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Biomedical subjects

M Seibold

Publications and source records attributed to M Seibold.

At least 19 recordsLinked to original sources

Lethal double infection with Acremonium strictum and Aspergillus fumigatus during induction chemotherapy in a child with ALL.

Fungal infections are a major cause of morbidity and mortality in patients during chemotherapeutic treatments and malignant hematologic disease. We present a case of a double fungal infection with disseminated Acremonium strictum (A. strictum) and pulmonary Aspergillus fumigatus (A. fumigatus) and its rapid clinical course. A 17-year-old boy with prolonged neutropenia developed a disseminated fungal infection during induction chemotherapy of his acute lymphoblastic leukemia. The infection was rapidly lethal despite neutrophil recovery and early antifungal combination therapy with amphotericin B and caspofungin. Since there are only a few reports about invasive Acremonium infections, we present this case with regard to differences in the clinic pathologic features of Aspergillosis and other opportunistic fungal infections due to Fusarium or Acremonium species.

Acremonium↗

[Cutaneous alternariosis. Clinical diagnosis and therapeutic options].

Localized skin infections caused by the pigmented fungi of the genus Alternaria are being increasingly observed. In the past, primarily patients receiving long-term glucocorticoid therapy were likely to have this mycosis, which is commonly traumatic, but now it is frequently encountered in organ transplantation patients. Possible therapeutic options and differential diagnosis are discussed by means of two case reports--a female renal transplant patient infected by A. alternata and a patient with iatrogenic Cushing syndrome infected by A. infectoria. Histopathological differentiation from other fungal infections may be difficult but is of therapeutic and prognostic significance. Finding short hyphae in tissue sections is an important clue. Since A. infectoria shows little conidial growth in culture, rDNA ITS sequencing offers another diagnostic possibility. Therapy has not yet been standardized. Along with surgical intervention, systemic itraconazole is the usual choice.

Aged↗

Combination therapy of disseminated Fusarium oxysporum infection with terbinafine and amphotericin B.

A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality.

Amphotericin B↗

Validation of the sterilization procedure of allogeneic avital bone transplants using peracetic acid-ethanol.

Different procedures are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone transplants. The most efficient methods are considered to be gamma irradiation and thermal inactivation as well as chemical sterilization methods like the peracetic acid-ethanol treatment (PES). Following national and international standards or draft standards, the antimicrobial effectiveness of this procedure was evaluated. Due to the standardizable size as well as the clinical relevance, defatted human spongiosa cuboids (15x15x15 mm) served as model system. After treatment with PES for 2 and 4 hours, respectively, the titre of living micro-organisms was determined in the supernatant and the cuboid. A reduction in the titre of viable micro-organisms below the detection level (reduction factor >5 log10) was already achieved after an incubation time of 2 hours (Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Candida albicans as well as spores of Bacillus subtilis). No viable micro-organisms could be detected in any of the PES-treated test cuboids. Spores of Aspergillus niger were also completely inactivated. The PES procedure proved to be a reliable method for the sterilization of human bone transplants derived from spongiosa.

Bacteria↗

A novel type of metastatically spreading subcutaneous aspergillosis without epidermal lesions following allogeneic stem cell transplantation.

Systemic mycosis is among the most feared opportunistic infections in the immunocompromised host. Difficulty and delay in diagnosis and treatment often result in poor outcomes. In this communication a metastatically spreading form of subcutaneous aspergillosis developed in a patient with a history of allogeneic stem cell transplantation for relapsed Hodgkin's lymphoma. Strikingly, necrotizing cutaneous papules or ulcerating lesions were absent. Diagnosis was accomplished after excision of a clinically non-suggestive subcutaneous nodule. Despite prompt initiation of antimycotic therapy the outcome was fatal; dosage of conventional and liposomal amphotericin B was limited due to treatment-related toxicities. This case report describes a novel form of aspergillosis and underlines the need for an aggressive diagnostic approach in severely immunocompromised patients.

Adult↗

Susceptibility testing of Candida species: comparison of NCCLS microdilution method with Fungitest.

