷ307 00 0203080306 0607, 040ｸ70404000206ｨBfi02 07 030002060207 0000 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 02fi0408 0402060ｹ0 6 5-03 02020700000ｹ0 fi0408 02 06 0402060ｹ0 00 020308-036ｧ9 000ｹ044. ﾒ 0207 070703080908 0203fiapple08 0806 Pihlajamaki 02 06 040ｸ707. 陦000601 07 fi0206 09 02 02 0707030ｷ30409 00 0203080306 0607 02 06 0208020306000801 ｨBfi03090ｹ0 0400 0607080803000ｹ0 apple0003060804 閨0ｹ0 02090ｹ0 02060703 07-6ｧ9 0ｹ0 040ｸ70404000206ｨBfi02 07 030002060207 0000 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 07020600060203086 506 0207 0ｸ70207 46. ﾒ 0207 0209 060001 090ｷ3096ｧ8 02090ｹ0 apple0308 07 08000303006ｧ904 0ｹ0 apple - 07000303 06026ｧ80ｹ0 閨03000ｸ707 0ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0208 2004 30,31, 06 apple0604020603090200 fi0206 0906 020907 apple00030608046ｧ8 02090ｹ0 05000404 0308076ｧ902090ｹ0, 02 04020003 閨0409 S. pneumoniae apple080ｸ7 apple0800080706030902 07 applefi 0208 030607080807030ｸ70909 apple 06 060607 2-6 00020607 apple080ｸ7 006ｧ904 07 03076 50006 6 5-03 02020700000ｹ0 0208 apple03080909086ｦ000000708 02036ｧ900090708 006ｧ904 07 0ｸ76 70903fi020003000ｹ0 MIC 04020907 apple000706020603036ｧ90709 040ｸ70902030602060207 0000 04020003 閨0409 applefi apple 06 0607 0402 08apple086ｧ9 0007 006ｧ904 07 04080309090903006ｧ9 6 5-03 02020700000ｹ048. ﾇ 03030903080ｸ7046ｧ9 020ｷ307 0900090807fi020ｷ307 apple080ｸ7 08 0909086ｦ007 04020907 07006ｦ003000409 070300020206020607 0402000300040607 S. pneumoniae 00000207 applefi 0408036ｧ809090409 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ0 0007 006ｧ907 06 applefi030ｸ702 02 02 070809026ｧ8. O06 apple030802000607fi0000070806 6 506080308-090602086ｧ9 000904 07060400086ｧ9 apple 03080ｸ7040607ｨB080702 06 04020807 apple6ｧ907 02 3, 02 06 apple00030603 006 50707080ｸ707 020907 00 apple080207030ｸ76 70903 02 06 00apple060308096ｧ8 070300020206020607 020306070ｷ307 apple080ｸ7 6ｧ802 07 apple 03fi0702000ｹ0 0400 04 0009036ｧ8 040ｸ70902 閨0702030ｷ30409 02 0207 020907 閨07 030109 02090ｹ0 090ｷ3096ｧ80ｹ0, 020907 07020602 02070402 0409 020ｷ307 000ｸ7 6ｧ9040309020ｷ307 0402000300040607 applefi 0703000202060207 04020003 閨0409 applefi 020807 6ｧ9 0608 6ｧ8 applefi 070303080ｸ70ｹ0 010007060402 閨0ｹ0 02 0207 0209 060703020006 6ｧ8 00000207 0209 030003 apple006ｧ9, 02 03060ｹ0 02 06 0209
13124 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 096ｧ907 02 0ｹ0 3. 090603 07086ｧ9 000904 07060400086ｧ9 apple080ｸ7 0003000907006ｦ0080ｸ707 0209 0404 閨0409 000002 016ｦ0 0408036ｧ8090904090ｹ0 07020600060203086 506 020607 02 06 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae. 090603 07fi0ｹ0 000904 07060400fi0ｹ0 ﾞapple080207030ｸ76 709 070300020206020607 020306070ｷ307 ﾞ07020602 02070402 0409 02 0207 6ｧ8 00000207 0209 030003 apple006ｧ9 ﾞ0707apple020ｸ70109 070208046ｧ80ｹ0 04020807 0100070604026ｧ8 090003060903 086ｧ8 ﾇ 030406026ｧ8 04030ｷ3036ｧ9 02080ｸ7 030607080807030ｸ70909 apple08020003006ｧ902 06 02 0207 apple030006086 709-086ｧ9 applefi 000ｸ7 6ｧ904030902 04020003 閨0409 02 06 0003070406040208 03060300fi 070300020206020607 0402000300040607. 0900 0209 0408036ｧ809090409 02080ｸ7 07020600060203086 506 02086ｦ0 0001 08 076ｧ9ｨB080702 06 02 000ｸ7 6ｧ904030902 04020003 閨0409 02 06 0000apple0603 閨09080702 0603 (00apple060203 02086ｦ007) 0806 07030002020602086ｧ9 020306070806. ﾇ 07020600060203086 506 026ｧ8 090ｷ3096ｧ8 0003 020206070006 6ｧ8 0001 08 076ｧ9ｨB0006 020907 000ｸ7 6ｧ90403090209 04030ｷ3036ｧ9, 閨020406 06040200 0ｸ7010707080702 06 0806 apple0603 07fi020902000ｹ0 apple080602060400086ｦ0 0000 07030002020602fi 0402 閨030004080ｹ0 applefi 07030308 0100070604026ｧ8. ﾞ0703000202060207 04020003 閨0409 07 apple026ｦ00404080702 06 de novo 04020807 0100070604026ｧ8 02 0207 0209 060703020006 0408036ｧ8090904090ｹ0 02090ｹ0 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ0, 040ｸ7076ｧ8030ｷ30ｹ0 0ｷ30ｹ0 apple0802 閨03000400 0409000006 020607 000002 03030701000ｷ307, 02 06 00apple060203 02086ｦ007 閨07 070206 020ｷ307 000ｸ7 6ｧ9040309020ｷ307 0402000300040607 de novo 0707apple020ｸ70109 02 06 00apple0602030702090409 070300020206020607 040200-0300040607 04020807 0100070604026ｧ8 02 0207 0209 060703020006 02090ｹ0 090ｷ3-096ｧ80ｹ07,12,20,49. 00apple0ｷ30ｹ0 6ｧ8 09 閨040006 07 08000303006ｧ9, 08 020003000ｸ702 6ｧ9080ｹ0 000904 07060400fi0ｹ0, 0903 6ｧ8 09 de novo 0707apple020ｸ70109 070208046ｧ80ｹ0 0400 0304060207 000ｸ7 6ｧ904030902 04020003 閨0409 02080ｸ7 S. pneumoniae 02 0207 0209 060703020006 02090ｹ0 030003 apple006ｧ9 0ｹ0 apple 03 020903006ｧ902 06 04apple070706 39. ﾇ 06 apple6ｧ904020ｷ30409 0ｸ7026ｧ8 閨040006 00apple066 5006 5 060ｷ303006ｧ9 applefi 000003 閨02000ｹ0 000002 6 508036ｧ80ｹ0 02090ｹ0 04030ｷ3036ｧ9 0ｹ0 02080ｸ7 030607080807030ｸ70909 0400 apple 06-0607, 00000207 applefi 0408036ｧ809090409 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ050, 51. O06 apple0603 07fi0200030806 000904 07060400086ｧ9 08 6ｧ9070002 06 fi0206 006ｧ907 06 09 apple080207030ｸ76 709 070300020206020607 020306070ｷ307 6ｧ8 09 applefi0202090409 0ｸ7-020607 02 0207 6ｧ8 00000207 0209 030003 apple006ｧ9 50-52. 05 apple03 鐶pple0006 0ｷ30402fi0408 07 00apple06040900 0703006ｧ9 fi0206, 07 02 06 08 030607080807030ｸ70909 0ｹ0 apple08020003006ｧ9 020907 026ｦ00306 0001 0000076ｧ8 0808-03006ｧ9 0ｹ0 02 06 0607 0804090ｹ0 070300020206020607 0402000300040607 S. pneumoniae 04020907 02080607fi020902, 00apple060308096ｧ8 070300020206020607 040200-0300040607 0000 0209 0408036ｧ809090409 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ0 00apple0803006ｧ9, 02080ｸ70307040604020807 03000ｷ3030902060207, 07 040ｸ7006 5006ｧ9 02 06 0400 08apple080608 6ｧ8apple080200 07030308 040900006ｧ908 02080ｸ7 080309 07060400086ｦ0 0ｸ7apple0703040006 0000090703080ｹ0 03060300fi0ｹ0 0402000300040607 02080ｸ7 00060203086 56ｧ9080ｸ7 apple080ｸ7 0002026ｧ903000702 06 04020807 07020600060203086 506 02fi apple 030709080702. ｦ - 020806080ｹ0 0000090703080ｹ0 03060300fi0ｹ0 0ｸ7apple0703040006 02070300 08080307 0402 0409-00006ｧ9 fiapple080ｸ7 閨040006 07 apple020ｸ70403006ｧ9 03086ｧ9000ｷ30109. 縺06 apple 0307-00060900, 0400 apple00036ｧ9apple020ｷ30409 0801006ｧ9 0ｹ0 00 閨04090ｹ0 0ｷ3026ｧ90206 0ｹ0 0ｸ7apple0703-040006 0000090703080ｹ0 03060300fi0ｹ0 0402000300040607 S. pneumoniae 040208 00 閨0408 080ｸ70ｹ0. 0307 07020600060203086 506 02fi 030806applefi07 apple080ｸ7 04080309-09006ｧ902 06 0906 030003 apple006ｧ9 02090ｹ0 0ｷ3026ｧ90206 0ｹ0 006ｧ907 06 6ｧ9040ｷ30ｹ0 apple0608 apple0603 07fi 07 00apple0603 閨090006 0703000202060207 04020003 閨0409 S. pneumoniae apple ｯ fi, 0206 07 0208 6ｧ9 0608 08070300 0208 04030904060008apple0806-086ｦ00702 07 0906 030003 apple006ｧ9 080ｸ7030803086ｧ9000ｷ301090ｹ0. ﾒ 02 ｯ 0ｸ702fi 020807 0203fiapple08, 09 00apple 閨0202 0409 02090ｹ0 04036ｧ804090ｹ0 020ｷ307 020607080308070607 040209 030003 apple006ｧ9 030806000601000ｷ307 02080ｸ7 07 apple07000ｸ704020602086ｦ0 00apple0803006ｧ9 07 閨040006 000009 036ｦ002000309 00apple6ｧ9apple020ｷ30409 04020907 0707apple020ｸ70109 070208-046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0400 0ｸ702 閨0ｹ0 apple ｯ fi, 0206 09 04036ｧ80409 02080ｸ70ｹ0 040209 030003 apple006ｧ9 020ｷ307 080ｸ70308030806000601000ｷ307 49. 