TY - JOUR
T1 - Multicenter prospective observational study of fungal keratitis in Japan
T2 - analyses of in vitro susceptibility tests for combinations of drugs
AU - Multicenter Study Group of Fungal Keratitis in Japan
AU - Kimura, Keigo
AU - Inoue, Yoshitsugu
AU - Asari, Seishi
AU - Sunada, Atsuko
AU - Ohashi, Yuichi
AU - Shimomura, Yoshikazu
AU - Sotozono, Chie
AU - Hatano, Hiroshi
AU - Fukuda, Masahiko
AU - Eguchi, Hiroshi
AU - Araki-Sasaki, Kaoru
AU - Suzuki, Takashi
AU - Hoshi, Saichi
AU - Tobe, Toru
AU - Yaguchi, Takashi
AU - Makimura, Koichi
AU - Tagawa, Yoshitsugu
AU - MasaharaYokokura, Hidetaka Shunji
AU - Uematsu, Megumi
AU - Namba, Hiroyuki
AU - Todokoro, Daisuke
AU - Oshika, Tetsuro
AU - Kaji, Yuichi
AU - Obata, Hiroto
AU - Amano, Shiro
AU - Miyai, Takashi
AU - Usui, Masahiko
AU - Goto, Hiroshi
AU - Kumakura, Shigeto
AU - Takamura, Etsuko
AU - Shinozaki, Kazumi
AU - Yamada, Masakazu
AU - Shigeyasu, Chika
AU - Inada, Noriko
AU - Sawa, Mitsuru
AU - Mochizuki, Manabu
AU - Morohoshi, Kei
AU - Kimura, Tairo
AU - Nakagawa, Hisashi
AU - Usui, Norio
AU - Kitagawa, Kazuko
AU - Mochizuki, Kiyofumi
AU - Kinoshita, Shigeru
AU - Maeda, Naoyuki
AU - Soma, Takeshi
AU - Fujimoto, Hisataka
AU - Inoue, Yoshitsugu
AU - Miyazaki, Dai
AU - Chikama, Tai ichiro
AU - Sonoda, Koh Hei
N1 - Funding Information:
This work was supported by Japan National Society for the Prevent of Blindness. The members of Multicenter Study Group of Fungal Keratitis in Japan―Yoshitsugu Tagawa (Hokkaido University), Hidetaka Masahara (Eguchi Eye Clinic), Shunji Yokokura, Megumi Uematsu (Tohoku University), Hiroyuki Namba (Yamagata University), Daisuke Todokoro (Gunma University), Tetsuro Oshika, Yuichi Kaji (University of Tsukuba), Hiroto Obata (Jichi Medical University), Shiro Amano, Takashi Miyai (University of Tokyo), Masahiko Usui, Hiroshi Goto, Shigeto Kumakura (Tokyo Medical University), Etsuko Takamura, Kazumi Shinozaki (Tokyo Women's Medical University), Masakazu Yamada, Chika Shigeyasu (National Institute of Sensory Organs, National Tokyo Medical Center), Noriko Inada, Mitsuru Sawa (Nihon University), Manabu Mochizuki, Kei Morohoshi (Tokyo Medical and Dental University), Tairo Kimura (Ueno Eye Clinic), Hisashi Nakagawa (Tokushima Eye Clinic), Norio Usui (Shinkawabashi Hospital), Hiroshi Hatano (Hatano Eye Clinic), Saichi Hoshi (Fujieda Municipal General Hospital), Kazuko Kitagawa (Kanazawa Medical University), Kiyofumi Mochizuki (Gifu University), Shigeru Kinoshita, Chie Sotozono (Kyoto Prefectural University), Naoyuki Maeda, Takeshi Soma, Hisataka Fujimoto (Osaka University), Yoshikazu Shimomura, Masahiko Fukuda (Kindai University), Yoshitsugu Inoue, Dai Miyazaki (Tottori University), Tai-ichiro Chikama (Hiroshima University), Koh-Hei Sonoda, Naoyuki Morishige (Yamaguchi University), Hiroshi Eguchi, Tatsuro Miyamoto (University of Tokushima), Hiroshi Shiota (Kaisei General Hospital), Yuichi Ohashi, Toshihiko Uno, Atsushi Shiraishi, Takashi Suzuki (Ehime University), Shigeki Okamoto (Okamoto Eye Clinic), Tamaki Sumi (Kochi Medical School), Eiichi Uchio, Masahiko Ozawa (Fukuoka University), Kaoru Araki-Sasaki, Naoki Kumagai (Ideta Eye Hospital), Koki Matsumoto (Kumamoto Shinto General Hospital), Yu Monden (Kurume University), Masafumi Uematsu (Nagasaki University), Kazunori Miyata, Ryohei Nejima (Miyata Eye Hospital), Seishi Asari, Atsuko Sunada, Keigo Kimura (Osaka University Hospital), Takashi Yaguchi (Chiba University), Koichi Makimura (Teikyo University).
