渡辺 哲

A 50-year-old man with chronic renal failure (hemodialysis treatment) and interstitial pneumonia (IP) was referred to our hospital for exacerbation of IP. We immediately administered a mechanical ventilation, broad spectrum antibiotics, steroid pulse therapy, and endoxan pulse therapy in the intensive care unit, but alveolar opacities became worse. Subsequently, an intrapulmonary cavity appeared in the left middle lung field on the chest X-ray and we also administered amphotericin B. However he died of tension pneumothorax on the tenth day of hospitalization. In an autopsy the rupture of the intrapulmonary cavity of the left S3 region was detected and we diagnosed as invasive pulmonary mucormycosis by Grocott stain of the cavitary lesion. We report a rare case that complicated by fatal tension pneumothorax during treatment with a ventilator in invasive pulmonary mucormycosis and review the literature.

A 66-year-old male treated with everolimus for renal cell carcinoma developed exertional dyspnea. Chest computed tomography revealed diffuse interstitial shadows on both lungs. Bronchoalveolar lavage and the drug-induced lymphocyte stimulation test confirmed the diagnosis of drug-induced interstitial lung disease due to everolimus therapy. However, discontinuation of everolimus in combination with corticosteroid therapy did not prevent disease progression. On the basis of a PCR assay for Pneumocystis jirovecii and elevated β-D-glucan levels, trimethoprim-sulfamethoxazole was administered immediately, resulting in a dramatic improvement. This case demonstrated that pneumocystis pneumonia should always be considered and treated during everolimus therapy, even when drug-induced interstitial lung disease is suspected.

輸入真菌症の原因菌は一般に極めて感染力が強く、基礎疾患のない健常人でも感染が成立する。近年症例数が増加しており、棲息地域が限局されているため流行地への渡航歴の聴取が診断にいたる重要なポイントになることが多い。人種的な相違から日本人では重篤化する例も散見されており、注意が必要である。疾患としてはコクシジオイデス症、ヒストプラズマ症、パラコクシジオイデス症、ブラストミセス症、マルネッフェイ型ペニシリウム症等があり、さらにガッティ型クリプトコッカス症を含める場合もある。それぞれ流行地、病態などに特徴がみられる。診断のためには何をおいても「本疾患を思いつく」ことが重要であるが、血清検査は特殊なものが多いため確定診断は必ずしも容易ではない。本来は病理学的検査もしくは培養検査が有用であるが、感染事故防止のために疑わしい場合には培養検査は行わず、専門医療機関(千葉大学真菌医学研究センターまたは国立感染症研究所)へのコンサルテーションを行うべきである。(著者抄録)

日和見感染の代表として、もっぱらホストの免疫能が注目される深在性真菌症であるが、医療施設内に生息する真菌によって感染する機会も多いと考えられる。もともと真菌は建物などに定着・増殖し、空気中に浮遊する性質が強いが、医療施設ではアスペルギルス等を中心に、屋根裏や空調、水周りなどに多く生息し感染の機会をうかがっている。HEPA(高性能粒子除去)フィルターを始めとする対策がとられているものの、ひとつ管理を誤ると深刻なアウトブレイクの危険性もあり、機器の管理や症例数のモニタリングなど、日頃から慎重な対応が求められる。(著者抄録)

The immunogenicity of pandemic influenza A H1N1 virus (A/H1pdm) vaccine might be modified by prior seasonal trivalent influenza vaccine (sTIV) administration. We conducted a retrospective analysis of immunogenicity of 243 health care workers (number of sTIV-positive [sTIV(+)] subjects, 216; number of sTIV(-) subjects, 27) by hemagglutination inhibition. There was no significant difference in the ratios of antibody titers of >= 40 (41.2% versus 48.1%; P = 0.49) and fold increases in geometric mean titer (3.8 versus 4.5; P = 0.37). sTIV injected 7 to 10 days prior to A/H1pdm vaccine administration did not interfere with the immunogenicity of the latter.

