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1 ｧ8 BO06EIO08 6ﾑ8 A04 ﾌ6ｾ4, 18: , 2006 ﾞ03 ﾞ6ｾ4 ﾒ ﾌ09 ﾇ6ｾ4 ﾇ 01036ｧ apple020ｸ ｧ80ｹ ｸ7 apple07000ｸ fi ｸ7 X. ﾞ fiapple080ｸ703080ｹ0, 6ﾑ ｧ9 090ｹ0 縺 ｧ8 ﾒ ｧ8 ﾞ0905, ｦﾐappleapple ｧ908, ｧ ｧ ｦ ｸ702 6ｧ9 0403fi0706 apple ｧ ｹ0, ｹ0, ｦ ｦ0 6ｦ ｹ ｧ80ｹ ｸ7 apple07000ｸ fi ｸ7 (Streptococcus pneumoniae) , ｧ9 000ｹ ｸ703 閨0ｷ30ｹ ｦ , apple080ｸ7 040ｸ ｸ707 閨 apple08020ｸ7046ｧ ｹ apple000ｸ ｧ80ｹ0 090ｷ3096ｧ80ｹ0. ﾇ apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae 040ｸ7076ｧ8030ｷ30ｹ ｧ fi03080ｷ30409 (transformation), ｧ8 apple03fi ｦ0 0ｸ ｦ0 applefi , 閨 apple ｧ ｧ apple ｧ9-080ｸ7. ﾇ 026ｦ ｧ ｷ 閨 fi ｧ ｸ ｹ0 040ｸ700apple020ｷ 閨0ｷ ｷ ｸ ﾞapplefi 00apple ｧ80ｹ0 apple03000ｸ703070ｹ0, fi ｹ0 apple ｹ ｦ007080ｸ apple020ｸ ｧ80ｹ0 006ｧ ｧ , apple080ｸ7 apple ｧ9 00 apple ｸ ｧ8 00apple ｷ307, apple080ｸ7 apple030800apple6ｧ fi fi ｸ70909, 6ｧ ｹ0 000ｸ7 6ｧ ｹ ｷ3036ｧ9 0ｹ0 applefi 閨 ｹ fi ｹ0. ﾌ06 apple030804apple ｹ0 apple ｦ ｹ ｧ80ｹ ｸ7 S. pneumoniae apple03 鐶pple ｦ ｸ7036ｧ90ｷ30ｹ ｷ ｹ ｧ804090ｹ apple ｸ70400fi, apple0600fi03080ｷ ｷ ｸ ｸ709006ｧ9 0ｹ 閨030ｷ ｸ ｦ ｹ 閨0ｹ0 apple080ｸ7 閨04080ｸ707 apple ｧ9 apple ｸ ｧ apple080ｸ apple ｦ apple ｧ , ｹ ｧ ｸ ｸ 閨0ｹ0 fi ｹ0, 0ｷ30402fi apple ｹ0 0ｸ702 閨0ｹ ｨB apple fi ｦ ﾇ ｧ ｸ7 040ｸ7ｨB000ｸ70900 閨07080ｸ7 00apple02 6ｦ ｸ7 apple07000ｸ ｦ ｧ9080ｸ7 006ｧ ｸ707 02fi ｸ apple fi 020ｷ apple ｸ70400fi. 6ﾑ86ｧ ｷ fi000ｷ30ｹ apple ｧ804080ｸ fi020ｸ7apple ｸ ｧ9080ｸ7 apple080ｸ apple fi 閨 ｹ : Streptococcus pneumoniae, ｧ8, , ｹ0, 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: 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.

2 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 6ﾑ ｷ3096ｧ8 O apple07000ｸ fi ｹ0 (Streptococcus pneumoniae) apple ｧ9 閨07 applefi fi ｧ ｷ ｹ0 apple ｧ80ｹ ｧ9 0ｹ0. O ｹ0 apple080ｸ7 apple ｧ9 040ｸ70407fi ｦ0apple02080ｸ707 閨07 000ｸ7036ｦ ｷ307, applefi ｧ9 00 閨0409 0ｷ3026ｧ apple apple6ｧ 閨 apple07000ｸ ｧ9, ｧ ｧ ,2. ﾞ ｧ9 apple ｹ0 fiapple0ｷ30ｹ apple ｧ907000ｹ0, apple08-036ｧ907000ｹ0, ｧ9 000ｹ0, ｸ702036ｧ907000ｹ ｨBfi0309 6ｧ apple fi07 apple ｧ apple ｷ307 apple07000ｸ ｷ307. 6ｾ ｷ ｸ702 6ｧ90ｷ , ｧ8 0707apple020ｸ ｧ80ｹ ｸ ｧ9080ｸ ｸ70ｹ0 apple ｹ0 0ｸ702086ｦ00ｹ0 閨 ｸ ｧ apple000ｸ ｧ8 apple08020ｸ7046ｧ 閨 ｧ ｧ fi ｷ , fiapple0ｷ30ｹ0 006ｧ ｸ70208apple00apple026ｧ9 06 ( ｸ7026ｧ ｸ80408apple03 076ｧ90709), apple apple07000ｸ ｷ307 1,3,4. 6ｾ apple 03086ｦ fiapple090409, ｸ7ｨB ｧ 閨 ｦ ｹ ｧ80ｹ ｸ7 S. pneumoniae ｸ apple000ｸ ｦ0 apple 閨 ｹ0, apple 03080ｸ ｨB apple ｧ ｸ ｧ ｹ apple030ｷ304090ｹ ｹ ｧ80ｹ ｸ ｧ9080ｸ fi020902, ｸ ｧ9ｨB apple03fi 閨 apple ｧ80ｹ ﾑ fi ｾ ｸ707 閨 apple ｧ ｧ80ｹ ｸ7 S. pneumoniae ｹ0 020ｸ70306fi ｹ ｹ apple026ｦ 閨 ｦ ｧ ｹ ｹ ｦ 閨03080ｹ0, 040ｸ7ｨB ｦ apple fi ｹ 閨0ｹ apple fi 02090ｹ ｧ80ｹ ｸ7 S. pneumoniae fi ｾ404 閨 ｦ ｧ80ｹ ｸ7 S. pneumoniae apple000ｸ ｦ0 apple 閨 ｹ0 O fi0ｹ0 000ｸ ｧ9 0ｹ0 0007fi0ｹ 閨04080ｸ70ｹ0 S. pneumoniae apple fi apple ｧ9ｨB , fiapple0ｷ30ｹ ｸ70ｹ ｦ00ｹ0, ｧ8 040ｸ70902 閨 ｷ30409 (Minimal Inhibitory Concentration, MIC) 02080ｸ ｸ 閨 ｹ0 0ｸ702fi. ﾇ MIC 006ｧ ｸ 閨 ｷ ｸ ｸ7 apple080ｸ7 apple ｧ ｧ ｹ0 0707apple020ｸ701090ｹ ｸ ｧ9080ｸ7 in vitro, 0ｸ7applefi 閨07000ｹ0 040ｸ707036ｧ802000ｹ ｧ8 MIC ｧ ｧ ｸ 閨04080ｸ70ｹ ｸ 閨 fi , ｧ8 MIC ｧ ｸ ｧ ｸ 閨04080ｸ70ｹ0. ﾇ ｧ ｹ0 09ｦﾐC apple07070ｷ3 applefi apple086ｧ ｧ8 006ｧ ｧ apple ｧ9ｨB ｸ ｧ 縺06 02 apple fi ｧ9ｨB apple ｧ ｹ0 MIC ｦ0 000ｸ ｧ9 0ｹ apple036ｧ803080ｸ70ｹ ｧ80ｹ0, apple080ｸ ｧ9ｨB ｧ applefi07, ｧ8 0007fi0ｹ 閨04080ｸ70ｹ0 S. pneumoniae 0400 閨07 040ｸ 閨 fi apple ｧ fi ｧ9 08 apple apple fi0ｹ ｸ ｧ9080ｸ7 apple ｦ ｦ ｹ0 040ｸ ｹ ｸ ｸ7 applefi 0ｸ702 閨0ｹ0 apple080ｸ7 apple ｦ 閨07 000ｸ7 6ｧ 閨 ｹ03,6. 