2 2 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb Neisseria gonorrhoeae ceftriaxone CTRX % 2010 CTRX 20 FQ staphylococci, E. faecium, N.

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Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 1 1 2013 69 11,762 2015 11 16 1994 2013 69 19 11,762 FQ 33 Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae FQ S. pneumoniae 8 H. influenzae 2002 β- H. influenzae 2010 2013 2002 25.8%, 2004 40.0%, 2007 50.1%, 2010 57.9%, 2013 57.1% FQ Escherichia coli MIC 4 μg/ml levofloxacin 34.4% Klebsiella pneumoniae E. coli FQ Staphylococcus aureus MRSA FQ sitafloxacin 55.3% FQ 15.8 18.0%S. aureus FQ 87.0 99.3% Enterococcus faecium FQ 6.8 24.7% Pseudomonas aeruginosa FQ 83.4 89.3% 88.1 93.7% 80% FQ P. aeruginosa 2007 1.6% Acinetobacter spp. FQ Imipenem 2.7% 14 Acinetobacter 0.2% 1

2 2 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Neisseria gonorrhoeae ceftriaxone CTRX 2007 100% 2010 CTRX 20 FQ staphylococci, E. faecium, N. gonorrhoeae, E. coli 30% 31.7 87.1% ciprofloxacin 80% FQ 80% β- Extended-spectrum β-lactamase: ESBL Escherichia coli, Klebsiella pneumoniae 1 β- Metallo-β-lactamase MBL 2 Carbapenem-resistant Enterobacteriaceae CRE Multiple drug-resistant Acinetobacter : MDRA 3 1994 FQ FQ 4 7 FQ Escherichia coli 2000 FQ FQ ESBL 2013 1 12 69 19 11,762 Quinolone resistance determining region QRDR β- 1. 69 2013 1 12 19 11,762 Table 1 Table 2 1 1 10 2. levofloxacin LVFX ciprofloxacin CPFX tosufloxacin TFLX sitafloxacin STFX pazufloxacin PZFX nalidixic

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 3 3 Table 1. List of the levofloxacin surveillance group acid NA benzylpenicillin PCG ampicillin gentamicin GM amikacin AMK linezolid ABPC clavulanic acid/amoxicillin CVA/AMPC LZD daptomycin DAP piperacillin PIPC tazobactam/piperacillin TAZ/ PIPC oxacillin MPIPC cefaclor CCL cefotiam 3. CTM cefdinir CFDN cefpodoxime CPDX ceftazidime CAZ cefotaxime CTX ceftriaxone CTRX cefpirome CPR meropenem MEPM panipenem PAPM imipenem IPM aztreonam MIC Neisseria gonorrhoeae AZT minocycline MINO clarithromycin MIC CAM azithromycin AZM vancomycin Table 3 VCM sulfamethoxazole/trimethoprim ST

4 4 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Table 2. The number of isolates Clinical and Laboratory Standards Institute CLSI M100-S24 8 CLSI European Committee on Antimicrobial Susceptibility Testing EUCAST 9 Staphylococcus aureus MIC S. aureus MSSA MPIPC MIC 2 μg/ml S. aureus MRSA MPIPC MIC 4 μg/ ml staphylococci MIC staphylococci MSCNS MPIPC MIC 0.25 μg/ml staphylococci MRCNS MPIPC MIC 0.5 μg/ml Streptococcus pneumoniae S. pneumoniae PSSP PCG MIC 0.06 μg/ml PISP PCG MIC 0.12 1 μg/ml S. pneumoniae PRSP PCG MIC 2 μg/ml 4. Haemophilus influenzae β- H. influenzae 10 β-

Table 3. Test drugs and the range of their concentrations for determination of MIC Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 5 5

