[Cryptococcus species--etiological agents of zoonoses or sapronosis?]. / Cryptococcus-Arten--Erreger einer Zooanthroponose oder Sapronose?

Cryptococcus strains are doubtless the cause of a sapronosis which occurs worldwide as cryptococcosis in humans and warm-blooded animals. The etiological agent is Cryptococcus neoformans with the varieties neoformans and gattii. The infection proceeds from environmental sources and not from animals suffering from cryptococcosis. Therefore the designation as zooanthroponosis is not right. There is a correlation between the geographical distribution of the varieties of Cryptococcus neoformans in the environments and the clinical manifestation of cryptococcosis. The reservoir of var. neoformans, serotypes A and D, are worldwide pigeons and pet birds which are frequent healthy carriers. They excrete these yeasts with their excrements. Bird droppings favour the propagation of cryptococci in natural substrates. The cryptococcal infection arises from inhalation of contaminated dust. Variety gattii, serotype B, occurs mainly in tropical and subtropical climates and its environmental niche has been identified in Eucalyptus trees. Var. gattii was detected in the air and in decaying wood debris under the canopies of these trees. Serotype C was isolated once from almond trees in Colombia. Cryptococcoses in men caused by var. gattii are endemic in Australia, California, Brazil and other tropical and subtropical regions. Modern molecular typing procedures are available for studying ecological problems of cryptococci and epidemiological questions of cryptococcosis. Immunosuppressed individuals, especially HIV infected persons and AIDS patients, should avoid contact with pigeons and pet birds.

[Habitats for Candida in medical and hygienic respects]. / Standorte für Candida aus medizinisch-hygienischer Sicht.

The at present acknowledged 163 species of the genus Candida are living in different habitats. Agents of human candidosis have a comparatively restricted natural distribution, and have been discovered primarily in association with men and animals. Candida albicans holds an exceptional position opposite to the nearly 20 non-C. albicans-species with medical importance. Primary habitat is the digestive tract of men and warm-blooded animals. C. albicans is not ubiquitously distributed in the nature. Carriers of Candida may contaminate their immediate environment with yeasts, but that contamination does not usually spread far. C. albicans survives poorly on dry surfaces, a little bit longer in moist materials. Some non-C. albicans-species have their habitat also in the digestive tracts of men and animals, but different to C. albicans they are also ubiquitously distributed in the surroundings (soil, plants, foods, forages) and are much more resistant to environmental influences. The most important source of Candida species in human diseases is endogenous. The via exogen contamination arising mycoses are involved above all by non-C. albicans-species. The different habitats of the Candida species are decisive for the direct and indirect transmission of yeasts to humans and also for the preventive measures against endogenous and exogenous nosocomial Candida mycoses.

[Differentiation and characterization of yeasts pathogenic for humans (Candida albicans, Exophiala dermatitidis) and algae pathogenic for animals (Prototheca spp.) using Fourier transform infrared spectroscopy (FTIR) in comparison with conventional methods]. / Differenzierung und Charakterisierung von humanpathogenen Hefen (Candida albicans, Exophiala dermatitidis) und tierpathogenen Algen (Prototheca spp.) mittels Fourier-Transform-Infrarot-Spektroskopie (FT-IR) im Vergleich zu konventionellen Methoden.

