【市販後調査報告】 多剤耐性 Pseudomonas aeruginosa に対 …

1 VOL. 59 NO. 1 29.. Pseudomonas aeruginosa .. 1 .. 2 .. 3 .. 4 .. 5 .. 22 3 12 22 9 8 . Pseudomonas aeruginosa . 2000 10 2007 4 .. P. aeruginosa 54 BC ' . MIC 2 2 MIC BC.. colistin rifampicin 32 . amikacin aztreonam 31 colistin aztreonam 29 .. Key words: multidrug-resistant Pseudomonas aeruginosa synergy breakpoint checkerboard titration method Pseudomonas aeruginosa AmpC . MBL . DNA I . D2 1 .. 2000 10 2007 4 . Multidrug-resistant P. P. aeruginosa . aeruginosa MDRP Random amplified polymor- MDRP phic DNA pattern analysis . 54 . in vitro MBL MDRP MBL MDRP 35 MBL .. MDRP MBL MDRP 19 MDRP. imipenem IPM . amikacin AMK . levofloxacin LVFX MIC 16 g! mL . 32 g! mL 8 g! mL MBL . 1 MBL IMP-1 . BC VIM-2 .. Tateda BC ' 2 BC .. 2007 BC MDRP BC BC ' . Acinetobacter spp .. Fig. 1.

2 P. aeruginosa BC Clinical and Laboratory Standards Insti- . 5 4 30. 30 J A N. 2 0 1 1. MEPM (8, 4) CAZ (16, 8) AZT (16, 8) PIPC (32, 16) AMK (16, 8) MEPM (8, 4). CPFX (2, 1). CPFX (2, 1). CPFX (2, 1). CPFX (2, 1). CPFX (2, 1). CPFX (2, 1). MEPM (8, 4) CAZ (16, 8) AZT (16, 8) PIPC (32, 16) RFP (4, 2) CAZ (16, 8). AMK (16, 8). AMK (16, 8). AMK (16, 8). AMK (16, 8). AMK (16, 8). AMK (16, 8). MEPM (8, 4) CAZ (16, 8) AZT (16, 8) CPFX (2, 1) RFP (4, 2) AZT (16, 8). CL (2, 1). CL (2, 1). CL (2, 1). CL (2, 1). CL (2, 1). CL (2, 1). MEPM (8, 4) CAZ (16, 8) AZT (16, 8) CPFX (2, 1) PIPC (32, 16). RFP (4, 2). RFP (4, 2). RFP (4, 2). RFP (4, 2). Control RFP (4, 2). Fi . Br eak -poi ntChe cke rboa rdPl ate . Ta ble1.. Br eak -poi ntChe cke rboa rdPl atec ate gor ywi tha mik aci npl usme rope nem MI.

3 Cf orAMK MICforAMK MI. CforMEPM MI. Cf orMEPM. i nte rpr eta tion a lone pl usMEPM al one plusAMK. Str ongsy ner gima). s 1. 6 . 8 8 . 4. Moderatesynerg ismb) 1. 6 1. 6 8 8. Inv aldc). i 1. 6 16 8 8. unknownd) . 8 . 8 . 4 . 4. a ). S t rongsynergi sm:Confir me dbyc ombi nat ionwhenbact eri ag r owthwasi nhibit edcompl ete lyi nall4wel ls b). Mode rat es y ne r gism:Confi rmedbyc ombi nati onwhenbacte riagr owthwasinhi bit edin2or3of4well s c). Invali d:Synerg ynotc onf irmedbyc ombi nati on d). unk nown:Synergynotpossi bleduetosi ngleag entMICles sthanMICrange tute CLSI M100-S18 P. aeruginosa ATCC II . 27853 1 . 3 BC piperacillin PIPC .. Strong synergism . AMK colistin CL CLSI . Moderate synergism . Invalid . 1 2 Rifampicin RFP . Unknown 4 Table CLSI . 1 MIC . MIC MIC MIC.

