Improving the conduct and reporting of clinical trials.
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Amphotericin B↗
Biomedical subjects
H Bernhardt
Publications and source records attributed to H Bernhardt.
Funguria and Candida-specific immunoglobulins in patients with systemic candidosis.
UNLABELLED: Funguria, indirect anti-Candida haemagglutination test (C-IHT) and Candida-specific immunoglobulins C-IgM, C-IgG and C-IgA were investigated under suspicion of systemic candidosis in critically ill patients. A total of 143 urine cultures were studied for Candida from 74 adults and a median count of log 3.0 CFU ml-1 was found. Most isolated Candida species were Candida albicans and Candida glabrata. In 14 cases of candidaemia there was no regular agreement between the finding of Candida species in blood and urine. In cases with candiduria > = or log 3.0 CFU ml-1 a stronger increase of C-IHT titres and all three Candida-specific immunoglobulins after 5-7 days was observed. Some statistically significant correlations were found between the levels of urinary yeast counts and immunological parameters concerning C-IHT, C-IgA and C-IgG on the first day and after 5-7 days. Clinical findings in some cases coincided well with funguria and courses of titres before and after treatment. CONCLUSION: In critically ill patients suspected of having systemic candidosis not only blood cultures should be made. Cultural studies with specimens taken from different sites including funguria are essential for a complete specific serological investigation.
Aged↗
Oesophageal candidosis in intensive care patients.
We conducted upper intestinoscopies in 124 intensive care patients, six of whom had oesophageal candidosis. Of these, two also had Candida plaque in the stomach. The patients at the intensive care unit (ICU) had a mean Apache-II score of 26.7; whereas the score was 29.5 in patients with Candida oesophagitis. A significant increase of Candida antibodies was found in 59 of 124 patients (47.6%), including all patients with oesophageal candidosis. Presumably, mycotic infections of other sites were present. The severity by which mucous membranes were affected correlated well with microscopically evident invasiveness.
Candida↗
Fungal resistance.
Fungal resistance is caused by an acquisition of intrinsically resistant species, by selection of resistant strains from a population or by mutation of an initially susceptible strain. According to different classes of antimycotics there are different resistance mechanisms: differences in the uptake mechanisms, drug target alterations, mostly the ergosterol-biosynthesis pathway, and the efflux or pumping mechanisms to the outside.
Animals↗
[Difficulties of fungus detection in corneal culture medium].
UNLABELLED: It is not always possible to prevent the growth of microorganisms in organ culture for cornea preservation, despite many prophylactic measures. It is especially difficult to prove the presence of fungi in the cultural medium. MATERIALS AND METHODS: A culture medium was examined for sterility after 8 days' storage of cornea in organ culture. To prove the presence of fungi a culture of Sabouraud 2% glucose-agar was prepared and its growth examined by light microscopy. RESULTS: After 8 days of preservation we noticed a color change in the cultural medium and suspected contamination with fungi. Coagulase-negative Staphylococci could be cultivated from the conjunctival smear obtained before preparation of the cornea only. Routine screening of microbiological contamination did not show any results. We were able to identify an Aspergillus species only after preparing a special culture. The conjunctival smear as well as the cultural medium of the other eye of the same donor showed no contamination. CONCLUSIONS: In spite of the fact that microbiological contamination can be seen macroscopically, it is difficult to prove the presence of a specific microorganism and even more so when dealing with fungus. Especially in these cases the incubation of the cornea in media might have an advantage because contamination can be suspected by just looking at the medium. By excluding these preparations from transplantation we can possibly prevent infections, even when routine examinations show negative results.
Aspergillus↗
Candida albicans clinical isolates inactivated by formalin with different adherence to buccal epithelial cells induce proinflammatory and regulatory cytokines in human peripheral blood mononuclear cells.
Besides the activation of phagocytes, the release of cytokines is the most important immunological defence mechanism of an organism against infection with Candida albicans. On the other hand cytokines induced in the organism by the yeast itself are able to modulate the immune responses of the host. We investigated whether eight clinically isolated strains of C. albicans inactivated by formalin as well as a laboratory strain were able to induce proinflammatory and regulatory cytokines in peripheral blood mononuclear cells (PBMC) of four different donors. Under our assay conditions the yeast strains induced the cytokines interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in PBMC to varying extents, but not the cytokine interleukin-4 (IL-4). We observed a difference in the reaction of the individual donors to the stimulus C. albicans but on the other hand the extent of the cytokine signal seemed to be dependent on the yeast strain as well. No correlation was found between the ability of the individual C. albicans strains to induce cytokines in PBMC and their ability to adhere to buccal epithelial cells. Determination of the cytokine induction potential of C. albicans strains possibly may contribute to the detection of new virulence factors of this yeast.
