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346 ( 78) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 2007 72 12,919 NTT

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 347 ( 79)

348 ( 80) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 349 ( 81) 2009 5 26 1992 2007 72 19 12,919 Streptococcus pyogenes Streptococcus pneumoniae Moraxella catarrhalis Haemophilus influenzae (FQs) S. pyogenes Escherichia coli FQs E. coli 30% FQs Staphylococcus aureus (MRSA) FQs Sitafloxacin (STFX) 45% 95% S. aureus (MSSA) FQs 10% Staphylococci (MRCNS) FQs Staphylococci (MSCNS) MRSA MSCNS FQs MSSA Enterococcus faecalis FQs 22.5% 29.6% Enterococcus faecium FQs STFX (58.3%) 85% Pseudomonas aeruginosa FQs 21 27% 13 21% 5.6% 1.8% Acinetobacter spp. FQs 2.7% Neisseria gonorrhoeae FQs 86 88% 15 FQs Staphylococci Enterococci E. coli P. aeruginosa N. gonorrhoeae 90%

350 ( 82) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 (FQs) b- FQs DNA IV (LVFX) 1,2) FQs FQs 1992 LVFX FQs 3,4) FQs Escherichia coli 2000 FQs FQs b (ESBL) MRSA Streptococcus pneumoniae (PRSP) ESBL E. coli Klebsiella pneumoniae b- MBL DNA 5) FQs FQs 2007 1 12 72 19 12,919 7 1 19 12,919 Table 1 Table 2 2007 1 12 BML 80 C 2 Levofloxacin (LVFX) Ciprofloxacin (CPFX) Tosufloxacin (TFLX) Sitafloxacin (STFX) Benzylpenicillin (PCG) Ampicillin (ABPC) Clavulanic acid Amoxicillin (CVA/AMPC) Piperacillin (PIPC) Oxacillin (MPIPC) Cefaclor (CCL) Cefotiam (CTM) Cefdinir (CFDN) Cefpodoxime (CPDX) Ceftazidime (CAZ) Cefotaxime (CTX) Ceftriaxone (CTRX) Cefpirome (CPR) Meropenem (MEPM) Panipenem (PAPM) Imipenem (IPM) Aztreonam (AZT) Minocycline (MINO) Clarithromycin (CAM) Azithromycin (AZM) Telithromycin (TEL) Vancomycin (VCM) Sulfamethoxazole Trimethoprim (ST) Gentamicin (GM) Amikacin (AMK)

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 351 ( 83) Table 1. The number of isolates and their source.

352 ( 84) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 2. List of the levofloxacin surveillance group. Chloramphenicol (CP) 3 (MIC) Neisseria gonorrhoeae MIC Table 3 Clinical and Laboratory Standards Institute (CLSI, 2008) 6) MIC S. pneumoniae CLSI (2007) S. pneumoniae (PSSP) PCG MIC 0.06 mg/ml PRSP PCG MIC 2

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 353 ( 85) Table 3. Test drugs and the range of their concentrations for determination of MIC.

354 ( 86) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 4. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. mg/ml CLSI 1 1) Table 4 Table 7 Streptococcus pyogenes CPFX (86.8%) MINO (90.4%) CAM (76.8%) AZM (74.5%) 98% STFX FQs 6 8 FQs (QRDR) (Table 4) S. pneumoniae FQs CPFX (87.0%) 98% MIC 90 0.06 2.0 m g/ml STFX MIC 90 0.06 mg/ml FQs VCM TEL CVA/AMPC PAPM CTRX 100% 99.7% 99.3% 99.3% 97.3% IPM 84.2%