4 4 Table 2 . MIC MBL MDRP MBL MDRP 35 ceftaz- 3 2 idime CAZ . ciprofloxacin CPFX AMK . meropenem MEPM 34 . MBL MDRP MBL MDRP 19. MIC BC AMK CPFX MEPM .. 2 . Table 3 MIC. BC . VOL. 59 NO. 1 31. Ta ble2.. Ant imi crobi als usc ept ibi li tyt estr esul tsa gai nstmul ti drug -re sis tantPs eudo monasae rug ino sa I. sol ate s Dr ug MBL MDRPa)(. n 3. 5) MBL MDRPb)(. n 1. 9) TOTAL(. n 5. 4). S I R S I R S I R. MEPM 0 1 3. 4 0 7 1. 2 0 8 4. 6. CPFX 0 0 3. 5 0 3 1. 6 0 3 5. 1. CAZ 0 0 3. 5 8 3 8 8 3 4. 3. AMK 0 0 3. 5 0 1 1. 8 0 1 5. 3. AZT 2 1. 1 2. 2 0 7 1. 2 2 1. 8 3. 4. CL 1. 1 2. 1 3 9 1. 0 0 2. 0 3. 1 3. PIPC 2 5 2. 8 3 4 1. 2 5 9 4. 0. RFP 0 0 3. 5 0 0 1. 9 0 0 5. 4. Abbr e viat ions:S ,susce ptible ;I,i ntermediate ;R,r e sis tant MEPM:me rope ne m,CPFX:c i prof loxaci n,CAZ:c ef tazi dime,AMK:a mika cin,AZT:a z tre ona m, CL:c ol is tin,PI PC:pi pe ra cil li n,RFP:rif ampi c in a).

5 MBL MDRP:me tal lo- -lact ama s e-producingmulti drug-r esi sta ntPseudomo nasaer uginosa b). MBL MDRP:nonme tall o- -la ctamas e -produci ngmul t idrug -res ist antPseudomonasae r ugino sa Ta ble3.. Ant ibi oti ccombi nat ions yne rgi sm wi thBr eak -poi ntChe cke rboa rdPl ate St rong Moder ate St rongsyne rgi sm . Dr ugc ombi nat ion s trai ns s ynerg ism s yner gis m Moder atesyne rgi sm CPFX MEPM 3. 8 2 0 2. CPFX CAZ 4. 7 2 3 5. CPFX AZT 4. 1 2 6 8. CPFX PI. PC 4. 7 4 4 8. CPFX AMK 5. 1 0 0 0. AMK MEPM 5. 4 4 9 1. 3. AMK CAZ 4. 7 4 2 6. AMK AZT 4. 8 5 2. 6 3. 1. AMK PIPC 4. 8 1. 0 5 1. 5. AMK RFP 5. 3 0 0 0. CL MEPM 2. 9 1. 4 9 2. 3. CL CAZ 2. 2 1. 3 7 2. 0. CL AZT 3. 1 2. 0 9 2. 9. CL CPFX 2. 6 1. 0 7 1. 7. CL RFP 3. 2 2. 7 5 3. 2. RFP MEPM 5. 1 2 3 5. RFP CAZ 4.

6 7 2 2 4. RFP AZT 4. 1 2 9 1. 1. RFP CPFX 5. 3 0 0 0. Unknown 10 . CPFX CL 17. 26 54 . CL 8 . RFP 27 CL aztreonam 19 . AZT 20 54 45. AMK AZT 26 83 . AMK MEPM CL MEPM CL AZT CL RFP . 9 54 34 63 .. CL RFP 32 AMK III . AZT 31 CL AZT 29 CL P. aeruginosa MDRP . 17 . CL . 32 J A N. 2 0 1 1. CL RFP .. MDRP .. 19 . CPFX . BC 1 19 RFP CL . MDRP 25 . CPFX AZT CPFX gentamicin 64 . BC . FIC index 1 CPFX . CLSI . 2 . BC 2 MIC . piperacillin! tazobactam AMK cefoperazone! sulbac- CL P. aeruginosa MIC tam AZT cefepime CFPM AMK CFPM . 4 g! mL MIC90 2 g! mL BC CPFX . 1 2 g! mL arbekacin ABK AZT. CL BC . 2 ABK P. aeruginosa . MDRP . BC BC .. BC P. aeruginosa MBL .. MBL MDRP CAZ . MBL MDRP . CAZ MBL . 54 CL RFP CAZ MBL . AMK AZT . AZT MBL BC MDRP MBL . MBL .. AZT MIC P. aeruginosa .. AMK AZT.