09 閨0308 0806 apple03fi03096 7090ｹ0/apple0003060803060400086ｦ0 02090ｹ0 070208-046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 07020600060203086 506 0207 08070300 02 O06 040203 0209090602 閨0ｹ0 apple080ｸ7 閨04080ｸ707 apple030802 03006ｧ9 6ｧ8 02 06 0008 0300080403006ｧ9 0906 020907 apple03fi03096 709 6ｧ8 020807 apple0003060803060400fi 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0402 07020600060203086 506 0207 08070300 02 040ｸ707086 76ｧ9ｨB080702 06 04020807 apple6ｧ907 02 4, 02 06 apple000306-03 006 50707080ｸ707 020907 00030702020ｷ30409 02090ｹ0 04036ｧ804090ｹ0 020ｷ307 0702060006-0203086 506 020607, 020907 020308apple08apple086ｧ9090409 020ｷ307 0408030909086ｦ00000070ｷ307 030003 apple000ｸ70206020607 0404090007020ｷ307 ( fi0409, 060703020006 030003 - apple006ｧ9 0ｹ0, 00apple060308096ｧ8 07020600060203086 506 020607 0203apple.) 02 06 02 閨03080ｹ0 0007 0303 02020602086ｦ00ｹ0 0203fiapple080ｸ70ｹ0 07020600000206apple0604090ｹ0 02080ｸ7 apple0308-096ｧ907 02 0ｹ0 4. 09 閨0308 0806 apple080ｸ7 閨04080ｸ707 apple030802 03006ｧ9 0906 020907 apple03fi03096 709 6ｧ8/02 06 020807 apple0003060803060400fi 02090ｹ0 070208046ｧ80ｹ0 020ｷ307 0006-020308080309 070604000607 0402 0408030909086ｦ0000007 07020600060203086 506 0207 08070300 02 090003060803060400fi0ｹ0 04036ｧ804090ｹ0 07020600060203086 506 020607 ｦﾌ0003026ｧ90ｷ30409 060709070ｷ304090ｹ0 00060203086 506 020607 030806000601000ｷ307 ｦ 0308apple08apple086ｧ9090409 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ0 086 70903fi02000309 fi0409 01036ｧ80409 07020600060203086 506 020607 apple080ｸ7 0003 0406040208apple0806086ｦ007 020907 00apple06-0308096ｧ8 070300020206020607 0402000300040607 09060203fi02000309 060703020006 030003 apple006ｧ9 0ｹ0 050003 apple006ｧ9 0000 040ｸ707 0ｸ7 0400fi 07020600060203086 506 020607 ﾒ0ｸ7020306026ｧ8 0007 0303 096ｧ8 07020600060203086 506 020607 ｦﾌ0003026ｧ90ｷ30409 040ｸ70000fi03080ｷ304090ｹ0 02080ｸ7 04030007086ｦ00ｹ0 0000 0208 030003 - apple000ｸ7020602fi 04046ｧ800 6ﾑ807 0303 02020602086ｧ9 0203fiapple0806 0009 0404000206ｨBfi0000070806 0000 0408036ｧ809090409 07020600060203086 506 020607 E006 5080306 0400fi0ｹ0 縺06 020807 S. pneumoniae, 0803060400 閨07000ｹ0 applefi 0ｸ702 閨0ｹ0 02060ｹ0 000003fi 080ｸ70ｹ0 閨04080ｸ707 040ｸ7ｨB09026ｧ804060009 apple08020003000400 020602fi020902 (6 503 鐶pple00 02006ｧ900000708)
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 125 6 5036ｧ800 02080ｹ0, fiapple0ｷ30ｹ0 006ｧ907 06 09 000ｸ703006ｧ9 04036ｧ80409 apple07000ｸ70008070608-020802020602086ｦ0 00006 508036ｧ9080ｸ77,12,20,49. ﾞ) 090003060803060400fi0ｹ0 040ｸ70702 0908090307080904090ｹ0 0702060006-0203086 506 020607. ｦ 08 0900090807fi0ｹ0 fi0206 08 040900 07020602fi020003080ｹ0 apple - 030709080702 0ｹ0 0906 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 006ｧ907 06 09 0408036ｧ809090409 07020600060203086 506 020607, 閨040006 08 09096ｧ8040006 apple080303 閨0ｹ0 040603000ｹ0 0400 apple03080903070000 02 0003 閨0904080ｸ7 02090ｹ0 02 02 0707030ｷ304090ｹ0 02 06 0803030803080906026ｧ80ｹ0 040ｸ70702 09080903070809-046ｧ80ｹ0 02080ｸ70ｹ0. 09040208apple09 04036ｧ80409 07020600060203086 506 020607 096ｧ9070002 06, 0400 070303080200 07030308 6 5 0300fi, 0402060ｹ0 apple0003060404fi020003000ｹ0 040603000ｹ0, 0700apple020ｸ70900 閨07000ｹ0 02 06 0009. 縺06 apple 0307 00060900, 0400 040603000ｹ0 fiapple0ｷ30ｹ0 0806 ﾇ070ｷ300 閨07000ｹ0 0908030602006ｧ9000ｹ0 02 06 09 罍 03036ｧ9, 閨040006 020002-000903060ｷ303006ｧ9 09 040ｸ704076ｧ8 040ｸ70702 090809030708090409 07020600060203086 506-020607 08 030007020ｷ307 0906 0608090007006ｧ90ｹ0 03080600060100060ｹ0 02080ｸ7 070ｷ302-03080ｸ7 07 apple07000ｸ704020602086ｦ0 53,54. 6ｾ400 apple080608 6 5 0300fi, fi000ｷ30ｹ0, 0002-040203 02006ｧ9000ｹ0 00070900 閨030ｷ304090ｹ0 02 06 apple0003060803060400086ｦ0 02090ｹ0 0408036ｧ8-090904090ｹ0 07020600060203086 506 020607 006ｧ907 06 fi07020ｷ30ｹ0 apple08020003000400 0206-02 閨0ｹ0 04020807 apple0003060803060400fi 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae; O06 040400020602 閨0ｹ0 000003 閨02000ｹ0 apple080ｸ7 閨04080ｸ707 0900080406000ｸ703006ｧ9 0007 006ｧ907 06 apple080303 閨0ｹ0 02 06 040ｸ7ｨB0902086ｦ00702 06 apple 03 0207020ｷ3. 6ｾ4020907 ｦﾐ0403 07 6ｧ9, 09 00030702020ｷ30409 02090ｹ0 04036ｧ804090ｹ0 0702060006-0203086 506 020607, 02 06 06 06 6ｧ9020003 00 0203080306 0607 02 06 0208020306-000801 ｨBfi03090ｹ0, 02 0207 0208 060704020900 1990-1994 040ｸ70708 006ｦ0-02090200 applefi 00006ｧ90ｷ30409 02080ｸ7 apple0804080402086ｦ0 020ｷ307 0402000300040607 S. pneumoniae apple080ｸ7 6ｧ802 07 0703000202060207 04020907 apple000706020603036ｧ9-0709 55. 6ｾ40209 6ｾ403086 500076ｧ9, 09 00030702020ｷ30409 02090ｹ0 040ｸ707080306026ｧ80ｹ0 02-02 0707030ｷ304090ｹ0 07020600060203086 506 020607 02 0207 16% apple00036ｧ9apple080ｸ7 000002 016ｦ0 1999 02 06 2003, 0000 00apple0600 閨03080ｸ70ｹ0 00030702020ｷ30409 02090ｹ0 040ｸ70702 0908090307080904090ｹ0 02090ｹ0 0008010ｸ7020603036ｧ907090ｹ0-0203 6 5080ｸ703 0706-02086ｦ0 02 06 020ｷ307 020607080308070607 02 0207 29% 02 06 24% 07026ｧ9-0402080604, 040ｸ70708 006ｦ002090200 applefi 00030702020ｷ30409 02080ｸ7 apple0804080402086ｦ0 020ｷ307 070300020206020607 04020907 apple000706020603036ｧ90709 0402000300040607 S. pneumoniae applefi 23% 0400 apple00036ｧ9apple080ｸ7 15%. ﾇ 00006ｧ90ｷ30409 02090ｹ0 070208046ｧ80ｹ0 020803086ｦ003090400 0ｸ7026ｧ8 02090ｹ0 02 02 0707030ｷ304090ｹ0 0000 02 030ｸ70402 閨03090409 0007fi0ｹ0 閨02080ｸ70ｹ056. 6ｾ4020907 ｦ 0ｸ86 50707, 09 00030702020ｷ3-0409 02090ｹ0 02 02 0707030ｷ304090ｹ0 6 5-03 0202 000607 02 0207 46% 000002-016ｦ0 1999 02 06 2001 040ｸ70708 006ｦ002090200 applefi 00006ｧ90ｷ30409 02080ｸ7 apple08-04080402086ｦ0 apple036ｧ803080ｸ70ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020907 apple000706020603036ｧ90709 applefi 25% 0400 9% 57. 030402fi0408, 0806 apple030804apple07030006000ｹ0 apple0003060803060400086ｦ0 02090ｹ0 040ｸ7-0702 0908090307080904090ｹ0 07020600060203086 506 020607 0007 08 6ｧ9070002 06 07 040ｸ70708 006ｦ0080702 06 apple070702 applefi 00030702020ｷ30409 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae. 6ｾ400 0006 apple00030608046ｧ8 02080ｸ7 Wiskonsin 020ｷ307 ﾇ070ｷ300 閨070ｷ307 090803060200060607 apple03 0900 0208apple08066ｧ803090200 0208 1998 040ｸ707020807060400 閨0709 apple030804apple07030006 apple0003060803060400086ｦ0 02 06 0803030803080906026ｧ80ｹ0 04036ｧ804090ｹ0 020ｷ307 07020600060203086 506 020607 apple080ｸ7 0408-030909086ｦ00702 06 0402 apple 06 0607, 00 閨04 applefi 040ｸ704020900 0206026ｧ8 000709-00 閨030ｷ30409 02fi0408 020ｷ307 apple 06 060702030ｷ307 fi0408 02 06 020ｷ307 090807060607. 