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 355 ( 87) Table 5. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. 18.3% 61.3% 80% (Table 4) PSSP S. pneumoniae (PISP) PRSP 52.3% 40.2% 7.5% PRSP CTRX 90% Staphylococcus aureus (MSSA) FQs MIC 90 0.06 1.0 mg/ml FQs 90.2 99.3% STFX FQs 90% ABPC 60.3% CAM AZM CPDX 76.4% 76.4% 61.5% 80% Table 5 FQs S. aureus (MRSA) MIC 90 STFX 8.0 m g/ml >16 mg/ml >64 mg/ml FQs 5.6 55.2% FQs VCM 0.0% 35.2% VCM (Table 5) Staphylococci (MSCNS) FQs MIC 90 0.12 4.0 mg/ ml FQs 87.2 99.3% CAM 79.9% AZM 79.5%

356 ( 88) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 6. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. 86.6% 100% FQs STFX (Table 6) Staphylococci MRCNS MIC 90 MRSA FQs MIC 90 0.5 >16 mg/ml 27.9 97.9% STFX MIC 90 0.5 mg/ml MINO 97.9% VCM (Table 6) Enterococcus faecalis FQs 70.4% 77.5% 100% ABPC CVA/AMPC VCM (Table 7) Enterococcus faecium VCM (100%) MINO (48.7%) STFX (41.7%) TEL (38.4%) 15% (Table 7) 2) Table 8 Moraxella catarrhalis FQs MIC 90 0.015 0.06 mg/ml 534 FQs ABPC 15.2% CVA/ AMPC b CTM 86.1% 95%

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 357 ( 89) Table 7. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. N. gonorrhoeae FQs MIC 90 0.25 32 mg/ml 11.8 13.6% STFX MIC 90 0.25 mg/ml FQs MIC 90 CTRX 0.12 mg/ml AZM 1.0 mg/ml CFDN 0.5 mg/ml MINO 0.5 mg/ml CAM 2.0 mg/ml ABPC 4.0 mg/ml CVA/AMPC 4.0 mg/ml ABPC CVA/AMPC (NPPNG) NPPNG CTX 92.3% CTRX 100% CAZ 54.5% MINO 50% 44.5% 3) Table 9 Table 14 E. coli FQs MIC 90 1.0 32 mg/ml STFX (91.8%) 73.6% 73.8% 30% CTM (12.8%) (Table 9) K. pneumoniae FQs MIC 90 0.12 0.25 mg/ml FQs 97.1 99.2% IPM PAPM (Table 9) Citrobacter spp. Enterobacter spp. FQs MIC 90 0.5 1.0 mg/ml 0.25

358 ( 90) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 8. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. 1.0 m g/ml FQs Citrobacter spp. 90.9 95.1% Enterobacter spp. 91.6 95.4% IPM PAPM (Table 10) Proteus mirabilis FQs MIC 90 1.0 8.0 mg/ml 75.7 93.6% MINO 6.4% ST CP 70.0% 74.6% FQs (Table 11) Proteus FQs MIC 90 0.12 1.0 mg/ml 91.5 97.6% FQs PAPM (100%) IPM (99.6%) CTX (97.4%) CAZ (96.7%) 4.3% 80.7% (Table 11) Serratia marcescens FQs MIC 90 0.5 2.0 mg/ml 83.6 96.0% IPM PAPM CAZ MIC 90 CAZ CTX CPDX 3 128 mg/ml 5% (Table 12) Salmonella spp. FQs MIC 90 0.03 0.06 mg/ml 98.6 100% FQs 90% (Table 12) Haemophilus influenzae FQs MIC 90 0.004 0.015 mg/ml 675 1 STFX FQs

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 359 ( 91) Table 9. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. (LVFX MIC 8.0 mg/ml) (Table 13) b- (BLNAR) 675 338 (50.1%) 338 311 (92.0%) CFDN b- (BLPAR) 48 (7.1%) CVA/AMPC (CVA/AMPC MIC 8.0 mg/ml) 20 Acinetobacter spp. FQs MIC 90 0.5 4.0 mg/ml 88.3 93.8% MINO IPM PAPM CAZ 97.5% 96.3% 94.8% 88.0% 50% (Table 13) 598 16 (2.7%) 16 14 Acinetobacter baumannii Pseudomonas aeruginosa FQs MIC 90 4.0 64 mg/ml 72.3 78.6% FQs STFX 80% PIPC (92.0%) AMK (92.0 %) CAZ (86.6%) MEPM (86.2%) GM (85.9%) (Table 14) P. aeruginosa FQs MIC 90 2.0 16 m g/ml 79.2 87.1% FQs AMK 97.3% PIPC 93.9% GM 91.2% (Table 14) CPFX, IPM, AMK (MDRP)