6ﾑ apple ｧ90709, 閨0ｹ0 MIC apple080ｸ ｧ9ｨB080ｸ ｸ ｧ9, ｧ ｧ ｸ7 S. pneumoniae 006ｧ ﾜ0.06, ﾝ2 00g/ml 07026ｧ 縺 ｹ apple08036ｧ907000ｹ ｹ ｹ0 ( ｧ90009, fi0709) ｧ9 020ｷ MIC applefi fiapple ｹ ｧ9000ｷ301090ｹ0 applefi S. pneumoniae: 07 apple03fi ｧ 閨0ｹ0 MIC apple080ｸ ｧ9ｨB080ｸ ｧ ｸ ｧ9080ｸ7 006ｧ apple 閨0ｹ0 ( ﾝ2 00g/ml) apple ｯ fi, ｧ9000ｷ apple6ｧ9ｨB ｹ0 006ｧ ｹ0 ( ﾝ4 00g/ml) apple 03 apple07070ｷ3, ｸ707 鐶pple0006 apple080ｸ7 閨 apple000ｸ fi apple0802 閨 ｦ0apple ｧ80ｹ ｸ7 S. pneumoniae ｦ ｧ ｧ8 090ｷ3096ｧ8, fi applefi fiapple ｹ ｧ9000ｷ301090ｹ ｹ applefi ｧ ｸ ｧ ｸ ｦ0 apple080ｸ ｧ ｾ40ｸ 閨 applefi fi ｸ ｸ apple06020ｸ ｸ 閨0ｹ0 040ｸ ｹ ｧ ｸ ｦ0 fiapple080ｸ7 閨 apple020ｸ ｧ ｧ9000ｷ , , 09 apple ｧ 閨 ｦ0 0707apple020ｸ701090ｹ ｧ80ｹ apple000ｸ ｧ80ｹ0 apple08020ｸ7046ｧ9 0ｹ0 閨 ｧ ｹ0 fiapple0ｷ30ｹ ｧ ｧ9 00 閨0409 0ｷ3026ｧ90206, 00apple0006 6ｧ ｧ904 0ｸ ｷ ｷ ｧ908 0ｸ70903fi 6ｧ 閨 ｸ70ｹ0, 07026ｧ , 006ｧ apple 閨0709, apple07000ｸ ｧ 閨0409 0ｸ7026ｧ8 006ｧ fi ｧ80ｹ0, 08086ｦ0 apple , fiapple0ｷ30ｹ ｹ0, 00apple06-020ｸ ｸ ｸ 閨0ｹ0 040ｸ ｹ ｸ70ｹ0 apple07006ｦ ｹ ﾞ02fi00 fi000ｷ30ｹ , 閨07000ｹ0 applefi 02060ｹ0 apple07000ｸ 閨0ｹ ｹ0, ｧ ｸ 閨070ｷ307 fi04000ｷ apple ｧ9 apple03080ｹ apple 03fi ｧ apple ｧ 閨 ,12, 09 apple 閨030ｷ3 6ｦ ｹ ｧ80ｹ0, 0000 apple 03080ｸ7046ｧ apple080ｸ7 閨04080ｸ707 apple08036ｦ0 0ｸ 閨0ｹ0 MIC, 00apple ｧ9 apple ｧ ｸ ｧ ｧ9- ｨB0ｷ304090ｹ ｸ ｦ0. 6ｾ 閨0409 S. pneumoniae ｸ ｧ ｧ apple ｧ90709 (MIC ﾝ8 00g/ml) ｹ ｹ0 閨04080ｸ707 apple ｷ303006ｧ ﾑ80ｸ70306apple ｹ0 ﾇ070ｷ300 閨07000ｹ ｧ9000ｹ013,14.

3 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, ﾑ8apple ｧ ｹ ｧ80ｹ ｸ7 S. pneumoniae O ｸ ｹ0 apple ｧ ｷ3apple ｦ ｧ8 apple080ｸ7 apple ｧ9ｨb applefi S. pneumoniae apple ｧ ｸ707 閨 apple09096ｧ ｹ0 020ｷ ｸ ｧ9080ｸ7 applefi ｷ3apple ｷ3apple08, ｧ ｧ904 0ｸ704090ｹ ｸ ｧ9080ｸ fi, apple080ｸ ｧ ｧ9000ｷ ｦ 08 apple fi ｧ9 0ｹ ｸ7 S. pneumoniae 006ｧ apple08036ｦ ｦ apple apple ｯ fi, ｸ70ｹ ｧ ｹ0, 00apple ｧ9 07 apple ｧ applefi apple ｧ apple ｧ apple ｨB applefi ｷ ｦ00ｹ0 apple ｹ0, fiapple0ｷ30ｹ ｸ ｷ fi0ｹ , 閨 ｹ ｹ 閨 ｹ ｧ apple06 02fi fi, ｹ applefi ｦ00ｹ0 apple ｹ0 apple080ｸ ｦ ｧ8 7,16,17. O06 040ｸ700apple020ｷ ｧ ｧ90ｹ0 00apple ｧ ｧ apple 閨 ｧ90200 applefi 000ｸ7 6ｧ ｧ90200 applefi , , 閨0409 S. pneumoniae, ｧ ｸ702086ｧ9 apple080ｸ7 040ｸ ｸ ｷ 閨 fi apple08036ｦ0 apple fi applefi apple080ｸ7 閨04080ｸ ｧ9000ｷ30109 applefi S. pneumoniae 7, 閨0ｹ 閨0ｹ0 020ｷ307 apple08030ｸ ｸ ｦ ｸ ｸ7 S. pneumoniae 閨04080ｸ ｷ ｧ9 046ｧ apple fi applefi fi020ｸ7apple ｧ9 fi apple ｧ9 020ｷ apple080ｸ ｧ9ｨB080ｸ ｧ ｹ ｹ0 076ｧ802080ｸ 閨07080ｸ70ｹ ｦ0apple080ｸ70ｹ0, fiapple0ｷ30ｹ0 006ｧ B, 9V, 9A, 14, 19F F ｧ fi fi ｧ ｸ 閨 fi020ｸ7apple ｧ9ｨB ｦ apple fi ｹ ｧ80ｹ apple fi ｧ fi 閨0409 0ｸ ｷ ｦ0apple0ｷ307 apple ｧ9ｨb080ｸ ｸ ｦ fi ｸ ｸ70ｹ0 0803fi020ｸ7apple080ｸ70ｹ ｸ707 鐶pple0006 0ｸ7086ｧ ｦ 閨 ｦ00ｹ0 apple ｹ fi 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 ｨB ｧ 閨070006, 閨 ｧ802080ｸ ｸ 閨07080ｸ70ｹ ｸ70ｹ0, ｸ ｧ fi ,19. 縺06 03fi09080ｸ70ｹ0 fi0406 applefi030ｸ ｦ00ｹ0, ｧ9 applefi 0ｸ702086ｦ00ｹ ｸ70ｹ ｸ70ｹ0 閨04080ｸ707 apple ｧ ｧ , fiapple0ｷ30ｹ ｧ9 000ｹ0, ｨBfi ｸ702036ｧ ,20. 6ﾑ8apple 閨0ｹ 閨02000ｹ ﾑ fi 閨04080ｸ ｧ fi0206, fiapple0ｷ30ｹ ｹ0 6ﾑ80ｸ7030ｷ3apple 0ｸ8-02 閨0ｹ ｹ ｹ0 ﾇ070ｷ300 閨07000ｹ ｧ9000ｹ0, 09 apple ｧ9 020ｷ apple080ｸ7 apple applefi 0ｸ ｧ90ｹ ｧ90ｹ0 6ｧ ｧ90ｹ apple07000ｸ ｧ ｧ9000ｷ ｧ802080ｸ ｸ70ｹ0 apple 03 apple07070ｷ ｦ0apple080ｸ70ｹ0. O fi020ｸ7apple0806 0ｸ702086ｧ9 apple apple02 6ｦ ｸ7ｨB000ｸ 閨 fi ｸ7 S. pneumoniae, apple080ｸ ｸ702 6ｧ9 0403fi ｸ ｧ ｹ ｾ400 fi, apple06apple fi 02090ｹ ｧ80ｹ ｸ7 S. pneumoniae ﾑ , 0806 apple fi ｹ0 applefi 02060ｹ 閨02000ｹ0 apple080ｸ7 閨04080ｸ ｸ703006ｧ9 applefi apple 03 閨04080ｸ ｧ ｸ ｹ0 apple 閨0ｹ ｹ ｹ0, fiapple0ｷ30ｹ0 09 ﾞ ｧ ﾒ036ｧ ｾ402060ｹ 閨02000ｹ0 0ｸ702 閨0ｹ0 02 apple ｧ80ｹ ｸ7 S. pneumoniae apple ｧ ｸ700 6ｧ applefi 13.1%-22% ( ｧ8) applefi 3.8%-12% (apple036ｧ803090ｹ ｧ8), ｸ ｸ7026ｧ applefi 16.8%-42.8% ｧ ｧ8 6ｦ 閨 ｧ apple ｧ80ｹ0 apple080ｸ7 006ｧ ｧ ｹ 閨0ｹ ｹ ｧ9 0ｹ ｸ ｦ 閨0409 apple080ｸ7 006ｧ ｷ300 閨 ｸ ｧ apple ｧ90709 apple 03080ｸ7046ｧ9 ｨB ｧ , fiapple0ｷ30ｹ ｸ ｸ7026ｧ90709, ｸ702036ｧ ｨBfi0309, ｦ apple fi applefi 閨0409 apple080ｸ7 6ｧ ｸ7 6ｧ apple ｧ applefi ｸ ｧ apple ｷ3apple000ｸ ｧ90ｷ307 applefi fi ﾑ , apple apple08066ｧ apple ｧ8 閨03000ｸ ｧ80ｹ ｸ7 S. pneumoniae, 0000 apple030ｷ ｸ7036ｧ ｹ ｧ80ｹ0 ﾒ ｧ80ｹ ｸ apple ｧ9080ｸ7 ﾞ ｸ ｧ8 ﾒ applefi apple 閨0ｹ0 apple 閨0ｹ ｹ ｹ029,30. ﾇ 閨03000ｸ707 apple ｸ70208apple086ｧ 閨 ｸ ｧ9 0ｹ ｸ7 S. pneumoniae applefi ｸ ｧ ｸ apple ｧ9 0ｹ , ｹ applefi ｧ apple07000ｸ ｧ ｧ9000ｷ ｧ 閨0ｹ apple ｧ80ｹ ｸ ｧ9080ｸ ｦ0 020ｷ fi030ｷ ｷ ｹ ｹ0. 