6 6 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 5. QRDR S. pneumoniae, Streptococcus pyogenes, H. influenzae, E. coli, K. pneumoniae QRDR 11 S. pneumoniae gyra Ser81, Glu85 gyrb Asp435, Glu474 parc Ser79, Asp83 pare Asp435, Glu474 S. pyogenes gyra Ser81, Glu85 parc Ser79, Asp83 H. influenzae gyra Ser84, Asp88 parc Ser84, Glu88 E. coli gyra Ser83, Asp87 parc Ser80, Glu84 K. pneumoniae gyra Ser83, Asp87 parc Ser80 LVFX MIC 20% 20 MIC 20 LVFX MIC 10 MIC 10 6. ESBL E. coli, K. pneumoniae, Proteus mirabilis CTX CVA, CAZ CVA MIC CTX, CAZ MIC 8 ESBL PCR CTX-M 7. -β- Metallo-β-lactamase MBL CAZ IPM Acinetobacter spp. Pseudomonas aeruginosa SMA MBL PCR IMP-1 IMP-2 VIM-1 VIM-2 8. P. aeruginosa, Acinetobacter spp. P. aeruginosa Acinetobacter spp. MIC CPFX 4 μg/ml, IPM 16 μg/ml, AMK 32 μg/ml P. aeruginosa MDRP multi-drug resistant P. aeruginosa Acinetobacter spp. MDRA multi-drug resistant Acinetobacter spp. 1. 1 Table 4 1 S. aureus MSSA 725 MSSA FQ MIC 90 0.12 4 μg/ ml 87.0 99.3% FQ STFX FQ ABPC 48.8%, CPDX 53.4%, CAM AZM 74.3%, 72.3%, PIPC 89.9% 97.8 100% 2 S. aureus MRSA 665 MRSA FQ MIC 90 16 64 μg/ml STFX 55.3% FQ 15.8 18.0% FQ VCM, LZD, DAP 100% 0 55.6% MRSA Community-acquired MRSA CA-MRSA LVFX 1 μg/ml MINO 4 μg/ml CAM 2 μg/

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 7 7 Table 4. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of Clinical and Laboratory Standards Institute

8 8 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Table 4. Continued

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 9 9 Table 4. Continued ml 9.3% 62/665 3 staphylococci MSCNS 516 MSCNS FQ MIC 90 0.12 8 μg/ml 81.6 98.6% FQ CAM, AZM 76.7%, 75.2% 93.6 100% 4 staphylococci MRCNS 677 MRCNS MIC 90 MRSA FQ STFX MIC 90 1 μg/ml 93.5% FQ MIC 90 16 64 μg/ml 24.1 28.4% VCM, LZD DAP 100% 5 S. pneumoniae 599 S. pneumoniae FQ MIC 90 0.06 4 μg/ml CPFX 74.3%, PZFX 89.6% FQ 97.8 100% STFX MIC 90 0.06 μg/ml 100% FQ VCM, CVA/AMPC, PAPM, CTRX 100%, 98.2%, 98.2%, 97.2% 14.0 85.6% CAM,

10 10 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 AZM 80% S. pneumoniae 599 PSSP, PISP, PRSP 345 57.6% 220 36.7% 34 5.7% PSSP FQ LVFX 98.8%, CPFX 74.5%, TFLX 99.1%, STFX 100%, PZFX 88.1% PRSP LVFX 88.2%, CPFX 41.2%, TFLX 94.1%, STFX 100%, PZFX 76.5% FQ PSSP PRSP CPFX, PZFX 33.3 11.6 STFX PSSP, PRSP 100% 6 S. pyogenes 384 S. pyogenes FQ MIC 90 0.06 4 μg/ml PZFX, CPFX 72.4%, 78.9% 96.1 100% FQ CAM 64.6%, AZM 63.5%, MINO 87.2% 100% 7 Enterococcus faecalis 629 E. faecalis FQ 71.1 87.3% FQ MPIPC, CCL, CTM, MINO, CAM, AZM 0 42.6% 92.1 100% ABPC, CVA/AMPC, VCM, DAP 8 Enterococcus faecium 511 E. faecium FQ 6.8 24.7% FQ VCM 100%, LZD 99.4%, DAP 99.4% 0 39.7% Table 5. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of Clinical and Laboratory Standards Institute