Due to the Fourier-Transform Infrared Spectroscopy (FT-IR) of strain specific traits demonstrated to be a suitable and efficient method for diagnostic and epidemiological determinations for the yeasts Candida albicans, Exophiala dermatitidis and the chlorophylless algae of the genus Prototheca. FT-IR leads in a rapid and economical way to reproducible results according to the spectral differences of intact cells (IR-fingerprints). Different genera, species and sub-species respectively, different strains can be recognized and grouped into different clusters and subclusters. The FT-IR analysis of Candida albicans isolates (n = 150) of 22 newborns-at-risk of an intensive care unit showed, that 86% of the children were colonised with several (2-4) different strains in the oral cavities and faeces. Stationary cross-infections could definitely be determined. Exophiala dermatitidis isolates (n = 31), mostly isolated repetitively within a period of 3 years from sputa of patients suffering from cystic fibrosis could be characterized and grouped patient-specifically over the total sampling period. Of 6 from 8 patients (75%) their individual strains remain the same and could be tracked over the three years. Cross-infections during the stationary treatment could be clearly identified by FT-IR. The Prototheca isolate (n = 43) from live-stock and farm environment showed clear distinguishable clusters differentiating the species P. wickerhamii, P. zopfii and P. stagnora. In addition, the biotypes of P. zopfii could be distinguished, especially the subclusters of variants II and III. It could be demonstrated, that FT-IR is suitable for the routine identification and differentiation of yeasts and algae. However, in spite of the gain of knowledge by using FT-IR for the characterization of microorganisms, the conventional phenotyping and/or genetic analysis of yeast or algae strains cannot be replaced completely. For a final taxonomic classification a combination of conventional methods on FT-IR together with more sophisticated molecular genetic procedures is necessary.

[Candida infections in infancy and early childhood]. / Candida-Infektionen im Säuglings- und Kleinkindesalter.

Candida infections in infancy can manifest themselves as skin, mucosal or systemic candidiasis. Eighty to nintey percent of all candida infections in this age group are caused by Candida albicans. Whereas in neonates, infections mostly occur sub partu, in older children predisposing underlying diseases get an increasing etiological importance. The diagnosis is based on microscopic and cultural detection of yeast as well as on the course of the titers of Candida antigen and antibodies. For topical antifungal treatment of skin and mucosa infections, different preparations of the polyenes nystatin and amphotericin B have been proven to be most effective. In systemic candidiasis the combination of amphotericin B and 5-flucytosin is the treatment of choice. In view of the potential severe side effects of this combination therapy, fluconazol as a sole treatment represents an effective alternative. Prophylaxis against Candida infections comprises sticking to hygienic regimes, mycological surveillance of risk groups and oral application of antimycotics.

[Vertical transmission of Candida and its consequences]. / Subpartale Ubertragung von Candida und ihre Konsequenzen.

The subpartal transmission of Candida albicans from the vagina of the mother to the newborn is an old and often discussed problem. Thereby the decrease of the infection rate and the prevention of systemic mycoses due to Candida--especially in newborns of risk--are the main objectives. At the end of pregnancy C. albicans is found in vaginal secretions in 25-30% of the women. 70-85% of these women subpartally contaminate their infants with this yeast. Thus 22-24% of all infants acquire C. albicans sub partus. From this situation the following conclusions may be drawn: 1. A prepartal prophylaxis for mycoses in pregnant women with vaginal Candida colonization is to obtain by an intravaginal treatment with polyene or azole antimycotics at the end of pregnancy. Recommendations are offered. 2. A prophylaxis for mycoses in newborns which are especially disposed for systemic candidosis by several factors of risk is to initiate. The oral application of polyene antimycoticas during the considerable endangering by mycoses has been proved to be useful. Referring to this recommendations are offered.

Phenotypic and genotypic differentiation of several human and avian isolates of Cryptococcus neoformans.

The Cryptococcus neoformans strains isolated from two human cases could be diagnosed as Cr. neoformans var. neoformans by differentiation on the basis of their characteristics determined by proline, canavanine and EDTA urease tests. The results of the serovar assignment were: for the isolate from the meningoencephalitis patient with lethal outcome, serovar A; for the strain isolated from the osteomyelitis patient with benign course, serovar D. Also, the PCR fingerprinting using primers (GACA)4, (CAC)5 and FM 1 resulted in a clear and reproducible assignment of the Cr. neoformans strains to the varieties neoformans and gattii, respectively, and, in addition, it confirmed the serovar assignment. No statistically confirmed differences in virulence between the osteomyelitis and the meningoencephalitis strain could be established by i.v. testing in mice, nor did the PCR with several primers provide any clues to a genetically determined higher virulence of the meningoencephalitis strain. The different classification as serovars A and D does not allow any conclusions concerning different virulence. It was not possible to retrospectively establish the sources of infection of the two Cr. neoformans infections, but pigeon faeces may well have played a role as a reservoir for one of the illnesses.

[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.