6ｾ40208 00010700090708 apple080ｸ7 020803086ｦ003090400 020907 0002040203 02006ｧ9 000709-00 閨030ｷ304090ｹ0, 06 apple0604020603090200 00030702020ｷ30409 02090ｹ0 02 02 0707030ｷ3-04090ｹ0 07020600060203086 506 020607 applefi 11%-23%, 040ｸ70902030602060207 0000 070303000ｹ0 apple0003060804 閨0ｹ0, 040ｷ3036ｧ90ｹ0 07 apple 03 0209030903006ｧ9 00006ｧ90ｷ30409 02080ｸ7 apple0804080402086ｦ0 020ｷ307 070300020206020607 0402000300040607 S. pneumoniae 58. ﾞ070703080909 apple030804apple07030006 apple080ｸ7 閨09060700 0400-090308020602 閨0ｹ0 02080607fi020902000ｹ0 02090ｹ0 ﾞ03070402 0ｹ0 040ｸ70708 006ｦ002090200 applefi 00006ｧ90ｷ30409 02090ｹ0 02 02 0707030ｷ304090ｹ0 020ｷ307 07020600060203086 506-020607 02 0207 30-35%, 040ｷ3036ｧ90ｹ0 fi000ｷ30ｹ0 06 06 6ｧ902000309 00006ｧ90ｷ30409 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 04020907 apple000706020603036ｧ90709 59. ｦ 閨03080ｹ0, 040208 Tennessee 020ｷ307 ﾇ070ｷ300 閨070ｷ307 090803060200060607, apple 03fi000806 0002040203 02006ｧ9 apple0003060803060400086ｦ0 02090ｹ0 02 02 0707030ｷ3-04090ｹ0 07020600060203086 506 020607 040ｸ70708 006ｦ002090200 applefi 00030702020ｷ30409 0ｸ7026ｧ80ｹ0 02 0207 11%, 040ｷ3036ｧ90ｹ0 000002 6 508036ｧ8 0402 apple080408040207 070208046ｧ80ｹ0 020ｷ307 0402000300040607 S. pneumoniae apple080ｸ7 apple080008-0706030902 07 applefi 06000604 0ｸ7020602 閨0ｹ0 03080600060100060ｹ0. 6ｾ40209 000003 閨0209 0ｸ7026ｧ8 0ｷ30402fi0408 0007 閨09060700 apple030804 060803060400fi0ｹ0 000ｸ7 06040309-046ｧ9 0ｹ0 0402000300040607 02080ｸ7 00060203086 56ｧ9080ｸ7 applefi 0306070808 030ｸ70909060207 006ｧ90900 02 0ｸ709060607 080803 閨0ｷ307 60. ﾞapplefi 02060ｹ0 apple 03 apple07070ｷ3 000003 閨02000ｹ0 08 6ｧ9070002 06 02 02 ｯ 03-046ｧ807 fi0206 0806 apple030804apple07030006000ｹ0 apple0003060803060400086ｦ0 02090ｹ0 040ｸ70702 0908-090307080904090ｹ0 020ｷ307 07020600060203086 506 020607, fi02 07 096ｧ907080ｸ707 0000 040ｸ704020900 020602fi 0203fiapple08, 0004020607ｨB080702 0ｹ0 02 0ｸ702fi04030807 0402080ｸ70ｹ0 03000602080ｸ70309086ｦ00ｹ0 0ｸ709006ｧ9 0ｹ0 02 06 040208 02080607fi, 00apple0803086ｦ007 apple03070900 0206 07 00apple06026ｦ004080ｸ707 020807 apple0003060803060400fi 02090ｹ0 02 02-0707030ｷ304090ｹ0. 030402fi0408, 08 apple06020003080ｹ0 0402fi04080ｹ0 02090ｹ0 00006ｧ90ｷ304090ｹ0 020ｷ307 apple08040804020607 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 0007 08 6ｧ9-070002 06 fi0206 00apple06020ｸ7090407070002 06 apple070702. O06 0203066 5006ｧ90ｹ0 03fi090806 0906 ｯ 0ｸ702fi 0007 006ｧ907 06 09070ｷ30402086ｧ9, 08 6ｧ9070002 06 fi000ｷ30ｹ0 fi0206 0400 0803060400 閨07000ｹ0 applefi 02060ｹ0 000003 閨02000ｹ0 0007 0000040803076 5090400 030200-02fi0ｹ0 0403fi07080ｹ0 applefi 02fi0200 apple080ｸ7 00apple0602006ｦ00403090200 09 00006ｧ90ｷ30409 02090ｹ0 02 02 0707030ｷ304090ｹ0 020ｷ307 07020600060203086 506 020607 08 030007020ｷ307 00-040306 020807 apple030804 060803060400fi 020ｷ307 apple08040804020607 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 58,59. 0900 00 030900 02060207 00080702 閨03 閨040006 0006-0403006ｧ9 fi0206 09 00030702020ｷ30409 0402 apple080408040207 070208046ｧ80ｹ0 020ｷ307 0006-0203086 56ｧ90ｷ307 07 00 閨070002 06 07 apple 03 0209030903006ｧ9 0000 030200026ｧ8 02-030ｸ70402 閨03090409 applefi 02fi0200 apple080ｸ7 00apple06020ｸ7090407070002 06 08 apple000306080306-0400fi0ｹ0 02090ｹ0 02 02 0707030ｷ304090ｹ0 020ｷ307 07020600060203086 506 020607 08 03-0007020ｷ307 61. 090303080ｹ0 03fi09080ｹ0 0906 020807 08apple086ｧ908 0400 0207apple0806000ｹ0 applefi 02060ｹ0 000003 閨02000ｹ0 0007 apple 03 0209036ｧ803090200 00006ｧ90ｷ30409 02090ｹ0 070208046ｧ80ｹ0 006ｧ907 06 6ｧ9040ｷ30ｹ0 fi0206 08 6 5 0300fi0ｹ0 00030702020ｷ304090ｹ0 02090ｹ0 02 02 0707030ｷ3-04090ｹ0 020ｷ307 07020600060203086 506 020607 ( applefi 11%-35% 58-60 ) 0007 6ｧ802 07 0302000207 0000090703080ｹ0. 6ｾ400 apple0003060804 閨0ｹ0 0000 000009070308 00apple06apple0803 0400fi 070300020206020607 0402000300040607 apple0603 07fi07 07 apple 06-02006ｧ902 06 apple0608 03 040206026ｧ8 00006ｧ90ｷ30409 02090ｹ0 02 02 0707030ｷ304090ｹ0 06040200 07 0ｸ7apple070301080ｸ707 0803 0207 apple08020003 閨0400 02. ｦﾌ) ｦ 0308apple08apple086ｧ9090409 030003 apple000ｸ70206020607 0404090007020ｷ307. ﾇ 03080906026ｧ8 apple6ｧ9040ｷ3 applefi 0ｸ7026ｧ8 020907 apple030804 閨0909060409 006ｧ907 06 fi0206, 02fi0009 02 06 07 09 04036ｧ80409 07020600060203086 506 020607 apple000306080306-0403006ｧ9 0402060ｹ0 apple 03 6ｧ9020902000ｹ0 0007 006ｧ90100060ｹ0, 03 apple08020003006ｧ9 apple07-0702080200 00 閨0408 00apple060308096ｧ80ｹ0 0906 020907 0000080707060409 070300020206020607 0402000300040607. 6ﾑ86ｧ907 06 0ｸ707 02fi fi000ｷ30ｹ0 07 096ｧ907080ｸ707 020308apple08apple0806-6ｧ80400060ｹ0 0402 030003 apple000ｸ702060207 04046ｧ800 02, 06040200 09 apple0603 07fi0209-
13126 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 02 00000807070604090ｹ0 070208046ｧ80ｹ0 07 0003 0406040208apple0806006ｧ902 06. O06 020308apple08apple08066ｧ80400060ｹ0 0ｸ702 閨0ｹ0 閨04080ｸ707 apple030802 03006ｧ9 0906 020907 apple03fi- 03096 709 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02 06 0703030ｷ307 0006020308080309 0706-04000607 apple030907 02080ｸ7 S. pneumoniae (fiapple0ｷ30ｹ0 0906 apple 0307 000609-00 020ｷ307 Mycobacterium tuberculosis, Plasmodium falciparum, Shigella spp. 02 06 0703030ｷ307 0307090206020607 02-0207 Gram 00060203086 56ｧ90ｷ307), 02 06 apple00030603 006 50707080ｸ707 0209 0408036ｧ8-09090409 0ｸ76 709030607 fi04000ｷ307 07020600060203086 506 020607, 0209 04036ｧ80409 08 030007020ｷ307 apple080ｸ7 0003 0406040208apple0806086ｦ007 020907 00apple060308096ｧ8 070300-020206020607 0402000300040607, 020907 00030702020ｷ30409 02090ｹ0 060703020006 0ｹ0 0300-03 apple006ｧ9 0ｹ0, 020907 02 0ｸ702fi0403080709 0408036ｧ809090409 040ｸ707 0ｸ7 0400086ｦ0 07020600060203086 506 020607 6ｧ8 020907 020ｸ7020306026ｧ8 0007 0303 096ｧ8 0ｸ7020607, 02 06 02 閨03080ｹ0 0209 6 50003026ｧ90ｷ30409 040ｸ70000fi03080ｷ304090ｹ0 02080ｸ7 04030007086ｦ00ｹ0 0000 0208 030003 apple000ｸ7020602fi 04046ｧ800 (096ｧ907. 4) 7,20. ﾇ 0408036ｧ809090409 0ｸ76 709030607 fi04000ｷ307 07020600060203086 506-020607, 000202fi0ｹ0 02080ｸ7 fi0206 00apple0803006ｧ9 07 006ｧ907 06 apple08020003000400 0206-026ｧ8 04020907 07020600000206apple060409 030806000601000ｷ307 applefi 00 閨020306 0703000202060207 04020003 閨0409, fiapple0ｷ30ｹ0 6ｧ8 09 07 08 閨0303090200 apple03080909086ｦ0-000007, 03000ｷ303006ｧ902 06 applefi 03020002086ｦ00ｹ0 040ｸ7090903 08006ｧ90ｹ09,12,20 fi0206 006ｧ907 06 0ｸ707 02fi 07 040ｸ7006 507030006 02 06 04020907 apple03fi03096 709 6ｧ8 020807 apple0003060803060400fi 02090ｹ0 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae. ﾇ 07apple086 709 0ｸ7026ｧ8 6 5 046ｧ9ｨB0002 06 040208 fi0206 0000 02060ｹ0 0ｸ76 70903 閨0ｹ0 fi0400060ｹ0 03 00apple0602000ｸ70403006ｧ9 0002036ｧ9ｨB0ｷ30409 020ｷ307 000ｸ7-6ｧ9040309020ｷ307 030307 02 06 020ｷ307 00 閨020306 070300020206020607 0402000300-040607 02080ｸ7 00060203086 56ｧ9080ｸ7, 02fi0408 040208 040900006ｧ908 02090ｹ0 03086ｧ9000ｷ301090ｹ0 fi0408 02 06 040208 030607080807030ｸ70909 7,9,12,20. ﾇ 0001070300066 709 02090ｹ0 080803006ｧ9 0ｹ0 070300020206020607 0402000300040607 applefi 020807 0100070604026ｧ8 03 閨040006 0ｷ30ｹ0 040ｸ707 鐶pple0006 020807 apple0003060803060400fi 02090ｹ0 06 04apple0803070ｹ0 0ｸ7020607 04020907 02080607fi020902. 