360 ( 92) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 10. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. 5.6% 33 1.8% 12 MDRP b 66.7% 83.3% FQs MSSA MRSA MRSA FQs 1992 7 MRSA MRSA (Hospital-associated MRSA) Pandemic clone Multilocus Sequence Typing ST5 SCCmec type II PFGE type USA100 7) FQs 8) S. pyogenes CPFX (86.8%) FQs 98% CAM 1996; 5.6%, 1998; 6.5%, 2000; 7.5%, 2002; 9.0%, 2004; 14.8%, 2007; 23.2% AZM 2000; 7.9%, 2002; 9.2%, 2004; 13.2%, 2007; 25.5% T 9)

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 361 ( 93) Table 11. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. prtf1 b- 10) S. pyogenes S. pneumoniae 47.7% PISP PRSP S. pneumoniae CAM AZM 80% 23S RNA S. pneumoniae ermb mefa ermb MIC ermb mefa 11)

362 ( 94) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 12. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. S. pneumoniae 12) S. pneumoniae FQs CPFX (13.0%) 0.0 1.2% FQs DNA IV 2 13) FQs CPFX MIC LVFX FQs 14) LVFX CPFX MIC 1 mg/ml S. pneumoniae 401 461 474 QRDR LVFX (MIC 4 mg/ml) 8 2 7 3 1 CPFX (MIC 4 mg/ml) 25 1 7 8 10 QRDR CPFX LVFX MIC 1 2 mg/ml 393 1 22 1 QRDR LVFX 8 3 FQs

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 363 ( 95) Table 13. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. PRSP 15) FQs FQs E. coli 7 2000 FQs 2007 E. coli FQs 8.2 26.4% LVFX 1994; 2.1%, 1996; 2.5%, 1998; 3.3%, 2000; 8.2%, 2002; 11.8%, 2004; 18.8% 2007; 26.2% E. coli FQ E. coli K. pneumoniae P. mirabilis CFDN 4.5 13.0% CFDN ESBL PCR E. coli 64 (8.6%) K. pneumoniae 35 (5.3%) P. mirabilis 59 (10.8%) ESBL ESBL 16) E. coli P. mirabilis E. coli ESBL

364 ( 96) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 Table 14. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of CLSI. FQs ESBL E. coli 47 K. pneumoniae 3 P. mirabilis 25 LVFX Salmonella Salmonella typhimurium DT104 17) FQs 18) ABPC CP MINO ST 4 Salmonella spp. 1 LVFX (MIC: 8.0 mg/ml) H. influenzae BLPAR BLNAR BLPAR BLNAR BLNAR BLPAR 7 19) BLNAR CFDN H. influenzae b- PBPs BLNAR BLNAR FQs P. aeruginosa FQs 7 FQs