[Effect of orally administered polyene antimycotics on the intestinal colonization with yeasts: possibilities and limitations]. / Einfluss oral verabreichter Polyenantimykotika auf die Hefepilzbesiedlung des Darmtraktes: Möglichkeiten und Grenzen.

On the basis of intestinal yeast colonization different consequences for therapeutic and prophylactic administration of polyene antimycotics have to be drawn. Immunocompromised neutropenic patients should orally receive polyene antifungal drugs (nystatin or amphotericin B) for a long time during the period of increased risk for systemic candidosis. The level of daily dosing is dependent on age, physiological status of the gastrointestinal tract, and underlying disease of the patient. In immunocompetent persons the normal commensal yeast flora should not be suppressed by antifungal chemoprophylaxis if no clinical indications are present, because permanent eradication of yeast in the intestinal tract ist not attainable. About 5 to 15 days after finishing the administration of polyene antimycotics the fungi are detectable again in the faeces in low quantities. The influence of orally administered polyene drugs in the intestinal tract may be detected shortly after starting the application. Thus efficient concentrations of nystatin and amphotericin B are continuously present in the faeces 24 to 48 hours after beginning until 2 to 10 days after finishing the administration. During this time the quantity of yeast in the faeces is evidently reduced or not longer detectable by fungal culture. The oral administration of polyene antimycotics for a long time in persons without immunodepression and without heavy intestinal yeast colonization is not justified.

[Disseminated aspergillosis and mucormycosis. A case report]. / Disseminierte Aspergillose und Mucormykose. Ein Fallbericht.

This paper reports a simultaneous pulmonary infection due to Aspergillus fumigatus and Rhizomucor pusillus which evolved to disseminated aspergillosis and mucormycosis in a leukaemic and neutropenic 40-year-old woman. Both fungi were cultured ante mortem from bronchial secretion. Although high doses of intravenous amphotericin B were administered, the course of the infection was fatal. At autopsy, aspergilli were demonstrated by histology in lungs and brain, and zygomycetes were found to have invaded liver and kidneys.

[Allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF): clinical significance, diagnosis and therapy]. / Die allergische bronchopulmonale Aspergillose (ABPA) bei Patienten mit Mukoviszidose (CF): Klinische Bedeutung, Diagnostik und Therapie.

Intermittent or long term treatment with antibiotics, progredient destruction of the lungs as well as dystrophy of individuals are predisposing factors for the colonization of the respiratory tract with Aspergillus fumigatus in CF patients. Allergic bronchopulmonary aspergillosis (ABPA) is a significant problem in CF patients. It has been reported with an incidence of 10%. The diagnosis of ABPA in patients with CF is difficult since it is common for both diseases to have several of the same clinical and laboratory features. Prednisolone with an initial dose of between 0,5-1,0 mg/kg/day remains the treatment of choice for ABPA. The doses reduction and the duration of the treatment depend on clinical findings and on serum IgE levels.

[Lethal meningeal encephalitis from Cryptococcus neoformans var. neoformans in a girl without serious immunodeficiency]. / Tödliche Meningoenzephalitis durch Cryptococcus neoformans var. neoformans bei einem Mädchen ohne schwerwiegende Immundefekte.

Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection. The detection of high quantities of cells of Cryptococcus neoformans (about 10,000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable. The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole. After 18 days the cerebrospinal fluid was sterile. Nevertheless considerable lesions of the brain arised. The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy. Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms.

[Fluconazole and itraconazole susceptibility testing with clinical yeast isolates and algae of the genus Prototheca by means of the Etest]. / Fluconazol- und Itraconazol-Sensibilitätsprüfung an klinischen Hefe-Isolaten und Algen der Gattung Prototheca mittels Etest.

