Successful treatment of disseminated Geotrichum capitatum infection with a combination of caspofungin and voriconazole in an immunocompromised patient

Disseminated Geotrichum capitatum infection is uncommon, and has been reported exclusively in immunocompromised patients. The prognosis is poor with a mortality rate of approximately 50–75%. We report a case of disseminated G. capitatum infection in a severely neutropenic patient who was receiving chemotherapy for acute myeloblastic leukaemia. G. capitatum was isolated from blood cultures, skin lesions, bronchoalveolar lavage fluid, throat swabs and stools. The infection was successfully cured with a combination of voriconazole and caspofungin.     

Disseminated Geotrichum capitatum Infection in a Patient with Acute Myeloid Leukemia: Disseminierte Geotrichum capitatum-Infektion bei einem Patienten mit akuter myeloischer Leukamie

A case of invasive Geotrichum capitatum infection is reported; a young patient had an acute leukemia for which he received a chemotherapy, and presented sepsis with blood cultures for Geotrichum capitatum, namely Dipodascus spicifer; this pathogen only described in cactus rot, is responsible for the first case of a human disseminated infection reported in literature. Then he developed a splenic and epididymic infection, with positive cultures for Geotrichum capitatum after splenectomy and castration. Treatment with amphotericin B and itraconazole was started with low minimal inhibitory concentration (0.1 microgram/ml). The patient died of massive hemoptisis. Autopsy findings demonstrated a lung, brain and kidneys seeding.     

Treatment of chronic disseminated Geotrichum capitatum infection with high cumulative dose of colloidal amphotericin B and itraconazole in a leukaemia patient

Summary. A case of disseminated granulomatous Geotrichum capitatum infection is reported. A young patient with blastic crisis of chronic myelogenous leukaemia developed septicaemia caused by G. capitatum in the post-chemotherapy aplastic phase. Subsequently, disseminated infection of the liver, spleen, pancreas and kidneys was observed. Treatment with high cumulative doses of a lipid formulation of amphotericin B (Amphocil®, 20.2 g in 11 weeks) and maintenance with itraconazole resolved clinical manifestations of G. capitatum granulomatous disseminated disease and controlled reactivation of the infection during the two subsequent courses of cytotoxic chemotherapy.
Zusammenfassung. Es wird über einen Fall von disseminierter, granulomatöser Geotrichum capitatum -Infektion berichtet. Eine junge Patientin mit blastischer Krise bei chronisch-myeloischer Leukämie entwickelte eine Septikämie, verursacht durch G. capitatum in der ablastischen Phase nach zytotoxischer Chemotherapie. Anschließend wurden Disseminierungen in Leber, Milz, Pankreas und Nieren beobachtet. Die Behandlung erfoigte mit hohen Dosen einer Amphotericin B-Lipid-Formulierung, nämlich 20.2 g Amphocil®über 11 Wochen, sowie einer Erhaltungstherapie mit Itraconazol. Diese Behandlung führte zur Heilung der klinischen Manifestationen der Pilzin-fektion und verhinderte die Reaktivierung des Prozesses während zweier nachfolgender Behand-lungsperioden mit zytotoxischer Chemotherapie.     

Fatal Blastoschizomyces capitatus sepsis in a neutropenic patient with acute myeloid leukemia: first documented case from Greece

Blastoschizomyces capitatus (formerly known as Geotrichum capitatum and Trichosporon capitatum) is a rare, yet an emerging, cause of invasive infections in immunosuppressed patients. Profound and prolonged neutropenia is the crucial predisposing factor for this yeast infection. Blastoschizomyces capitatus was isolated from peripheral blood cultures of a profoundly neutropenic patient with acute myeloid leukemia (M2 FAB). Despite administration of antifungal chemotherapy with liposomal amphotericin B at 4.5 mg kg(-1) daily, the patient succumbed 4 days after initiation of treatment. Infections attributed to B. capitatus have generally a poor prognosis, although the yeast shows in vitro susceptibility to antifungal agents. Low flucytosine, caspofungin acetate, voriconazole and amphotericin B minimum inhibitory concentration values were also recorded with our isolate. The clinical relevance of the in vitro susceptibility testing against the isolate and the current antifungal chemotherapy regimens against B. capitatus systemic infections are discussed.     

