A review of German Scedosporium prolificans cases from 1993 to 2007.

Scedosporium prolificans is one of the most life-threatening fungal opportunistic pathogens due to its high resistance to common systemic antifungal agents. While a close relative of Pseudallescheria boydii, S. prolificans has a more limited geographic range being primarily found in Australia, USA and Spain. Infections have also been reported from several other European countries and from Chile. Twenty patients with Scedosporium prolificans infection or colonization from August 1993 to May 2007 were retrospectively reviewed in Germany. They had all been identified at or reported to the Reference Laboratory for Pseudallescheria/Scedosporium spp. in Berlin. Twelve of 13 patients with haematological disorders and/or on immunosuppressive therapy developed a fatal invasive scedosporiosis. Colonization of the respiratory tract was reported for one patient after heart-lung-transplantation, all six patients with cystic fibrosis and one with chronic sinusitis. Molecular studies of the S. prolificans isolates confirmed that parts of the 18S, the Internal Transcribed Spacer (ITS) regions and the D1/D2 domain of the 28S region of rDNA are monomorphic. However, sequencing of parts of the translation elongation factor EF1-alpha (EF-1alpha) and the chitin synthase (CHS-1) genes revealed the presence of three and two distinct genotypes, respectively. Two informative mutations were found in EF-1alpha and a single nucleotide exchange in the CHS-1 gene.

Selective decontamination of the digestive tract and fungal infection in acute leukemia patients.

For prevention of infection we used an SD design including antibacterial (trimethoprim 480 mg/daily, sulfamerazine 720 mg/daily, and polymyxin 0.25 mg/daily) and antifungal (4-6 million IU nystatin/daily) components. We analyzed retrospectively 138 treatment periods in 108 patients. The intensified chemotherapy resulted in severe granulocytopenia below 0.1 x 10(9)/liter over 25.2 days. In 19 patients there was suspicion of major fungal infection; therefore they were given amphotericin B and 5-fluocytosine. Fourteen of them died; major fungal infections were documented in 5 cases. In 18% of all the deceased we found major fungal infections. There was a correlation between fungal infection, the late stages of the hematological malignancy, and the lesions on the oropharyngeal mucosa. However, in terms of the serological and culture findings no correlation appeared to exist between the group with and the group without fungal infection. The SD regime is meant to suppress the Candida cell concentration in the digestive tract but has no influence on Aspergillus in the respiratory tract.

[Fungal infection]. / Pilzinfektionen.

Untreated dermatological mycoses are easy to diagnose. Once treatment with corticosteroids has been initiated the diagnosis of a mycosis can be difficult. In the immunosuppressed patient (AIDS patients) typical dermatological manifestations can be lacking. Systemic antimycotic therapy requires precise detection of the pathogen concerned. Mistakes still made in surgical practice are incision of a tumour in the case of tinea profunda and the extraction of nails affected by fungi. In the healthy person yeasts are transient organisms present in the mouth and intestinal tract in contrast, the mouth and intestinal tract of patients in risk make up a reservoir of candida infection that can affect the internal organs. Cryptococcosis and aspergillosis are inhaled mycoses. Factors predisposing to mycoses influence the duration and the outcome of the course of illness. The most important of these factors in surgical practice is the immunosuppression. Systemic mycoses are difficult to recognize. In many cases organ mycoses can be diagnosed by CT. Continuous investigations of diagnostic cultures and serological tests can contribute to the diagnosis. Only cryptococcosis can be ascertained early by specific antigen demonstration in the serum. For this reason continuous serological testing for cryptococci is essential in AIDS patients.

[Early detection and diagnosis of invasive mycoses]. / Frühzeitiges Erkennen und Diagnostik invasiver Mykosen.