Candida albicans↗
The continuous flow culture as an in vitro model in experimental mycology.
We used the model of continuous flow culture (cfc) to study the growth of Candida species. This model allows special test conditions: a long generation time of 15-20 hs, controlled limitation of nitrogen sources and carbohydrates, comparison of the growth under aerobic and anaerobic conditions simultaneously. These conditions were used to study the effect of antimycotic drugs, mainly during a long time of 7 to 10 days. Germ tube formation as a virulence factor was more abundant and faster in cfc of strains with a stronger adherence to buccal epithelium cells. Co-cultivation of C. albicans and C. glabrata allowed conclusions for their colonization in vivo. A biofilm on the glass wall of the culture vessel led to mycelium formation by C. albicans. Concomitantly the growth of C. glabrata was favoured. Growth of C. albicans in the gastrointestinal flora was reduced by masses of bacteria and their multiple metabolic activities. A remarkable growth of C. albicans was only to be seen if the ecosystem was destroyed e.g. by antibacterial antibiotics. The influence of fluconazole in a long-term follow up study under anaerobic conditions showed an inhibition of C. albicans in 99.9%. This means fungicidal efficacy.
Candida↗
Influence of ciprofloxacin and other antimicrobial drugs on different Escherichia coli strains in continuous-flow cultures under aerobic and anaerobic conditions.
In continuous-flow culture, long generation times and high bacterial counts favour survival of bacteria. A chemotherapeutic agent that achieves a bactericidal effect under these circumstances can therefore be seen as highly effective. In our continuous-flow culture we obtained bactericidal effects with ciprofloxacin 1-2 mg/L, cefotaxime 4 mg/L and mezlocillin 32 mg/L. These effects were seen irrespective of whether conditions were aerobic or anaerobic. There were no significant differences between monocultures and mixed cultures simulating faecal flora with the various Escherichia coli strains tested. Cefotaxime had an initial effect but an increase in counts was then observed as a result of regrowth of E. coli survivor strains in aerobic monoculture and mixed cultures. Mezlocillin was completely bactericidal in monocultures, but regrowth occurred in mixed cultures under anaerobic conditions. Neither the bacterial composition of this culture nor the resistance pattern explained this regrowth. These results were observed in long-term experiments followed for up to 7 days. We conclude that the antibiotics tested are highly effective against E. coli under unfavourable conditions simulating in-vivo situations.
Aerobiosis↗
[Fungi in the intestine--normal flora or pathogens?].
Candida spp. und C. albicans are common within the microbial ecosystem of the human orointestinal tract. Candida in low quantities is found at various sites in healthy subjects. In patients with typical risk factors, mainly in immunocompromised hosts, an increased growth of Candida occurs. In cases with multiple sites colonised there will be an increased risk of severe Candida infections. The metabolic activity of Candida in the gut is very low under anaerobic condition and limitation of nutrients.
Candida↗
Mycological aspects of gastrointestinal microflora.
There are two aspects about the presence of Candida in the human orointestinal tract: (i) it is a part of normal human flora and (ii) it is a risk factor for immunocompromised patients. The orointestinal tract can be considered a reservoir for Candida species, several of which are from the oral cavity, stomach, duodenal juice and faeces. Their germ counts in normal small and large bowel do not exceed 10(4) cfu/ml resp.g. The input of Candida to a well-developed faecal flora system under continuous flow culture conditions did not lead to a multiplication of the yeast. The take in of faecal flora into a Candida continuous flow culture diminish Candida germ counts. If, however, the faecal flora was destroyed, e.g. by antibiotics, we found the yeasts multiplying, with the formation of germ tubes and mycelial structures. Colonization by Candida has to be seen as a starting-point of the development of subsequent candidosis in immunosuppressed or intensive care patients. The best protection against Candida colonization in the gut is the existence of a normal bacterial flora. Lactulose, which promotes the Gram-positive potential of faecal flora, may protect indirectly by supporting the indigenous flora.