Pathogenicity of Trichosporon capitatum for normal and irradiated mice and the efficacy of miconazole on experimental systemic trichosporosis in mice

The authors describe the course of experimental trichosporosis in normal and X-irradiated ICR mice after i.v. inoculation with Trichosporon capitatum. The irradiated animals were considerably more sensitive to infection than normal animals. The LD50 challenge dose used was by approximately two orders lower (1 X 10(3) c.f.u. ml-1) in irradiated mice than in control animals. The histopathological examination of the internal organs of the infected mice demonstrated that the greatest tissue damage was associated with the kidneys, liver and spleen. However, the infectious agent was also found in heart, lungs and brain. The degree of impairment of the tissues was dependent on the inoculation dose and on the irradiation status. Miconazole (50 mg kg-1) was administered i.p. immediately after inoculation with Ts. capitatum and resulted in an alteration of infection and prolonged survival time. Miconazole was ineffective when challenge dose were used which produced 100% mortality (1 X 10(6) and 1 X 10(4) c.f.u. ml-1 for normal and irradiated mice, respectively). With the use of these doses also the course of infection was nearly identical both in the miconazole-treated and untreated animals.     

Geotrichosis of oral mucosa

Summary. A livid, sharply defined enanthema of the oral mucosa with ulcerations on the soft palate in a patient presenting with de novo acute myeloid leukaemia with prolonged, therapy-induced granulocytopenia (lt 0.5 nl^-1 for 113 days!) was diagnosed as geotrichosis. Geotrichum capitatum was identified both in vivo and in vitro. Pneumonic infiltrates in the upper lobes of both lungs were treated with amphotericin B infusions. Healing of the aforementioned enanthema was only achieved after addition of 5-fluorocytosine to therapy. Susceptibility determinations with several Geotrichum capitatum isolates led to the conclusion that amphotericin B was unsuitable as a therapeutic agent in this case. 5-Fluorcytosine and itraconazole exhibited superior antifungal and antimycotic activity.
Zusammenfassung. Ein livides, scharf begrenztes Enanthem der Mundschleimhaut mit Ulzerationen am weichen Gaumen bei einer de novo akuten myeloischen Leukämie mit extrem langer, therapiebedingter Granulozytopenie (lt 0.5 nl^-1über 113 Tage!) wird als Geotrichose angesehen. Geotrichum capitatum wurde in vivo und in vitro nachgewiesen. Pneumonische Infiltrate in beiden Lungenoberlappen waren Anlaß zu einer Infusionstherapie mit Amphotericin B. Eine Abheilung des obengenannten Enanthems wurde allerdings erst nach Umstellung der Therapie auf 5–Fluorcytosin-Infusionen erzielt. Resistenzbestimmungen mit mehreren Isolaten hinterließen den Eindruck, daß Amphotericin B als Therapeutikum hier nicht geeignet war. 5–Fluorcytosin und Itraconazol zeigten einen besseren antimyzetischen Effekt und antimykotische Wirksamkeit.     

Hemmung extrazellulärer Sproßpilzproteinasen durch Pepstatin A und Leupeptin im Plattentest: Inhibition of Extracellular Proteinases from Yeasts by Pepstatin A and Leupeptin in vitro

