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Multicenter prospective observational study of fungal keratitis in Japan: analyses of in vitro susceptibility tests for combinations of drugs

2022; Springer Science+Business Media; Volume: 66; Issue: 3 Linguagem: Inglês

10.1007/s10384-022-00907-2

1613-2246

Keigo Kimura, Yoshitsugu Inoue, Seishi Asari, Atsuko Sunada, Yuichi Ohashi, Yoshikazu Shimomura, Chie Sotozono, Koji Hatano, Masahiko Fukuda, Hiroshi Eguchi, Kaoru Araki‐Sasaki, Takashi Suzuki, Saichi Hoshi, Toru Tobe, Takashi Yaguchi, Koichi Makimura, Yoshitsugu Tagawa, Hidetaka Shunji MasaharaYokokura, Megumi Uematsu, Hiroyuki Namba, Daisuke Todokoro, Tetsuro Oshika, Yuichi Kaji, Hiroto Obata, Shiro Amano, Takashi Miyai, Masahiko Usui, Hiroshi Gotô, Shigeto Kumakura, Etsuko Takamura, Kazumi Shinozaki, Masakazu Yamada, Chika Shigeyasu, Noriko Inada, Mitsuru Sawa, Manabu Mochizuki, Kei Morohoshi, Tairo Kimura, Hisashi Nakagawa, Norio Usui, Koji Hatano, Saichi Hoshi, Kazuko Kitagawa, Kiyofumi Mochizuki, Shigeru Kinoshita, Chie Sotozono, Naoyuki Maeda, Takeshi Soma, Hisataka Fujimoto, Yoshikazu Shimomura, Masahiko Fukuda, Yoshitsugu Inoue, Dai Miyazaki, Tai-ichiro Chikama, Koh-Hei Sonoda, Naoyuki Morishige, Hiroshi Eguchi, Tatsuro Miyamoto, Hiroshi Shiota, Yuichi Ohashi, Toshihiko Uno, Atsushi Shiraishi, Takashi Suzuki, Shigeki Okamoto, Tamaki Sumi, Eiichi Uchio, M. Ozawa, Kaoru Araki‐Sasaki, Naoki Kumagai, Koki Matsumoto, Yu Monden, Masafumi Uematsu, Kazunori Miyata, Ryohei Nejima, Seishi Asari, Atsuko Sunada, Keigo Kimura, Takashi Yaguchi, Koichi Makimura,

Fungal Infections and Studies

To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan.Multicenter prospective observational study.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).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.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.