Fungitest is a new commercially available and easy-to-perform breakpoint test system using six antifungal agents. We compared this test with a modified standard method described by the National Committee for Clinical Laboratory Standards (NCCLS). One hundred isolates of Candida species were tested with both methods. Based on the same breakpoints, the correlation of qualitative results between the reference method and Fungitest was high. Best results were obtained after incubation of Fungitest for 48 h. Overall agreement was high, an excellent correlation was given with amphotericin B and flucytosine (100% and 99%, respectively), whereas itraconazole showed only 86% concordance. When Fungitest was read after 24 h the agreement was lower ranging from 100% to 75%. Some of the breakpoints used with Fungitest differ from the breakpoints recommended by NCCLS, whereas others have not been elaborated by the NCCLS. The adaptation of Fungitest breakpoints to NCCLS and determination of further breakpoints have to be discussed before Fungitest can be recommended for routine use.

Amphotericin B↗

Case reports. Disseminated cryptococcoses without cryptococcal antigen detection.

During the last decade cryptococcoses were most frequently diagnosed in AIDS patients, where serologically high amounts of glucoronoxylomannan (GXM) were detectable. Disseminated cryptococcoses without cryptococcal antigen detection is unusual. Between August and October 1998 disseminated cryptococcoses were diagnosed in three patients consecutively although cryptococcal antigen was not detectable. Only one of the patients was HIV infected.

AIDS-Related Opportunistic Infections↗

Differentiation between Candida dubliniensis and Candida albicans by fatty acid methyl ester analysis using gas-liquid chromatography.

Candida dubliniensis is often found in mixed culture with C. albicans, but its recognition is hampered as the color of its colonies in primary culture on CHROMagar Candida varies. Furthermore, definite identification of C. dubliniensis is difficult to achieve, time-consuming, and expensive. Therefore, a method to discriminate between these two closely related yeast species by fatty acid methyl ester (FAME) analysis using gas-liquid chromatography (Sherlock Microbial Identification System [MIS]; MIDI, Inc., Newark, Del.) was developed. Although the chromatograms of these two species revealed no obvious differences when applying FAME analysis, a new library (CADLIB) was successfully created using Sherlock Library Generation Software (MIDI). The amount and frequency of FAME was analyzed using library training files (n = 10 for each species), preferentially those comprising reference strains. For testing the performance of the CADLIB, clinical isolates genetically assigned to the respective species (C. albicans, n = 32; C. dubliniensis, n = 28) were chromatographically analyzed. For each isolate tested, MIS computed a similarity index (SI) indicating a hierarchy of possible strain fits. When using the newly created library CADLIB, the SIs for C. albicans and C. dubliniensis ranged from 0.11 to 0.96 and 0.53 to 0. 93 (for all but one), respectively. Only three isolates of C. albicans (9.4%) were misidentified as C. dubliniensis, whereas all isolates of C. dubliniensis were correctly identified. Resulting differentiation accuracy was 90.6% for C. albicans and 100% for C. dubliniensis. Cluster analysis and principal component analysis of the resulting FAME profiles showed two clearly distinguishable clusters matching up with two assigned species for the strains tested. Thus, the created library proved to be well suited to discriminate between these two species.

AIDS-Related Opportunistic Infections↗

Evaluation of phenotypic markers for selection and identification of Candida dubliniensis.

