(Multi-drug resistant Pseudomonas aeruginosa; MDRP) 35 MDRP Etest (AB BIODISK) ceftazidime (CAZ) CAZ. Cefepime (CFPM) ciprofloxacin (CPFX)

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1 Micro Scan Walk Away (Multi-drug resistant Pseudomonas aeruginosa; MDRP) 35 MDRP Etest (AB BIODISK) ceftazidime (CAZ) CAZ 25 (71.4 ), CAZ 10 (28.6 ) CAZ 10 Etest Cefepime (CFPM) ciprofloxacin (CPFX) Aztreonam (AZT) amikacin (AMK) b- AMK MIC mg/ml -b- 5 4 MIC AZT AMK -b- MDRP Key words: -b- Pseudomonas aeruginosa P. aeruginosa (Multi-drug resistant Pseudomonas aeruginosa; MDRP) 1) ( ) 67 TEL: FAX: fukushima_nao@kurume-u.ac.jp 2) MDRP MDRP 3) MDRP 4) MDRP P. aeruginosa DNA A 5) Vol. 16 No

2 128 P. aeruginosa b- 6), 7) b- 8) 9) cefepime (CFPM) aztreonam (AZT) -b- CFPM ciprofloxacin (CPFX) AZT amikacin (AMK) MDRP P. aeruginosa 1508 Micro Scan Walk Away96 MIC imipenem (IPM) 16 mg/ml, AMK 32 mg/ml, CPFX 4 mg/ml MDRP b- -b- -b- SMA ceftazidime (CAZ) IPM Arakawa 10) 3. Piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), sulbactam/cefoperazone (SBT/CPZ), CAZ, CFPM, meropenem (MEPM), AZT, fosfomycin (FOM), IPM, AMK, CPFX MIC 18 3ml Inoculum Water McFarland 0.5 II Etest (AB BIODISK) MIC MIC 5. 2 CAZ 10 CFPM CPFX AZT 11), 12) AMK 2 Etest MIC II 10 CFPM 35 1 CPFX CPFX MIC CPFX 35 1 CFPM CFPM MIC AZT AMK MIC Fractional Inhibitory Concentration Index ( ) A MIC B MIC A MIC B MIC 6. FOM 2 MIC II 10 FOM FOM 35 1 CFPM 35 1 CPFX CPFX MIC FOM 35 1 CPFX 35 1 CFPM CFPM MIC FOM AZT AMK MIC 2 FOM CFPM CPFX, AZT AMK 2 Vol. 16 No

3 b- Etest MIC -b- MIC Table 1 -b- 5 (5/35, 14.3 ) 11 CAZ CAZ 25 (25/35, 71.4 ), CAZ 10 (10/35, 28.6 ) Table 2 CFPM CPFX 10 1 (1/10, 10 ), 3 (3/10, 30 ) 4 (4/10, 40 ) 6 (6/10, 60 ) -b- 5 Table 1. In vitro activity of antibacterial agents and metallo-b-lactamase producibility against 35 strains of MDRP isolated in Kurume University Hospital Strain no. Material Metallo PIPC T/P S/C CAZ CFPM IPM MEPM AZT FOM AMK CPFX 1 Urine Feces Urine Pus Throat swab Sputum Urine Wound Urine Urine Sputum Feces Feces Drain Urine Sputum Wound Urine Urine Urine Urine Blood Urine Urine Urine Urine Urine Urine Urine Urine Urine Urine Blood Blood Wound PIPC: Piperacillin, T/P: Tazobactam/Piperacillin, S/C: Sulbactam/Cefoperazone, CAZ: Ceftazidime, CFPM: Cefepime, IPM: Imipenem, MEPM: Meropenem, AZT: Aztreonam, FOM: Fosfomycin, AMK: Amikacin, CPFX: Ciprofloxacin, Metallo: Production of metallo-b-lactamase Vol. 16 No

4 130 Table 2. Combined e#ects of cefepime and ciprofloxacin, aztreonam and amikacin against MDRP Strain no. Cefepime Ciprofloxacin Aztreonam Amikacin Alone Combination Alone Combination Alone Combination Alone Combination Table 3. E#ect of fosfomycin-pretreatment followed by combined exposure of cefepime and ciprofloxacin, aztreonam and amikacin against MDRP Strain no. Cefepime Ciprofloxacin Aztreonam Amikacin Alone Combination Alone Combination Alone Combination Alone Combination AZT AMK 10 7 (7/ 10, 70 ), 3 (3/10, 35.7 ) 10 MIC range AZT 6 96 mg/ml, AMK 6 64 mg/ml 3. FOM 2 FOM Table 3 CFPM CPFX 10 3 (3/10, 30 ), 1 (1/10, 10 ) 4 (4/10, 40 ) FOM b- 5 FOM AZT AMK 10 7 (7/10, 70 ), 3 (3/10, 30 ) 10 MIC range AZT 6 96 mg/ml, AMK 6 32 mg/ml FOM 10 4 MDRP 5 MDRP 13) 2004 P. aeruginosa 306 MDRP 5 (1.6 ) P. aeruginosa 1508 MDRP 35 (2.3 ) 4 Vol. 16 No