6ｾ400 006ｧ9 000003 閨0209 apple080ｸ7 apple000306030700-6 5 0700 941 apple 06 0607 090306026ｧ9 0ｹ0 3-6 00020607, 6 503 閨03090200 fi0206 0ｸ7-0207 0402 08apple086ｧ9 006ｧ90400 04080309090903006ｧ9 04 0009036ｧ8 fi0409 6 5-03 - 0202 000607 (00060203fi02000309 applefi 0209 0007 000602070ｸ7fi00000709) 6ｧ8 09 0300-03 apple006ｧ9 006ｧ90400 06 0302 閨040006 apple0003060404fi02000308 applefi 5 0900 閨03000ｹ0, 006ｧ904 07 000009 036ｦ002000309 apple0603 07fi020902 07 08 閨03080ｸ707 070300020206-0207 04020003 閨0409 S. pneumoniae 040ｸ70902030602060207 0000 apple 06 0607 apple080ｸ7 006ｧ904 07 03076 50006 020907 02 02070303090309 fi0409 6ｧ8 0402 08apple086ｧ9 09 060703020006 02090ｹ0 030003 apple006ｧ9 0ｹ0 6ｧ802 07 閨0ｷ30ｹ0 5 0900 閨03000ｹ062. 縺00-090807fi0ｹ0 apple0707020ｷ30ｹ0 006ｧ907 06 fi0206 0806 040ｸ7090200070203060400060ｹ0 020ｷ307 070206-00060203086 506 020607 apple080ｸ7 apple 0602086ｦ00702 06 0906 07 096ｧ9070006 0002036ｧ9ｨB0ｷ3-0409 02 06 020ｷ307 00 閨020306 070300020206020607 0402000300040607 S. pneumoniae applefi 0208 030607080807030ｸ70909 0007 閨04080ｸ707 040ｸ7040209-00 02060207 060003000ｸ7070903006ｧ9. 03020406 0007 閨040006 apple030804 060803060403006ｧ9 apple0806000ｹ0 006ｧ907 06 0806 00 0302000207 0ｸ76 70903 閨0ｹ0 fi0400060ｹ003 0906 02070300 07020600060203086 506 02fi 08070300 0208, 0806 08apple086ｧ9000ｹ0 03 00apple06026ｦ004080ｸ707 020907 0002036ｧ9ｨB0ｷ30409 02080ｸ7 00060203086 56ｧ9080ｸ7. ｦ 閨03080ｹ0, 09 apple0802000300-0400 020602fi020902 02090ｹ0 0408036ｧ8090904090ｹ0 0ｸ76 709030607 fi04000ｷ307 04020907 apple03fi03096 709 6ｧ8 apple0003060803060400fi 02090ｹ0 070208046ｧ80ｹ0 0400 00apple6ｧ9apple00 08 apple0309030ｸ70400086ｦ0 0007 閨040006 00000300020903006ｧ9 apple030808apple02060207 02 06 040ｸ7-0700apple060ｹ0 0007 00apple0803086ｦ007 07 0001 0403086ｦ007 0408 036ｧ8 040ｸ700apple00-03070400 02. ﾇ 07apple086 709 apple080ｸ7 0ｸ7apple08040209036ｧ9ｨB0006 0209 04036ｧ80409 08 030007-020ｷ307 apple080ｸ7 0003 0406040208apple0806086ｦ007 020907 00apple060308096ｧ8 070300020206020607 0402000300040607, 6 5 046ｧ9ｨB0002 06 026ｦ00306 0402060ｹ0 040900 07020602 閨0ｹ0 06 0808-03 閨0ｹ0 000002 016ｦ0 020ｷ307 07020600060203086 506 020607 0402060ｹ0 08 0300 02080206-0709020602 閨0ｹ0 02 06 08 0300 0208 0ｸ707 000602 閨0ｹ0 02080ｸ70ｹ0 06 06fi020902000ｹ0. 縺06 apple 0307 00060900, apple030802000600 閨07080ｸ7 0906 02060ｹ0 6 5-03 02020700000ｹ0, apple08020003000400 0206026ｧ8 0002036ｧ9ｨB0ｷ30409 020ｷ307 00060203086 56ｧ90ｷ307 00apple06020ｸ709-0407070002 06 fi02 07 09 040ｸ70902 閨0702030ｷ30409 02080ｸ7 08 03000702080ｸ7 040208 040900006ｧ908 02090ｹ0 03086ｧ9000ｷ301090ｹ0 0ｸ7apple00036 5 6ｧ9070006 020907 0206006ｧ8 02090ｹ0 MIC 02080ｸ7 0006020308080309 07060400086ｦ0 0906 ﾝ40% 02080ｸ7 040308070602086ｦ0 06-04026ｧ800 02080ｹ0 apple080ｸ7 0000040803 6 5006ｧ9 000002 016ｦ0 020ｷ307 fi04000ｷ307 63. 0900 6 5070409 08 0300 02080206070902060207 00 0800 閨07, fi02 07 09 0206006ｧ8 02090ｹ0 MIC 02080ｸ7 S. pneumoniae 006ｧ907 06 0402 00apple6ｧ9apple00 02090ｹ0 0007-0607000004090ｹ0 (0.12-1 00g/ml) 6ｧ8 apple036ｧ803080ｸ70ｹ0 (2 00g/ml) 070208-046ｧ80ｹ0 04020907 apple000706020603036ｧ90709, 00fi0708 09 0008010ｸ7020603036ｧ90709 02 06 09 020008020306 01fi0709 00apple06020ｸ709040707080ｸ707 040ｸ7090200070203060400060ｹ0 040208 00-0408 080ｸ70ｹ0 apple080ｸ7 apple030903086ｦ007 020907 apple 03 apple07070ｷ3 apple030800applefi03000409, 000706 09 020008080ｸ70308016ｧ90009 00apple06020ｸ7090407070006 080306 0207 00apple 0302006ｧ90ｹ0 040ｸ7090200070203060400060ｹ0 0906 020907 07020600000206apple060409 S. pneumoniae 0000 0007 060700000409 070208046ｧ8 04020907 apple000706020603036ｧ90709. 090303000ｹ0 020008 030804apple08036ｧ907000ｹ0, fiapple0ｷ30ｹ0 09 020008 0203fi0309, 09 0308-03 02 0300apple 閨0809 02 06 09 02000806016ｧ90009, 0007 00apple06020ｸ709040707080ｸ707 03-02000207 0ｸ76 70903 閨0ｹ0 040ｸ7090200070203060400060ｹ0 040208 00 閨0408 080ｸ70ｹ0 0906 020907 0002036ｧ9ｨB0ｷ30409 020ｷ307 0402000300040607 S. pneumoniae 0000 0007 06070000-0409 6ｧ8 apple036ｧ80309 070208046ｧ8 20,63,64. ｦ 086ｦ00208 040900 6ｧ9070006 fi0206 09 0408-036ｧ809090409 020ｷ307 020003000ｸ702 6ｧ90ｷ307 0ｸ7020607 020008 030804apple080306070607 0400 apple000306apple02060400060ｹ0 0801006ｧ9 0ｹ0 00 閨04090ｹ0 0ｷ3026ｧ90206 0ｹ0 00apple0803006ｧ9 02000306-0207 07 000ｸ70708006ｧ9 020907 00apple0602030702090409 070300020206020607 0402000300-040607 S. pneumoniae, 0008fi040807 02 閨020806 04020003 閨0409 0000apple00-0306 閨04080702 06 04020807 03040602fi apple0309030ｸ70400fi 020ｷ307 0402000300040607 02080ｸ7 00060203086 56ｧ9080ｸ7 apple080ｸ7 apple0308020703000400 0209 03086ｧ9000ｷ30109. ﾇ 0ｸ7applefi03000409 0ｸ7026ｧ8 00apple 030903006ｦ002090200 0400 040ｸ709020306020602 閨0ｹ0 020306070602 閨0ｹ0 000003-02000ｹ0, fiapple080ｸ7 09 020008 0203fi0309 02 06 02000806016ｧ90009 6ｧ802 07 030609fi02000308 apple08020003000400 020602 閨0ｹ0 applefi 020907 0008010ｸ7020603036ｧ90709 04020907 0002036ｧ9- ｨB0ｷ30409 070300020206020607 0402000300040607 S. pneumoniae applefi 0208 00 閨0408 080ｸ70ｹ0 02 03060ｹ0 02 06 04020907 00030702020ｷ30409 02080ｸ7 apple08060206-0400086ｦ0 020ｷ307 0402000300040607 0ｸ7020607 040208 030607080807030ｸ70909 9,20,65. 09 0307 02 000ｸ7036ｧ800 02 0ｸ70207, fi000ｷ30ｹ0, 0400 040ｸ709020002030600 閨07000ｹ0 080007 000ｹ0 040300070607, apple 0602086ｦ00702 06 02 06 apple070306 02 0307 040400-06 0400 閨07000ｹ0 000003 閨02000ｹ0 0400 00apple6ｧ9apple00 08 apple0309030ｸ70400086ｦ0 apple0308020006-00 閨07080ｸ7 07 06 apple0604020ｷ303006ｧ9 0208 02 0207 applefi0408 09 04036ｧ80409 040ｸ7-09020002030600 閨070ｷ307 07020600060203086 506 020607 6ｧ8 080007 0ｷ307 0ｸ7020607 000ｸ70708006ｧ9 6ｧ8 apple00030608036ｧ9ｨb0006 020907 0000080707060409 070300020206020607 040200-0300040607 S. pneumoniae 04020907 02080607fi020902. ﾇ apple03fi02 0409 0906 6 50307040ｸ7070409 020ｷ307 0408030909086ｦ00000070ｷ307 030003 apple000ｸ70206020607 0404090007020ｷ307 apple080ｸ7 apple00030603 006 50707080ｸ707 070206-00060203086 506 0207 08070300 02 (096ｧ907. 4) 040209036ｧ9ｨB0002 06 04020907 07apple086 709 fi0206 02 08030609086ｧ8000003 04046ｧ800 02 080007fi0ｹ0 08 6ｧ90700-02 06 07 006ｧ907 06 apple08020003000400 02060207 0400 03020002 閨0ｹ0 apple000306apple0206-0400060ｹ066, 080002 閨03080ｸ7 0003 02020607080ｸ707 020907 閨0203000409 02080ｸ7 0803-09 07060400086ｦ0 0402 07020600060203086 506 0207 02 06 02 0207 040ｸ707 鐶pple0006 apple0603 07fi07 07 0003 02020607080ｸ707 02 06 020907 0707apple020ｸ70109 070300020206-