Candida dubliniensis is often associated with C. albicans in cultures. Easy-to-perform selective isolation procedures for these closely related species do not exist. Therefore, we evaluated previously described discriminatory phenotypic markers for C. dubliniensis. A total of 150 oral rinses from human immunodeficiency virus (HIV)-infected patients were cultured on CHROMagar Candida. Dark green colonies described as being indicative of C. dubliniensis and other green colonies, 170 in total, were isolated. Chlamydospore formation, intracellular beta-D-glucosidase activity, ability to grow at 42 degrees C, carbohydrate assimilation pattern obtained by the API ID 32C, and Fourier transform infrared (FT-IR) spectroscopy were used for phenotypic characterization. Sequencing of the 5' end of the nuclear large-subunit (26S) ribosomal DNA gene was used for definitive species identification for C. dubliniensis. C. dubliniensis was found in 34% of yeast-colonized HIV-infected patients. The color of the colonies on CHROMagar Candida proved to be insufficient for selecting C. dubliniensis, since only 30 of 53 proven C. dubliniensis isolates showed a dark green color in primary cultures. The described typical chlamydospore formation can give only some indication of C. dubliniensis. The assimilation pattern proved to be insufficient to discriminate C. dubliniensis from C. albicans. All C. dubliniensis strains showed no or highly restricted growth at 42 degrees C and a lack of beta-D-glucosidase activity. Unfortunately, atypical C. albicans strains can also exhibit these phenotypic traits. FT-IR spectroscopy combined with hierarchical clustering proved to be as reliable as genotyping for discriminating the two species.

AIDS-Related Opportunistic Infections↗

Cytotoxicity of triterpenoid saponins. Part 2: Relationships between the structures of glycosides of polygalacic acid and their activities against pathogenic Candida species.

Glycosides of polygalacic acid (2 beta,3 beta,16 alpha,23-tetrahydroxy-olean-12-ene-28-oic acid) is isolated from the aerial parts of Solidago virgaurea L. subsp. virgaurea, Heteropappus altaicus (Willd.) Novopokr. and Heteropappus biennis (Ldb.) Tamamsch. or produced by degradation of these genuine saponins were tested against humanpathogenic strains of Candida albicans, C. glabrata, C. krusei and C. tropicalis using a micro-dilution assay. The antifungal action can be influenced the variation of the etherglycosidically bonded carbohydrate units at C-3 as well as of the acylglycosidically bonded oligosaccharide at C-28 of the aglycone.

Antineoplastic Agents, Phytogenic↗

[Clinical fluconazole and itraconazole resistance of oro-gastrointestinal candidiasis in a patient with AIDS].

We report on a 32-year-old male patient with advanced acquired immunodeficiency syndrome (AIDS), who had severe candidiasis of the gastrointestinal tract. Treatment with fluconazole, 200 mg/day, was introduced. After oral intake of fluconazole over 5 months itraconazole 200 mg/day was given for 1 month. However, fungal infection still persisted. The antifungal activity of fluconazole, itraconazole and ketoconazole against Candida albicans was evaluated by means of the microdilution test by determining the 90% inhibitory concentration of each drugs. A high minimal inhibitory concentration (MIC) was detected for fluconazole (50 micrograms/ml) revealing fluconazole resistance. The susceptibility to itraconazole was borderline (MIC 0.125 micrograms/ml) and that to ketoconazole was markedly lowered (MIC 0.25 micrograms/ml). Plasma levels of itraconazole were also found to be lowered. In HIV patients the gastrointestinal absorption of azole derivatives is often reduced. Therefore, the clinical resistance of Candida albicans to itraconazole can be explained by reduced susceptibility after azole therapy and also by the decreased absorption of the drug in HIV patients.

AIDS-Related Opportunistic Infections↗

[Controversies in the standardization of susceptibility testing on yeasts to azole antimycotics].

Due to the different physical-chemical conditions of the therapeutical azoles it is necessary to choose an adequate testing procedure. In the group of azoles caused by its hydrophilia fluconazole susceptibility testing can be handled easily. However it is not possible to take the same test conditions for itraconazole as for fluconazole due to the extreme high hydrophobicity of itraconazole. The current recommendations of NCCLS should be considering these problems. Therefore it is necessary to standardize susceptibility testing for all azoles possible.

Antifungal Agents↗

[The Etest--an alternative to the NCLLS standard for susceptibility testing of yeasts?].

The Etest and the NCCLS method are not much differing in respect to their reproducibility. Only single observations exist on the clinical correlation of both tests. The correlation between both tests are known as being dependent on the yeast species and antifungals used. Due to the easy and simple handling the Etest is attractive for routine laboratories. The Etest has to be more evaluated before it can be generally recommended. The NCCLS method also is not validated until now. Different test methods should be compared thoroughly with the above mentioned standard.