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 11 11 2 Table 5 1 Moraxella catarrhalis 504 M. catarrhalis FQ MIC 90 0.015 0.06 μg/ml 100% FQ ABPC 14.1% 89.1 100% CVA/AMPC ABPC β- 2 N. gonorrhoeae 58 N. gonorrhoeae FQ MIC 90 LVFX, CPFX, TFLX 16 32 μg/ml 25.9% STFX MIC 90 0.5 μg/ml FQ ABPC CVA/AMPC 1.7%, 0% CTRX 1 MIC 1 μg/ml, 1.7% MIC LVFX 1 μg/ml, CVA/AMPC 2 μg/ml, AZM 0.5 μg/ml, MINO 1 μg/ml 3 Table 6 1 E. coli 712 E. coli FQ MIC 90 STFX 16 32 μg/ml 65.0 65.7% STFX MIC 90 2 μg/ml FQ FQ 51.3 100% IPM, PAPM 2 Klebsiella spp. 662 Klebsiella spp. FQ MIC 90 0.25 0.5 μg/ml 94.4 97.1% E. coli 30% FQ ABPC 6.3%, ST 32.2% 84.1 99.7% 3 Citrobacter spp. 543 Citrobacter spp. FQ MIC 90 0.25 1 μg/ml 91.3 96.1% FQ ABPC 12.9% 40.0 99.8% IPM, PAPM, GM, AMK 97% 4 Enterobacter spp. 628 Enterobacter spp. FQ MIC 90 0.12 0.5 μg/ml 93.8 97.8% FQ ABPC, CVA/AMPC, CCL, CTM, CFDN, CPDX, ST 6.4 59.7% 71.0 99.7% PAPM, MINO, GM, AMK 90% 5 P. mirabilis 512 P. mirabilis FQ MIC 90 1 8 μg/ml 80.5 93.6% FQ MINO 1.6% 60.2 100% TAZ/PIPC 6 Proteus spp. 417 Proteus spp. FQ MIC 90 0.25 1 μg/ml 92.6 98.3% FQ 90% NA, PIPC, TAZ/PIPC, CAZ, CTX, GM, AMK 7 Serratia spp. 590 Serratia spp. FQ MIC 90 0.5 2 μg/ml 86.3 98.3% FQ ABPC 3.7%, CVA/AMPC 2.9%, CCL 0.5%, CTM 0.8%, CFDN 3.6, ST 3.7% CAZ, PAPM, GM, AMK 99% AMK

12 12 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Table 6. In vitro activities of drugs against clinical isolates and percentages of isolates susceptible to test drugs on the basis of Clinical and Laboratory Standards Institute 8 Salmonella spp. 123 Salmonella spp. FQ MIC 90 0.03 0.06 μg/ml 91.9 96.7% FQ ST 73.2%, ABPC 82.9%, PIPC 83.7, MINO 87.0% 90%

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 13 13 Table 6. Continued 9 H. influenzae 620 H. influenzae FQ MIC 90 0.004 0.03 μg/ml 99.5 100% LVFX MIC 8 μg/ml 1 STFX MIC 0.5 μg/ml β- BLNAR,

14 14 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Table 6. Continued ABPC MIC 2 μg/ml 620 354 57.1% 323 91.2% CFDN MIC 2 μg/ml β- BLPAR, ABPC MIC 2 μg/ ml 45 7.3% 16 35.6% CVA/AMPC MIC 8 μg/ml 10 Acinetobacter spp. 512 Acinetobacter spp. FQ MIC 90

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 15 15 Table 6. Continued 0.25 4 μg/ml 89.5 93.8% FQ CCL, CTM, CFDN, CPDX, ST, ABPC 0.2 22.7% TAZ/PIPC, PAPM, IPM, MINO, GM, AMK 90% IPM 512 14 2.7% 9 Acinetobacter baumannii MDRA 0.2% 1/512 11 P. aeruginosa 1,175 P. aeruginosa FQ MIC 90 2 16 μg/ml 1 4 μg/ml MIC 90 2 8 83.4 89.3% 88.1 93.7% FQ