Publisher Copyright:
© 2022, Japanese Ophthalmological Society.
PY - 2022
Y1 - 2022
N2 - Purpose: To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan. Study design: Multicenter prospective observational study. Methods: Eighteen isolates of yeast-like fungi and 22 isolates of filamentous fungi collected by the Multicenter Prospective Observational Study of Fungal Keratitis in Japan were studied. Specially manufactured minimum inhibitory concentration (MIC) measurement plates were used to test the effectiveness of 10 combinations of two antifungal drugs against the isolates. The combinations were pimaricin (PMR) + voriconazole (VRCZ), PMR + fluconazole (FLCZ), PMR + miconazole (MCZ), PMR + micafungin (MCFG), VRCZ + FLCZ, VRCZ + MCZ, VRCZ + MCFG, VRCZ + amphotericin–B (AMPH-B), MCZ + FLCZ, and MCZ + MCFG. The checkerboard microdilution method was used, and the fractional inhibitory concentration (FIC) index was calculated based on the guidelines of The Clinical & Laboratory Standards Institute (CLSI). Results: In yeast-like fungi, additive effects were observed between PMR and MCFG in 77.8% of the isolates, and they were also observed between the azoles. Synergistic effects were observed on 11.1% of the isolates for MCZ and FLCZ. On the other hand, antagonistic effects were present between PMR and azoles with 88.9% between PMR and VRCZ, 72.2% between PMR and FLCZ, and 94.4% between PMR and MCZ. In filamentous fungi, additive effects were observed between PMR and MCFG in 40.9% of the isolates, and between VRCZ and MCZ in 40.9% of the isolates. Antagonistic effects were observed for PMR and the azoles. Conclusions: The combination of drugs prescribed for fungal keratitis incurs a possibility of synergistic, additive, indifferent, or antagonistic effects, depending on drug combinations and fungal strains.
AB - Purpose: To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan. Study design: Multicenter prospective observational study. Methods: Eighteen isolates of yeast-like fungi and 22 isolates of filamentous fungi collected by the Multicenter Prospective Observational Study of Fungal Keratitis in Japan were studied. Specially manufactured minimum inhibitory concentration (MIC) measurement plates were used to test the effectiveness of 10 combinations of two antifungal drugs against the isolates. The combinations were pimaricin (PMR) + voriconazole (VRCZ), PMR + fluconazole (FLCZ), PMR + miconazole (MCZ), PMR + micafungin (MCFG), VRCZ + FLCZ, VRCZ + MCZ, VRCZ + MCFG, VRCZ + amphotericin–B (AMPH-B), MCZ + FLCZ, and MCZ + MCFG. The checkerboard microdilution method was used, and the fractional inhibitory concentration (FIC) index was calculated based on the guidelines of The Clinical & Laboratory Standards Institute (CLSI). Results: In yeast-like fungi, additive effects were observed between PMR and MCFG in 77.8% of the isolates, and they were also observed between the azoles. Synergistic effects were observed on 11.1% of the isolates for MCZ and FLCZ. On the other hand, antagonistic effects were present between PMR and azoles with 88.9% between PMR and VRCZ, 72.2% between PMR and FLCZ, and 94.4% between PMR and MCZ. In filamentous fungi, additive effects were observed between PMR and MCFG in 40.9% of the isolates, and between VRCZ and MCZ in 40.9% of the isolates. Antagonistic effects were observed for PMR and the azoles. Conclusions: The combination of drugs prescribed for fungal keratitis incurs a possibility of synergistic, additive, indifferent, or antagonistic effects, depending on drug combinations and fungal strains.
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U2 - 10.1007/s10384-022-00907-2
DO - 10.1007/s10384-022-00907-2
M3 - Article
C2 - 35348983
AN - SCOPUS:85129780498
JO - Japanese Journal of Ophthalmology
JF - Japanese Journal of Ophthalmology
SN - 0021-5155
ER -