Dermatophytoses are among the most frequently diagnosed skin infections worldwide. However, the distribution of pathogenic species and the predominating anatomical sites of infection vary with geographical location and change over time. The aim of this study was to determine the epidemiological and aetiological factors of dermatophytoses in Crete, Greece over the last 5-year period (2011-2015) and their incidence in relation to the gender and the age of the patients. We compared our findings with those previously reported from the same area and from other parts of the world. A total of 2,910 clinical specimens (skin scrapings, nail clippings, and hair specimens) obtained from 2,751 patients with signs of dermatomycoses were examined using direct microscopy and culture. Overall, 294 specimens (10.1%) were proved mycologically positive for dermatophytes. The age of the patients ranged from 2 to 86 years (mean age, 37 years). Tinea corporis was the predominant clinical type of infection, followed by tinea unguium, tinea pedis, tinea capitis, tinea faciei, tinea cruris and tinea manuum. Among dermatophytes, eight species were isolated: Microsporum canis (35.8%), Trichophyton rubrum (35.1%), Trichophyton mentagrophytes (23.3%), Epidermophyton floccosum (2.5%), Microsporum gypseum (1.8%), Trichophyton violaceum (0.7%), Trichophyton verrucosum (0.4%), and Trichophyton tonsurans (0.4%). In our area, the most common dermatophyte was M. canis followed by T. rubrum. Increased migration, mass tourism, and climate changes will contribute to further changes in the epidemiology of dermatophytoses in our area. Continuing studies are necessary for determining the new epidemiological trends and to implement the appropriate control measures.

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In this study, we report the first isolation of Aspergillus allahabadii from a Japanese cormorant with pulmonary aspergillosis. We performed molecular identification and antifungal susceptibility testing with the E-test. A 7-month-old male cormorant died because of uric acid deposition secondary to dehydration. Whitish nodular lesions were present on the caudal thoracic air sac in the right thoracic cavity. Histopathology revealed multifocal pyogranulomatous necrotic lesions with numerous fungal hyphae in the thoracic air sac. Identification of the etiologic agent was confirmed by comparative analyses of the sequences of the internal transcribed spacer (ITS) region and β-tubulin-encoding genes. According to the E-test, the minimum inhibitory concentrations of the isolate to amphotericin B, fluconazole, itraconazole, and voriconazole were 0.75 μg/ml, >256 μg/ml, 0.38 μg/ml, and 0.38 μg/ml, respectively.

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We previously showed a prophylactic effect of Lactobacillus pentosus strain S-PT84 against oral candidiasis in mice. In the present study, we evaluated the protective effect of S-PT84 against Candida infection of the gastrointestinal tract. As the first step, we used an in vitro assay to compare the inhibitory effects of several lactobacilli (S-PT84 and Lactobacillus pentosus type strain JCM1558^T, Lactobacillus gasseri type strain JCM1131^T and Lactobacillus casei type strain JCM1134^T) on mycelial growth of Candida albicans. S-PT84 directly adhered to Candida cells and showed the strongest growth-inhibitory activity among the tested Lactobacillus strains. In the second experiment, we used an in vivo assay to evaluate the effect of S-PT84 ingestion on severity score of stomach lesion and gastric inflammation in a mouse model of gastrointestinal candidiasis. The severity scores were significantly improved by oral administration of S-PT84 (6 mg/ 200 μL), consistent with decreased coverage of stomach lesions by patchy whitish plaques. The attenuation of stomach lesion severity by S-PT84 was more pronounced than that obtained with L. gasseri type strain JCM1131^T, consistent with the results of the above in vitro study. Histological analysis also indicated that S-PT84 prevented the adhesion of C. albicans to the stomach surface and suppressed stomach inflammation caused by neutrophil infiltration. Furthermore, S-PT84 also suppressed the vascular permeability observed in Candida-infected stomach. These results suggest that oral administration of S-PT84 might be effective not only in inhibiting Candida infection but also in preventing gastric inflammation induced by Candida infection.