Zusammenfassung: Auf Serumalbuminagar mch Staib wurde eine Proteinaseaktivitüt bei 23% der Candida-albicans-, bei 78% der Candida-tropicalis- und bei 64% der Candida-pantpsilosis- Stömme nachgewiesen. Andere fakultativ-pathogene Sproßpilze wie Candida guilliermondü, Candida krusei, Candida pseudotropicalis, Candida (Tomlopsis) glabrata und Trichosporon capitatum verhielten sich durchweg proteinasenegativ. Mein das Ausmaß der induzierbaren Proteolyse liefert somit im Einzelfall kein eindentiges Indiz über den Krankheitswert eines Pilzes. Unter dem Einfluß von Pepstatin A wurde die Proteolyse völlig gehemmt, während Leu- peptin nur einen geringen Aktivitätwerlust bewirkte.
Summary: Activity of secretory proteinases was detected on serum albumin agar by the method of Staib for 23% of Candida albicans strains, 78% of Candida tropicalis strains, and 64% of Can- dida parapsilosis strains. Tested strains of Candida guilliermondü, Candida h s e i, Candida pseudotropicalis, Candida (Tomlopsis) glabrata, and Trichosporon capitatum were free of any detectable extracellular prateinases. In a particnlar case the degree of inducible proteolysis can- not be the sole criterion for virulence of any of these potential pathogens. Proteolysis was completely inhibited by Pepstatin A, whereas Leupeptin caused only a slight decrease of enzyme activity.     

Referate

Specific precipitin bands in the serology of Histoplasmosis Amer. Rev. Resp. Dis., 87, 1963, 438–440.
Die Myzetome an der französischen Küste von Somali (überblick über 50 zwischen 1954 und 1962 beobachtete Fälle)
Anwendung fluoreszierender Antikörperverfahren beim Studium pathogener Dematium-Pilze. 1. Differenzierung von Cladosporium carrionii und Cladosporium bantianum
Saprophytäre und parasitäre Morphologie pathogener Pilze
Immunologic der Hefe Hansenula wingei
Ein Antigen zum Nachweis der Überempfindlichkeit gegen Cryptococcus neoformans
Experimentelle Infektion des Kaninchens mit Trichosporon capitatum     

Zum Wachstum von Sproßpilzen auf actidionhaltigen Nährböden

Es wurden 74 verschiedene Sproßpilzarten auf ihr Vermögen hin untersucht, in Nährböden mit 400 bis 500 μg Actidion/ml zu wachsen. Von mehreren im klinischen Untersuchungsmaterial häufig vorkommenden Arten konnte jeweils eine größere Anzahl von Stämmen überprüft werden. Dabei zeigte sich, daß sich alle Stämme von Candida albicans, Candida guilliermondii, Candida lipolytica, Candida tropicalis, Candida pseudotropicalis, Trichosporen capitatum und Trichosporen cutaneum gut, hingegen Candida krusei, Candida parapsilosis und Cryptococcus neoformans nicht entwickeln konnten. Torulopsis candida, Torulopsis famata, Torulopsis glabrata und Torulopsis inconspicua sowie auch Candida mycoderma und Pichia membranaefaciens haben sowohl actidionempfindliche als auch -unenipfindliche Stämme.

Summary

Several strains (numbers varying from 1 to 60) of 74 different (individual) species of yeasts were cultivated on media (Mycoselagar, maltextract-agar) containing 400–500 μ/ml Actidione, to study infraspecific variation of Actidione-sensitivity. Among the yeasts of clinical importance in all the strains of Candida albicans (30), C. guilliermondii (30), C. lipolytica (20), C. tropicalis (25), C. pseudotropicalis (4), Trichosporon capitatum (5), and T. cutaneum (15), growth was not reduced, while all the strains of Candida krusei (25), C. parapsilosis (60), and Cryptococcus neoformans (6) more or less absolutely failed to grow under these conditions. Within the species Torulopsis candida, T. inconspicua, Candida mycoderma and Pichia membranaefaciens sensitive and insensitive strains were seen.     