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 127 020607 0402000300040607. 046ｦ008 000003 閨02000ｹ0 0400 apple 06 06 02030602086ｦ00ｹ0 04030007006ｧ90ｹ0 陦000601 07 fi0206 09 0408036ｧ809090409 6 5-03 0202 000607 0400 000009070309 fi0409 02 06 0906 6 503 046ｦ0 040308070602fi 060704020900 006ｧ9-07 06 030609fi02000308 apple0603 07fi 07 08 09096ｧ8040006 0400 080803006ｧ9 070300-020206020607 0402000300040607 S. pneumoniae 00000207 0209 030003 apple006ｧ9 apple ｯ fi0206 09 0408036ｧ809090409 0400 00060203fi02000309 fi0409 02 06 0906 apple00-03060404fi020003000ｹ0 00 閨03000ｹ062,67. 030402fi0408 0402060ｹ0 000003 閨02000ｹ0 0ｸ702 閨0ｹ0 0007 006ｧ907 06 0ｸ707 02fi 07 06000ｸ702030607060403006ｧ9 apple0806080ｹ0 6ｧ802 07 08 apple030ｷ302 03040602fi0ｹ0 apple 030709080702 0ｹ0 apple080ｸ7 0404000206ｨBfi02 07 0000 020907 00030702020ｷ30409 02090ｹ0 070208046ｧ80ｹ0: 09 000602036ｧ8 060703020006 030003 apple006ｧ9-0ｹ0 6ｧ8 09 000009070309 fi0409 02080ｸ7 08 03000702080ｸ7. 6ﾑ8apple06apple03 閨0807, 0006 06apple036ｧ8 020ｸ708036ｧ8 apple08030ｸ7020007020306026ｧ8 000003 閨0209 046ｦ00902030604090ｹ0 02090ｹ0 56ｧ8000003090ｹ0 0000 0209 106ｧ800000309 0408036ｧ809090409 0008010ｸ7020603036ｧ907090ｹ0-0203 6 5080ｸ703 070602086ｦ0 0906 030003 apple006ｧ9 02090ｹ0 0801006ｧ9 0ｹ0 00 閨04090ｹ0 0ｷ3026ｧ90206 0ｹ0 0007 陦00060100 040900 070206026ｧ8 06 08080307 04020807 apple0806-02060400fi 0000 0703000202060207 04020003 閨0409 S. pneumoniae 00000207 0209 030003 apple006ｧ9 68. T 閨03080ｹ0, 0806 Dagan 02 06 040ｸ707. 陦000601 07 fi0206 0400 apple 06 06 02030602086ｦ00ｹ0 04030007006ｧ90ｹ0 000002 6 50803 閨0ｹ0 04020807 apple0309030ｸ7-0400fi 020ｷ307 0402000300040607 S. pneumoniae apple080ｸ7 apple0806026ｧ9ｨb080ｸ707 0208 030607080807030ｸ70909 6ｧ8 09 040ｸ7006 5 6ｧ907080ｸ707 00 閨04 0402060ｹ0 apple030602000ｹ0 3-4 00 閨03000ｹ0 applefi 020907 閨07 030109 02090ｹ0 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ051. 0900 6 5070409 02 00 0800 閨07 0ｸ70207, 08 03fi03080ｹ0 02090ｹ0 0408036ｧ8090904090ｹ0 6 503 046ｦ00200030ｷ307 030003 apple000ｸ70206020607 0404090007020ｷ307 04020807 apple0003060803060400fi 6ｧ8 020907 apple03fi03096 709 02090ｹ0 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 006ｧ907 06 00086ｧ96 50803080ｹ0. ﾇ 030003 apple006ｧ9 0000 apple0003060404fi020003 02080ｸ7 0007fi0ｹ0 0702060006-0203086 506 0207 閨040006 0008 0300080403006ｧ9 0906 020807 apple0003060803060400fi 02090ｹ0 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 0400 070303000ｹ0 03080600060100060ｹ0, fiapple0ｷ30ｹ0 applefi 020807 06fi HIV 6ｧ8 0208 M. tuberculosis. 0900 00 0800 閨0708 fi000ｷ30ｹ0 fi0206 09 030003 apple006ｧ9 020ｷ307 apple07000ｸ700080706080208020206020607 03080600060100-0ｷ307 040ｸ7076ｧ8030ｷ30ｹ0 06 0302006ｧ9 036ｧ909000ｹ0 00 閨03000ｹ0, 000706 09 de novo 0707apple020ｸ70109 070208046ｧ80ｹ0, 00 閨040ｷ3 0409000006 020607 000002 03030701000ｷ307 02080ｸ7 S. pneumoniae, apple03080ｹ0 02060ｹ0 apple0003060404fi020003000ｹ0 080007 000ｹ0 07020600060203086 506 020607 006ｧ907 06 04apple070706 39, 09 0408036ｧ809090409 06apple036ｧ80ｹ0 6ｧ8 020306apple036ｧ80ｹ0 090ｷ3096ｧ80ｹ0 0007 08 6ｧ9070002 06 07 閨040006 03 閨0409 04020907 apple03fi03096 709 02090ｹ0 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 7. ﾇ 020ｸ7020306026ｧ8 0007 0303 096ｧ8 07020600060203086 506 020607 08 03-0007020ｷ307 閨040006 08020600 0403006ｧ9, 0000 apple0806026ｧ903 apple08020003 閨0400 02, 0906 020807 apple0003060803060400fi 02090ｹ0 0707apple020ｸ701090ｹ0 070208046ｧ80ｹ0 0402 0006-0203fi6 506 apple080ｸ7 apple030802 03086ｦ007 070804080208000006 02 閨0ｹ0 03080600060100060ｹ0 (020ｸ7036ｧ90ｷ30ｹ0 03070902060207 02 0207 Gram) 69. 縺06 020907 apple00036ｧ9apple020ｷ3-0409 02080ｸ7 S. pneumoniae, fi000ｷ30ｹ0, 09 apple030804 閨0909060409 0ｸ7026ｧ8 0007 08 6ｧ9070002 06 07 閨040006 07fi0900, 08086ｦ0 09 000009070309 apple03000608-6 709086ｧ9 020ｷ307 apple000306apple020604000ｷ307 006ｧ907 06 03080600060100060ｹ0 02090ｹ0 020806-07fi020902 0ｹ0. ﾇ 6 50003026ｧ90ｷ30409 02090ｹ0 040ｸ70000fi03080ｷ304090ｹ0 02080ｸ7 04030007086ｦ00ｹ0 apple03080ｹ0 0208 030003 apple000ｸ7020602fi 04046ｧ800 apple0603 07fi02 02 07 040ｸ700-6 50703030006 040208 030003 apple000ｸ7020602fi apple0802 閨03000400, 0ｸ7010707080702 0ｹ0 0208 040308070602fi 060704020900 fiapple080ｸ7 0806 040ｸ7090200070203060400060ｹ0 02080ｸ7 07020600060203086 506 02086ｦ0 08 03000702080ｸ7 0402080ｸ70ｹ0 060402086ｦ00ｹ0 006ｧ907 06 apple07-070ｷ3 applefi 020907 MIC 6, 0ｷ30402fi0408 006ｧ907 06 6 5 閨6 5 0608 02 0207 applefi- 0408 00apple0803006ｧ9 07 apple00030608036ｧ9040006 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae. 090003 閨02000ｹ0 apple07070ｷ3 0400 0ｸ702fi 0208 03 閨00 0007 閨04080ｸ707 apple03 0900 0208apple08060903006ｧ9. 縺06 02 0003030907060207 00 0800-07, fiapple080ｸ7 02 07020600060203086 506 0207 08070300 02 apple 03 閨04080702 06 0402 08 0300 02006ｧ9 02fi00 02 06 040ｷ3036ｧ90ｹ0 06 020306026ｧ8 040ｸ70702 096ｧ8, 6ｧ9040ｷ30ｹ0 07 閨040006 apple0003060404fi02000309 040900 046ｧ9 09 00040ｸ70000fi03080ｷ3-040903 020ｷ307 08 0300 0208apple08060607 02 06 02080ｸ7 02080607086ｦ0 040209 0408036ｧ8-09090409 6ｧ8 04036ｧ80409 07020600060203086 506 020607 00fi0708 00000207 applefi 08 09096ｧ9 0906 0203086ｦ0. ) 0907000ｸ70008070608020802020602fi 00006 5fi030608. ｦ 08 00apple02 6ｦ007-0008 040ｸ7ｨB000ｸ70900 閨0708 00006 5fi030608 02 0207 02080ｸ7 S. pneumoniae, apple080ｸ7 02 020003000ｸ702 6ｧ9 0403fi0706 020ｸ7020308080803006ｧ9 02 06 04020907 6ﾑ8030307, apple00030608036ｧ9ｨb0006 fi0406 00fi0708 02060ｹ0 03080600060100060ｹ0 030307 02 06 020807 apple080602060400fi 02080ｸ7 030607080807030ｸ70909 applefi 040ｸ7090200-02030600 閨07080ｸ70ｹ0 080308026ｦ0apple080ｸ70ｹ0 02080ｸ7 00060203086 56ｧ9080ｸ7, apple080ｸ7 閨040006 0006-0403006ｧ9 fi0206 040ｸ707 閨080702 06 0000 0ｸ76 70903fi apple0804080402fi 070208046ｧ80ｹ0 0402 07020600060203086 506 0207 70,71. 090603 07fi07 030806applefi07 09 000ｸ703006ｧ9 0408036ｧ8-09090409 02080ｸ7 00006 508036ｧ9080ｸ7 04020807 apple 06 06 02030602fi apple0309030ｸ70400fi 07 08 09096ｧ8040006 040209 00006ｧ90ｷ30409 020ｷ307 apple08040804020607 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae, 03fi090ｷ3 0001070300066 7090ｹ0 020ｷ307 080308026ｦ0apple0ｷ307 apple080ｸ7 0ｸ702fi 02 036ｦ0apple020006 71. 