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 365 ( 97) P. aeruginosa FQs 20) 5.6% 33 1.8% 12 2 7.8% 46 7.4% 50 b- b- bla IMP-1 P. aeruginosa S. marcescens K. pneumoniae Citrobacter freundii A. baumannii 21) P. aeruginosa bla IMP-1 P. aeruginosa UTI 5.3% RTI 2.1% 16 Acinetobacter spp. 14 A. baumannii 15 FQs Staphylococci Enterococci E. coli N. gonorrhoeae P. aeruginosa 90% 1) HOOPER, D. C.: Mechanisms of action and resistance of older and newer fluoroquinolones. Clin. Infect. Dis. (2 Suppl.): S24 28, 2000 2) CROOM, K. F. & K. L. GOA: Levofloxacin: a review of its use in the treatment of bacterial infections in the United States. Drugs 63: 2769 2802, 2003 3) YAMAGUCHI, K.; A. OHNO & Levofloxacin Surveillance Group: Investigation of the susceptibility trends in Japan to fluoroquinolones and other antimicrobial agents in a nationwide collection of clinical isolates: a longitudinal analysis from 1994 to 2002. Diagn. Microbiol. Infect. Dis. 52: 135 143, 2005 4) 2004 77 18,639 Jpn. J. Antibiotics 59: 428 451, 2006 5) SUMMERS, A. O.: Genetic linkage and horizontal gene transfer, the roots of the antibiotic multi-resistance problem. Anim. Biotechnol. 17: 125 135, 2006 6) Clinical and Laboratory Standards Institute: Performans standards for antimicrobial susceptibility testing; Fifteenth informational Supplement. Approved Standard M100-S18. CLSI 28: 2008 7) BOUCHER, H. W. & G. R. COREY: Epidemiology of methicillin-resistant Staphylococcus aureus. Clin. Infect. Dis. 46 (Suppl. 5): S344 S349, 2008 8) MARANGON, F. B.; D. MILLER, M. S. MUALLEM, et al.: Ciprofloxacin and levofloxacin resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis. Am. J. Ophthalmol. 137: 453 458, 2004 9) FACINELLI, B.; C. SPINACI, G. MAGI, et al.: As-

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THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 367 ( 99) In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,919 clinical isolates obtained from 72 centers in 2007 KEIZO YAMAGUCHI, AKIRA OHNO, YOSHIKAZU ISHII and KAZUHIRO TATEDA Department of Microbiology and Infectious Diseases, Toho University School of Medicine MORIHIRO IWATA Department of Clinical Laboratory, Toho University Omori Medical Center and Levofloxacin-Surveillance Group MAKOTO KANDA Asahikawa City Hospital MINORU YASUJIMA Hirosaki University Hospital KOUJI AKIZAWA and CHIKARA SHIMIZU Hokkaido University Hospital MAKOTO MIKI Japanese Red Cross Sendai Hospital SHINICHIROU KON, KASTUSHI NAKAMURA and KEIKO MATSUDA Municipal Muroran General Hospital MASATO HAYASHI, SYUNJI OKUBO and SYUNKOU TOYOSHIMA Hiraka General Hospital MAKOTO TOMINAGA Yamagata University Hospital TAKUO NAKAGAWA Kozirakawa Shiseidou Hospital AKIHIRO SUGITA, TATSUMI ITO and JUN KATO Yuri-Kumiai General Hospital MITSUO KAKU Tohoku University Graduate School of Medicine IMAO SEKINE and JOJI SHIOTANI The Cancer Institute Hospital of JFCR HAJIME HORIUCHI and YOKO TAZAWA Kanto Medical Center, NTT EC AKIRA SUWABE and KUMIKO YAMAHATA Iwate Medical University Hospital AKIKO YONEYAMA Toranomon Hospital CHIZUKO KAWAMURA Aomori Prefectural Central Hospital HIROMI TASHIRO, HIROKO HORIUCHI and YOSEI KATAYAMA Hachinohe City Hospital KAZUNARI KUMASAKA Nihon University Itabashi Hospital (Present: Ageo Chuo sogo Hospital) KAZUHIKO KOIKE The University of Tokyo Hospital