Mycological examinations on the fungal flora of the chicken comb

A total of 500 combs of adult chickens from two different locations in Germany (Hessen and Schleswig-Holstein) were clinically and mycologically examined. The chickens came from three battery cages (n = 79), one voliere system (n=32), six flocks maintained on deep litter (n = 69) and 12 flocks kept on free outdoor range (n=320). Twenty-two of the 500 chicken combs (4.4%) were found to have clinical signs: only non-specific lesions neither typical of mycosis nor of avian pox such as desquamation with crust formation, yellow to brown or black dyschromic changes, alopecia in the surrounding area and moist inflammation. Only seven of the 22 clinically altered combs showed a positive mycological result; the non-pathogenic and geophilic Trichophyton terrestre in one case and non-pathogenic yeast in six cases. The following fungi were seen in the different housing systems: 13 dermatophytes (2.6% of 500 samples): 12 x T. terrestre, 1 x Trichophyton mentagrophytes, 11 isolates of Chrysosporium georgiae (2.2% of 500 samples) and 149 isolates of yeasts (29.8%): Malassezia sympodialis: n = 52, Kloeckera apiculata: n = 33, Trichosporon capitatum (syn. Geotrichum capitatum): n = 23, Trichosporon cutaneum/Trichosporon mucoides: n = 12, Trichosporon inkin (syn. Sarcinosporon inkin): n = 8 and Candida spp.: n = 21, including pathogenic or possibly pathogenic species: Candida albicans: n = 3, Candida famata: n = 4, Candida guilliermondii: n = 3, Candida lipolytica: n = 3, Candida dattila: n = 2 and one isolate each of Candida glabrata, Candida parapsilosis, Candida aaseri, Candida catenulata sive brumpti, Candida fructus and Candida kefyr sive pseudotropicalis. There is no stringent correlation between the clinical symptoms diagnosed on the chicken combs and the species of yeasts isolated. The causative agent of favus in chickens, Trichophyton gallinae, and the saprophytic yeast in pigeons, Cr. neoformans were not isolated. The most frequently isolated yeasts M. sympodialis and Kloeckera apiculata are suggested to be classified as members of the resident flora of the chicken comb.     

Pathogenicity of yeasts and algae isolated from bovine mastitis secretions in a murine model

Summary. The pathogenicity of strains of yeasts and algae isolated from bovine mastitis secretions was evaluated in immunosuppressed mice. Strains of Candida tropicalis (n = 3) were the most pathogenic, but all strains of Geotrichum capitatum (n = 5) and the colourless alga Prototheca zopfii (n = 5) were also lethal to mice at the highest dose of 1 times 10⁷ CFU per mouse. Reisolation of the inoculated micro-organisms and the occurrence of histopathological lesions within organs of mice challenged with 1 times 10³ to 1 times 10⁷ CFU per animal revealed strains of C. krusei (n = 17), C. kefyr (n = 6) and C. rugosa (n = 6) to have a moderate pathogenicity, whereas strains of C. valida (n = 1) and C. catenulata (n = 2) were weakly pathogenic and non-pathogenic respectively.
Zusammenfassung. Die Pathogenität von Hefe- und Algen-Isolaten aus Rindermastitis-Sekreten wurde in immunsupprimierten Mäusen untersucht. Candida tropicalis -Stämme ( n = 3) zeigten die stärkste Pathogenität, aber auch Stämme von Geotrichum capitatum (n = 5) und der farblosen Alge Prototheca zopfii (n = 5) waren in der höchsten Inokulationsdosis von 1 times 10⁷ CFU für Mäuse letal. Rückisolierungsversuche und histopathologische Läsionen an Organen von Mäusen, die mit 1 times 10³-1 times 10⁷ CFU pro Tier inokuliert worden waren, belegten eine mäßige Pathogenität von C. krusei (n = 7), C. kefyr (n = 6) und C. rugosa (n = 6), während sich C. valida (n = 1) und C. catenulata (n = 2) nur als schwach oder nicht pathogen erwiesen.     