030402fi0408 6ｧ8 09 閨040006 07 08000303006ｧ9 72, 02 06 006ｧ907 06 apple0603 07fi 07 apple 03 0209030903006ｧ9 0400 000009 036ｦ002000309 閨0202-0409 040208 00 閨03030807 73, 09 0000080707060409 02 06 0402 06 026ｧ8 00apple06020307-02090409 080308026ｦ0apple0ｷ307 02080ｸ7 S. pneumoniae apple080ｸ7 0007 apple00030603 00-6 50707080702 06 040208 00006 5fi030608 0ｸ702fi. ﾇ apple0003 0602 閨030ｷ3 040ｸ7ｨB6ｧ802090409 02090ｹ0 0404 閨04090ｹ0 000002 016ｦ0 apple07000ｸ70008070608020802020602086ｦ0 00006 508036ｧ9080ｸ7 02 06 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 010008006ｦ0090006 applefi 0208 040208applefi 02090ｹ0 07 0402fiapple0904090ｹ0 0ｸ7026ｧ80ｹ0. 6ｾ40ｸ700apple0003070400 02 O 040900 07020602fi020003080ｹ0 apple 030709080702 0ｹ0 020607 6ｦ007080ｸ7 0906 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 006ｧ907 06 09 0408036ｧ809090409 07020600060203086 506 020607 08 030007020ｷ307, 000706 09 026ｦ0-0306 0001 0000076ｧ8 0906 0209 0607 080409 020ｷ307 070300020206020607 040200-0300040607 00 閨04 04020907 02080607fi020902 006ｧ907 06 08 030607080807030ｸ70909 0ｹ0 040ｸ700apple020ｷ300 0206020607 080803 閨0ｷ307. O06 000002 6 50803 閨0ｹ0 apple080ｸ7 apple0308-02 03006ｧ9 09 0408036ｧ809090409 07020600060203086 506 020607 040209 04030ｷ3036ｧ9 02080ｸ7 030607080807030ｸ70909 08 6ｧ9070002 06 07 040400026ｧ9ｨB080702 06 apple00030604-04fi02000308 0000 020907 00 apple080207030ｸ76 70903 02 06 0402 06 026ｧ8 00apple06020307-02090409 070300020206020607 020306070ｷ307 apple080ｸ7 apple030800apple6ｧ80304 07 0400 0006-0203fi 03060300fi 6ｧ8 020907 07020602 02070402 0409 02090ｹ0 000ｸ7 6ｧ904030902090ｹ0 04030ｷ3036ｧ9 0ｹ0 applefi 0703000202060207 04020003 閨0409 02090ｹ0 02080607fi020902 0ｹ0. De novo 0707apple020ｸ70109 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae 02-0207 0209 060703020006 07020600060203086 506 026ｧ80ｹ0 090ｷ3096ｧ80ｹ0, 0ｷ30ｹ0 apple08-02 閨03000400 0409000006 020607 000002 03030701000ｷ307, 040ｸ7006 5 6ｧ9070006 04apple07-0706, fiapple0ｷ30ｹ0 0906 apple 0307 00060900 02 0207 020907 0707apple020ｸ70109 070208046ｧ80ｹ0 0402060ｹ0 0206070803fi07000ｹ0. O06 apple030804apple07030006000ｹ0 apple0003060803060400086ｦ0 02090ｹ0 070208046ｧ80ｹ0 02080ｸ7 S. pneumoniae apple03 鐶pple0006 026ｦ00306 07 00040206 0403086ｦ007 04020907
13128 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 00030702020ｷ30409 02090ｹ0 04036ｧ804090ｹ0 07020600060203086 506 020607 04020807 apple0309030ｸ70400fi, apple00030603 006 50707080702 0ｹ0 00070900 閨030ｷ30409 02fi0408 020ｷ307 030006-02080ｸ703090607 0ｸ709006ｧ9 0ｹ0, 06040200 07 040ｸ70702 09080903 08086ｦ007 0702060006-0203086 506 0207 08070300 02 fi02 07 apple03070900 0206 0007 006ｧ902070ｸ70702 06, fi0408 02 06 02080ｸ7 02080607086ｦ0, 06040200 07 000907 02 apple0308000903006ｦ00002 06 040ｷ3036ｧ90ｹ0 06 020306026ｧ8 040ｸ70702 096ｧ8. 6ﾑ86ｧ907 06 apple0603 07fi, 080ｸ70406 04020602fi0ｹ0 apple0003060803060400fi0ｹ0 02090ｹ0 070208046ｧ80ｹ0 07 apple 0602006ｧ9 040900 07020602086ｦ0 6 5 0300086ｦ0 00006ｧ90ｷ30409 02090ｹ0 02 02 0707030ｷ304090ｹ0 020ｷ307 0702060006020308-6 506 020607, 000706 006ｧ907 06 046ｧ909080ｸ70308 fi0206 02 fiapple0806 apple08020003-0400 02 03 08 07086ｦ007 00000207 applefi 03020002fi 02 0603fi, apple0603 07fi- 02 02 0207apple0806 0403fi0706, 08applefi0200 09 apple030804apple07030006 apple03 鐶pple0006 07 006ｧ907 06 040ｸ70700046ｧ80ｹ0. ﾇ 04036ｧ80409 07020600060203086 506 020607 apple080ｸ7 0003-0406040208apple0806086ｦ007 020907 00apple060308096ｧ8 070300020206020607 0402000300040607, 02-03060ｹ0 02 06 09 0408036ｧ809090409 0ｸ7020607 0400 0ｸ76 70903 閨0ｹ0 fi0400060ｹ0, apple08-020003086ｦ007 0007 0303 02020602 閨0ｹ0 apple030802070400060ｹ0 0906 020907 07020600000206apple06-0409 02080ｸ7 apple03086 5036ｧ800 02080ｹ0 02090ｹ0 070208046ｧ80ｹ0, apple080ｸ7 fi000ｷ30ｹ0 0403000607- ｨB080702 06 apple0003060404fi02000309 060003006ｦ007090409. ｦ 閨03080ｹ0, 09 000ｸ703006ｧ9 0408036ｧ809090409 02080ｸ7 040ｸ7ｨB000ｸ70900 閨07080ｸ7 apple07000ｸ70008070608020802020602086ｦ0 0000-6 508036ｧ9080ｸ7 apple0603 07fi07 07 apple00030608036ｧ9040006 0209 06 04apple080307 070300-020206020607 0402000300040607 04020807 apple0309030ｸ70400fi, 006ｧ907 06 0709070ｷ3040208 fi000ｷ30ｹ0 07 040208 00 閨03030807 00apple060203 026ｧ804080ｸ707 020306070806 02080ｸ7 0006-0203086 56ｧ9080ｸ7 apple080ｸ7 0007 02 036ｦ0apple02080702 06 applefi 0208 00006 5fi030608. ﾇ 0707apple020ｸ70109 070208046ｧ80ｹ0 020ｷ307 00060203086 56ｧ90ｷ307 040ｸ707 閨00-02 06 0000 040900 070206026ｧ8 0708040903fi020902 02 06 03070902fi020902. 6ﾑ86ｧ907 06 0403 閨080ｹ0 fi030ｷ307 020ｷ307 03000602080ｸ703090607 0ｸ709006ｧ9 0ｹ0 fi0406 00fi0708 09 02-02 07fi090409 02080ｸ7 apple03086 5036ｧ800 02080ｹ0 030307 02 06 09 040ｸ70700060408080307, 0000 02070300 0203fiapple08, 04020907 07020600000206apple06046ｧ8 02080ｸ7. 09 0307030309-03, 03 apple03 鐶pple0006 07 040ｸ7070004060402006ｧ9 09 apple030804apple07030006 0906 02-02 07fi090409 02080ｸ7 08 06070800 閨07080ｸ7 02 06 02080ｸ7 03fi03080ｸ7 apple080ｸ7 00apple08-03006ｧ9 07 apple 6ｧ9ｨB080ｸ707 apple 030709080702000ｹ0 fiapple0ｷ30ｹ0 09 00apple060308096ｧ8 040ｸ7090200-02030600 閨070ｷ307 07020600060203086 506 020607, 09 0408030909086ｦ000000709 fi0409 02 06 09 060703020006 02090ｹ0 030003 apple006ｧ9 0ｹ0, 0000 040208applefi 020907 07006ｦ0-03000409 apple08020003000400 0206020607 040203 02090906020607 0906 020807 apple00-03060803060400fi 02090ｹ0 00000807070604090ｹ0 6ｧ8 06 026ｧ8030904090ｹ0 070300020206020607 0402000300040607 S. pneumoniae 04020907 02080607fi020902. ｦﾌ066 50306080903 086ｧ9 1. Cartwright K. Pneumococcal disease in western Europe: burden of disease, antibiotic resistance and management. Eur J Pediatr 2002, 161: 188-95. 2. Obaro SK, Monteil MA, Henderson DC. The pneumococcal problem. BMJ 1996, 312: 1521-5. 3. Kaplan SL, Mason EO, Jr. Management of infections due to antibiotic-resistant Streptococcus pneumoniae. Clin Microbiol Rev 1998, 11: 628-44. 4. Heffelfinger JD, Dowell SF, Jorgensen JH, Klugman KP, Mabry LR, Musher DM, et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med 2000, 160: 1399-408. 5. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Sixteenth Informational Supplement. CLSI document M100-S16. Wayne, PA: Clinical and Laboratory Standards Institute, 2006. 6. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998, 26: 1-10; quiz 1-2. 7. Schrag SJ, Beall B, Dowell SF. Limiting the spread of resistant pneumococci: biological and epidemiologic evidence for the effectiveness of alternative interventions. Clin Microbiol Rev 2000, 13: 588-601. 8. Rothermel CD. Penicillin and macrolide resistance in pneumococcal pneumonia: does in vitro resistance affect clinical outcomes? Clin Infect Dis 2004, 38 Suppl 4: S346-9. 9. Dagan R, Klugman KP, Craig WA, Baquero F. Evidence to support the rationale that bacterial eradication in respiratory tract infection is an important aim of antimicrobial therapy. J Antimicrob Chemother 2001, 47: 129-40. 