6ｾ apple6ｧ apple 03080ｸ ｨB ｸ70708apple apple 閨 , 0906 fi ｹ apple ｧ ｹ ｧ902090ｹ0. 00apple0ｷ30ｹ0 08 6ｧ , 006ｧ apple ｧ80ｹ ｸ7 S. pneumoniae apple ｧ90709 (020ｸ7036ｧ90ｷ30ｹ ｧ8), ｸ ｧ90009, ｸ ｸ7026ｧ90709, ｸ702036ｧ ｨBfi0309. ﾇ ｧ ｸ7 S. pneumoniae ｹ0 0700fi ｹ fi07000ｹ ｧ ｧ90709, ｹ ｸ7026ｧ90709, 006ｧ apple03080ｹ apple 03fi ｧ ｧ ｧ80ｹ ｸ7 S. pneumoniae ｦ ｸ ｦ00ｹ0 0402fi04080ｸ70ｹ ｦ ｸ7 S. pneumoniae. O ｧ9 0ｸ702086ｧ9 0402fi ｹ ｧ9-

4 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 096ｧ ｹ (%) ｹ0 (IR) apple036ｧ803080ｸ70ｹ0 (R ) ｧ80ｹ S. pneumoniae apple080ｸ7 apple applefi ｸ ｸ apple ﾑ ﾑ ｸ ｷ ｧ90709 ﾒ ｸ ｧ90009 ﾒ fi0709 6ﾑ8030ｸ ｸ7026ｧ90709 ｦ ｸ702036ｧ90709 ﾒ ｨBfi0309 IR 20,3 1,8 0,8 0,8 1,6 18,7 R 14,8 24 0, ,8 25, ｧ 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apple 閨 閨 ｸ ｸ S. pneumoniae ﾞapple 閨 閨 ｸ ｸ S. pneumoniae ｧ9 00 閨040ｷ3 020ｷ307 08apple086ｧ90ｷ fi apple026ｦ ｧ8 7,32 040ｸ ｧ9ｨB apple6ｧ O fi0ｹ ｹ0 020ｷ ｧ9- ｨB ｦ ｧ ｸ70ｹ 閨07ｨB0ｸ700 apple080ｸ 閨04080ｸ ｦ ｸ7 020ｸ ｦ ｹ ｸ7 S. pneumoniae, 02060ｹ fi ｹ0 apple ｸ 閨0ｹ0 apple030ｷ302000ｹ107000ｹ0 (PBPs) 32,33. ﾇ 0707apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae ｹ ｹ ｧ ｹ0 020ｷ ｧ90ｷ307 apple080ｸ7 020ｷ apple ｦ ｹ0 PBPs apple ｨB080ｸ fi ｦ ｹ0 020ｷ307 apple030ｷ302000ｸ ｸ ｸ 閨 ｷ30ｹ 閨04080ｸ707 apple ｧ9 apple PBPs 0ｸ ｦ ｦ ｸ70ｹ0 (PBPs 1a, 1b, 2x, 2a, b) ｧ ｦ ｦ ｸ70ｹ032. 縺 apple020ｸ70109 apple036ｧ803080ｸ70ｹ ｧ80ｹ ｸ7 S. pneumoniae, 03 apple03 鐶pple ｸ ｦ ｹ apple fi ｹ0 applefi 006ｧ9 PBPs. 6ｾ40ｸ7076ｧ8030ｷ30ｹ0, ｹ ｹ0 apple030ｷ302000ｹ107000ｹ0 PBP2x PBP2b ｦ ｧ ｹ ｹ ｧ apple030800applefi apple020ｸ70109 apple036ｧ803080ｸ70ｹ ｧ80ｹ0, apple080ｸ7 apple ｹ ｹ0 PBPs, fiapple0ｷ30ｹ0 09 PBP1a ｦ ｧ ｦ ｧ9 0707apple020ｸ701090ｹ ｧ80ｹ ｸ7 S. pneumoniae ｹ ｧ9 000ｹ0. O apple ｹ ｧ9ｨB ｧ8 (efflux) 02080ｸ ｸ7 閨010ｷ3 applefi ｦ , 00 閨040ｷ ｧ9 0ｹ0 apple080ｸ7 020ｷ apple ｧ applefi ｧ mef(a). ｦ 閨 ｸ7 S. pneumoniae apple 閨0708 0ｸ702fi fi 076ｧ802080ｸ fi020ｸ7apple08 09, 07000ｸ7036ｧ ｸ70407fi ｦﾌfi ﾞ ｧ8, 閨04080ｸ ｧ ｹ ｧ90ｹ ｧ90ｹ ｧ9 000ｹ0, fiapple0ｷ30ｹ0 006ｧ ｸ ｸ7026ｧ90709, ｸ7026ｧ ｨB ｸ7026ｧ fi0408, 閨0409 0ｸ ｧ ｸ7 6ｧ ｸ ｧ ｧ8, fiapple0ｷ30ｹ0 006ｧ ｧ90ｹ ｧ9 000ｹ0, ｧ9 000ｹ0 ( ｸ7026ｧ90709), apple ｧ ｹ0 ｦﾌ (02080ｸ70ｸ80708apple ｧ90709/ apple ｧ90709) ｧ9 000ｹ0 ( ｸ7026ｧ90709) 32,35. O 006ｦ ｹ fi0ｹ ｧ80ｹ0 apple ｷ apple086ｧ ｷ ｸ ｧ9080ｸ7 erm(b) ｹ ｸ ｹ0, apple080ｸ ｸ ｧ ｧ907090ｹ S ｷ fi RNA 02080ｸ ｧ9080ｸ7, 0000 apple0802 閨 ｧ ｹ ｧ80ｹ ｧ80ｹ ｸ ｹ ｧ ｹ0 046ｦ ｧ80ｹ ｸ fi O fi020ｸ7apple080ｹ0 apple080ｸ ｧ fi 0ｸ702fi apple ｷ30ｹ0 MLS B, apple 03080ｸ ｨB0006 apple036ｧ ｧ fi03000ｹ ｹ ｧ9 000ｹ0, ｧ9 000ｹ apple ｧ907000ｹ0, apple ｧ ｸ7-0407fi ﾑ80ｸ70306apple09 32,35,36. 6ｾ ｹ ｸ7-036ｧ ｦ fi020ｸ7apple MLS B, ｧ8 040ｸ70407fi apple086ｧ9 apple ｦ apple 03080ｸ ｨB ｸ ｹ ｹ ｹ ｧ ｹ ｧ9 0707apple020ｸ701090ｹ ｧ80ｹ ｸ7 S. pneumoniae ﾞ fi0ｹ0 apple ｷ307 6ｾ402fi04080ｹ fi0ｹ ｧ80ｹ ｹ0 (apple ｧ907000ｹ0, ｸ 閨0ｹ apple08036ｧ907000ｹ0) apple030ｷ302000ｹ107000ｹ0 (PBPs) ｧ8 0402fi04080ｸ ｧ9 000ｹ0 23S ｷ fi RNA ｧ8 0402fi04080ｸ7, ｧ8 (efflux) ﾒ fi07000ｹ0 DNA 090ｸ apple080ｸ IV ｧ8 0402fi04080ｸ7, ｧ8 (efflux) ｦ ｸ702036ｧ S ｷ ｧ8 0ｸ7apple ｧ8 0402fi04080ｸ ｷ fi S ｷ ｧ8 0ｸ7apple ﾑ807ｨB0ｸ ｧ apple08apple086ｧ ｸ ｸ7 ﾒ ｨBfi ｸ ｸ ｧ ｸ ｧ8 0402fi04080ｸ7

