title: Analysis of the influence of drug resistance factors on the efficacy of combinations of antibiotics for multidrug-resistant Pseudomonas aeruginosa isolated from hospitals located in the suburbs of Kanto area, Japan.
abstract: Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa are very difficult to treat. The aim of this study was to develop more effective treatments by investigating in vitro the effects of combinations of antibiotics against 47 MDR P. aeruginosa isolates harbouring various resistance factors. The isolates included 41 (87%) metallo-β-lactamase (MBL)-positive strains, 37 (79%) strains with mutations in OprD and 46 (98%) strains carrying the genes encoding aminoglycoside-modifying enzymes (AMEs). The quinolone resistance-determining region was mutated in all of the strains. These strains were classified into 16 groups according to amplified fragment length polymorphism and resistance factors. The effects of combinations of antibiotics on 16 representative strains were determined using a 'Break-point Checkerboard Plate' assay. Combinations of amikacin+aztreonam (coverage rate, 81.3%) and arbekacin+aztreonam (93.8%) inhibited growth. In contrast, combinations of ciprofloxacin+meropenem (6.3%) and ciprofloxacin+ceftazidime (12.5%) were much less effective. Aztreonam and arbekacin (or amikacin) are not substrates for MBLs and AMEs, respectively. We conclude that the combined effects of these drugs were possibly because of resistance factors.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Tokyo 104 8002, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Tokyo 104 8002, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143 8540, Japan. Electronic address: yishii@med.toho-u.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143 8540, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.affiliation: Kameda General Hospital, Chiba 296-8602, Japan.
authors.forename: Toyoko
authors.initials: T
authors.lastname: Oguri
authors.affiliation: Dokkyo Medical University Hospital, Tochigi 321 0293, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Dokkyo Medical University Hospital, Tochigi 321 0293, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Okuzumi
authors.affiliation: Tokyo Medical University Ibaraki Medical Center, Ibaraki 300 0395, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oishi
authors.affiliation: Tokyo Medical University Ibaraki Medical Center, Ibaraki 300 0395, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tsukahara
authors.affiliation: National Cancer Center Hospital, Tokyo 104 0045, Japan.
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Mori
authors.affiliation: Department of Infectious Diseases, Toranomon Hospital, Tokyo 105 8470, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoneyama
authors.affiliation: Department of Infectious Diseases, Toranomon Hospital, Tokyo 105 8470, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Araoka
authors.affiliation: Yokohama City University Hospital, Kanagawa 236 0004, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mitsuda
authors.affiliation: Yokohama City University Hospital, Kanagawa 236 0004, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Sumitomo
authors.affiliation: Graduate School of Medicine, The University of Tokyo, Tokyo 113 8655, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Moriya
authors.affiliation: Graduate School of Medicine, The University of Tokyo, Tokyo 113 8655, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Respiratory Diseases, Misyuku Hospital, Tokyo 153 051, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nakamori
authors.affiliation: Department of Respiratory Diseases, Misyuku Hospital, Tokyo 153 051, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Shibayama
authors.affiliation: Shizuoka Cancer Center, Shizuoka 411 8777, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Ohmagari
authors.affiliation: Shizuoka Cancer Center, Shizuoka 411 8777, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143 8540, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
keywords: Combination effect; Multidrug-resistant Pseudomonas aeruginosa; Resistance factor