Antifungal Agents↗

Osteomyelitis due to Cryptococcus neoformans in advanced age. Case report and review of literature.

In an 84-year-old man cryptococcosis with a pronounced osteomyelitic course (involvement of a rib, two thoracic vertebrae, the sacrum and a femur) was diagnosed histologically post mortem, thus directing attention to cryptococcosis in advanced age. The presumptive chronic course of the Cryptococcus neoformans (Cr. n.) infection in this patient was ascribed to chronic kidney failure, diabetes mellitus and chronic obstructive lung disease. Special reference is made to the mycological and radiological diagnosis of cryptococcosis of the bones as well as to its pathogenesis, therapy and epidemiology.

Aged↗

[Cryptococcus neoformans meningoencephalitis and multiple infections in AIDS].

A 40-year old homosexual AIDS patient recovering from a Pneumocystis carinii pneumonia developed a Cryptococcus neoformans infection with involvement of the central nervous system (CNS) which could be treated successfully with amphotericin B and flucytosine. After a symptom-free interval of 4 1/2 months, a new acute fatal disease of the CNS did not reveal a cryptococcosis relapse but a necrotizing Toxoplasma encephalitis, a cytomegalovirus infection and striking cultural findings of Staphylococcus aureus in all organs examined. Neither by culture nor by histology Cr. neoformans could be detected in the CNS or in the other organs examined. The temporal course of the Cr. neoformans infection and its specific diagnosis are commented. It is demonstrated that (during or after successful therapy of Pneumocystis carinii pneumonia) a specific cultural examination of specimens from the respiratory tract for Cr. neoformans is needed, in order to recognize a Cr. neoformans infection in its primary stage, i.e. before hematogenous dissemination of Cr. neoformans leading to the secondary stage of the infection.

Acquired Immunodeficiency Syndrome↗

Cryptococcosis in AIDS patients: observations concerning CNS involvement.

The clinical course and response to therapy of seven patients with cryptococcosis and AIDS were reviewed. One patient was still in the primary stage of cryptococcosis in AIDS, i.e. the stage that is characterized by the sole cultural detection of Cryptococcus neoformans in the respiratory tract. The other six patients were in the secondary stage, where C. neoformans can be detected from the cerebrospinal fluid (CSF), blood, urine, faeces and other body sites. The main presenting features (headache, fever, nausea) were due to central nervous system involvement, although meningism and mental changes were rarely present, and CSF changes were very subtle. Treatment with amphotericin B and flucytosine was very effective, there being no more growth of fungi in cultures in most cases. Adverse reactions to the drugs used occurred frequently and consisted mainly of anaemia, hepatosis and fever. Diagnosis in the primary stage of cryptococcosis may improve the prognosis.

Acquired Immunodeficiency Syndrome↗

Aspergillus findings in AIDS patients suffering from cryptococcosis.

Because of the known pathogenicity of Cryptococcus neoformans and of aspergilli depending on defined but different immunodeficiencies of the host, the evaluation of their simultaneous cultural detection in specimens of the respiratory tract of AIDS patients is of epidemiological, diagnostic, pathogenetic and therapeutic interest. In 10 out of 15 AIDS patients the following species of the genus Aspergillus could be isolated either once or repeatedly during the course of Cr. neoformans infections in specimens from the respiratory tract: A. fumigatus, A. flavus, A. nidulans, A. niger and A. glaucus. From the 10 different case reports the conclusion can be drawn that the cultural findings of aspergilli in specimens from the respiratory tract during the course of cryptococcosis were of no pathogenic significance. Rather, they should be interpreted as inhaled and not yet germinated conidia still capable of growth lacking primary pathogenicity for the AIDS patient. The significance of serodiagnosis for the evaluation of the simultaneous occurrence of Cr. neoformans and Aspergillus spp. is demonstrated and discussed.

Acquired Immunodeficiency Syndrome↗