An invasive mycosis may cause death in high-risk patients. An early systemic antimycotic therapy can save life. Therefore, a continuous mycological monitoring in one week intervals is necessary in high-risk patients beginning with the day of admission. This monitoring should be done three to five times a week when an organ manifestation is suspected. Due to the continuous monitoring, the assignment of the results is much easier for the clinician. The goal of the mycological monitoring is to obtain an early hint of a fungus infection. The results of the culture as well as serum titers of antigen and antibodies have to be interpreted in connection with the clinical picture of the underlying disease and the actual risk of infection. Negative results do not rule out a mycosis! Positive results do not always proof an invasive mycosis. Only by interpreting the time course of the mycological findings and the patient's clinical status, an invasive mycosis may be diagnosed with some certainty. In any case, additional procedures like radiological techniques (i.e. CT-scan), histology etc. should be used.

Fungal infections in acute leukemia patients during selective decontamination of the digestive tract--a clinical, laboratory and pathological study.

Selective decontamination (SD) is used for prevention of bacterial as well as fungal infection in acute leukemia patients during remission induction therapy. We analyzed 138 treatment periods of 108 patients. The intensified chemotherapy resulted in severe granulocytopenia below 0.1 X 10(9) l for over 25.2 days. In 19 patients there was a suspect of major fungal infection, for which they were given antimycotics (in 15 cases amphotericin B and 5-fluocytosin). Fourteen of them died. Major fungal infections were documented in 5 cases. In 18% of the deceased we found major fungal infection (7 cases of Candida sp., 5 cases of Aspergillus, one case of Candida as well as mucor). There was a correlation between fungal infection, the late stages of the haematological malignancy and the lesions appearing on the oropharyngeal mucosa. However, no correlation appeared to exist in the serological and culture findings between the groups with and without fungal infection. The SD-regime is meant to suppress the Candida cell concentration in the digestive tract but has no influence on Aspergillus in the respiratory tract. The clinical occurrence of major fungal infections published in the E.O.R.T.C.--Gnotobiotic Project Group was 8.2%. According to the literature there is in the eighties a tendency for an increased incidence of aspergillosis. The use of the SD-regime as prophylaxis as well as early antifungal therapy appear to be of great advantage in reducing the frequency of fungal infections in immunocompromised patients.

Problems and results of selective decontamination in leukemia patients.

Infectious complications play a major part during the cytostatic treatment of patients suffering from acute leukemia, as well as in bone marrow transplantations. For infection prevention, the method of selective decontamination (SD) of the digestive tract was used. This procedure eliminates the potentially pathogenic aerobic bacteria and yeasts while leaving the anaerobic intestinal microflora unaffected. The protocol of the Gnotobiotic Project Group was used in treating 33 patients with SD and the results were compared with those from a comparable control group consisting of cases selected from files who had been treated without SD in the past. A statistical difference was obtained in favor of the SD patients regarding frequency and severity of infection, time between admission and the first signs of infection, days febrile, and in the additional necessity of antibiotics (p less than 0.01). SD involves in addition to a scheduled intake of tablets, microbiological surveillance, personal hygiene and an intact hemostasis, and optimal results can be obtained given the help of the patients' compliance. SD has won a secured place in treatment tailored upon the pathophysiological concept of infection prevention, even though there are problems remaining, e.g., gram-positive cocci, yeasts and infection of the oropharynx.

[Blastomycoid flora of the urogenital tract in nonpregnant and pregnant patients]. / Untersuchungen zur Sprosspilzbesiedlung des Urogenitaltrakes bei Nichtschwangeren und Schwangeren

Vaginal and vulva smears and urine obtained by catheters from 232 pregnant and 251 non-pregnant women were examined for the growth of yeasts. These fungi could be grown from the vulvo-vaginal smears from 26,7% of the pregnant women. Yeasts were found in 6,4% of the urine samples. In the case of non-pregnant women, fungi were found in 19,9% of the vulvo-vaginal smears, whereas 3,2% of the urine samples contained yeasts. The growth of yeasts was encouraged by the addition of various urine dilutions using to a nutrient solution containing Candida albicans of Torulopsis glabrata the urine obtained via catheters from both pregnant and non-pregnant women. There was no difference in the intensity of the effect between the two urine charges. Due to the relatively rare occurrence of yeasts in the urine from pregnant and non-pregnant women it suspected that the increased frequency of vaginal mycoses during pregnancy is not caused by a general disposition, but that locally effective factors are responsible.