5 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 閨02000ｹ026, ﾇ 0707apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae 0402 apple fi applefi ｦ , fiapple0ｷ30ｹ ｹ0, ｧ9 000ｹ0, ｸ ｧ ｷ fi0309, 04apple ｧ ｧ ｧ apple ｧ9080ｸ739. 6ｾ40ｸ7076ｧ8030ｷ30ｹ ｧ8 apple 閨040ｷ fi03080ｷ304090ｹ0 (transformation), ｧ8 apple03fi ｹ ｦ0 0ｸ ｦ0 applefi 閨 閨040ｷ ｸ707 0ｸ ｦ0, 6ｧ fi apple08ｨBfi (transposons), ｧ ｧ DNA apple080ｸ7 apple 閨04080ｸ ｧ9 06 apple080ｸ ｧ9ｨB ｦ00ｹ ｧ80ｹ07,39. 6ﾑ801 6ｧ apple ｦ apple020ｸ ｧ80ｹ ｨBfi ｹ ｧ80ｹ ｹ fi ｹ0, apple080ｸ7 040ｸ ｧ apple03 閨0ｹ 閨0ｹ ｹ0. ﾒ 06 apple fi000ｷ30ｹ0, apple020ｸ70109 apple036ｧ803080ｸ70ｹ ｧ80ｹ ｹ fi07000ｹ0 apple030800apple0803 閨 apple apple03 閨0ｹ ｹ0 6ｧ ｦ0 0ｸ ｦ0 00 閨040ｷ fi03080ｷ304090ｹ07,40. ﾇ ｷ307 apple 03 apple07070ｷ apple020ｸ701090ｹ ｧ80ｹ0 閨 ｧ fi ｹ0 0ｸ ｧ80ｹ ｹ ｹ ｧ80ｹ ｸ7 S. pneumoniae apple ｸ70400fi ｸ707 鐶pple apple ｧ8 020ｷ ｷ apple ｦ ｹ ｧ80ｹ0 0ｸ7026ｧ80ｹ applefi07 02 fi 閨 , apple fi applefi , 08 apple fi0ｹ0 6ｧ ｧ9000ｷ ｸ apple ｸ ｦ0 applefi 閨0409 S. pneumoniae ｧ ｸ applefi ｸ ｷ 閨0ｷ 閨 fi ﾇ de novo 0707apple020ｸ ｧ80ｹ 閨0409 apple080ｸ7 6ｧ ｸ7 6ｧ , 0ｷ30ｹ0 apple0802 閨 ｹ ｦ ｹ ｧ80ｹ0 090ｷ3096ｧ80ｹ0, 040ｸ ｧ apple fi fiapple0ｷ30ｹ fi07000ｹ0, fiapple080ｸ ｧ9 02fi ｧ apple ｧ ｧ ｦ ｹ0 MIC, 006ｧ ｸ707 02fi 閨0409 S. pneumoniae ｧ ｧ904080ｸ fi apple036ｧ ｧ8 40. ｦ fi0200 fi000ｷ30ｹ0, ｧ ｧ ｷ303006ｧ ｦ ｹ0 apple ｹ ｧ80ｹ ｸ7 S. pneumoniae; ｦ 閨00 0ｸ702fi 07 apple026ｦ ｸ7-07 閨 ｧ ｧ ｸ7 S. pneumoniae Eapple 閨0ｹ 閨02000ｹ0 applefi ｹ ｹ012, applefi ﾑ 閨04080ｸ ｧ fi apple03fi apple006ｧ apple ｧ fi apple ｦ007080ｸ apple fi 閨0409 S. pneumoniae ｸ 閨07, ｾ40ｸ fiapple080ｸ703080ｹ ｸ707. 陦 fi apple 03080ｸ7046ｧ S. pneumoniae ｸ70909 apple ｧ9 0ｹ ｸ ｨBfi ｧ 閨 閨03000ｹ0 apple ｹ0 036ｧ ｹ ｸ7 006ｧ ｹ022. O00086ｧ90ｷ30ｹ Arason ｸ707., apple ｹ0 apple08030ｸ7apple ｧ ｸ ｷ307 apple 03 09fi07020ｷ ｦ007080ｸ7, 陦 fi apple ｧ9 0ｹ0 00 閨 apple ｦ ｧ ｸ ｨBfi apple 03080ｸ7046ｧ ｸ apple ｧ S. pneumoniae ｹ fi ｸ fi020902, 0806 Granizo ｸ707. 陦 fi ｦ ｹ ｷ304090ｹ ｦﾐ04apple 076ｧ9, apple00036ｧ , 040ｸ ｨBfi apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae ｹ ｧ ｹ ｧ9000ｹ O06 Garcia-Rey ｸ707., 閨03080ｸ 閨 ｷ304090ｹ apple ｧ80ｹ ｸ7 S. pneumoniae ｹ0 apple 閨0ｹ ｹ0 ｦﾐ04apple 076ｧ9 0ｹ0, 陦 fi ｷ ｧ9 0ｹ0 applefi 02060ｹ0 6ｦ 閨0ｹ ｧ9000ｹ , 020ｷ ｷ , 040ｸ ｨBfi apple020ｸ ｧ80ｹ0 02fi ｹ ｹ0 fi ｹ ｧ9 000ｹ044. ﾒ fiapple Pihlajamaki ｸ707. 陦 fi ｷ ｨBfi03090ｹ ｹ0 apple 閨0ｹ ｹ ｧ9 0ｹ0 040ｸ ｨBfi apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae ｸ ﾒ ｷ3096ｧ ｹ0 apple ｧ904 0ｹ0 apple ｧ80ｹ0 閨03000ｸ707 0ｹ ｧ80ｹ ｸ7 S. pneumoniae ,31, 06 apple fi apple ｧ ｹ ｧ902090ｹ0, 閨0409 S. pneumoniae apple080ｸ7 apple applefi ｸ70909 apple apple080ｸ7 006ｧ ｹ apple ｦ ｧ ｧ ｸ fi ｹ0 MIC apple ｧ ｸ 閨0409 applefi apple apple086ｧ ｧ ｧ ｹ048. ﾇ ｸ7046ｧ9 020ｷ fi020ｷ307 apple080ｸ ｦ ｦ S. pneumoniae applefi ｧ ｧ80ｹ0 090ｷ3096ｧ80ｹ ｧ applefi030ｸ ｧ8. O06 apple fi ｧ ｧ9 apple 03080ｸ ｨB apple6ｧ , apple ｸ apple ｸ apple ｧ ｷ307 apple080ｸ7 6ｧ apple 03fi ｹ ｧ8 040ｸ70902 閨 ｷ 閨 ｹ0 090ｷ3096ｧ80ｹ0, ｷ ｸ7 6ｧ ｷ applefi 閨0409 applefi ｧ ｧ8 applefi ｸ70ｹ 閨0ｹ ｧ apple006ｧ9, ｹ

6 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 2 096ｧ ｹ ｧ ｧ9 apple080ｸ ｦ0080ｸ 閨 ｦ ｧ ｹ apple020ｸ701090ｹ ｧ80ｹ ｸ7 S. pneumoniae fi0ｹ fi0ｹ0 ﾞapple ｸ ｷ307 ﾞ ｧ apple006ｧ9 ﾞ0707apple020ｸ ｧ80ｹ ｧ ｧ8 ﾇ ｧ ｷ3036ｧ ｸ ｸ70909 apple ｧ apple ｧ9 applefi 000ｸ7 6ｧ 閨 fi ｧ ｸ ｦ ｧ9ｨB ｸ7 6ｧ 閨 apple0603 閨 (00apple ｦ007) ｧ ﾇ ｧ8 090ｷ3096ｧ ｧ ｧ9ｨB ｸ7 6ｧ ｷ3036ｧ9, 閨 ｸ apple fi ｹ0 apple ｦ fi 0402 閨 ｹ0 applefi ｧ8. ﾞ 閨 apple026ｦ de novo ｧ ｧ ｹ ｹ 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 ｷ307, apple ｦ007 閨 ｷ ｸ7 6ｧ ｷ de novo 0707apple020ｸ apple ｧ ｹ0 090ｷ3-096ｧ80ｹ07,12,20,49. 