5 131 MDRP P. aeruginosa 14) MDRP 57 CAZ 57 -b- MDRP CAZ (71.4 ) CAZ MDRP -b b- MDRP -b- MDRP MDRP 3 MDRP MDRP MDRP in vitro CFPM CPFX 40 CFPM, CPFX MIC AZT AMK AMK 200 mg mg/ml 10 6 AMK MIC AMK 10 4 AMK MIC AZT AMK FOM b- FOM FOM 15) P. aeruginosa FOM 16 18) FOM FOM FOM 2 MIC FOM 2 MDRP in vivo in vitro -b- MDRP in vivo MDRP polymyxin B 19) -b- MDRP 1) Tsuji, A., I. Kobayashi, T. Oguri, et al An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan. J. Infect. Chemother. 11: ) Cao, B., H. Wang, H. Sun, et al Risk factors and clinical outcomes of nosocomial multi-drug resistant Pseudomonas aeruginosa infections. J. Hosp. Infect. 57: ) Pulse Field Gel Electrophoresis (PFGE) 79 4) Jpn. J. Antibiot. 59: ) Vol. 16 No

6 132 6 (MDRP) 7: ) Burgess, D. S., S. Nathisuwan Cefepime, piperacillin/tazobactam, gentamaicin, ciprofloxacin, and levofloxacin alone and in combination against Pseudomonas aeruginosa. Diagn. Microbiol. Infect. Dis. 44: ) Drago, L., E. D. Vecchi, L. Nicola, et al In vitro selection of resistance in Pseudomanas aeruginisa and Acinetobacter spp. by levoflaxacin and ciprofloxacin alone and in combination with b-lactams and amikacin. J. Antimicrob. Chemother. 56: ) Oie, S., A. Sawa, A. Kamiya, et al In-vitro e#ects of combination of antipseudomonal antibiotics against multi-drug resistant Pseudomonas aeruginosa. J. Antimicrob. Chemother. 44: ) b-lactamase Jpn. J. Antibiot. 55: ) Arakawa, Y., N. Shibata, K. Shibayama, et al Convenient test for screening metallo-blactamase-producing gram-negative bacteria by using thiol compounds. J. Clin. Microbiol. 38: ) Lewis, R. E., D. J. Diekema, S. A. Messer, et al Comparison of Etest, chequerboard dilution and time-kill studies for the detection of synergy or antagonism between antifungal agents tested against Candida species. J. Antimicrob. Chemother. 49: ) Manno, G., E. Ugolotti, M. L. Belli, et al Use of the E test to assess synergy of antibiotic combinations against isolates of Burkholderia cepacia-complex from patients with cystic fibrosis. Eur. J. Clin. Microbiol. Infect. Dis. 22: ) Meropenem 2004 Jpn. J. Antibiot. 58: ) : ) NaIB FOM b- 46: ) fosfomicin 47: ) BACTERIAL ADHERENCE & BIOFILM 17: ) Suzuki, K., N. Asano, K. Araki, et al Effectiveness of fosfomycin combined with other antimicrobial agents multidrug-resistant Pseudomonas aeruginosa isolates using e$cacy time assay. J. Infect. Chemother. 8: ) Sobieszczyk, M. E., E. Y. Furuya, C. M. Hay, et al Combination therapy with polymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infections. J. Antimicrob. Chemother. 54: Combined E#ects of Antibacterial Agents against Multi-drug Resistant Pseudomonas aeruginosa Detected in Kurume University Hospital Nao Fukushima, Chiyoko Tanamachi, Kouji Hashimoto, Rie Horita, Kazunori Nakata, Kimitaka Sagawa Department of Laboratory Medicine, Kurume University Hospital, Asahimachi 67, Kurume, Fukuoka , Japan Thirty-five strains of MDRP (Multi-drug resistant Pseudomonas aeruginosa) identified with Micro Scan Walk Away96 (DADE BEHRING) were isolated, from January 2002 to march 2005 in Kurume University Hospital. Antimicrobial susceptibilities of these strains were re-examined using Etest for various antimicrobial agents. The most e#ective agent against the strains was ceftazidime (CAZ) (susceptible; 25 strains (71.4 ) and resistant; 10 strains (28.6 )). Because these 10 strains did not show susceptibility with any antimicrobial agents, we examined combined e#ects of antimicrobial agents against these strains by Etest. Acombination of cefepime and ciprofloxacin was e#ective on 4 strains (40 ; 1for synergistic e#ect, 3 for additive e#ect) and that of aztreonam (AZT) and amikacin (AMK) was e#ective to all 10 strains (100 ; 7 for synergistic e#ect, 3 for additive e#ect). However, five of these 10 strains, produced metallo-b-lactamase, 6 Vol. 16 No

7 133 showed high MIC to AMK (32 64 mg/ml) even in the combination test. Four of the 5 remained strains which did not produce metallo-b-lactamase showed good susceptibilities to the combination of AZT and AMK. These results suggest that although it is di$cult to obtain the significant e#ect against MDRP producing metallo-b-lactamase, the combination of agents is clinically useful for the infectious diseases due to non metallo-b-lactamase producing MDRP. Further studies are needed to find a new e#ective combination of antimicrobial agents to MDRP-infectious. Vol. 16 No

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