Incidence and management of proven and probable fungal infections in patients with acute leukemia: a single center experience

The incidence of fungal infections and the role of liposomal amphotericin B (Ambisome) in proven and probable infections were evaluated in acute leukemic patients, intolerant to conventional amphotericin B. During 1999-2002, 307 febrile episodes occurred in 231 patients. Fungi were responsible for 3% of bloodstream infections. Ambisome was employed in 5 fungal sepsis (1 Candida albicans, 1 C. famata, 1 C. tropicalis, 1 C. krusei, 1 Geotrichum capitatum) 2 Aspergillosis, 2 probable fungal pneumonia cases. A favorable response was achieved in 78% of patients (4 fungemia, 2 aspergillosis, 1 probable), an unfavorable response in 1 C. krusei fungemia and in 1 probable pneumonia. Our antimicrobial pattern documented a high resistance rate to azoles. We concluded that Ambisome is an effective and well tolerated agent and its introduction has changed the outcome for many patients, although in some refractory diseases other strategies must be considered.     

几种血液系统恶性肿瘤的医院感染调查及对策

通过对我院几种血液系统恶性肿瘤２８８例医院感染调查显示，发生医院感染１８９例，感染率６５．５％，共发生医院感染３６６例次，例次感染率１２７．１％，医院感染部位以呼吸道、口腔及败血症为主，而且主要发生于诱导缓解期。同时针对各种危险因素提出相应对策。     

降钙素原在恶性血液病化疗后中性粒细胞缺乏合并感染中的临床意义

目的探讨降钙素原(PCT)在恶性血液病化疗后中性粒细胞缺乏患者合并感染时对病原体诊断的临床意义。方法根据感染的微生物类型,将135例入组患者分为细菌感染组、真菌感染组和病毒感染组;细菌感染组中微生物学确诊为G-菌感染组和G+菌感染组。除行常规血培养及感染灶分泌物培养等检查外,均在发热12 h内行血清PCT测定。PCT测定采用快速半定量固相免疫测定法。综合分析患者的临床表现、微生物检查、影像学检查及治疗疗效回顾性诊断患者感染的微生物类型。结果细菌感染组血清PCT值较真菌感染组及病毒感染组均明显增高,差异均有统计学意义(P均<0.05);真菌感染组与病毒感染组比较差异无统计学意义(P>0.05);G-菌感染组较G+菌感染组PCT值增高(P<0.05)。结论在恶性血液病化疗后中性粒细胞缺乏合并感染的患者中,血清PCT值对预测细菌感染是一个快速可靠的指标。血清PCT值越高,细菌感染可能性越大,G-菌感染可能性更大。对于真菌感染、病毒感染诊断具有阴性预测意义。     

陕西省榆林地区妇女人群HPV感染亚型分布研究

目的:对陕西省榆林地区妇女人群人乳头状瘤病毒(human papillomavirus,HPV)感染及亚型分布特征进行研究。方法:采用PCR-反向斑点杂交技术对735例宫颈脱落细胞标本进行HPV基因分型检测。结果:735例妇女人群中共检出HPV阳性者220例,总感染阳性率为29.93%(220/735),其中高危型感染阳性率为25.85%（190/735,包括多重高危感染）,低危感染阳性率为2.31%（17/735）;高低危混合感染阳性率为1.77%(13/735)。在被检测的16个高危HPV亚型中,最常见类型依次为16、58、53、52、18和51型,未检测出45型;在被检测的3种低危HPV亚型中依次为6、11、43型。HPV阳性者中单一基因型感染率23.67%（174/735）,占HPV感染79.09%(174/220);单一高危型感染率为21.36%（157/735）,占HPV感染71.36%(157/220),占单一感染90.23%（157/174）。多重感染率为6.26%（46/735）,占HPV感染20.91%（46/220）;在多重感染中以二重感染最为常见达4.35%（32/735）,占HPV总感染14.55%(32/220)。不同年龄段妇女人群HPV感染率分别为29.41%、31.92%、31.33%、28.40%、32.65%和41.66%,各组数据无统计学差异（P>0.05）。结论:陕西省榆林地区妇女人群宫颈HPV感染率较高,在单一感染中以16、52、58、33、51和11比较常见;在多重感染中以16、58、53、52、18和51型比较常见,综合统计则以16、52、58、53、51和18型感染比较常见。各年龄段妇女人群均有较高的感染率。     