[Therapeutic experience with 5-chloro-8-hydroxyquinoline]. / Therapeutische Erfahrungen mit 5-Chlor-8-Hydroxychinolin.

This paper reports on the clinical trials of an antimycoticum using 5-chlorine-8-hydroxychinolin as an antimycotic agent. 142 patients with surface dermatomycoses were treated locally with the preparation for 5 to 6 weeks. Clinical and mycological healing was achieved in 68% of the cases. The results of the treatment, the epicutaneous tests and the additional UV exposition are discussed. The best results of treatment were obtained in the case of superficial dermatomycoses, in particular Trichophytia inguinalis.

[Intracutaneous tests with phytohemagglutinin for detection of cell-mediated immunity (author's transl)]. / Intrakutane Testungen mit Phythämagglutinin zur Erfassung der zellulären Immunität.

Patients with various forms of dermatosis and healthy control subjects were simultaneously tested intracutaneously with specific antigens (candidin, trichophytin, kabikinase, tuberculin and the mumps skin test antigen) and the non-specificmitogen PHA-P. A positive delayed reaction was observed in 98% of the healthy subjects and 76,6% of the dermatosis patients following intracutaneous application of 2 microgram PHA-P.--The results of these studies suggest that the PHA-P intracutaneous test might be suitable as a screening method for diagnozing cellular immun-defects.

[Analysis of Candida-specific antibodies in saliva]. / Nachweis von Candida-spezifischen Antikörpern im Speichel.

We developed an enzyme immunoassay for the estimation of candida-specific IgA antibodies in saliva. In patients with stomatitis prothetica (n = 46) we found a higher concentration (p < 0.05) before therapy in comparison to normal controls.

[Cryptococcosis of the skin]. / Hautkryptokokkose.

In a woman patient who had received a kidney transplant 9 years previously, we diagnosed a cryptococcosis of the skin on the right arm. The results of clinical and mycological investigations and the forms of treatment applied are discussed.

Proliferation of human bone marrow cells in vitro: inhibition by Candida albicans components.

We studied the influence of human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and Candida albicans (CA) components, either alone or in combination, on the proliferation of human bone marrow cells in vitro (colony-forming assay). The number of colonies per 10(5) bone marrow cells after cultivation with rhGM-CSF [maximal (plateau) colony formation] was: 46.2 +/- 9.1 (n = 6); after cultivation with rhGM-CSF in combination with CA components the numbers of colonies were as follows: 0.05 mg protein/ml, 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml, 20.8 +/- 3.6 (n = 3). The mechanisms responsible for this inhibition of colony formation are still unknown. They may be of pathogenetic significance in CA infection.

[African histoplasmosis]. / Afrikanische Histoplasmose.

This is a case report of two patients who suffered from African histoplasmosis. Clinical, histological, and mycological characteristics, and the treatment are described.

[Persistence and variability of yeasts isolated from hospitalized patients: a comparison of results from Rostock and Dresden]. / Konstanz und Variabilität des Hefenachweises bei stationären Patienten: Ein Vergleich der Untersuchungsergebnisse von Rostock und Dresden.

We investigated the yeast colonizations of hospitalized patients at time of the admission to hospital (< or = 3d; 1161 patients) and during stay in hospital (> 3d-several months; 568 patients). At admission to hospital 58% of patients had yeasts in one of the investigated specimens. During stay in hospital the part of patients with yeasts increased up to 81.7%. We established remarkable differences in proof of yeasts in patients of different area of risk. The spectrum of yeasts of the patients in Rostock and Dresden shows a similar shift in frequency of the different Candida species. C. albicans was the predominant yeast. But during hospitalization we saw an elevation of patients with C. glabrata infection from 7.4 to 22.5% and C. krusei infection from 2.8% to 11.8%. There were a remarkable correlation to the area of risk. In 30.8% of the patients we observed a change in yeast spectrum: from negative cultures to positive specimens or from one Candida species to another one.

[North American blastomycosis]. / Nordamerikanische Blastomykose.