10. Jacobs MR. In vivo veritas: in vitro macrolide resistance in systemic Streptococcus pneumoniae infections does result in clinical failure. Clin Infect Dis 2002, 35: 565-9. 11. Piglansky L, Leibovitz E, Raiz S, Greenberg D, Press J, Leiberman A, et al. Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children. Pediatr Infect Dis J 2003, 22: 405-13. 12. Aguilar L, Gimenez MJ, Garcia-Rey C, Martin JE. New strategies to overcome antimicrobial resistance in Streptococcus pneumoniae with beta-lactam antibiotics. J Antimicrob Chemother 2002, 50 Suppl S2: 93-100. 13. Doit C, Loukil C, Fitoussi F, Geslin P, Bingen E. Emergence in France of multiple clones of clinical Streptococcus pneumoniae isolates with high-level resistance to amoxicillin. Antimicrob Agents Chemother 1999, 43: 1480-3. 14. Schrag SJ, McGee L, Whitney CG, Beall B, Craig AS, Choate ME, et al. Emergence of Streptococcus pneumoniae with very-high-level resistance to penicillin. Antimicrob Agents Chemother 2004, 48: 3016-23. 15. Raymond J, Le Thomas I, Moulin F, Commeau A, Gendrel D, Berche P. Sequential colonization by Streptococcus pneumoniae of healthy children living in an orphanage. J Infect Dis 2000, 181: 1983-8. 16. Gray BM, Converse GM, Dillon HC, Jr. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 1980, 142: 923-33. 17. Vives M, Garcia ME, Saenz P, Mora MA, Mata L, Sabharwal H, et al. Nasopharyngeal colonization in Costa- Rican children during the first year of life. Pediatr Infect Dis J 1997, 16: 852-8. 18. Klugman KP. Pneumococcal resistance to antibiotics. Clin Microbiol Rev 1990, 3: 171-96. 19. Doern GV, Brueggemann AB, Blocker M, Dunne M, Holley HP, Jr., Kehl KS, et al. Clonal relationships
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 129 among high-level penicillin-resistant Streptococcus pneumoniae in the United States. Clin Infect Dis 1998, 27: 757-61. 20. Nuermberger EL, Bishai WR. Antibiotic resistance in Streptococcus pneumoniae: what does the future hold? Clin Infect Dis 2004, 38 Suppl 4: S363-71. 21. Syriopoulou V, Daikos GL, Soulis K, Michos A, Alexandrou H, Pavlopoulou I, et al. Epidemiology of invasive childhood pneumococcal infections in Greece. Acta Paediatr Suppl 2000, 89: 30-4. 22. Syrogiannopoulos GA, Katopodis GD, Grivea IN, Beratis NG. Antimicrobial use and serotype distribution of nasopharyngeal Streptococcus pneumoniae isolates recovered from Greek children younger than 2 years old. Clin Infect Dis 2002, 35: 1174-82. 23. Hausdorff WP, Yothers G, Dagan R, Kilpi T, Pelton SI, Cohen R, et al. Multinational study of pneumococcal serotypes causing acute otitis media in children. Pediatr Infect Dis J 2002, 21: 1008-16. 24. Tsolia MN, Stamos G, Ioannidou S, Trefler R, Foustoukou M, Kafetzis D, et al. Genetic relatedness of resistant and multiresistant Streptococcus pneumoniae strains, recovered in the Athens area, to international clones. Microb Drug Resist 2002, 8: 219-26. 25. Kanavaki S, Mantadakis E, Karabela S, Anatoliotaki M, Makarona M, Moraitou H, et al. Antimicrobial resistance of Streptococcus pneumoniae isolates in A- thens, Greece. Eur J Clin Microbiol Infect Dis 2005, 24: 693-6. 26. Ioannidou S, Tassios PT, Zachariadou L, Salem Z, Kanelopoulou M, Kanavaki S, et al. In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities. Clin Microbiol Infect 2003, 9: 704-7. 27. Maraki S, Christidou A, Tselentis Y. Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae isolates from Crete, Greece. Int J Antimicrob Agents 2001, 17: 465-9. 28. Kanavaki S, Karabela S, Marinis E, Legakis NJ. Antibiotic resistance of clinical isolates of Streptococcus pneumoniae in Greece. J Clin Microbiol 1994, 32: 3056-8. 29. Katsarolis I, Poulakou G, Matthaiopoulou I, Tsiodras S, Roilides E, Kafetzis DA, et al. Antimicrobial resistance of pneumococci isolated from the nasopharynx of healthy children and clinical isolates in Greece in 2004. In: 15th European Congress of Clinical Microbiology and Infectious Disease. Copenhagen, Denmark; 2005. 30. Antachopoulos C, Tsiakou M, Michailidou E, Kansouzidou A, Karapavlidou P, Sikalidou P, et al. Antimicrobial drug susceptibility of Streptococcus pneumoniae isolates from healthy children of the area of Thessaloniki in 2004. In: 23rd Annual Meeting of European Society of Pediatric Infectious Diseases. Valencia, Spain; 2005. 31. Poulakou G, Katsarolis I, Matthaiopoulou I, Panagopoulos P, Avlamis A, Antachopoulos C, et al. In vitro activity of telithromycin against erythromycin-susceptible and resistant pneumococci. In: 15th European Congress of Clinical Microbiology and Infectious Diseases. Copenhagen Denmark; 2005. 32. Charpentier E, Tuomanen E. Mechanisms of antibiotic resistance and tolerance in Streptococcus pneumoniae. Microbes Infect 2000, 2: 1855-64. 33. Hakenbeck R, Grebe T, Zahner D, Stock JB. ｦﾌeta-lactam resistance in Streptococcus pneumoniae: penicillinbinding proteins and non-penicillin-binding proteins. Mol Microbiol 1999, 33: 673-8. 34. Grebe T, Hakenbeck R. Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of beta-lactam antibiotics. Antimicrob Agents Chemother 1996, 40: 829-34. 35. Edelstein PH. Pneumococcal resistance to macrolides, lincosamides, ketolides, and streptogramin B agents: molecular mechanisms and resistance phenotypes. Clin Infect Dis 2004, 38 Suppl 4: S322-7. 36. Reinert RR, Ringelstein A, van der Linden M, Cil MY, Al- Lahham A, Schmitz FJ. Molecular epidemiology of macrolide-resistant Streptococcus pneumoniae isolates in Europe. J Clin Microbiol 2005, 43: 1294-300. 37. Fotopoulou N, Tassios PT, Beste DV, Ioannidou S, Efstratiou A, Lawrence ER, et al. A common clone of erythromycin-resistant Streptococcus pneumoniae in Greece and the UK. Clin Microbiol Infect 2003, 9: 924-9. 38. Bogaert D, Hermans PW, Grivea IN, Katopodis GS, Mitchell TJ, Sluijter M, et al. Molecular epidemiology of penicillin-susceptible non-beta-lactam-resistant Streptococcus pneumoniae isolates from Greek children. J Clin Microbiol 2003, 41: 5633-9. 39. Tomasz A. Antibiotic resistance in Streptococcus pneumoniae. Clin Infect Dis 1997, 24 Suppl 1: S85-8. 40. Eliopoulos GM. Quinolone resistance mechanisms in pneumococci. Clin Infect Dis 2004, 38 Suppl 4: S350-6. 41. Arason VA, Kristinsson KG, Sigurdsson JA, Stefansdottir G, Molstad S, Gudmundsson S. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. Bmj 1996, 313: 387-91. 42. Dowell SF, Schwartz B. Resistant pneumococci: protecting patients through judicious use of antibiotics. Am Fam Physician 1997, 55: 1647-54, 57-8. 43. Kristinsson KG. Epidemiology of penicillin resistant pneumococci in Iceland. Microb Drug Resist 1995, 1: 121-5. 44. Garcia-Rey C, Aguilar L, Baquero F, Casal J, Dal-Re R. Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae. J Clin Microbiol 2002, 40: 159-64. 45. Granizo JJ, Aguilar L, Casal J, Garcia-Rey C, Dal-Re R, Baquero F. Streptococcus pneumoniae resistance to
