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

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

doi:10.1007/s10384-022-00907-2

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…In this context the study of ocular isolates is relevant because some fungi that show emerging resistance, such as Candida glabrata and Candida auris , are currently rare corneal pathogens [ 47 ]. Although there are relatively few studies of corneal isolates [ 32 , 39 , 50 , 51 ], an increase in resistance for natamycin and voriconazole against Fusarium spp and Aspergillus spp has been reported [ 52 ]. We could find no published evidence for a difference in the susceptibility profile of common corneal isolates from the UK compared to isolates from other regions.…”

Section: Discussionmentioning

confidence: 99%

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

Tuft,

Stone,

Burton

et al. 2023

Eye

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Objective To report the identification and results of susceptibility testing for fungal isolates from the cornea or contact lens care systems. Materials and methods In this retrospective epidemiological study, we searched the results of fungal cultures from cornea or contact lens systems referred for identification and susceptibility testing to the United Kingdom National Mycology Reference Laboratory between October 2016 and March 2022. For each fungal isolate, we recorded the genus and species of the fungus and the minimum inhibitory concentration (MIC) to six antifungal agents available to treat corneal infection (amphotericin, econazole, itraconazole, natamycin, posaconazole, and voriconazole). Results There were 600 isolates from 585 patients, comprising 374 (62%) from corneal samples and 226 from contact lenses and care systems, of which 414 (69%) isolates were moulds (filamentous fungi) and 186 (31%) were yeasts. The most frequent moulds isolated were Fusarium spp (234 isolates, 39%) and Aspergillus spp (62, 10%). The most frequent yeasts isolated were Candida spp (112, 19%), predominantly Candida parapsilosis (65, 11%) and Candida albicans (33, 6%), with 35 isolates (6%) of Meyerozyma guilliermondii. In vitro susceptibility was greatest for natamycin (347 moulds tested, mode 4 mg/L, range 0.25–64 mg/L; 98 yeasts tested, mode 4 mg/L, range 0.5–32 mg/L), with susceptibility for 94% for moulds and 99% yeasts. Of the 16 isolates interpreted as highly resistant to natamycin (MIC ≥16 mg/L), 13 were Aspergillus flavus complex. Conclusions In vitro susceptibility supports the use of natamycin for the empiric treatment of fungal keratitis in the UK.

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Section: Discussionmentioning

confidence: 99%

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

Tuft,

Stone,

Burton

et al. 2023

Eye

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show abstract

“…49 In this context the study of ocular isolates is relevant because some fungi that show emerging resistance, such as Candida glabrata and Candida auris, are currently rare corneal pathogens. 47 Most data on the prevalence of resistance to antifungal agents are for isolates from systemic infections, with relatively few studies of corneal isolates, 32,39,50,51 although an increase in resistance for natamycin and voriconazole against Fusarium spp and Aspergillus spp has been reported. 52 We could nd no published evidence from the UK for a difference in the susceptibility pro le of common corneal isolates compared to isolates from other regions.…”

Section: Discussionmentioning

confidence: 99%

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

Tuft

Stone²,

Burton

et al. 2023

Preprint

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Objective To report the identification and results of susceptibility testing for fungal isolates from the cornea or contact lens care systems.Materials and methods In this retrospective epidemiological study, we searched the results of fungal cultures from cornea or contact lens systems referred for identification and susceptibility testing to the United Kingdom National Mycology Reference Laboratory between October 2016 and March 2022. For each fungal isolate, we recorded the genus and species of the fungus and the minimum inhibitory concentration (MIC) to six antifungal agents available to treat corneal infection (amphotericin, econazole, itraconazole, natamycin, posaconazole, and voriconazole).Results There were 600 isolates from 585 patients, comprising 374 (62%) from corneal samples and 226 from contact lenses and care systems, of which 414 (69%) isolates were moulds (filamentous fungi) and 186 (31%) were yeasts. The most frequent moulds isolated were Fusarium spp (234 isolates, 39%) and Aspergillus spp (62, 10%). The most frequent yeasts isolated were Candida spp (112, 19%), predominantly Candida parapsilosis (11%) and Candida albicans (6%), with 35 isolates (6%) of Meyerozyma guilliermondii. In vitro susceptibility was greatest for natamycin (347 moulds tested, mode 4 mg/L, range 0.25-64 mg/L; 98 yeasts tested, mode 4 mg/L, range 0.5–32 mg/L), with susceptibility for 94% for moulds and 99% yeasts. The isolates interpreted as highly resistant to natamycin (N, 14) were predominantly Aspergillus flavus complex.Conclusions In vitro susceptibility supports the use of natamycin for the empiric treatment of fungal keratitis in the UK.

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“…41 42 Most data on the prevalence of resistance to antifungal agents is derived from testing isolates from systemic infections, with relatively few studies of corneal isolates. [43][44][45][46] Methods to assess fungal resistance include broth dilution, disc dilution, antifungal impregnated gradient strips and agar screening as described by EUCAST or the CSLI. Resistance may also be intrinsic (eg, resistance of Candida krusei to fluconazole) or an acquired trait following prolonged drug exposure.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…The prevalence of acquired resistance to antifungal agents is generally lower than antibiotic resistance, but the treatment options are more limited 41 42. Most data on the prevalence of resistance to antifungal agents is derived from testing isolates from systemic infections, with relatively few studies of corneal isolates 43–46. Methods to assess fungal resistance include broth dilution, disc dilution, antifungal impregnated gradient strips and agar screening as described by EUCAST or the CSLI.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial resistance in topical treatments for microbial keratitis: protocol for a systematic review and meta-analysis

et al. 2023

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IntroductionThere is evidence for increased resistance against the antimicrobials used to treat keratitis. This review aims to provide global and regional prevalence estimates of antimicrobial resistance in corneal isolates and the range of minimum inhibitory concentrations (MIC) with their associated resistance breakpoints.Methods and analysisWe report this protocol following Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. We will conduct an electronic bibliographic search in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Eligible studies will report in any language data for the resistance or MIC for antimicrobials against bacterial, fungal or amoebic organisms isolated from suspected microbial keratitis. Studies that only report on viral keratitis will not be included. There will be no time restrictions on the date of publication. Screening for eligible studies, assessment of risk of bias and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. We will resolve disagreements between the reviewers by discussion and, if required, a third (senior) reviewer will arbitrate. We will assess the risk of bias using a tool validated in prevalence studies. The certainty of the evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. Pooled proportion estimates will be calculated using a random-effects model. Heterogeneity will be assessed using the I2statistic. We will explore differences between Global Burden of Disease regions and temporal trends.Ethics approval and disseminationEthics approval is not required as this is a protocol for a systematic review of published data. The findings of this review will be published in an open-access, peer-reviewed journal.PROSPERO registration numberCRD42023331126.

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

Cited by 4 publications

References 40 publications

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

Antifungal susceptibility profiles for fungal isolates from corneas and contact lenses in the United Kingdom

Antimicrobial resistance in topical treatments for microbial keratitis: protocol for a systematic review and meta-analysis

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