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We previously showed a prophylactic effect of Lactobacillus pentosus strain S-PT84 against oral candidiasis in mice. In the present study, we evaluated the protective effect of S-PT84 against Candida infection of the gastrointestinal tract. As the first step, we used an in vitro assay to compare the inhibitory effects of several lactobacilli (S-PT84 and Lactobacillus pentosus type strain JCM1558^T, Lactobacillus gasseri type strain JCM1131^T and Lactobacillus casei type strain JCM1134^T) on mycelial growth of Candida albicans. S-PT84 directly adhered to Candida cells and showed the strongest growth-inhibitory activity among the tested Lactobacillus strains. In the second experiment, we used an in vivo assay to evaluate the effect of S-PT84 ingestion on severity score of stomach lesion and gastric inflammation in a mouse model of gastrointestinal candidiasis. The severity scores were significantly improved by oral administration of S-PT84 (6 mg/ 200 μL), consistent with decreased coverage of stomach lesions by patchy whitish plaques. The attenuation of stomach lesion severity by S-PT84 was more pronounced than that obtained with L. gasseri type strain JCM1131^T, consistent with the results of the above in vitro study. Histological analysis also indicated that S-PT84 prevented the adhesion of C. albicans to the stomach surface and suppressed stomach inflammation caused by neutrophil infiltration. Furthermore, S-PT84 also suppressed the vascular permeability observed in Candida-infected stomach. These results suggest that oral administration of S-PT84 might be effective not only in inhibiting Candida infection but also in preventing gastric inflammation induced by Candida infection.

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Onychomycosis is a fungal infection of the nail apparatus caused by dermatophytes, Candida and non-dermatophytic molds. It is highly prevalent in the general population worldwide and also responsible for significant morbidity and complications and does not usually cure itself. Thus, the condition needs to be treated in view of physical and psychological problems produced. Currently, oral medications using terbinafine are the most effective therapy, but it has relatively limited therapeutic success, particularly for long-term management. Such existing oral therapies are associated with high recurrence rates and treatment failure, as well as with potential adverse events and drug-drug interactions. In the light of these issues, development of more efficacious and safer alternatives for the treatment of onychomycosis is warranted.
Ravuconazole and its prodrugs are promising new drug candidates for oral therapy of onychomycosis, among which a water-soluble prodrug, mono-lysine phosphoester derivative (E1224 or BFE1224) is in the most advanced stage of clinical development; a Phase II dose-finding study has been successfully completed and Phase III comparative studies are in progress in Japan.
This review aims to summarize our current status of knowledge and information on ravuconazole and its prodrugs, particularly BFE1224, as the potential oral treatment option for onychomycosis. It also summarize the clinical features of onychomycosis with particular stress on its etiology, epidemiology, and current therapeutic options and their limitations. Given its clinical usefulness, BFE1224 may become a valuable addition to the current armamentarium for the treatment of onychomycosis.

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Pneumocystis jirovecii is a prototypical opportunistic pathogen, causing an asymptomatic or mild infection in normal hosts and fulminating pneumonia (Pneumocystis pneumonia, PCP) in immunocompromised hosts. PCP is a leading cause of morbidity and mortality in immunocompromised patients such as AIDS patients. Microscopic detection of cysts and trophic forms of P. jirovecii in respiratory secretions is simple and useful but may underestimate the P. jirovecii infection. Conventional polymerase chain reaction (PCR) and nested PCR increase the sensitivity and specificity to identify PCP and provide an approach to discriminate PCP from pulmonary P. jirovecii colonization, but the targeted genes and cut-off value from quantitative real-time PCR remain to be determined. Serum (1-3)-β-D-glucan level and the specific serum antibody titer are ancillary indicators for PCP diagnosis. The successful cultivation of P. jirovecii in vitro is an important progress for PCP research. The diagnosis of PCP relies on the combination of these laboratory examinations as well as the clinical presentations.

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黒色真菌による感染症を黒色真菌感染症と呼ぶが，その原因菌は単一ではなく，臨床像や菌の寄生形態もさまざまである．本症は，黒色分芽菌症 (chromoblastomycosis)，黒色顆粒菌腫 (black-grain mycetoma)，黒色菌糸症 (phaeohyphomycosis) に大別される．原因となる黒色真菌は多種類あるが，これまでわが国で最も多い原因菌はFonsecaea pedrosoiであり，黒色分芽菌症では分離菌の90%を占めるとされてきた．一方Fonsecaea monophoraは，rRNA遺伝子のITS領域の分子系統解析の結果から，Fonsecaea 属をF. pedrosoi，F. monophora とそれ以外の種に分類したことにより派生してきた菌種である．今回，われわれは顔面および上腕に生じたchromomycosisの2例を経験した．2例とも真菌培養およびスライドカルチャーではF. pedrosoiとF. monophoraの鑑別ができなかったが，分子系統解析の結果，いずれもF. monophora が原因菌であることが確認された．分子系統解析の導入により，これまでF. pedrosoi と報告されていたもののなかにもF. monophora が多く含まれることはすでに明らかになっており，Fonsecaea 属を原因菌とする過去の報告例をどのように扱うべきか，改めて考えてみる時期にきているように思われる．

