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Table 1.Resistance criteria Fig.1.The resistance rates of piperacillin,ceftazidime, cefsulodin,imipenem,aztreonam,gentamicin,tobramycin,amikacin,isepamicin,fosfomycin and ofloxacin against 2,793 strains of Pseudomonas aeruginosa isolated from 1994 through 1997.

Fig.2.Sensitivity distribution of imipenem,meropenem, panipenem and tobramycin against 181 strains of Pseudomonas aeruginosa isolated from clinical materials in 1997. Fig.3.Sensitivity distribution of ceftazidime,cefpirome, cefepime and cefozopran against 181 strains of Pseudomonas aeruginosa isolated from clinical materials in 1997. Fig.4.The resistance rates of ceftazidime,cefpirome,cefepirne,cefozopran,imipenem,meropenem,panipenem, and tobramycin against 181 strains of Pseudomonas aeruginosa isolated in 1997. Fig.5.Bactericidal effects of meropenem and tobramycin alone and in combination against colonies of Pseudomonas aeruginosa strain No.23.

Fig.6.Bactericidal effects of cefozopran and tobramycin alone and in combination against colonies of Pseudomonas aeruginosa strain No.28. Fig.7.Bactericidal effects of ceftazidime and tobramycin alone and in combination against colonies of Pseudomonas aeruginosa strain No.79. Table 2.Comparison of fractional inhibitory concentration(fic) indices in two-antibiotic combinations against Pseudomonas aeruginosa

15) Livermore D M, Yang Y: Comparative activity of 2) National Committee for Clinical Laboratory Standards: Approved standard M100-S8. Method for dilution antimicrobial susceptibility test for bacteria that grow aerobically-4 th. ed. National Committee for Clinical Laboratory Standards. Villanova. Pa., 1998 6) Elion G B, Singer S, Hichings G H: Antagonists of nucleic acid derivativeslg. Synergism in combination of biochemically related antimetabolites. J. Biol. Chem. 208: 477 `488, 1954 7) Busch D F, Sutler V L, Finegold S M: Activity of combination of antimicrobial agents against Bacteroides fragilis. J. Infect. Dis. 133: 321 `328, 1976 8) Parsley T L, Provonchee R B, Glicksman C, et al.: Synergistic activity of trimethoprim and amikacin against gram negative bacilli. Antimicrob. Agents Chemother. 12: 349 `352, 1977 12) Iaconis J. P, Pitkin D H, Sheikh W, et al.: Comparison of Antibacterial Activity of Meropenem and Six Other Antimicrobials Against Pseudomonas aeruginosa Isolated from North American Studies and Clinical Trials. Clin. Infect. Dis. 24: S 191 `S196, 1997 13) Edwards J R: Meropenem: a microbiological overview. J. Antimicrob. Chemother. 36(Suppl. A): 1 ` 17, 1995 14) Jones R N: The current and future impact of antimicrobial resistance among nosocomial bacterial pathogens. Diagn. Microbiol. Infect. Dis. 15: 3S ` 10S, 1992 meropenem against Pseudomonas aeruginosa strains with well-characterized resistance mechanisms. J. Antimicrob. Chemother. 24(Suppl. A): 149 `159, 1989 16) Fujita J, Nagayama K, Takahara J. Comparison of in vitro activity of carbapenems and tosufloxacin against clinically-isolated strains of Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. ú» Ã ïž 43: 187 `195, 1995 19) Sumita Y, Fukusawa M: Meropenem Resistance in Pseudomonas aeruginosa. Chemotherapy 42: 47 20) Visalli M A, Jacobs M R, Appelbaum P C: Determination of Activities of Levofloxacin Alone and Combined with Gentamicin, Ceftazidime, Cefpirome, and Meropenem against 124 Strains of Pseudomonas aeruginosa by Checkerboard and Time Kill Methodology. Antimicrob. Agents Chemother. 42: 953 `955, 1998

Susceptibility of Pseudomonas aeruginosa and bactericidal effects of antimicrobial agent combinations against colonies of Pseudomonas aeruginosa Kohki Takahashi1) and Harushige Kanno2) Department of Laboratory Medicine, Chiba University Hospital, 1-8-1, Inohana, Chuo-ku, Chiba 260-8677, Japan Department of Laboratory Medicine, Chiba University Medicine The 2, 793 strains of Pseudomonas aeruginosa isolated from clinical materials in our laboratory during a four year period from 1994 through 1997 were examined to study their susceptibility to eleven drugs. As a rule, the criteria of resistance to each drug used in this study followed those of NCCLS. The resistance rates for tobramycin (10. 1%) and ceftazidime (10. 9%) were the lowest among piperacillin, ceftazidime, cefsulodin, imipenem, aztreonam, gentamicin, tobramycin, amikacin, isepamicin, fosfomycin and ofloxacin. The 181 strains of P. aeruginosa isolated in 1997 were examined to study their susceptibility to eight drugs. The resistance rates for meropenem(13. 2%)and tobramycin(13. 8%)were the lowest among ceftazidime, cefpirome, cefepime, cefozopran, imipenem, meropenem, panipenem and tobramycin. The combinations of meropenem plus tobramycin, cefozopran plus tobramycin, and ceftazidime plus tobramycin showed marked bactericidal effects against colonies of the selected strains of P. aeruginosa tested. Of these combinations, meropenem plus tobramycin showed the greatest bactericidal effect. By means of the microtiter broth dilution checkerboard method, combinations of ceftazidime plus tobramycin, meropenem plus tobramycin, and cefozopran plus tobramycin were found to be synergistic against 84. 3%, 78. 6%, and 67. 1%, respectively, of the 70 strains of P. aeruginosa tested. No antagonism was observed in this study. These combinations may be useful for P. aeruginosa infections.

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