368 (100) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 SHIGEMI KONDOU and SHIGEKI MISAWA Juntendo University School of Medicine NOBUYUKI TANIGUCHI Jichi Medical School MISTURU MURATA and YOSHIO KOBAYASHI Keio University School of Medicine YUKIO OZAKI and TAKASHI UCHIDA University of Yamanashi Hospital HIDEYUKI OKAMOTO Kawaguchi Municipal Medical Center KENICHIRO YAMAZAKI Saitama Red Cross Hospital MOTOI OKADA Koshigaya Municipal Hospital KOSUKE HARUKI Dokkyo Medical University Koshigaya Hospital HARUSHIGE KANNO and MASANORI AIHARA Takane Hospital SHIGEFUMI MAESAKI and GIICHI HASHIKITA Saitama Medical University Hospital EIJI MIYAJIMA Yokohama City University Medical Center MIDORI SUMITOMO Yokohama City University Hospital TAKEFUMI SAITO Ibarakihigashi National Hospital NOBUO YAMANE, CHIEKO KAWASHIMA and TAKAHISA AKIYAMA Ashikaga Red Cross Hospital TAMIO IEIRI, YOSHITAKA YAMAMOTO and YUKI OKAMOTO Dokkyo Medical University Hospital MASAMI MURAKAMI Gunma University Hospital KAZUHISA INUZUKA Anjo Kosei Hospital HIDEO GONDA and IKUO YAMAGUCHI Toyohashi Municipal Hospital YOSHINORI FUJIMOTO, JUNJI IRIYAMA and YUKO ASANO Ogaki Municipal Hospital HITOSHI GENMA Fukuroi Municipal Hospital (Present: Genma Clinic) MASATO MAEKAWA Hamamatsu University School of Medicine HITOSHI YOSHIMURA Mie Prefectural Shima Hospital KANAME NAKATANI Mie University Hospital HISASHI BABA Nagoya University Hospital SATOSHI ICHIYAMA Kyoto University Hospital SHINICHI FUJITA Kanazawa University Hospital

THE JAPANESE JOURNAL OF ANTIBIOTICS 62 44 369 (101) HIDETOSHI OKABE, KUNIHIKO MORO and MASAYO SHIGETA Shiga University of Medical Science HARUYOSHI YOSHIDA, MASANOBU YAMASHITA and YUKIO HIDA University of Fukui Hospital TAKAYUKI TAKUBO and TADASHI KUSAKABE Osaka Medical College Hospital HIROYA MASAKI, HITOSHI HEIJYOU and HIDEO NAKAYA Kansai Medical University Takii Hospital KUNIMITSU KAWAHARA Osaka Prefectural Medical Center for Respiratory and Allergic Diseases MASAO KUWABARA Hirosima Prefectural Hospital TOSHIRO OKAZAKI, HIROMITSU FUJIWARA and HIROMI OTA Tottori University Hospital ASTUSHI NAGAI Shimane University Hospital JUN FUJITA and KIYOSHI NEGAYAMA Kagawa University Hospital TETSURO SUGIURA and MIKIO KAMIOKA Kochi Medical School MITSUHARU MURASE Ehime University Hospital REIKO SANO Nara Medical University Hospital SYUJI MATSUO and HISASHI KONO Tenri Hospital YOSUKE YUZUKI, NORIO IKEDA and MASAYA IDOMUKI Japanese Red Cross Society Wakayama Medical Center NOBUHISA YAMANE and ISAMU NAKASONE Faculty of Medicine, University of the Ryukyus AKIHIKO OKAYAMA University of Miyazaki Hospital YOSUKE AOKI, KOJI KUSABA and YUKARI NAKASHIMA Saga Medical School Hospital MASAYUKI SOMA and GO YAMAMOTO Nishi-kobe Medical Center SYOHIRO KINOSHITA and SEIJI KAWANO Kobe University Hospital MIKIO OKA Kawasaki Medical School NOBUCHIKA KUSANO Okayama University Hospital HIROAKI MIYANOHARA Kagoshima University Medical and Dental Hospital KAZUFUMI HIRAMATSU and TETSUNORI SAIKAWA Oita University Hospital KATSUNORI YANAGIHARA, JUNICHI MATSUDA and SHIGERU KOHNO Nagasaki University Hospital of Medicine and Dentistry

370 (102) THE JAPANESE JOURNAL OF ANTIBIOTICS 62 _ 4 DONGCHON KANG Kyushu University Graduate School of Medical Sciences KOICHI MASHIBA Kitakyushu Municipal Medical Center JUNKO ONO Fukuoka University Hospital We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcus faecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21 27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13 21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86 88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.