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近年，外用爪白癬治療薬が次々に開発・上市され，長年抗真菌薬の経口投与に限られていた爪白癬治療法に新たな選択肢が増えてきている．本研究では，わが国で上市されている5％ルリコナゾール外用液および10％エフィナコナゾール外用液の特性把握のため，薬剤塗布後の爪中薬物濃度および爪中薬物の抗真菌活性を比較した．In vitroヒト爪薬物透過性試験では，薬剤をヒト爪に単回投与後，爪を表面から薄切したサンプルの薬物濃度を測定し，爪中薬物濃度分布を算出した．また，in vitroヒト爪スライス阻止円試験では，薬剤を1日1回14日間投与し，爪スライスを含菌培地にのせ，阻止円の有無から阻止円形成率を算出した．その結果，ヒト爪薬物透過性試験では，5％ルリコナゾール外用液は，10％エフィナコナゾール外用液にくらべ，爪全層において高い爪中薬物濃度を示し，測定ポイントごとの比較では，1.7～8.4倍の濃度差が認められた．また，ヒト爪スライス阻止円試験における，5％ルリコナゾール外用液および10％エフィナコナゾール外用液の平均阻止円形成率は，それぞれ71.0％および12.6％を示し，両剤間で統計学的な有意差が検出された．以上の結果から，2つの外用爪白癬治療薬は特性が異なり，5％ルリコナゾール外用液は，爪中への移行性および貯留性の良さが示されるとともに，爪中のルリコナゾールが抗真菌活性を維持していることが確認された．

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アスペルギルス症は深在性真菌感染症の重要な位置を占めている．アスペルギルス症の原因真菌はAspergillus fumigatusが最も重要であるが，そのほかにもAspergillus flavusやAspergillus niger, Aspergillus terreusなども重要な原因菌種である．また，近年になって隠蔽種と呼ばれる各Aspergillus sectionの代表的な種に非常によく似た菌種の存在が認識され，一部のアスペルギルス症の原因となっていることも分かってきた．最近の研究で，それらの菌種間では抗真菌薬に対する感受性や二次代謝産物の産生プロファイル (エクソメタボローム) が異なることも明らかとなってきた．一方，治療中のA. fumigatusアゾール耐性化や近年の欧州を中心とした環境中アゾール耐性A. fumigatusの出現も報告され，これら菌種を正確に同定し，加えて感受性を評価することの重要性が高まってきている．
本総説ではA. fumigatusを含めたアスペルギルス症原因菌種，特に隠蔽種について触れ，エクソメタボローム解析を利用した同定の可能性を述べる．加えて，A. fumigatusアゾール系抗真菌薬耐性について最近の報告を交えて概説したい．

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血液疾患の治療においては，化学療法や造血幹細胞移植後に生じる高度の好中球減少や免疫抑制により，侵襲性真菌症 (invasive fungal infections: IFIs) のリスクが高い．IFIsの主体はカンジダ症とアスペルギルス症であり，ムーコル症の頻度は決して高くはないが，IFIsの予防・治療の選択肢が広がるなかで増加傾向を示しており，抗真菌薬投与下でのブレイクスルーが散見されることもあって，その関心は高まっている．ムーコル症は，いったん発症すると急速に進行し致死的経過を辿ることが多く予後不良なため，早期診断・治療が不可欠だが，易感染性・易出血性などの観点から血液患者での侵襲的な手法による確定診断は概してむずかしい．特に，血液領域で多い肺型ムーコル症は，画像所見と臨床像が肺アスペルギルス症と酷似し，鑑別が困難な場合が多く，また現時点で有効な血清学的補助診断法もない．ムーコル症に対して抗真菌効果を有する薬剤が限られる中，わが国で利用可能なのはアムホテリシンB製剤のみであり，外科的切除も含めた包括的な治療戦略を考慮することが望ましい．

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現在の真菌感染症治療薬には抗真菌スペクトラムや副作用の問題があるため，治療薬選択の余地は狭く，有効な治療法の開発が急務となっている．有効な治療法の開発の1つの手段として，真菌のストレス環境下の応答機序（シグナル伝達や代謝など）の解明がある．本稿では，感染時に起こるさまざまなストレスのうち，鉄欠乏ストレスおよびそれに適応するために起こる代謝の変化に着目し，それらの応答システムの解明について，Candida glabrataを中心としたCandida酵母での研究の現状を紹介し，真菌症の治療戦略の創製の可能性に触れる．

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