16 16 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 CTX PAPM 20% 70% CAZ, GM, AMK 90% MDRP 1.6% 9/559 MDRP 2. QRDR S. pneumoniae, S. pyogenes, H. influenzae, E. coli, K. pneumoniae QRDR Table 7 1 S. pneumoniae LVFX MIC 8 μg/ml 10 5 50.0% QRDR 3 GyrA ParC GyrB ParC LVFX MIC 4 μg/ ml 3 MIC 1 μg/ml, MIC 2 μg/ml 87 11 12.6% 20 3 15.0% GyrA ParC, GyrB ParC, GyrA ParE 2 S. pyogenes LVFX MIC 4 μg/ml LVFX MIC 8 μg/ml 15 QRDR 12 GyrA ParC LVFX MIC 2 μg/ml MIC 2 μg/ml, MIC 1 μg/ml 20 19 95.0% 19 5 26.3% ParC 1 GyrA ParC MIC 0.5 μg/ml QRDR 3 H. influenzae LVFX MIC 4 μg/ml 1 MIC 8.0 μg/ml 1 GyrA ParC LVFX MIC 2 μg/ml MIC 0.03 μg/ml 0.06 0.25 μg/ml GyrA 0.5 μg/ml, 2 μg/ml GyrA ParC 4 E. coli LVFX MIC 4 μg/ml MIC 8 μg/ml 50 GyrA ParC LVFX MIC 2 μg/ml 0.125 2 μg/ml 77 67 87.0% 0.5 μg/ml 1 1 μg/ml 4 2 μg/ml 3 GyrA ParC 0.06 μg/ml 5 K. pneumoniae LVFX MIC 8 μg/ml 18 15 83.3% QRDR 12 GyrA ParC LVFX MIC 4 μg/ml 5 2 40.0% GyrA 1 GyrA ParC 1 LVFX MIC 2 μg/ml 180 11 6.1% GyrA 1 3. ESBL ESBL E. coli 17.8%

Table 7. MICs and types of substitutions identified in genes containing quinolone resistance determining regions Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 17 17

18 18 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Table 8. Detection rates of extended-spectrum β-lactamase producing strains Table 9. Detection rates of metallo-β-lactamase producing strains 127/712 K. pneumoniae 6.7% 37/552 P. mirabilis 10.9% 56/512 2004 2013 ESBL Table 8 ESBL E. coli 2004 2013 3.3% 17.8%, K. pneumoniae 2.1% 6.7% P. mirabilis ESBL 4. MBL MBL Acinetobacter spp. 1.0% 5/512 IMP-1 4 IMP-2 1 P. aeruginosa MBL 1.8% 10/559 IMP-1 10 8 MDRP P. aeruginosa MBL 2007 2013 Acinetobacter spp. 2004 2013 P. aeruginosa MBL Table 9 Acinetobacter spp., P. aeruginosa MBL 0 2% P. aeruginosa MBL 2004 7.2% 2013 1.8% 69 2013 11,762 19 FQ FQ 1994 LVFX,

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 19 19 CPFX, TFLX FQ STFX FQ PZFX 5 FQ MSSA FQ 87.0 99.3% MRSA FQ STFX 55.3% FQ 15.8 18.0% 1994 4 7 MRSA VCM, LZD, DAP MSSA VCM, DAP 3 VCM MIC 4 μg/ml 1 DAP MIC 2 μg/ml 1990 CA-MRSA CA-MRSA LVFX 1 μg/ml MINO 4 μg/ml CAM 2 μg/ml 1994 2007 2% 2010 4.6%, 2013 9.3% 2007 2010 2013 2013 75.8% 47/62 CA-MRSA USA300 12,13 VCM MRSA MIC 2 μg/ml 2002 2010 0.9% 8.9% 2013 2.0% VCM MIC 2 μg/ml S. pneumoniae FQ CPFX 74.3%, PZFX 89.6% 97.8 100% LVFX MIC 2 μg/ml MIC 1 μg/ml 2004 17.9% 2013 72.3% FQ DNA IV QRDR 2 14 LVFX MIC 1 μg/ml 87 11 MIC 2 μg/ ml 20 3 GyrA, GyrB, ParC, ParE MIC 1 μg/ml 2 MIC 2 μg/ml 1 QRDR S. pyogenes FQ PZFX, CPFX 72.4%, 78.9% 96.1 100% LVFX 2007 1.2%, 2010 1.4% 2013 2.9% QRDR LVFX MIC 4 μg/ml GyrA ParC LVFX MIC 1 μg/ml 2 μg/ml ParC QRDR FQ E. coli 2000 FQ 4 7 E. coli FQ 3.2 34.7% 4 7 E. coli LVFX 1998 2.5%, 2000 6.2%,