使用において特に注意を要する抗菌薬(以下、特定抗菌薬)の院内における適正使用の推進を目的として、感染制御チーム(以下、ICT)と連携して定点状況調査(以下、スナップ・ショット)を用いた使用状況の把握と病棟担当薬剤師による問題症例に対する介入を試みた。本取り組み開始前後1年間における特定抗菌薬の平均使用件数および14日以上の長期投与件数を比較したところ、いずれも開始後有意な減少が認められた。また、問題症例に対するICTの提言内容は、薬剤の選択と用法・用量の変更を要するものが半数以上を占め、これらの提言に対する遵守率は96%であった。以上、スナップ・ショットを用いた問題症例の抽出と、それに続く病棟担当薬剤師とICTの連携による指導等の取り組みにより、院内における特定抗菌薬の適正使用が推進されたと考えられた。(著者抄録)

Aspergillus fumigatus is an all-important pathogenic fungus and is known for its angiotropism. When it invades human organs, A. fumigatus makes direct contact with blood and its components by causing inflammation and invading vascular structures. To learn the effect of its contact with blood on the development of infection, we examined the effect of serum on A. fumigatus growth. In Dulbecco's modified Eagle's medium containing 10% fetal bovine serum, hyphal tip growth was accelerated, forming a thickened and well-networked biofilm associated with extracellular matrix, and fetuin A was identified as the active component in the serum that accelerates fungal growth leading to formation of a community. These results suggest that fetuin A is a novel accelerator of the growth of A. fumigatus and that it participates in the formation of thick biofilm. (C) 2012 Elsevier GmbH. All rights reserved.

日和見感染を主体とするわが国の真菌症に対し、輸入真菌症はその感染力の強さと病態や診断法の特殊性で際立った存在と言える。重症化すると対応が困難となる一方、他疾患と誤認しやすい点も重要であり、正しい知識をもっているか否かが診断の分かれ目となる。今後も増加が予想され、十分な警戒が必要である。(著者抄録)

ガッティ型クリプトコッカス症は、Cryptococcus gattii(C.gattii)による真菌感染症で、本来わが国には存在しない輸入感染症の1種である。C.gattiiはもともと健常人を中心に感染するなど高い病原性をもつ菌だったが、近年、これまでまれであった北米を中心に大流行が起こり、遺伝子変異を含めた性質の変化が推測されている。わが国で通常認められるC.neoformansによるクリプトコッカス症に比べると、健常人にも中枢神経病変を起こしやすく重篤化しやすいこと、血清診断で偽陰性が多いこと、抗真菌薬が効きにくく十分な治療が必要なことなどの点で注意が必要である。(著者抄録)

Stachybotrys chartarum, a ubiquitous fungus in our environment, has been suspected of causing respiratory symptoms in humans, such as acute infant pulmonary hemorrhage and asthma. We previously established a mouse model in which repeated inhalation of Stachybotrys chartarum spores caused pulmonary hypertension. To further investigate the model, particularly in the pulmonary circulation, mice were intra-tracheally injected with spores, 18 times over 12 weeks. Severe muscularization was observed in the small- to medium-sized pulmonary arteries. Bronchoalveolar lavage fluid revealed an increase in eosinophils accompanied by high concentrations of Th2-associated cytokines, IL-4, IL-5, but not Th1-associated IFN-gamma. The remodeling was temporary, resolving after cessation of spore inhalation. Chronic inhibition of the RhoA/Rho-kinase pathway by fasudil attenuated pulmonary arterial remodeling. These data suggest that Stachybotrys-mediated remodeling is caused by Th2-associated inflammation and can be resolved by Rho-kinase inhibition, either through direct effects on smooth muscle hypertrophy or through indirect effects on vascular inflammation. These data also show that extensive pulmonary vascular remodeling, often thought of as a fixed lesion, will spontaneously resolve in the absence of underlying molecular etiology.

Pandemic influenza A (H1N1) virus (AH1pdm) emerged in April 2009. An inactivated, split-virus, unadjuvanted AH1pdm vaccine was manufactured in Japan, and vaccination was initiated with top priority for healthcare workers (HCWs) on October 19, 2009. A retrospective cohort study was conducted to evaluate the effectiveness of a single-dose vaccine for HCWs in a hospital in Japan. A total of 1,567(84.5%) of 1,854 HCWs were vaccinated. Thirty-seven were infected with AH1pdm before the vaccine became available, and were excluded. The other 250 were not vaccinated for personal reasons. We analyzed the influenza infection rate with or without vaccination and related adverse events. Among the 1,817 HCWs without previous infection, 37 were infected with AH1pdm; 13(5.2%) of 250 unvaccinated HCWs became infected, which was a significantly higher rate than the 24 (1.5%) of 1,567 vaccinated HCWs (P = 0.001). Multivariate analysis revealed that age of 20-29 years was a risk factor for infection (adjusted odds ratio [aoR], 3.7; P < 0.001), and that vaccination was a preventive factor (aOR, 0.20; P < 0.001). Adverse events occurred in 549 of 1,060 HCWs, but most were mild. Although vaccination was carried out during AH1pdm epidemic expansion, the single-dose AH1pdm vaccine proved effective in HCWs, and severe adverse events were rare.