00apple0ｷ30ｹ0 6ｧ8 09 閨 ｧ9, ｸ702 6ｧ9080ｹ fi0ｹ0, ｧ8 09 de novo 0707apple020ｸ ｧ80ｹ ｸ7 6ｧ 閨 ｸ7 S. pneumoniae ｹ apple006ｧ9 0ｹ0 apple ｧ apple ﾇ 06 apple6ｧ904020ｷ ｸ7026ｧ8 閨 apple ｷ303006ｧ9 applefi 閨02000ｹ ｧ80ｹ ｹ ｷ3036ｧ9 0ｹ ｸ ｸ apple , applefi ｧ ｧ80ｹ0 090ｷ3096ｧ80ｹ050, 51. O06 apple fi ｧ9 08 6ｧ fi ｧ apple ｸ ｷ307 6ｧ8 09 applefi ｸ ｧ apple006ｧ apple03 鐶pple0006 0ｷ30402fi apple ｧ9 fi0206, ｸ ｹ0 apple ｧ ｦ ｧ ｧ9 0ｹ ｹ S. pneumoniae fi020902, 00apple ｧ ｧ ｧ80ｹ0 090ｷ3096ｧ80ｹ0 00apple ｧ9, 02080ｸ ｷ , ｸ ｧ apple ｧ8apple ｧ ｸ ｦ0 0ｸ7apple ｹ fi0ｹ ｸ ｧ9080ｸ7 apple080ｸ ｧ fi apple ｦ ｹ ｹ fi0ｹ0 0ｸ7apple ｧ9 fiapple080ｸ7 閨 apple020ｸ ｧ ｧ9000ｷ 縺06 apple , 0400 apple00036ｧ9apple020ｷ ｧ9 0ｹ0 00 閨04090ｹ0 0ｷ3026ｧ ｹ0 0ｸ7apple ｹ fi0ｹ S. pneumoniae 閨 ｸ70ｹ fi applefi07 apple080ｸ ｧ apple006ｧ ｹ0 0ｷ3026ｧ ｹ0 006ｧ ｧ9040ｷ30ｹ0 apple0608 apple fi 07 00apple0603 閨 閨0409 S. pneumoniae apple ｯ fi, ｧ apple ｦ apple006ｧ9 080ｸ ｧ9000ｷ301090ｹ0. ﾒ 02 ｯ 0ｸ702fi fiapple08, 09 00apple 閨 ｹ ｧ804090ｹ0 020ｷ apple006ｧ ｷ ｸ7 07 apple07000ｸ ｦ0 00apple ｧ9 07 閨 ｦ apple6ｧ9apple020ｷ apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae ｸ702 閨0ｹ0 apple ｯ fi, ｧ ｸ70ｹ apple006ｧ9 020ｷ ｸ ｷ 閨 apple03fi ｹ0/apple ｦ ｹ ｧ80ｹ ｸ7 S. pneumoniae O 閨0ｹ0 apple080ｸ7 閨04080ｸ707 apple ｧ9 6ｧ ｧ apple03fi ｧ apple fi 02090ｹ ｧ80ｹ ｸ7 S. pneumoniae ｸ ｧ9ｨB apple6ｧ , apple ｸ ｷ ｹ ｧ804090ｹ0 020ｷ , apple08apple086ｧ ｷ ｦ ｷ apple000ｸ ｷ307 ( fi0409, apple006ｧ9 0ｹ0, 00apple ｧ apple.) 閨03080ｹ ｦ00ｹ0 0203fiapple080ｸ70ｹ apple ｹ ｸ7 apple ｧ ｹ 閨 apple080ｸ7 閨04080ｸ707 apple ｧ apple03fi ｧ8/ apple fi 02090ｹ ｧ80ｹ0 020ｷ ｦ fi0ｹ ｧ804090ｹ ｦﾌ ｧ90ｷ ｷ304090ｹ ｷ307 ｦ 0308apple08apple086ｧ ｧ80ｹ0 090ｷ3096ｧ80ｹ fi fi ｧ apple080ｸ apple ｦ apple ｧ fi apple006ｧ9 0ｹ apple006ｧ ｸ707 0ｸ7 0400fi ﾒ0ｸ ｧ ｧ ｦﾌ ｧ90ｷ ｸ70000fi03080ｷ304090ｹ ｸ ｦ00ｹ apple000ｸ fi 04046ｧ800 6ﾑ ｧ9 0203fiapple ｨBfi ｧ E fi0ｹ0 縺 S. pneumoniae, 閨07000ｹ0 applefi 0ｸ702 閨0ｹ ｹ fi 080ｸ70ｹ0 閨04080ｸ ｸ7ｨB09026ｧ apple fi (6 503 鐶pple ｧ )

7 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, ｧ ｹ0, fiapple0ｷ30ｹ0 006ｧ ｸ703006ｧ ｧ80409 apple07000ｸ ｦ ｧ9080ｸ77,12,20,49. ﾞ) fi0ｹ0 040ｸ ｹ ｦ fi0ｹ0 fi fi ｹ0 apple ｹ apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae 006ｧ ｧ , 閨 ｧ apple 閨0ｹ ｹ apple 閨 ｸ ｹ ｷ304090ｹ ｧ80ｹ0 040ｸ ｧ80ｹ ｸ70ｹ apple ｧ ｧ , fi, ｹ0 apple fi ｹ ｹ0, 0700apple020ｸ70900 閨07000ｹ 縺06 apple , ｹ0 fiapple0ｷ30ｹ ﾇ070ｷ300 閨07000ｹ ｧ9000ｹ 罍 03036ｧ9, 閨 ｷ303006ｧ ｸ704076ｧ8 040ｸ ｷ ｧ90ｹ ｹ ｸ7 070ｷ ｸ7 07 apple07000ｸ ｦ0 53,54. 6ｾ400 apple fi, fi000ｷ30ｹ0, ｧ9000ｹ 閨030ｷ304090ｹ apple ｦ ｹ ｧ ｹ ｧ fi07020ｷ30ｹ0 apple 閨0ｹ apple fi 02090ｹ ｧ80ｹ ｸ7 S. pneumoniae; O 閨0ｹ 閨02000ｹ0 apple080ｸ7 閨04080ｸ ｸ703006ｧ ｧ apple 閨0ｹ ｸ7ｨB ｦ apple ｷ3. 6ｾ ｦﾐ ｧ9, ｷ ｹ ｧ804090ｹ , ｧ ｨBfi03090ｹ0, ｸ ｦ applefi 00006ｧ90ｷ ｸ7 apple ｦ0 020ｷ S. pneumoniae apple080ｸ7 6ｧ apple ｧ ｾ ｾ ｧ9, ｷ ｹ0 040ｸ ｧ80ｹ ｷ304090ｹ % apple00036ｧ9apple080ｸ ｦ , apple0600 閨03080ｸ70ｹ ｷ ｹ0 040ｸ ｹ ｹ ｸ ｧ907090ｹ ｸ ｦ ｷ % % 07026ｧ , 040ｸ ｦ applefi ｷ ｸ7 apple ｦ0 020ｷ apple ｧ S. pneumoniae applefi 23% 0400 apple00036ｧ9apple080ｸ7 15%. ﾇ 00006ｧ90ｷ ｹ ｧ80ｹ ｦ ｸ7026ｧ ｹ ｷ304090ｹ ｸ70402 閨 fi0ｹ0 閨02080ｸ70ｹ056. 6ｾ ｦ 0ｸ , ｷ ｹ ｷ304090ｹ % ｦ ｸ ｦ applefi 00006ｧ90ｷ ｸ7 apple ｦ0 apple036ｧ803080ｸ70ｹ ｧ80ｹ ｸ7 S. pneumoniae apple ｧ90709 applefi 25% % fi0408, 0806 apple030804apple ｹ0 apple ｦ ｹ0 040ｸ ｹ ｧ ｸ ｦ apple applefi ｷ ｹ ｧ80ｹ ｸ7 S. pneumoniae. 6ｾ apple ｧ ｸ7 Wiskonsin 020ｷ307 ﾇ070ｷ300 閨070ｷ apple apple08066ｧ ｸ 閨0709 apple030804apple apple ｦ ｧ80ｹ ｧ804090ｹ0 020ｷ apple080ｸ ｦ apple , 00 閨04 applefi 040ｸ ｧ 閨030ｷ fi ｷ307 apple ｷ307 fi ｷ ｾ apple080ｸ ｦ ｧ 閨030ｷ304090ｹ0, 06 apple ｷ ｹ ｷ ｹ applefi 11%-23%, 040ｸ ｹ0 apple 閨0ｹ0, 040ｷ3036ｧ90ｹ0 07 apple ｧ ｧ90ｷ ｸ7 apple ｦ0 020ｷ S. pneumoniae 58. ﾞ apple030804apple apple080ｸ7 閨 閨0ｹ fi ｹ ｹ0 ﾞ ｹ0 040ｸ ｦ applefi 00006ｧ90ｷ ｹ ｷ304090ｹ0 020ｷ %, 040ｷ3036ｧ90ｹ0 fi000ｷ30ｹ ｧ ｧ90ｷ ｹ ｧ80ｹ ｸ7 S. pneumoniae apple ｧ ｦ 閨03080ｹ0, Tennessee 020ｷ307 ﾇ070ｷ300 閨070ｷ , apple 03fi ｧ9 apple ｦ ｹ ｷ ｹ ｸ ｦ applefi ｷ ｸ7026ｧ80ｹ %, 040ｷ3036ｧ90ｹ ｧ apple ｧ80ｹ0 020ｷ S. pneumoniae apple080ｸ7 apple applefi ｸ 閨0ｹ ｹ0. 