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C Lass-Flörl

Publications and source records attributed to C Lass-Flörl.

7 recordsLinked to original sources
PubMed1999

Aspergillus osteoarthritis in acute lymphoblastic leukemia.

We report an unusual case of arthritis of the right wrist due to Aspergillus fumigatus without evidence for a generalized infection, following chemotherapy for acute lymphoblastic leukemia. The diagnosis was made by surgical biopsy. Amphotericin-B (Am-B) was not tolerated by the patient. Liposomal preparations of Am-B penetrate poorly into bone and cartilage. Therefore, oral itraconazole was given; the arthritis improved and chemotherapy was continued without infectious complications. Two weeks after complete hematopoietic recovery, an intracranial hemorrhage from a mycotic aneurysm of a brain vessel occurred, although the patient was still receiving itraconazole. We emphasize the importance of prompt and thorough efforts to identify the causative agent in immunocompromised patients with a joint infection. Itraconazole is effective in Aspergillus osteoarthritis but, due to its poor penetration into the brain, the combination with a liposomal formulation of Am-B is recommended.

Antifungal Agents↗
PubMed1999

Dissimilar attenuation of Candida albicans virulence properties by human immunodeficiency virus type 1 protease inhibitors.

The secreted aspartyl proteinase (Sap) of Candida albicans, which is believed to represent an important virulence factor of this opportunistic yeast, and the human immunodeficiency virus type 1 (HIV-1) protease, which is obligatory for the production of infectious virions, both belong to the same family of aspartyl proteinases. We have previously shown that the HIV-1 protease inhibitor Indinavir directly inhibits secretion and proteinase activity of Sap in a dose-dependent manner. Furthermore, at very high concentrations, viability of C. albicans is markedly reduced by Indinavir, indicating that HIV-1 protease inhibitors may possess antifungal activity. We thus proposed that these drugs may add to the resolution of mucosal candidiasis in HIV-1 infected subjects. We have now compared three different HIV-1 protease inhibitors. The rank order of Sap inhibition, already significant at 0.1 mg/ml for all protease inhibitors, was Ritonavir > Indinavir > Saquinavir. However, the cross-reactivity of Ritonavir to pepsin was also more pronounced compared with the other two. Indinavir did not affect Candida viability at concentrations up to 1 mg/ml, in line with our previous study. In contrast, at this concentration Saquinavir was even fungicidal as assessed by three different viability assays (colony formation assay, MTT assay, propidium iodide staining) whereas Ritonavir significantly affected the mitochondrial activity only (MTT assay). No influence on Candida viability was observed for any of the three at concentrations of 0.1 mg/ml or lower. It remains to be examined whether HIV-1 protease inhibitors or derivatives thereof may be suitable for in vivo therapy of subjects suffering from mucosal candidiasis resistant to current antimycotics.

Animals↗
PubMed1999

Pulmonary Aspergillus colonization in humans and its impact on management of critically ill patients.

Samples of lung tissues were obtained and analysed for Aspergillus carriage in 56 patients undergoing thoracic surgical intervention and 18 people who had an unexpected death. Out of 74 samples, 46 (63%) had evidence of pulmonary fungal colonization. The surgery population had a rate of 62% of fungal growth. Aspergillus was present in 39%. The autopsy population had a rate of 61% of fungal colonization. Aspergillus was present in 41%. In these cases eradication of fungal spores residing in the lung prior to aggressive chemotherapy and prevention of further spore uptake during hospitalization is indispensable in preventing pulmonary aspergillosis.

Aspergillosis↗
PubMed1998

In-vitro testing of susceptibility to amphotericin B is a reliable predictor of clinical outcome in invasive aspergillosis.

Invasive aspergillosis is a life-threatening fungal infection which, in neutropenic patients, is associated with an extremely high mortality rate despite optimal treatment. In order to investigate microbiological risk factors for treatment failures in more detail, Aspergillus spp. obtained from 29 patients with haematological diseases after myelo-ablative chemotherapy and bone marrow transplantation were analysed for their susceptibility to amphotericin B in vitro and this was compared with clinical outcome to see if there was a correlation. Aspergillus flavus was present in 12 (41 %) of the 29 patients, Aspergillus terreus in nine (31%) and Aspergillus fumigatus in eight (28%). The susceptibility of these isolates to amphotericin B varied between and within the three species. A. terreus was the only organism against which the MIC was consistently high, A. fumigatus and A. flavus showing variation between isolates in the degree of resistance to amphotericin B. The degree of in-vitro resistance was the only parameter correlating with clinical outcome in a univariate analysis and the only prognostic value in a multivariate analysis considering known risk factors. Irrespective of the species, all six patients with isolates against which the MIC was <2 mg/L survived, whereas most (22/23) of those with isolates resistant to > or = 2 mg/L died. Infections among the six survivors were caused by amphotericin B-susceptible A. fumigatus and A. flavus, but not A. terreus. We conclude that the outcome of aspergillus infection depends on the in-vitro susceptibility of the isolates to amphotericin B. Survival was poor in patients with isolates resistant to amphotericin B and good in those with amphotericin B-susceptible specimens. A. terreus was always associated with high resistance to amphotericin B and with poor survival.

Amphotericin B↗
PubMed1997

Molecular analysis of cyp51 from fluconazole-resistant Candida albicans strains.

The target enzyme for fluconazole is sterol 14 alpha-demethylase, a cytochrome P450 encoded by cyp51. One mechanism of fluconazole resistance likely to occur in Candida albicans is through an altered target site. To test this hypothesis DNA sequencing of the cyp51 coding sequence from 19 fluconazole-resistant and 19 fluconazole-sensitive C. albicans was undertaken. A number of point mutations were identified in the resistant isolates which were not present in the sensitive ones: F105L (five), E266D (five), K287R (one), G448G (one), G450E (one), G464S (three) and V488I (one). These alterations are discussed in the light of a molecular model of the enzyme regarding potential roles in resistance. It was also demonstrated that sequence-specific primers can be employed to identify polymorphisms which may be associated with resistance; diagnostic tests for resistant strains will prove of value in combating this serious clinical problem.

Antifungal Agents↗
PubMed1997

[Vancomycin resistant enterococci in Austria].

This study reports pheno- and genotypical analysis of 9 isolates of vancomycin-resistant enterococci (VRE) and 5 vancomycin-sensitive enterococci (VSE) in Austria: 5 E, faecium isolates of 4 patients (the sole patients demonstrating VRE at the University Hospital of Innsbruck in 1994 and 1995), 3 glycopeptide-sensitive isolates collected in Innsbruck in February 1996 for epidemiological analysis, and 6 enterococcus isolates from the University Hospitals of Vienna and Graz. The pheno- and genotypical analyses of all glycopeptide highly resistant E. faecium and E. faecalis isolates indicated the presence of VanA type resistance. One E. casseliflavus strain with intrinsic VanC-1 resistance showed a characteristic constitutive low-level resistance to vancomycin and susceptibility to teicoplanin. Genotyping with macro-restriction analysis demonstrated that 3 VRE isolates of the 5 E. faecium specimens were identical; the same applied to 2 VSE isolates. The two patients with VRE had been cared for at the same time in a surgical ICU and likewise, the two patients with VSE were simultaneously treated at a neurological ICU. The genotyping of E. faecalis strains showed that two strains of the three VRE isolates exhibited identical patterns. Epidemiological investigation did not reveal a mode of transmission for this cluster. Two of the 8 patients with VRE died within 60 days after isolation of the bacteria; the doctors in charge did not consider that the enterococci had been the cause of death. The results of our study indicate that oral vancomycin administration to humans is a primary cause of VRE in Austrian hospitals. In Austria approximately 66 kg vancomycin, 20% of it given orally, are administered to patients per year. Approx. 18-20 tons Avotan (active ingredient Avoparcin-10%)/year were used in Austria; as of April 1, 1997 the use of this animal foodstuff supplement is prohibited by the European Commission.

Administration, Oral↗