20 20 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 2002 8.6%, 2004 16.8%, 2007 23.4%, 2010 27.1%, 2013 31.9% 2002 2007 6.6 8.2% 2007 2013 3.7 4.8% LVFX 61.6% 76.3% 66.0% 77.2% 15 K. pneumoniae FQ E. coli QRDR E. coli LVFX MIC 2 μg/ml 168 67 39.9% GyrA ParC K. pneumoniae LVFX 180 11 6.1% GyrA E. coli, K. pneumoniae, P. mirabilis ESBL 17.8% 127/712 6.7% 37/552 10.9% 56/512 E. coli 2004 2013 3.3% 17.8% ESBL ESBL 16 ESBL LVFX E. coli ESBL 81.1%, ESBL 21.1% χ 2 P 0.0001 K. pneumoniae ESBL 21.6%, ESBL 1.9% χ 2 P 0.0001 P. mirabilis ESBL 48.2%, ESBL 3.3% χ 2 P 0.0229 ESBL LVFXK. pneumoniae, P. mirabilis FQ E. coli FQ ESBL FQ H. influenzae FQ 99.5 100% QRDR LVFX 0.06 0.25 μg/ml GyrA QRDR 0.5 μg/ml, 2 μg/ml, 8 μg/ml GyrA ParC QRDR FQ 17 FQ BLNAR BLNAR 2002 2010 25.8% 57.9% 2013 57.1% Salmonella spp. CLSI 2012 FQ LVFX S 2 μg/ml 0.12 μg/ml FQ NA FQ NA LVFX LVFX NA LVFX NA 8.1% 10/123 1.6% 2/123 P. aeruginosa FQ 83.4 89.3% 88.1 93.7% 80% LVFX 1994 52.3% 2010 21.3%, 2013 12.9% FQ

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 21 21 FQ MDRP MDRP 1.6% 9/559 MDRP MDRP Acinetobacter spp. IPM 96.9%, PAPM 94.5% IPM 14 6 MDRA 512 1 0.2% N. gonorrhoeae CTRX CTRX 2007 2010 4 5.0% 1 1.7% 20 LVFX FQ MRCNS, MRSA, E. faecium, E. coli, N. gonorrhoeae 30% CPFX 80% FQ 80% JA JA NTT

22 22 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 23 23 1 FOUQUET, M.; V. MORANGE & F. BRUYÈRE: Five years following of infections with extended-spectrum beta-lactamase producing enterobacteriaceae. Prog. Urol. 22: 17 21, 2012 2 HIRAKATA, Y.; K. IZUMIKAWA, T. YAMAGUCHI, et al.: Rapid detection and evoluation of clinical characteristics of emerging multiple-drugresistant Gram-negative rods carrying the metallo-β-lactamase gene bla IMP. Antimicrob. Agents Chemother. 42: 2006 2011, 1998 3 40 195 200, 2013 4 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 5 2004 77 18,639 Jpn. J. Antibiotics 59: 428 451, 2006 6 2007 72 12,919 Jpn. J. Antibiotics 62: 346 370, 2009 7 2010 72 12,866 Jpn. J. Antibiotics 65: 181 206, 2012 8 Clinical and Laboratory Standards Institute: Performance standards for antimicrobial susceptibility testing; Twenty-fourth informational Supplement M100-S24, 2014 9 European Committee on Antimicrobial Susceptibility Testing; Breakpoint tables for interpretation of MICs and zone diameters Version4.0, 2014 10 β- 13: 73 83, 1983 11 GERISCHER, U.: Direct sequencing of DNA produced in a polymerase chain reaction. Meth. Mol. Biol. 167: 53 61, 2001 12 MINE, Y.; I. NAKASONE, Y. YAMAMOTO, et al.: Dissemination of Panton-Valentine leukocidinpositive methicillin-resistant Staphylococcus aureus in Okinawa. J. Dermatol. 40: 34 38, 2013 13 MINE, Y.; W. HIGUCHI, K. TAIRA, et al.: Nosocomial outbreak of multidrug-resistant USA300 methicillin-resistant Staphylococcus aureus causing severe furuncles and carbuncles in Japan. J. Dermatol. 38: 1167 1171, 2011 14 WEIGEL, L. M.; G. J. ANDERSON, R. R. FACKLAM, et al.: Genetic analyses of mutations contributing to fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 3517 3523, 2001 15 REINERT, R. R.; D. E. LOW, F. ROSSI, et al.: Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline. J. Antimicrob. Chemother. 60: 1018 1029, 2007 16 KOMATSU, M.; M. AIHARA, K. SHIMAKAWA, et al.: Evaluation of MicroScan ESBL confirmation panel for Enterobacteriaceae-producing, extended-spectrum beta-lactamases isolated in Japan. Diagn. Microbiol. Infect. Dis. 46: 125 130, 2003 17 KIM, I. S.; N. Y. LEE, S. KIM, et al.: Reduced levofloxacin susceptibility in clinical respiratory isolates of Haemophilus influenzae is not yet associated with mutations in the DNA gyrase and topoisomerase II genes in Korea. Yonsei Med. J. 52: 188 191, 2011