Preliminary own results suggest, that the Etest (produced by AB BIODISK, Solna, Sweden) performed on casitone medium meets the requirements of a routine test of yeast susceptibility to fluconazole and itraconazole. Testing of 46 clinical yeast isolates, of 5 strains of Exophiala dermatitidis and 4 strains of algae of the genus Prototheca revealed species-, genus- and strain-specific variations of the susceptibility to fluconazole and itraconazole. Candida glabrata was less susceptible to both triazoles than the other Candida species with exception of Candida krusei. Exophiala dermatitidis was highly susceptible to itraconazole. Prototheca wickerhamii and P. zopfii were resistant to both triazoles. Casitone medium is most appropriate for the determination of susceptibility to fluconazole and itraconazole by the Etest. The results of the Etest were comparable with those of a breakpoint test (microdilution method).

Successful treatment of cerebral aspergillosis by stereotactic operation and antifungal therapy.

The following is a case report of a cerebral Aspergillus abscess in a male patient predisposed to this disease on account of many years of alcohol abuse. After timely identification of the pathogenic organism, the patient was cured by stereotactic operation in conjunction with antifungal therapy using amphotericin B and 5-fluorocytosine. The origin and the starting point of the infection remain obscure.

[Amphotericin B level in feces and serum during oral administration in newborns at risk]. / Amphotericin B-Spiegel in Faeces und Serum während oraler Verabreichung bei Risikoneugeborenen.

The aim of this study was to determine the efficacy of orally administered amphotericin B (Ampho B) on the elimination and suppression of yeasts in the orointestinal tract and on the clinical success regarding the Ampho B concentrations in faeces and serum. A total of 23 newborns at risk suffering from oral and/or cutaneous candidosis and massive colonization of yeasts in the orointestinal tract received Ampho-Moronal suspension (Squibb-Heyden, München) for 10 days: newborns < 1500 g 4 x 20 mg Ampho B/d and newborns > 1500 g 4 x 40 mg/d. Ampho B was detected in concentrations between 0.6 and 20 micrograms/g in the faeces of all patients 24 hours after beginning and 2-6 days after the end of the application. During this time Ampho B concentrations between 0.06 and 0.58 microgram/ml were also detected in the serum of the newborns. During the administration of Ampho-Moronal suspension for 10 days the initial available yeasts were eliminated in 18 patients (78%) out of the faeces. In 7 out of 17 patients (41%) the oral and cutaneous candidosis was cured. After finishing the administration of Ampho-Moronal Candida albicans was isolated again from the faeces during the following 5 days in half of the newborns who had reached negative mycological findings during the prophylaxis. For that reason Ampho-Moronal should be prophylactically administered for a longer time during the period of increased risk for systemic mycosis.

[Detection of Exophiala dermatitidis (Kano) De Hoog 1977 in septicemia of a child with acute lymphatic leukemia and in patients with cystic fibrosis]. / Nachweis von Exophiala dermatitidis (Kano) De Hoog 1977 bei Septikämie eines Kindes mit akuter lymphatischer Leukämie und bei Patienten mit Mukoviszidose.

In 1992 black yeasts of the species Exophiala dermatitidis were isolated for the first time from patients at the University Clinics in Dresden. Since that time this relatively rarely detected fungus has been frequently cultivated from clinical specimens. Our observations were: Patient with acute lymphatic leukaemia: In a 3 1/2 years old boy E. dermatitidis was isolated from 8 blood cultures during a septicaemic phase. Elimination of the fungus and decreasing of the fever were reached after removing a central venous catheter and treatment with amphotericin B and 5-fluorocytosine for 3 weeks. In this patient E. dermatitidis was assessed to be the cause of the septicaemia setting in via catheter. Patients with cystic fibrosis: In 8 of 51 mycologically surveyed patients E. dermatitidis was frequently - in 2 cases for a long time up to 7 months - isolated from sputum specimens. The occurrence of this fungus was considered to be a colonization with subclinical development. In these patients no fungal invasion or systemic mycosis were seen. The administration of itraconazole for 4 respectively 7 months did not succeed in eliminating E. dermatitidis out of the respiratory tract. It is recommended to include mycological longtime cultures in the surveillance of cystic fibrosis patients for detection of E. dermatitidis.

[Results of mycologic studies of donated breast milk]. / Ergebnisse mykologischer Untersuchungen gespendeter Frauenmilch.