6ｾ 閨0209 0ｸ7026ｧ8 0ｷ30402fi 閨 apple fi0ｹ0 000ｸ ｧ9 0ｹ ｸ ｧ9080ｸ7 applefi ｸ ｧ ｸ 閨0ｷ ﾞapplefi 02060ｹ0 apple 03 apple07070ｷ 閨02000ｹ0 08 6ｧ ｯ ｧ807 fi apple030804apple ｹ0 apple ｦ ｹ0 040ｸ ｹ0 020ｷ , fi ｧ907080ｸ ｸ fi 0203fiapple08, ｨB ｹ0 02 0ｸ702fi ｸ70ｹ ｸ ｦ00ｹ0 0ｸ709006ｧ9 0ｹ fi, 00apple ｦ007 apple apple06026ｦ004080ｸ apple fi 02090ｹ ｷ304090ｹ fi0408, 08 apple ｹ0 0402fi04080ｹ ｹ ｧ90ｷ304090ｹ0 020ｷ307 apple ｧ80ｹ ｸ7 S. pneumoniae ｧ fi apple06020ｸ apple O ｧ90ｹ0 03fi ｯ 0ｸ702fi ｧ ｷ ｧ9, 08 6ｧ fi000ｷ30ｹ0 fi 閨07000ｹ0 applefi 02060ｹ 閨02000ｹ fi0ｹ0 0403fi07080ｹ0 applefi 02fi0200 apple080ｸ7 00apple ｦ ｧ90ｷ ｹ ｷ304090ｹ0 020ｷ ｷ apple fi 020ｷ307 apple ｧ80ｹ ｸ7 S. pneumoniae 58, 閨03 閨 ｧ9 fi ｷ apple ｧ80ｹ0 020ｷ ｧ90ｷ 閨 apple ｧ ｧ ｸ70402 閨 applefi 02fi0200 apple080ｸ7 00apple06020ｸ apple fi0ｹ ｹ ｷ304090ｹ0 020ｷ ｷ ｹ0 03fi09080ｹ apple086ｧ apple ｹ0 applefi 02060ｹ 閨02000ｹ apple ｧ ｧ90ｷ ｹ ｧ80ｹ0 006ｧ ｧ9040ｷ30ｹ0 fi fi0ｹ ｷ304090ｹ ｹ ｷ ｹ0 020ｷ ( applefi 11%-35% ) ｧ ｹ0. 6ｾ400 apple 閨0ｹ apple06apple fi apple fi07 07 apple ｧ apple ｧ ｧ90ｷ ｹ ｷ304090ｹ ｸ7apple ｸ apple 閨 ｦﾌ) ｦ 0308apple08apple086ｧ apple000ｸ ｷ307. ﾇ ｧ8 apple6ｧ9040ｷ3 applefi 0ｸ7026ｧ apple 閨 ｧ fi0206, 02fi ｧ apple ｧ ｹ0 apple 03 6ｧ ｹ ｧ ｹ0, 03 apple ｧ9 apple 閨 apple ｧ80ｹ ﾑ86ｧ ｸ707 02fi fi000ｷ30ｹ ｧ907080ｸ apple08apple0806-6ｧ ｹ apple000ｸ ｧ800 02, apple fi0209-

8 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, ｹ ｧ80ｹ apple ｧ O apple08apple08066ｧ ｹ0 0ｸ702 閨0ｹ0 閨04080ｸ707 apple ｧ apple03fi apple020ｸ701090ｹ ｧ80ｹ ｷ apple ｸ7 S. pneumoniae (fiapple0ｷ30ｹ apple ｷ307 Mycobacterium tuberculosis, Plasmodium falciparum, Shigella spp ｷ Gram ｧ90ｷ307), apple ｸ ｧ ｸ fi04000ｷ , ｧ ｷ307 apple080ｸ apple ｦ apple ｧ , ｷ ｹ ｹ apple006ｧ9 0ｹ0, ｸ702fi ｧ ｸ707 0ｸ ｦ ｧ ｸ ｧ ｧ8 0ｸ , 閨03080ｹ ｧ90ｷ ｸ70000fi03080ｷ304090ｹ ｸ ｦ00ｹ apple000ｸ fi 04046ｧ800 (096ｧ907. 4) 7,20. ﾇ ｧ ｸ fi04000ｷ , fi0ｹ ｸ7 fi apple ｧ ｧ apple ｧ apple ｷ307 applefi 00 閨 閨0409, fiapple0ｷ30ｹ0 6ｧ 閨 apple ｦ , 03000ｷ303006ｧ applefi ｦ00ｹ0 040ｸ ｧ90ｹ09,12,20 fi ｧ ｸ707 02fi ｸ apple03fi ｧ apple fi 02090ｹ0 0707apple020ｸ701090ｹ ｧ80ｹ ｸ7 S. pneumoniae. ﾇ 07apple ｸ7026ｧ ｧ9ｨB fi ｹ0 0ｸ 閨0ｹ0 fi ｹ apple ｸ ｧ ｧ9ｨB0ｷ ｷ ｸ7-6ｧ ｷ ｷ 閨 ｸ ｧ9080ｸ7, 02fi ｧ ｹ ｧ9000ｷ301090ｹ0 fi ｸ ,9,12,20. ﾇ ｹ ｧ9 0ｹ applefi ｧ8 03 閨 ｷ30ｹ0 040ｸ707 鐶pple apple fi 02090ｹ apple ｹ0 0ｸ fi ｾ ｧ 閨0209 apple080ｸ7 apple apple ｧ9 0ｹ , 閨 fi0206 0ｸ apple086ｧ9 006ｧ ｧ ｧ8 fi ( fi applefi ｸ7fi ) 6ｧ apple006ｧ9 006ｧ 閨 apple fi applefi 閨03000ｹ0, 006ｧ ｦ apple fi 閨03080ｸ 閨0409 S. pneumoniae 040ｸ apple apple080ｸ7 006ｧ fi0409 6ｧ apple086ｧ ｹ apple006ｧ9 0ｹ0 6ｧ 閨0ｷ30ｹ 閨03000ｹ062. 縺 fi0ｹ0 apple ｷ30ｹ0 006ｧ fi ｸ ｹ0 020ｷ apple080ｸ7 apple ｦ ｧ ｧ9ｨB0ｷ ｷ 閨 S. pneumoniae applefi ｸ 閨04080ｸ ｸ ｸ ｧ 閨 apple ｧ9 apple ｹ0 006ｧ ｸ 閨0ｹ0 fi ｹ fi , apple086ｧ9000ｹ apple06026ｦ004080ｸ ｧ9ｨB0ｷ ｸ ｧ9080ｸ7. ｦ 閨03080ｹ0, 09 apple fi ｹ ｧ ｹ0 0ｸ fi04000ｷ apple03fi ｧ8 apple fi 02090ｹ ｧ80ｹ apple6ｧ9apple00 08 apple ｸ ｦ 閨 ｧ9 apple030808apple ｸ7-0700apple060ｹ apple ｦ ｦ ｧ8 040ｸ700apple ﾇ 07apple apple080ｸ7 0ｸ7apple ｧ9ｨB ｧ ｷ307 apple080ｸ apple ｦ apple ｧ , ｧ9ｨB ｦ ｹ 閨0ｹ 閨0ｹ ｦ0 020ｷ ｹ 閨0ｹ ｸ 閨0ｹ ｸ70ｹ fi ｹ0. 縺06 apple , apple 閨07080ｸ ｹ ｹ0, apple ｧ ｧ9ｨB0ｷ ｷ ｧ90ｷ307 00apple06020ｸ fi ｸ70902 閨 ｷ ｸ ｸ ｧ ｹ ｧ9000ｷ301090ｹ0 0ｸ7apple ｧ ｧ ｹ0 MIC 02080ｸ ｦ ﾝ40% 02080ｸ ｦ ｧ ｹ0 apple080ｸ ｧ ｦ0 020ｷ307 fi04000ｷ 閨07, fi ｧ ｹ0 MIC 02080ｸ7 S. pneumoniae 006ｧ apple6ｧ9apple ｹ ｹ0 ( g/ml) 6ｧ8 apple036ｧ803080ｸ70ｹ0 (2 00g/ml) ｧ80ｹ apple ｧ90709, 00fi ｸ ｧ fi apple06020ｸ ｸ ｸ ｹ ｸ70ｹ0 apple080ｸ7 apple ｦ apple 03 apple07070ｷ3 apple030800applefi , ｸ ｧ apple06020ｸ apple ｧ90ｹ0 040ｸ ｹ apple S. pneumoniae ｧ apple ｧ ｹ apple08036ｧ907000ｹ0, fiapple0ｷ30ｹ fi0309, apple 閨 ｧ90009, apple06020ｸ ｸ ｸ 閨0ｹ0 040ｸ ｹ 閨 ｸ70ｹ ｧ9ｨB0ｷ ｷ S. pneumoniae ｧ8 apple036ｧ ｧ8 20,63,64. ｦ 086ｦ ｧ fi ｧ ｷ ｸ702 6ｧ90ｷ307 0ｸ apple apple000306apple ｹ ｧ9 0ｹ0 00 閨04090ｹ0 0ｷ3026ｧ ｹ0 00apple ｧ ｸ ｧ apple S. pneumoniae, 0008fi 閨 閨 apple 閨 fi apple ｸ70400fi 020ｷ ｸ ｧ9080ｸ7 apple080ｸ7 apple ｧ9000ｷ ﾇ 0ｸ7applefi ｸ7026ｧ8 00apple ｦ ｸ 閨0ｹ 閨0ｹ ｹ0, fiapple080ｸ fi ｧ ｧ fi apple 閨0ｹ0 applefi ｸ ｧ ｧ9- ｨB0ｷ S. pneumoniae applefi 閨 ｸ70ｹ ｹ ｷ ｸ7 apple ｦ0 020ｷ ｸ ｸ ,20, ｸ7036ｧ ｸ70207, fi000ｷ30ｹ0, ｸ 閨07000ｹ ｹ , apple ｦ apple 閨07000ｹ 閨02000ｹ apple6ｧ9apple00 08 apple ｸ ｦ0 apple 閨07080ｸ apple ｷ303006ｧ applefi ｧ ｸ 閨070ｷ ｧ ｷ307 0ｸ ｸ ｧ9 6ｧ8 apple ｧ9ｨb S. pneumoniae fi ﾇ apple03fi ｸ ｷ ｦ ｷ apple000ｸ ｷ307 apple080ｸ7 apple ｸ (096ｧ907. 4) ｧ9ｨB apple fi ｧ ｧ fi0ｹ0 08 6ｧ ｧ apple 閨0ｹ0 apple000306apple ｹ066, 閨03080ｸ ｸ 閨 ｸ ｦ ｸ707 鐶pple0006 apple fi ｸ apple020ｸ

9 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, ｦ 閨02000ｹ apple ｦ00ｹ ｧ90ｹ0 陦 fi ｧ fi ｦ fi ｧ fi apple fi ｧ ｧ S. pneumoniae apple006ｧ9 apple ｯ fi ｧ fi fi apple fi ｹ0 00 閨03000ｹ062, fi ｹ 閨02000ｹ0 0ｸ702 閨0ｹ ｧ ｸ707 02fi ｸ ｧ9 apple ｹ0 6ｧ apple030ｷ fi0ｹ0 apple ｹ0 apple080ｸ ｨBfi ｷ ｹ ｧ80ｹ0: ｧ apple006ｧ9-0ｹ0 6ｧ fi ｸ ｸ7. 6ﾑ8apple06apple03 閨0807, apple036ｧ8 020ｸ708036ｧ8 apple08030ｸ ｧ 閨 ｦ ｹ ｹ0 56ｧ ｹ ｧ ｧ ｸ ｧ907090ｹ ｸ ｦ apple006ｧ ｹ ｧ9 0ｹ0 00 閨04090ｹ0 0ｷ3026ｧ ｹ 陦 ｧ apple fi 閨0409 S. pneumoniae apple006ｧ9 68. T 閨03080ｹ0, 0806 Dagan ｸ707. 陦 fi apple ｦ00ｹ ｧ90ｹ 閨0ｹ apple ｸ7-0400fi 020ｷ S. pneumoniae apple080ｸ7 apple ｧ9ｨb080ｸ ｸ ｧ ｸ ｧ907080ｸ 閨 ｹ0 apple ｹ 閨03000ｹ0 applefi 閨 ｹ ｧ80ｹ0 090ｷ3096ｧ80ｹ 閨07 0ｸ70207, 08 03fi03080ｹ ｹ ｧ ｹ ｦ ｷ apple000ｸ ｷ apple fi 6ｧ apple03fi ｹ0 0707apple020ｸ701090ｹ ｧ80ｹ ｸ7 S. pneumoniae 006ｧ ｧ ｹ0. ﾇ apple006ｧ apple fi ｸ7 0007fi0ｹ 閨 ｧ apple fi 02090ｹ0 0707apple020ｸ701090ｹ ｧ80ｹ ｹ ｹ0, fiapple0ｷ30ｹ0 applefi fi HIV 6ｧ M. tuberculosis 閨0708 fi000ｷ30ｹ0 fi apple006ｧ9 020ｷ307 apple07000ｸ ｷ ｸ7076ｧ8030ｷ30ｹ ｧ9 036ｧ909000ｹ0 00 閨03000ｹ0, de novo 0707apple020ｸ ｧ80ｹ0, 00 閨040ｷ ｷ ｸ7 S. pneumoniae, apple03080ｹ ｹ0 apple fi ｹ ｹ ｧ apple , ｧ apple036ｧ80ｹ0 6ｧ apple036ｧ80ｹ0 090ｷ3096ｧ80ｹ ｧ 閨 閨 apple03fi ｹ0 0707apple020ｸ701090ｹ ｧ80ｹ ｸ7 S. pneumoniae 7. ﾇ 020ｸ ｧ ｧ ｷ307 閨 ｧ9, 0000 apple ｧ903 apple 閨 , apple fi 02090ｹ0 0707apple020ｸ701090ｹ ｧ80ｹ fi6 506 apple080ｸ7 apple ｦ 閨0ｹ ｹ0 (020ｸ7036ｧ90ｷ30ｹ Gram) 69. 縺 apple00036ｧ9apple020ｷ ｸ7 S. pneumoniae, fi000ｷ30ｹ0, 09 apple 閨 ｸ7026ｧ ｧ 閨 fi0900, 08086ｦ apple ｧ9 020ｷ307 apple000306apple ｷ ｧ ｹ ｹ fi ｹ0. ﾇ ｧ90ｷ ｹ0 040ｸ70000fi03080ｷ304090ｹ ｸ ｦ00ｹ0 apple03080ｹ apple000ｸ fi 04046ｧ800 apple fi ｸ apple000ｸ fi apple0802 閨 , 0ｸ ｹ fi fiapple080ｸ ｸ ｹ ｸ ｦ ｸ ｸ70ｹ ｦ00ｹ0 006ｧ apple07-070ｷ3 applefi MIC 6, 0ｷ30402fi ｧ 閨 applefi apple ｧ9 07 apple ｧ apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae 閨02000ｹ0 apple07070ｷ ｸ702fi 閨 閨04080ｸ707 apple apple ｧ9. 縺 , fiapple080ｸ apple 03 閨 ｧ9 02fi ｷ3036ｧ90ｹ ｧ8 040ｸ ｧ8, 6ｧ9040ｷ30ｹ0 07 閨 apple fi ｧ ｸ70000fi03080ｷ ｷ apple ｸ ｦ ｧ ｧ ｧ fi applefi ｧ ｦ0. ) ｸ fi fi ｦ 08 00apple02 6ｦ ｸ7ｨB000ｸ70900 閨 fi ｸ7 S. pneumoniae, apple080ｸ ｸ702 6ｧ9 0403fi ｸ ｧ ﾑ , apple ｧ9ｨb0006 fi fi ｹ ｹ apple fi 02080ｸ ｸ70909 applefi 040ｸ 閨07080ｸ70ｹ ｦ0apple080ｸ70ｹ ｸ ｧ9080ｸ7, apple080ｸ7 閨 ｧ9 fi ｸ707 閨 ｸ fi apple fi ｧ80ｹ , fi applefi ｸ703006ｧ ｧ ｸ ｧ9080ｸ apple fi apple ｸ70400fi ｧ ｧ90ｷ ｷ307 apple ｧ80ｹ ｸ7 S. pneumoniae, 03fi090ｷ ｹ0 020ｷ ｦ0apple0ｷ307 apple080ｸ7 0ｸ702fi ｦ0apple fi0408 6ｧ8 09 閨 ｧ9 72, ｧ apple fi 07 apple ｧ ｦ 閨 閨 , ｧ8 00apple ｦ0apple0ｷ ｸ7 S. pneumoniae apple080ｸ apple fi ｸ702fi. ﾇ apple 閨030ｷ3 040ｸ7ｨB6ｧ ｹ 閨04090ｹ ｦ0 apple07000ｸ ｦ ｧ9080ｸ ｧ80ｹ ｸ7 S. pneumoniae ｦ applefi applefi 02090ｹ fiapple ｹ0 0ｸ7026ｧ80ｹ0. 6ｾ40ｸ700apple O fi ｹ0 apple ｹ ｦ007080ｸ apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae 006ｧ ｧ ｷ307, ｦ ｧ ｷ 閨 fi ｧ ｸ ｹ0 040ｸ700apple020ｷ 閨0ｷ307. O 閨0ｹ0 apple080ｸ7 apple ｧ ｧ ｷ3036ｧ ｸ ｸ ｧ ｧ9ｨB apple fi apple ｸ ｧ8 00apple ｷ307 apple080ｸ7 apple030800apple6ｧ fi fi 6ｧ ｹ0 000ｸ7 6ｧ ｹ ｷ3036ｧ9 0ｹ0 applefi 閨 ｹ fi ｹ0. De novo 0707apple020ｸ ｧ80ｹ ｸ7 S. pneumoniae ｧ80ｹ0 090ｷ3096ｧ80ｹ0, 0ｷ30ｹ0 apple08-02 閨 ｷ307, 040ｸ ｧ apple , fiapple0ｷ30ｹ apple apple020ｸ ｧ80ｹ ｹ fi07000ｹ0. O06 apple030804apple ｹ0 apple ｦ ｹ ｧ80ｹ ｸ7 S. pneumoniae apple03 鐶pple ｦ ｦ

