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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1 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS , ,762 FQ 33 Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae FQ S. pneumoniae 8 H. influenzae 2002 β- H. influenzae %, %, %, %, % FQ Escherichia coli MIC 4 μg/ml levofloxacin 34.4% Klebsiella pneumoniae E. coli FQ Staphylococcus aureus MRSA FQ sitafloxacin 55.3% FQ %S. aureus FQ % Enterococcus faecium FQ % Pseudomonas aeruginosa FQ % % 80% FQ P. aeruginosa % Acinetobacter spp. FQ Imipenem 2.7% 14 Acinetobacter 0.2% 1
2 2 2 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb Neisseria gonorrhoeae ceftriaxone CTRX % 2010 CTRX 20 FQ staphylococci, E. faecium, N. gonorrhoeae, E. coli 30% % 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 FQ FQ 4 7 FQ Escherichia coli 2000 FQ FQ ESBL ,762 Quinolone resistance determining region QRDR β ,762 Table 1 Table levofloxacin LVFX ciprofloxacin CPFX tosufloxacin TFLX sitafloxacin STFX pazufloxacin PZFX nalidixic
3 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS 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 4 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb 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 μg/ml S. pneumoniae PRSP PCG MIC 2 μg/ml 4. Haemophilus influenzae β- H. influenzae 10 β-
5 Table 3. Test drugs and the range of their concentrations for determination of MIC Feb THE JAPANESE JOURNAL OF ANTIBIOTICS
6 6 6 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb 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 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 Table 4 1 S. aureus MSSA 725 MSSA FQ MIC μg/ ml % FQ STFX FQ ABPC 48.8%, CPDX 53.4%, CAM AZM 74.3%, 72.3%, PIPC 89.9% % 2 S. aureus MRSA 665 MRSA FQ MIC μg/ml STFX 55.3% FQ % FQ VCM, LZD, DAP 100% % MRSA Community-acquired MRSA CA-MRSA LVFX 1 μg/ml MINO 4 μg/ml CAM 2 μg/
7 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS 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 8 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb Table 4. Continued
9 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS Table 4. Continued ml 9.3% 62/665 3 staphylococci MSCNS 516 MSCNS FQ MIC μg/ml % FQ CAM, AZM 76.7%, 75.2% % 4 staphylococci MRCNS 677 MRCNS MIC 90 MRSA FQ STFX MIC 90 1 μg/ml 93.5% FQ MIC μg/ml % VCM, LZD DAP 100% 5 S. pneumoniae 599 S. pneumoniae FQ MIC μg/ml CPFX 74.3%, PZFX 89.6% FQ % STFX MIC μg/ml 100% FQ VCM, CVA/AMPC, PAPM, CTRX 100%, 98.2%, 98.2%, 97.2% % CAM,
10 10 10 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb AZM 80% S. pneumoniae 599 PSSP, PISP, PRSP % % % 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 STFX PSSP, PRSP 100% 6 S. pyogenes 384 S. pyogenes FQ MIC μg/ml PZFX, CPFX 72.4%, 78.9% % FQ CAM 64.6%, AZM 63.5%, MINO 87.2% 100% 7 Enterococcus faecalis 629 E. faecalis FQ % FQ MPIPC, CCL, CTM, MINO, CAM, AZM % % ABPC, CVA/AMPC, VCM, DAP 8 Enterococcus faecium 511 E. faecium FQ % FQ VCM 100%, LZD 99.4%, DAP 99.4% % 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
11 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS Table 5 1 Moraxella catarrhalis 504 M. catarrhalis FQ MIC μg/ml 100% FQ ABPC 14.1% % CVA/AMPC ABPC β- 2 N. gonorrhoeae 58 N. gonorrhoeae FQ MIC 90 LVFX, CPFX, TFLX μg/ml 25.9% STFX MIC 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 μg/ml % STFX MIC 90 2 μg/ml FQ FQ % IPM, PAPM 2 Klebsiella spp. 662 Klebsiella spp. FQ MIC μg/ml % E. coli 30% FQ ABPC 6.3%, ST 32.2% % 3 Citrobacter spp. 543 Citrobacter spp. FQ MIC μg/ml % FQ ABPC 12.9% % IPM, PAPM, GM, AMK 97% 4 Enterobacter spp. 628 Enterobacter spp. FQ MIC μg/ml % FQ ABPC, CVA/AMPC, CCL, CTM, CFDN, CPDX, ST % % PAPM, MINO, GM, AMK 90% 5 P. mirabilis 512 P. mirabilis FQ MIC μg/ml % FQ MINO 1.6% % TAZ/PIPC 6 Proteus spp. 417 Proteus spp. FQ MIC μg/ml % FQ 90% NA, PIPC, TAZ/PIPC, CAZ, CTX, GM, AMK 7 Serratia spp. 590 Serratia spp. FQ MIC μg/ml % 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 12 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb 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 μg/ml % FQ ST 73.2%, ABPC 82.9%, PIPC 83.7, MINO 87.0% 90%
13 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS Table 6. Continued 9 H. influenzae 620 H. influenzae FQ MIC μg/ml % LVFX MIC 8 μg/ml 1 STFX MIC 0.5 μg/ml β- BLNAR,
14 14 14 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb Table 6. Continued ABPC MIC 2 μg/ml % % CFDN MIC 2 μg/ml β- BLPAR, ABPC MIC 2 μg/ ml % % CVA/AMPC MIC 8 μg/ml 10 Acinetobacter spp. 512 Acinetobacter spp. FQ MIC 90
15 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS Table 6. Continued μg/ml % FQ CCL, CTM, CFDN, CPDX, ST, ABPC % TAZ/PIPC, PAPM, IPM, MINO, GM, AMK 90% IPM % 9 Acinetobacter baumannii MDRA 0.2% 1/ P. aeruginosa 1,175 P. aeruginosa FQ MIC μg/ml 1 4 μg/ml MIC % % FQ