13130 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 erythromycin and penicillin in relation to macrolide and beta-lactam consumption in Spain (1979-1997). J Antimicrob Chemother 2000, 46: 767-73. 46. Pihlajamaki M, Kotilainen P, Kaurila T, Klaukka T, Palva E, Huovinen P. Macrolide-resistant Streptococcus pneumoniae and use of antimicrobial agents. Clin Infect Dis 2001, 33: 483-8. 47. Butler JC, Hofmann J, Cetron MS, Elliott JA, Facklam RR, Breiman RF. The continued emergence of drugresistant Streptococcus pneumoniae in the United States: an update from the Centers for Disease Control and Prevention ｯs Pneumococcal Sentinel Surveillance System. J Infect Dis 1996, 174: 986-93. 48. ｦ 04060702080ｸ7 09, ﾞ0702 04fiapple080ｸ703080ｹ0 01, ｦﾐ0ｷ3 020006006ｧ9 080ｸ7 ﾞ, 090604 09036ｧ9-080ｸ7 6ﾑ8, 02 0300070209 6ﾑ8, ﾒ 0ｸ8036ｧ9 090ｹ0 ﾒ, 02 06 040ｸ707. 6ﾑ80ｸ7 06040309046ｧ9 04020907 apple000706020603036ｧ90709 02 06 00030ｸ7030308000ｸ7026ｧ90709 02080ｸ7 Streptococcus pneumoniae 0400 apple 06 0607 apple 06 06020607 0402 03000607 02090ｹ0 05000404-0308076ｧ902090ｹ0 02 0207 0208 2004: 00apple6ｧ9 03 0409 apple03080909086ｦ0000007090ｹ0 036ｧ86 7090ｹ0 0702066 506080206020607. 43o 09 070003036ｧ8070608 09 06 06 02030602fi 6ｾ40ｸ707-030608. ﾒ0ｷ30ｹ0, 2005. 49. Klugman KP. Antibiotic selection of multiply resistant pneumococci. Clin Infect Dis 2001, 33: 489-91. 50. Cohen R, Bingen E, Varon E, de La Rocque F, Brahimi N, Levy C, et al. Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from antibiotic therapy for acute otitis media in children. Pediatr Infect Dis J 1997, 16: 555-60. 51. Dagan R, Leibovitz E, Greenberg D, Yagupsky P, Fliss DM, Leiberman A. Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients. Pediatr Infect Dis J 1998, 17: 880-5. 52. Feikin DR, Dowell SF, Nwanyanwu OC, Klugman KP, Kazembe PN, Barat LM, et al. Increased carriage of trimethoprim/sulfamethoxazole-resistant Streptococcus pneumoniae in Malawian children after treatment for malaria with sulfadoxine/pyrimethamine. J Infect Dis 2000, 181: 1501-5. 53. Gonzales R, Steiner JF, Lum A, Barrett PH, Jr. Decreasing antibiotic use in ambulatory practice: impact of a multidimensional intervention on the treatment of uncomplicated acute bronchitis in adults. Jama 1999, 281: 1512-9. 54. Guillemot D, Carbon C, Vauzelle-Kervroedan F, Balkau B, Maison P, Bouvenot G, et al. Inappropriateness and variability of antibiotic prescription among French office-based physicians. J Clin Epidemiol 1998, 51: 61-8. 55. Kristinsson KG. Effect of antimicrobial use and other risk factors on antimicrobial resistance in pneumococci. Microb Drug Resist 1997, 3: 117-23. 56. Cizman M, Srovin T, Pokorn M, Cad Pecar S, Battelino S. Analysis of the causes and consequences of decreased antibiotic consumption over the last 5 years in Slovenia. J Antimicrob Chemother 2005, 55: 758-63. 57. Hsueh PR. Decreasing rates of resistance to penicillin, but not erythromycin, in Streptococcus pneumoniae after introduction of a policy to restrict antibiotic usage in Taiwan. Clin Microbiol Infect 2005, 11: 925-7. 58. Belongia EA, Sullivan BJ, Chyou PH, Madagame E, Reed KD, Schwartz B. A community intervention trial to promote judicious antibiotic use and reduce penicillinresistant Streptococcus pneumoniae carriage in children. Pediatrics 2001, 108: 575-83. 59. Hennessy TW, Petersen KM, Bruden D, Parkinson AJ, Hurlburt D, Getty M, et al. Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: A controlled intervention trial in rural Alaska. Clin Infect Dis 2002, 34: 1543-50. 60. Perz JF, Craig AS, Coffey CS, Jorgensen DM, Mitchel E, Hall S, et al. Changes in antibiotic prescribing for children after a community-wide campaign. J ﾞ09 ﾞ 2002, 287: 3103-9. 61. Austin DJ, Kristinsson KG, Anderson RM. The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance. Proc Natl Acad Sci USA 1999, 96: 1152-6. 62. Guillemot D, Carbon C, Balkau B, Geslin P, Lecoeur H, Vauzelle-Kervroedan F, et al. Low dosage and long treatment duration of beta-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. J ﾞ09 ﾞ 1998, 279: 365-70. 63. Craig WA, Andes D. Pharmacokinetics and pharmacodynamics of antibiotics in otitis media. Pediatr Infect Dis J 1996, 15: 255-9. 64. Dagan R, Abramson O, Leibovitz E, Lang R, Goshen S, Greenberg D, et al. Impaired bacteriologic response to oral cephalosporins in acute otitis media caused by pneumococci with intermediate resistance to penicillin. Pediatr Infect Dis J 1996, 15: 980-5. 65. Dabernat H, Geslin P, Megraud F, Begue P, Boulesteix J, Dubreuil C, et al. Effects of cefixime or co-amoxiclav treatment on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media. J Antimicrob Chemother 1998, 41: 253-8. 66. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J 1997, 16: 680-95. 67. Schrag SJ, Pena C, Fernandez J, Sanchez J, Gomez V, Perez E, et al. Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial. J ﾞ09 ﾞ 2001, 286: 49-56. 68. Cohen R, Levy C, Boucherat M, Langue J, de La Rocque F. A multicenter, randomized, double-blind trial of 5 versus 10 days of antibiotic therapy for acute otitis media in young children. J Pediatr 1998, 133: 634-9. 69. Pujol M, Gudiol F. Evidence for antibiotic cycling in control of resistance. Curr Opin Infect Dis 2001, 14: 711-5. 70. Dagan R, Givon-Lavi N, Zamir O, Sikuler-Cohen M, Guy L, Janco J, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9- valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis 2002, 185: 927-36.
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 131 71. Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003, 348: 1737-46. 72. Porat N, Arguedas A, Spratt BG, Trefler R, Brilla E, Loaiza C, et al. Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine. J Infect Dis 2004, 190: 2154-61. 73. Temime L, Guillemot D, Boelle PY. Short- and long-term effects of pneumococcal conjugate vaccination of children on penicillin resistance. Antimicrob Agents Chemother 2004, 48: 2206-13. ﾞ03030903080903 086ｧ9 : E. 060809036ｧ9 090ｹ0 罍 09 06 06 020306026ｧ8 ﾒ03060706026ｧ8 ﾞ0905 ｦﾐappleapple0802030702000608 03080408020800006ｧ908 ﾒ0ｷ3070402 07020607080ｸ7applefi03000ｷ30ｹ0 49 546 42 05000404 0308076ｧ90209 Corresponding author: E. Roilides 3 rd Department of Pediatrics Aristotle University Hippokration Hospital Konstantinoupoleos 49 546 42 Thessaloniki Greece