We report the case of an African patient with North American blastomycosis. The clinical and mycological results and presented and the therapy explained.

Candidosis of the urinary tract with padding phenomenon of the renal pelvises in an infant with obstructive uropathy.

A male infant with obstructive uropathy developed yeast cell agglomerations which were detectable macroscopically and by image-generating techniques within both renal pelvises after Candida albicans infection of the urinary tract. Therapy with flucytosine induced excretion of 'fungal balls' via the urethra. Continuation of therapy with liposomal amphotericin B (AmBisome) prevented a relapse after development of fungal resistance against flucytosine. Sonographically or radiographically detectable formation of 'concrements' within the urinary tract of patients with an immature or compromised immune system and additional features such as obstructive urinary tract should suggest a localized or systemic mycosis, particularly in the context of long-term antibiotic treatment.

[Histoplasmosis group disease in bat researchers returning from Cuba]. / Histoplasmose-Gruppenerkrankung bei Fledermausforschern nach Kubaaufenthalt.

CASE HISTORY: Four males (age 25 to 40 years) and one female (age 25) were admitted to our hospital almost simultaneously with symptoms of fever up to 38 degrees C, dry cough, thoracodynia, dyspnoea, myalgia and arthralgia. All patients belonged to a team of eight German bat researchers who had returned from Cuba 10 days before, where they had investigated bats in caves. Another member of the team had only mild histoplasmosis and was followed in our outpatient clinic. Two scientists who wore their breathing masks continuously during their work in the caves did not fall ill. EXAMINATIONS: Chest X-rays of all in-patients showed pulmonary infiltrates correlating with the severity of their illness. In all patients specific IgG antibodies against Histoplasma capsulatum-antigen were found in the Western Blot assay, confirming the diagnosis of histoplasmosis. TREATMENT: Treatment with oral itraconazole 200 mg b.d was given to four inpatients for 6 weeks, in the fifth patient itraconazole was discontinued because of an increase of liver transaminases. CONCLUSION: Antimycotic treatment of advancing histoplasmosis seems appropriate also in immunocompetent patients. The high number of patients within this group suggests high numbers of Histoplasma capsulatum in the caves. Wearing breathing masks throughout the work in the caves may prevent histoplasmosis even in case of high infectious doses. Pre-travel recommendations for cave researchers have to emphasize the continuous use of breathing masks and vaccination against tetanus and rabies.

[Precipitating keratin antibodies in psoriasis vulgaris]. / Präzipitierende Keratin-Antikörper bei Psoriasis vulgaris.

A microprecipitation method was used to test sera of psoriasis patients and control persons for precipitating keratin interfilament antibody (KIF-Ab). Precipitating KIF-Ab were detected in 83% of the psoriasis patients. The sera of only 20.5% of controls without dermatological diseases and 40% of nonpsoriatic patients contained KIF-Ab. The mean KIF-Ab titer of the control and psoriasis group did not differ significantly. The different therapy had different effects on the detectability of precipitating KIF-Ab. Upon completion of dithranol treatment and clinical healing, all sera reacted with KIF from psoriasis scales (pso-sc). PUVA treatment lowered the Ab-titer as well as the number of seropositive sera. These results were confirmed by means of immunoblot and immunodot techniques. Sera from psoriasis patients contained Ab of the IgG and IgM-types against 65, 55 and 45 kD proteins. KIF-IgA-Ab were found frequently in the cases of severe forms of psoriasis.

[In vitro proliferation of human bone marrow cells--inhibition by components of Candida albicans]. / In-vitro-Proliferation menschlicher Knochenmarkzellen--Hemmung durch Candida-albicans-Bestandteile.

Candida albicans (CA) components influence the proliferation of human bone marrow cells in vitro (colony-forming assay). Number of colonies per 10(5) bone marrow cells after cultivation with rHuGM-CSF (maximal plateau colony formation): 46.2 +/- 9.1 (n = 6); after cultivation with rHuGM-CSF in combination with CA proteins: 0.05 mg protein/ml: 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml: 20.8 +/- 3.6 (n = 3).