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

Hiroshi Kataoka; Takashi Ida; Yoshikazu Ishii; Kazuhiro Tateda; Toyoko Oguri; Atsushi Yoshida; Katsuko Okuzumi; Tsuyoshi Oishi; Miyuki Tsukahara; Shin-Ichiro Mori; Akiko Yoneyama; Hideki Araoka; Toshihiro Mitsuda; Midori Sumitomo; Kyoji Moriya; Mieko Goto; Yoshitaka Nakamori; Akiyoshi Shibayama; Norio Ohmagari; Tomoaki Sato; Keizo Yamaguchi; ABX Combination Therapy Study Group (ACTs)

doi:10.1016/j.jgar.2013.03.005

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

J Glob Antimicrob Resist. 2013 Jun;1(2):91-96. doi: 10.1016/j.jgar.2013.03.005. Epub 2013 Apr 23.

Authors

Hiroshi Kataoka¹, Takashi Ida¹, Yoshikazu Ishii², Kazuhiro Tateda³, Toyoko Oguri⁴, Atsushi Yoshida⁵, Katsuko Okuzumi⁵, Tsuyoshi Oishi⁶, Miyuki Tsukahara⁶, Shin-Ichiro Mori⁷, Akiko Yoneyama⁸, Hideki Araoka⁸, Toshihiro Mitsuda⁹, Midori Sumitomo⁹, Kyoji Moriya¹⁰, Mieko Goto¹⁰, Yoshitaka Nakamori¹¹, Akiyoshi Shibayama¹¹, Norio Ohmagari¹², Tomoaki Sato¹², Keizo Yamaguchi³; ABX Combination Therapy Study Group (ACTs)

Affiliations

¹ Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Tokyo 104 8002, Japan.
² 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: [email protected].
³ 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.
⁴ Kameda General Hospital, Chiba 296-8602, Japan.
⁵ Dokkyo Medical University Hospital, Tochigi 321 0293, Japan.
⁶ Tokyo Medical University Ibaraki Medical Center, Ibaraki 300 0395, Japan.
⁷ National Cancer Center Hospital, Tokyo 104 0045, Japan.
⁸ Department of Infectious Diseases, Toranomon Hospital, Tokyo 105 8470, Japan.
⁹ Yokohama City University Hospital, Kanagawa 236 0004, Japan.
¹⁰ Graduate School of Medicine, The University of Tokyo, Tokyo 113 8655, Japan.
¹¹ Department of Respiratory Diseases, Misyuku Hospital, Tokyo 153 051, Japan.
¹² Shizuoka Cancer Center, Shizuoka 411 8777, Japan.

PMID: 27873584
DOI: 10.1016/j.jgar.2013.03.005

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.

Keywords: Combination effect; Multidrug-resistant Pseudomonas aeruginosa; Resistance factor.