From 1968 to 1989 altogether 37,000 specimens of donated and collected mother's milk were mycologically examined by means of a liquid medium (twofold concentrated Raulin solution). The yearly incidence of Candida albicans varied between 8.5 and 5.2%. 25% respectively 14.8% of the donors (n = 60 respectively 813) had delivered milk to the human milk bank which was contaminated by Candida albicans. The mother's milk was primarily contaminated by the donor's own suckling baby. 92.3% of these infants were infected with Candida albicans in the mouth and/or rectum and/or on the skin. Candida albicans was also detected in 46.2% on the nipples of the mothers. It is recommended to transport donated mother's milk at temperatures of 4-8 degrees C and to store the milk at -20 degrees C until the mycological examination is finished to exclude samples contaminated by Candida albicans. Judging our experience donated human milk to be fed in raw state should be regularly controlled mycologically. If the donated milk contains Candida albicans, the donation of milk should be interrupted and an antifungal treatment of the donor and her baby should be performed.

[Intestinal excretion of nystatin during and after oral administration to newborn infants at risk]. / Zur intestinalen Ausscheidung von Nystatin während und nach oraler Applikation bei Risikoneugeborenen.

The concentrations of nystatin excreted with faeces during and after oral application of 3 x 150,000 IU/d, either continuously for 14-21 days or every second day were determined in 42 newborns at risk by means of a bioassay (agar diffusion test). Results indicate that nystatin is distributed heterogeneously in the gastrointestinal tract. The excretion occurs discontinuously. 24 to 48 h after beginning of therapy there were effective concentrations of nystatin in the faeces. The daily application of 3 x 150,000 IU nystatin is recommended.

[Mycologic monitoring of newborn infants at risk during preventive administration of nystatin]. / Mykologische Uberwachung von Risikoneugeborenen während der prophylaktischen Verabreichung von Nystatin.

Altogether 80 newborns at risk were prophylactically treated with 3 x 150,000 IU nystatin/d per os for 14-21 d respectively on every second day for 14-21 d. The content of yeasts in the faeces was determined. In preterm infants with birth-weight below 1500 g the intestinal yeasts--especially Candida albicans--persisted much longer during nystatin application than in infants with higher birthweight and longer gestation-time. In newborns at risk, daily nystatin doses of 3 x 150,000 IU/d are recommended for the duration of disposition for systemic candidosis.

[Mycological surveillance of children with cystic fibrosis]. / Mykologische Uberwachung von Kindern mit Mukoviszidose.

The mycological surveillance included 121 patients aged 1 to 21 years treated from 1981 to 1987 in the Centre of Cystic Fibrosis in Dresden. The control groups comprised 136 resp. 140 healthy children aged 1 to 16 years. The study evaluated the incidence of fungi in the oral cavity, bronchial secreta, sputum, faeces and urine as well as the specific serum antibodies to Candida albicans and Aspergillus fumigatus in correlation to the course of the cystic fibrosis and the applied chemotherapy. The study pointed out a parallel run concerning the progression of the clinical manifestation of the basic disease, the duration of the required chemotherapy and the mycological findings indicating more and more pathological levels. The mycological results of the children with a moderate course of cystic fibrosis were conformable to the findings of the children of the control groups. Systemic candidosis or aspergillosis were not seen. Because patients suffering from cystic fibrosis are predisposed for infections with fungi, especially with Aspergillus fumigatus, the authors recommend a mycological surveillance of these patients depending on the clinical course of cystic fibrosis: once in twelve months for patients with mild symptoms and every third month for patients with severe symptoms.

[The significance of Candida antigen detection in internal medicine and surgical patients]. / Zur Aussagekraft von Candida-Antigen-Nachweisen bei internistisch-chirurgischen Patienten.

Three different Candida antigen tests were studied in internal-surgical patients: two tests for Candida mannan antigen (C-Mannan-Dresden, Pastorex-Candida and Cand-Tec test for cytoplasmatic antigen. Most positive findings could be seen by both tests for mannan. In cases with increased occurrence of fungi in feces, sputum, urine, and mouth smears the tests differently became negative. Some clinical cases are discussed. With increased positivity of titer courses of all 3 antigen tests the probability of detection of an endomycosis also increased.