Adult↗
Dynamics of Candida isolations from humans from 1992-1995 in Greifswald, Germany.
In the period 1992-95 there was a significant shift in the spectrum of Candida species in the University Hospital in Greifswald. During this time, the annual number of specimens taken for mycological investigations of adults increased threefold (total n = 11,568). The isolation rate of Candida species was 50.5%. The percentage of C. albicans isolates decreased from 76% to 54.4% with the lowest level in 1994. The opposite trend in the occurrence of non-C. albicans species was seen, for example the occurrence of C. glabrata, from 11.7% to 28.4%. We found only 98 strains of C. parapsilosis (1.4%) during the 4 years. The occurrence of Candida species in a variety of habitats was different. During the 4 years, the same annual percentages of C. albicans (mean 87.9%) were isolated from endoscopic oesophageal smears, whereas the distribution of Candida yeasts from the oral cavity, the respiratory tract, faeces and urine had changed. Over the years, at these locations, C. albicans was less frequently isolated and non-C. albicans species clearly increased. The highest occurrence of C. glabrata was found in urine, in which the isolation percentage almost doubled from 23.1% to 40.9% in 1994. In contrast to adults, in all specimens originating from a paediatric clinic that included neonatology the occurrence of C. albicans was high (83.5% in 1995), but the isolation rate of Candida species was low (12.3%). These results are important because of the differences in yeast susceptibility, of non-C. albicans species in particular, against antifungal drugs.
Adult↗
Adherence on buccal epithelial cells and germ tube formation in the continuous flow culture of clinical Candida albicans isolates.
Mucosal adherence and germ tube formation have been considered as important virulence factors of Candida albicans. We investigated 11 clinical isolates (among them six isolates from oesophageal thrush) for quantification of adherence to buccal epithelial cells and germ tube formation in the continuous flow culture in vitro, and correlated the results with the clinical data of the patients. Adherence varied considerably between the different C. albicans strains. Strains recovered from clinically, culturally and serologically confirmed oesophageal thrush adhered stronger to buccal epithelial cells. Isolates from cases with heavy colonisation but clinically without candidosis were less adherent. Only after 30 min germ tube formation was observed in the continuous flow culture. Strains with stronger adherence also showed significantly faster and increased germ tube formation. The patients with oesophageal thrush did not suffer any particular immunosuppression such as HIV infection, although in most cases chronic alcoholism was apparent. We conclude, that in cases with minor immunosuppression the expression of the virulence factors adherence and germ tube formation plays an important role in the pathogenesis of candidosis, whereas it may be of less importance in cases with severe immunosuppression. In the latter they may, however, influence outcome.
Candida albicans↗
[Candida identification: experiences with the Vitek automated system].
We report about our experiences obtained with the Vitek system (bioMerieux, Nürtingen) for identification of 1160 clinical Candida isolates. The Vitek system correctly identified 1005 (86.6%) Candida isolates (probability > or = 85%): 776 (66.9%) strains were identified after 24 h of incubation, 229 (19.7%) required 48 h of incubation. In 4.4% (n = 51) we found results with a lower probability (< 85%). After 24 h of incubation 38 (14.6%) of the 260 C. tropicalis isolates tested were misidentified as C. parapsilosis; we obtained the correct results after 48 h of incubation. 104 (9%) isolates were wrongly identified after 48 h of incubation. The majority of these strains (n = 82) were biochemically minimally reactive Candida species. Overall, the Yeast Biochemical Card system provides a reliable method for the rapid, automated identification of medically important Candida species.
Automation↗
[Modification of phagocytic microbicide function by antifungal agents--measuring luminol enhanced chemoluminescence in full blood].