肿瘤专科医院医院感染的流行病学分析

[目的]了解肿瘤专科医院患者医院感染的临床流行病学特征.[方法]对2000～2003年18 940例住院患者进行临床流行病学分析.[结果]医院感染率为5.8%(1103/18940),漏报率4.8%(53/1103);化疗科医院感染率最高(8.1%),占全院的60.2%,明显高于外科(占全院的2.8%)(P＜0.01)和放疗科(占17.0%)(P＜0.01);感染部位中呼吸道占首位,46.7%;真菌感染较严重,占送检病例的42.8%.[结论]化学治疗科及呼吸道感染、真菌感染问题,是肿瘤专科医院患者医院感染监控的重点.     

血液系统恶性肿瘤患者医院感染的临床分析及预防措施

目的　调查血液系统恶性肿瘤患者医院感染发生率及有关危险因素。方法　对我院几种血液系统恶性肿瘤患者 2 88例发生医院感染情况进行回顾性调查。结果　 2 88例患者中发生医院感染 189例 ,感染率 6 5 5 % ,共发生医院感染 36 6例次 ,例次感染率 12 7 1%。结论　医院感染部位以呼吸道、口腔及败血症为主 ,而且主要发生于诱导缓解期。同时针对各种危险因素提出相应对策。     

女性下生殖道HPV感染与宫颈上皮内瘤变及宫颈癌关系的病理研究

目的：探讨女性下生殖道高危型人乳头状瘤病毒（high risk human papillomavirus,HR－HPV）感染与宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）及宫颈癌的关系。方法：选择2013年2月－2015年4月我院收治的236例CIN及宫颈癌患者为观察组,进行下生殖道HPV（人乳头状瘤病毒）检测,分析CIN及宫颈癌与HPV感染的关系,并与对照组有宫颈炎但无CIN及宫颈癌的126例患者进行对比研究。结果：HR－HPV感染率随着患者CIN 的严重程度而升高,宫颈癌的HR－HPV感染率最高为91．89％,明显高于对照组差异具有统计学意义（P＜0．05）。HR－HPV双重感染率以及HR－HPV多重感染率与单一HR－HPV患者的病毒感染率相比较高,差异具有统计学意义（P＜0．05）。且患者随着病情的加重,单型、双重、多重HR－HPV感染率从CINⅠ期、CINⅡ期、CINⅢ期呈递增趋势。结论：HR－HPV感染及HR－HPV多重感染是导致宫颈上皮内瘤变及宫颈癌发生的重要诱因,对高危型 HPV 病毒的持续感染,及时的诊断并予以有效的治疗,能够阻滞癌前病变的发展,对于预防宫颈上皮内瘤变及宫颈癌,降低宫颈癌的死亡率具有重要临床意义。     

HCMV感染与滋养细胞HLA-E蛋白表达的相关性

目的：研究HCMV感染与滋养细胞HLA-E蛋白表达的相关性。方法：体外分离、培养的滋养细胞系HTP-8,用HCMV AD169标准病毒株感染细胞。免疫荧光法检测HCMV感染后滋养细胞中HLA-E蛋白的表达。结果：病毒感染后10天内,细胞胞浆和胞膜均有HLA-E蛋白表达,感染后1-5天表达水平较低,6-10天表达强度显著增强。结论：滋养细胞HLA-E蛋白的表达与HCMV感染有相关性。     

Gastric cytomegalovirus infection in bone marrow transplant patients: an indication of generalized disease

Cytomegalovirus infection in immunosuppressed patients is well known. It usually appears as an interstitial pneumonitis that may progress to a disseminated viral infection. The authors report on two patients who, after bone marrow transplantation, had signs and symptoms of gastric ulceration as the initial manifestation of cytomegalovirus infection. Both died with disseminated cytomegalovirus infection. Though gastric presentation is unusual for cytomegalovirus infection, epigastric pain and gastrointestinal hemorrhage in a bone marrow transplant patient may herald a potentially lethal viral infection.