10 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, ｷ ｹ ｧ804090ｹ apple ｸ70400fi, apple ｹ 閨030ｷ fi ｷ ｸ ｸ709006ｧ9 0ｹ0, ｸ ｦ fi02 07 apple ｧ902070ｸ , fi ｸ ｦ0, apple ｦ ｷ3036ｧ90ｹ ｧ8 040ｸ ｧ8. 6ﾑ86ｧ apple fi, 080ｸ fi0ｹ0 apple fi0ｹ ｹ ｧ80ｹ0 07 apple ｧ ｦ ｦ ｧ90ｷ ｹ ｷ304090ｹ0 020ｷ , ｧ ｧ909080ｸ70308 fi fiapple0806 apple ｦ applefi fi fi, apple fi apple fi0706, 08applefi apple030804apple apple03 鐶pple ｧ ｸ ｧ80ｹ0. ﾇ 04036ｧ apple080ｸ apple ｦ apple ｧ , ｹ ｧ ｸ ｸ 閨0ｹ0 fi ｹ0, apple ｦ 閨0ｹ0 apple ｹ apple ｸ7 apple ｧ ｹ ｹ ｧ80ｹ0, apple080ｸ7 fi000ｷ30ｹ ｨB apple fi ｦ ｦ 閨03080ｹ0, ｸ703006ｧ ｧ ｸ7 040ｸ7ｨB000ｸ70900 閨07080ｸ7 apple07000ｸ ｦ ｧ9080ｸ7 apple fi07 07 apple ｧ apple apple ｸ70400fi, 006ｧ ｷ fi000ｷ30ｹ 閨 apple ｧ804080ｸ ｸ ｧ9080ｸ7 apple080ｸ ｦ0apple applefi fi ﾇ 0707apple020ｸ ｧ80ｹ0 020ｷ ｧ90ｷ ｸ707 閨 ｧ fi fi ﾑ86ｧ 閨080ｹ0 fi030ｷ ｷ ｸ ｸ709006ｧ9 0ｹ0 fi fi fi ｸ7 apple ｧ ｹ ｸ , fiapple08, apple06046ｧ ｸ , 03 apple03 鐶pple ｸ ｧ9 09 apple030804apple fi ｸ 閨07080ｸ ｸ7 03fi03080ｸ7 apple080ｸ7 00apple ｧ9 07 apple 6ｧ9ｨB080ｸ707 apple ｹ0 fiapple0ｷ30ｹ apple ｧ8 040ｸ 閨070ｷ , ｦ fi ｹ apple006ｧ9 0ｹ0, applefi ｦ apple apple fi 02090ｹ ｹ0 6ｧ ｧ ｹ S. pneumoniae fi ｦﾌ ｧ9 1. Cartwright K. Pneumococcal disease in western Europe: burden of disease, antibiotic resistance and management. Eur J Pediatr 2002, 161: Obaro SK, Monteil MA, Henderson DC. The pneumococcal problem. BMJ 1996, 312: Kaplan SL, Mason EO, Jr. Management of infections due to antibiotic-resistant Streptococcus pneumoniae. Clin Microbiol Rev 1998, 11: 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: 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, Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998, 26: 1-10; quiz 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: Rothermel CD. Penicillin and macrolide resistance in pneumococcal pneumonia: does in vitro resistance affect clinical outcomes? Clin Infect Dis 2004, 38 Suppl 4: S 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: Jacobs MR. In vivo veritas: in vitro macrolide resistance in systemic Streptococcus pneumoniae infections does result in clinical failure. Clin Infect Dis 2002, 35: 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: 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: 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: 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: 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: 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: 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: Klugman KP. Pneumococcal resistance to antibiotics. Clin Microbiol Rev 1990, 3: Doern GV, Brueggemann AB, Blocker M, Dunne M, Holley HP, Jr., Kehl KS, et al. Clonal relationships

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13 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 18, 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: 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: 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: ﾞ ｧ9 : E ｧ9 090ｹ0 罍 ｧ8 ﾒ ｧ8 ﾞ0905 ｦﾐappleapple ｧ908 ﾒ0ｷ ｸ7applefi03000ｷ30ｹ ｧ90209 Corresponding author: E. Roilides 3 rd Department of Pediatrics Aristotle University Hippokration Hospital Konstantinoupoleos Thessaloniki Greece