7 BC 54 20 37 20 . 1 CL . AMK AZT 12 CL . 31 26 84 8 . 5 16 CL CL .. BC 54. 34 63 . CL . AMK AZT . CL RFP CL MDRP BC.. CL CL RFP . VOL. 59 NO. 1 33. Paterson D: Use of parenteral colistin for the treat- ment of serious infection due to antimicrobial- resistant Pseudomonas aeruginosa . Clin Infect Dis 2003;.. 37: 154-60. 8 . 1 MDRP . 2007; 34: 83-8 1 . 2 2008; 82: 466-70. 2005; 53: 476-82 9 Tascini C, Gemignani G, Ferranti S, Tagliaferri E, 3 Tateda K, Ishii Y, Matsumoto T, Yamaguchi K: Leonildi A, Lucarini A, et al: Microbiological activity Break-point Checkerboard Plate for screening of ap- and clinical efficacy of a colistin and rifampin combi- propriate antibiotic combinations against multidrug- nation in multidrug-resistant Pseudomonas aeruginosa resistant Pseudomonas aeruginosa .

8 Scand J Infect Dis infections. J Chemother 2004; 16: 282-7. 2006; 38: 268-72 10 . 4 Olive D M, Bean P : Principles and applications of . methods for DNA-based typing of microbial organ- Jpn J Antibiot 2006;. isms. J Clin Microbiol 1999; 37: 1661-9 59: 11-20. 5 Nishio H, Komatsu M, Shibata N, Shimakawa K, 11 . Sueyoshi N, Ura T, et al: Metallo- -lactamase- Aztreonam Arbekacin producing gram-negative bacilli: laboratory-based 2009; 24: surveillance in cooperation with 13 clinical laborato- 279-82. ries in the Kinki region of Japan. J Clin Microbiol 12 Checkerboard plate 2004; 42: 5256-63 aztreonam . 6 Clinical and Laboratory Standards Institute: Per- . formance standards for antimicrobial susceptibility 2009; 83: 133-5. testing; 18th informational supplement, CLSI docu- 13.

9 Ment M100-S18, Clinical and Laboratory Standards . Institute, Wayne, PA, 2008 2007 . 7 Linden P K, Kusne S, Coley K, Fontes P, Kramer D J, 2008 2010; 58: 7-13. Effect of antibiotic combinations by Break-point Checkerboard Plate against multidrug-resistant Pseudomonas aeruginosa Hisaaki Nishio , Masaru Komatsu , Noriyuki Sueyoshi , Kaneyuki Kida and Shohiro Kinoshita . 1 . Department of Clinical Laboratory, Shiga Medical Center for Adults, 5 4 30 Moriyama, Moriyama, Shiga, Japan 2 . Central Laboratory Technical Section 3., FALCO biosystems Ltd. 3 . Department of Clinical Laboratory, Social Insurance Shiga Hospital 4 . Department of Laboratory Medicine, Otsu Red Cross Hospital 5 . Department of Clinical Laboratory, Kobe University Hospital We studied antibiotic combination effects by Break-point Checkerboard Plate against multiple-drug- resistant Pseudomonas aeruginosa (MDRP).

10 Fifty-four MDRP strains collected from October 2000 to April 2007. from clinical laboratories in Kinki, Japan were tested using Break-point Checkerboard Plates to evaluate the effect with combined antibiotics. Amikacin plus aztreonam and colistin plus rifampicin showed a synergistic effect of 31!48 and 32!32. We concluded that these plates are useful in screening antibiotic combination ef- fects in the clinical setting.