24 24 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016 Surveillance of in vitro susceptibilities to levofloxacin and various antibacterial agents for 11,762 clinical isolates obtained from 69 centers in 2013 KEIZO YAMAGUCHI Department of Microbiology and Infectious Diseases, Department of Advanced and Integrated Analysis of Infectious Diseases, Toho University School of Medicine KAZUHIRO TATEDA, AKIRA OHNO and YOSHIKAZU ISHII Department of Microbiology and Infectious Diseases, Toho University School of Medicine HINAKO MURAKAMI Department of Clinical Laboratory, Toho University Omori Medical Center Antimicrobial susceptibility testing has been conducted continuously as postmarketing surveillance of levofloxacin LVFX since 1994. The present survey was undertaken to investigate in vitro susceptibilities of bacteria to 33 selected antibacterial agents, focusing on fluoroquinolones FQs, using 11,762 clinical isolates for 19 species collected from 69 centers during 2013 in Japan. The common respiratory pathogens Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae continue to show a high susceptibility to FQs, while the percentage of macrolide-resistant S. pneumoniae was markedly increased to around 80%. With H. influenzae, the percentage of β-lactamase-negative ampicillinresistant isolates had been increasing continuously from 2002, but no increase was observed from 2010 to 2013 25.8% in 2002, 40.0% in 2004, 50.1% in 2007, 57.9% in 2010, and 57.1% in 2013. Most strains of Enterobacteriaceae showed a high susceptibility to FQs, but the isolation frequency of levofloxacin-resistant Escherichia coli including intermediate resistance was 34.4%, showing a continuous increase. Another Enterobacteriaceae member, Klebsiella pneumoniae, showed low resistance to FQs in contrast with E. coli. Regarding methicillin-resistant Staphylococcus aureus MRSA, the percentage of FQ-susceptible isolates was low at 15.8 18.0%, with the exception of 55.3% susceptibility to sitafloxacin. On the other hand, methicillinsusceptible S. aureus MSSA isolates showed high susceptibility to FQs, at 87.0 99.3%. With Enterococcus faecium, the percentage of FQ-susceptible isolates was 6.8 24.7%. The percentage of FQ-susceptible Pseudomonas aeruginosa was 83.4 89.3% among isolates derived from urinary tract infections UTIs, while that from respiratory tract infections RTIs was 88.1 93.7%. This was summarized as susceptibility to FQs over 80% in both infections. A continuous decrease in FQ-resistant P. aeruginosa was noted, especially among isolates from UTIs. Regarding multidrug-resistant P. aeruginosa, the percentage has been decreasing continuously

Feb. 2016 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 25 25 since 2007 and was 1.6% from UTIs and 0% from RTI in this survey. Acinetobacter spp. showed high susceptibility to FQs. The percentage of imipenem-resistant Acinetobacter spp. was 2.7% 14 isolates and that of multidrug-resistant was 0.2% 1 isolate. In Neisseria gonorrhoeae, ceftriaxone CTRX had been showing 100% susceptibility until 2007, but CTRX-resistant strains have been detected in both 2010 and this survey. In conclusion, the resistance of methicillin-resistant staphylococci, E. faecium, N. gonorrhoeae, and E. coli to the FQs, which have been used clinically for over 20 years, was shown to be 30% or more 31.7 87.1% in the present surveillance regarding susceptibility. These results were similar to those from previous surveillance, and no species that started to show significant resistance to FQs were identified in the present surveillance. Regarding other bacterial species, susceptibility to ciprofloxacin less than 80% was observed in some, while susceptibility to other FQs was maintained at a high level, at 80% or more.