16 16 16 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb 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 % QRDR 3 GyrA ParC GyrB ParC LVFX MIC 4 μg/ ml 3 MIC 1 μg/ml, MIC 2 μg/ml % % 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 % % 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 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 μg/ml % 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 % QRDR 12 GyrA ParC LVFX MIC 4 μg/ml % GyrA 1 GyrA ParC 1 LVFX MIC 2 μg/ml % GyrA 1 3. ESBL ESBL E. coli 17.8%
17 Table 7. MICs and types of substitutions identified in genes containing quinolone resistance determining regions Feb THE JAPANESE JOURNAL OF ANTIBIOTICS
18 18 18 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb 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/ ESBL Table 8 ESBL E. coli % 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 MDRP P. aeruginosa MBL Acinetobacter spp P. aeruginosa MBL Table 9 Acinetobacter spp., P. aeruginosa MBL 0 2% P. aeruginosa MBL % % , FQ FQ 1994 LVFX,
19 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS CPFX, TFLX FQ STFX FQ PZFX 5 FQ MSSA FQ % MRSA FQ STFX 55.3% FQ % 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 % %, % % 47/62 CA-MRSA USA300 12,13 VCM MRSA MIC 2 μg/ml % 8.9% % VCM MIC 2 μg/ml S. pneumoniae FQ CPFX 74.3%, PZFX 89.6% % LVFX MIC 2 μg/ml MIC 1 μg/ml % % FQ DNA IV QRDR 2 14 LVFX MIC 1 μg/ml 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% % LVFX %, % % 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 % 4 7 E. coli LVFX %, %,
20 20 20 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb %, %, %, %, % % % LVFX 61.6% 76.3% 66.0% 77.2% 15 K. pneumoniae FQ E. coli QRDR E. coli LVFX MIC 2 μg/ml % GyrA ParC K. pneumoniae LVFX % GyrA E. coli, K. pneumoniae, P. mirabilis ESBL 17.8% 127/ % 37/ % 56/512 E. coli % 17.8% ESBL ESBL 16 ESBL LVFX E. coli ESBL 81.1%, ESBL 21.1% χ 2 P K. pneumoniae ESBL 21.6%, ESBL 1.9% χ 2 P P. mirabilis ESBL 48.2%, ESBL 3.3% χ 2 P ESBL LVFXK. pneumoniae, P. mirabilis FQ E. coli FQ ESBL FQ H. influenzae FQ % QRDR LVFX μg/ml GyrA QRDR 0.5 μg/ml, 2 μg/ml, 8 μg/ml GyrA ParC QRDR FQ 17 FQ BLNAR BLNAR % 57.9% % 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/ % 2/123 P. aeruginosa FQ % % 80% LVFX % %, % FQ
21 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS FQ MDRP MDRP 1.6% 9/559 MDRP MDRP Acinetobacter spp. IPM 96.9%, PAPM 94.5% IPM 14 6 MDRA % N. gonorrhoeae CTRX CTRX % 1 1.7% 20 LVFX FQ MRCNS, MRSA, E. faecium, E. coli, N. gonorrhoeae 30% CPFX 80% FQ 80% JA JA NTT
22 22 22 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb. 2016
23 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS FOUQUET, M.; V. MORANGE & F. BRUYÈRE: Five years following of infections with extended-spectrum beta-lactamase producing enterobacteriaceae. Prog. Urol. 22: 17 21, 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: , , 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 Diagn. Microbiol. Infect. Dis. 52: , ,639 Jpn. J. Antibiotics 59: , ,919 Jpn. J. Antibiotics 62: , ,866 Jpn. J. Antibiotics 65: , Clinical and Laboratory Standards Institute: Performance standards for antimicrobial susceptibility testing; Twenty-fourth informational Supplement M100-S24, European Committee on Antimicrobial Susceptibility Testing; Breakpoint tables for interpretation of MICs and zone diameters Version4.0, β- 13: 73 83, GERISCHER, U.: Direct sequencing of DNA produced in a polymerase chain reaction. Meth. Mol. Biol. 167: 53 61, MINE, Y.; I. NAKASONE, Y. YAMAMOTO, et al.: Dissemination of Panton-Valentine leukocidinpositive methicillin-resistant Staphylococcus aureus in Okinawa. J. Dermatol. 40: 34 38, 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: , 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: , 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: , 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: , 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: , 2011
24 24 24 THE JAPANESE JOURNAL OF ANTIBIOTICS 69 1 Feb 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 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 % in 2002, 40.0% in 2004, 50.1% in 2007, 57.9% in 2010, and 57.1% in 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 %, with the exception of 55.3% susceptibility to sitafloxacin. On the other hand, methicillinsusceptible S. aureus MSSA isolates showed high susceptibility to FQs, at %. With Enterococcus faecium, the percentage of FQ-susceptible isolates was %. The percentage of FQ-susceptible Pseudomonas aeruginosa was % among isolates derived from urinary tract infections UTIs, while that from respiratory tract infections RTIs was %. 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
25 Feb THE JAPANESE JOURNAL OF ANTIBIOTICS 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 % 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.
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