Fungus infections are becoming more important in surgical intensive medicine, and various preparations are now available to treat them. The goal of our investigations was to determine the influence of the antimycotics in current use on the microbicide phagocytic function by measuring chemiluminescence. To this end the luminol-enhanced chemiluminescence in whole blood samples from a total of 29 healthy donors was measured with a LKB 1251 Luminometer after stimulation with zymosan or a Canadida albicans preparation. We tested the substances amphotericin B, flucytosin (Ancotil), fluconazol (Diflucan) and itraconazol (Sempera), each in three different concentrations within the recommended dose range and compared the results with those in an untreated sample. For the insertions of amphotericin B or intraconazol after zymosan stimulation no significant differences in the measurements were found (50.84 vs 47.99 mV and 46.10 vs 47.89 mV) compared with the blank test. Similar situations revealed by the tests with C. albicans administration (15.21 vs 12.35 mV and 11.16 vs 11.91 mV). However, the tests with flucytosin in the higher concentration range, after stimulation with either zymosan or C. albicans, evidenced a significant reduction in the measurements (34.70 vs 52.74 mV, P<0.005, and 10.98 vs 14.57 mV, P<0.01). The tests with fluconazol showed a decrease of the chemiluminescence exclusively for the highest concentration in the C. albicans group (14.36 vs 17.20 mV, P<0.005). Our results indicate a negative influence of the phagocytes on the oxidative metabolism especially with flucytosin in the higher concentrations. This emphatically confirms demands for exact indications and dosage of antimycotics and their correct administration.
Antifungal Agents↗
[Candida in the ecological system of the orointestinal tract].
Within the microbial ecosystem of the orointestinal tract Candida spp. are common but not always detectable organisms. Therefore they belong to the transient flora. Candida spp. are found at various sites in healthy subjects in quantities between 10(2)-10(4)/ml or g. In different diseases an increased growth of Candida can occur depending on the presence of typical risk factors. In any case the yeasts only account for a minimal part of the bacterial flora. In this regard the contribution to the formation of metabolic products-in particular carbon dioxide, hydrogen and alcohols-is very small. Growth and development of Candida are dependent on nutrient and oxygen supply. In the colon under anaerobic conditions the flora competes for limited nutrients and fermentation is the dominant metabolic pathway in Candida. There is only minimal growth. Under aerobic conditions as can be demonstrated in experimental settings a marked growth with the formation of mycelium takes place. The generation time in vivo is much longer than under laboratory conditions and takes several hours. The detection of Candida in stool specimens can be interpreted in the first line only as a colonization. This is not equivalent with an infection, which, unfortunately, often is wrongly suggested in positive stool specimens.
Candida↗
[In vitro susceptibility testing of Candida species against fluconazole using the microdilution test with Alamar Blue].
The investigation of susceptibility of Candida species to fluconazole was performed in microdilution to a supplemented HR-medium. The sufficient reproducibility of the test was verified using special control isolates and isolates of patients. The excellent applicability of the method in routine diagnostics was evaluated by in vitro testing of susceptibility of 279 Candida isolates from patients being colonised or suffering from endomycoses. The Candida species showed different susceptibility against fluconazole: 96% of the C. albicans isolates were sensitive, 55% of the C. glabrata isolates had a reduced sensitivity, and 26% were resistant against fluconazole (MIC > 25 micrograms/ml). C. krusei isolates were highly resistant (9 of 11 strains).
Antifungal Agents↗
[Growth of Candida albicans in normal and altered fecal flora in the continuous flow culture model].
We used the model of fecal microflora under continuous flow culture (cfc) conditions to study the growth of Candida albicans in mixed cultures. The development of Candida is usually limited by the high germ counts of aerobic and anaerobic bacteria. Neither by the continuous inflow of C. albicans-cfc-monocultures nor by intermittent input of highly concentrated suspensions of C. albicans into the system a growth in fecal flora could be obtained. If the system was run under aerobic conditions a development of C. albicans with few hyphal growth could be observed. After some days however, the fecal flora again suppressed a further development of the yeasts. Only a marked destruction of the aerobic and anaerobic microflora by antibiotics resulted in a growth or overgrowth of Candida albicans.
Anti-Bacterial Agents↗
[Mycotic complications in patients with chronic liver diseases and pancreatitis].
UNLABELLED: We studied 15 patients with mostly alcoholic liver diseases and 25 patients with acute or chronic pancreatitis with regard to occurrence of yeasts in different microbiological samples and corresponding serological findings. In about a half of the patients with liver diseases yeast counts and serological titres were already raised in the first mycological investigation. Patients with pancreatitis, however, showed only little or negative cultural and serological results. This changed during the course of disease, where they developed significantly higher yeast counts and serotitres. Finally two case reports are presented: two patients with infected pancreatic pseudocysts (including a case of aspergillosis). CONCLUSIONS: in patients with decompensated chronic liver diseases an early search for mycological complications is recommended. In pancreatic diseases these complications are rather seen later in the course of the disease, especially under intensive care conditions. Therefore, we encourage surveillance cultures and control of serotitres in these patients.
Acute Disease↗