Search

Pulmonary fungal infections in non-neutropenic ICU-patients are not frequent, however, their incidence is increasing with high morbidity and mortality, leading to prolonged stay in ICU wards and to excessive costs dependent on difficult delayed diagnosis. Candida as well as Aspergillus spp. are most important pathogens, but also species of less frequent genera must be taken into account, such as Fusarium, Scedosporium, Cryptococcus and others. Newly evaluated antimycotic agents, such as voriconazole and caspofungin, apart from fluconazole, are not only new options, but must be regarded as agents of choice in non-neutropenic patients.

Not only have the systemic mycoses clearly increased in number but also mycoses of the skin are more common than presumed in the past. Today onychomycosis is found in up to 10% of human beings. Onychomycosis can compromise quality of life markedly. Common tinea pedis is one of the most important risk factors for erysipelas of the lower legs. The clinical presentation of oral candidosis in HIV-infected patients is changing; Candida dubliniensis has been identified as another important causative microorganism. Onychomycosis today in most cases can be cured using terbinafine or itraconazole. When choosing the ideal drug in a given case, both the benefit risk ratio and the benefit cost ratio have to be taken into account. Liposomally encapsulated amphotericin B represents a major breakthrough in the treatment of systemic mycoses or fever of unknown origin. The same applies to liposomally encapsulated econazole with respect to tinea pedis. In regard to the pathogenesis of Candida infections the family of secreted aspartic proteinases plays a major role as a virulence factor and possible future target for antimycotic treatment.

For the in vitro sensitivity assessment of moulds different methods of micro- and macro-dilution assays as well as agar diffusion assays in different media formulations have been described so far. Until now, no standardized method has been preferred. The aim of the present study is to establish and to evaluate a microdilution assay for the in vitro chemosensitivity testing of Aspergillus fumigatus. This method should show a late onset of superficial growth and sporulation as well as a relative independency of the test inoculum. As reference substances, amphotericin B (CAS 1397-89-3) and 5-fluorocytosine (CAS 2022-85-7), which are both used for therapy of systemic mycoses, have been tested. Both substances show an excellent water solubility in liquid media. Fifty clinical isolates of A. fumigatus were used for the testings. The strains showed a better growth in Isosensitest (ISO)-medium than in Yeast-Nitrogen-Glucose (YNG)-medium. Growth was submers++ during the observation time, adherent to the bottom of the microtiter plate. Superficial growth with sporulation only occurred in a late stage of growth. Only a weak inoculum effect could be observed and the MIC (minimal inhibitory concentration) values determined macroscopically as well as using an ELISA reader showed to be almost comparable with a clearly defined breakpoint for the MIC discrimination. For amphotericin B, lower MIC values were observed in ISO-medium (0.25-2 micrograms/ml; median M = 1 microgram/ml) than in YNG-medium (0.25 microgram/ml; M = 1 microgram/ml). For 5-fluorocytosine, in both media MIC-values of > or = 32 micrograms/ml with a median of 64 micrograms/ml in ISO-medium and 128 micrograms/ml in YNG-medium were observed, respectively. With this test procedure, a standardized chemosensitivity testing can be performed for strains of A. fumigatus by a test system which is relatively easy to handle. These in vitro sensitivity data have to be correlated with clinical data as well as data obtained from animal studies. Only after this assessment final therapeutic consequences should be drawn from these in vitro findings.

The chronically recidivist vulvo-vaginal candidiasis is one of the most stubborn problematic diagnosis in the dermatology and gynaecology ward. Prognosis and therapy are primarily determined by the causative micro-organism and the interaction of the fungal species with the currently available antifungal agents. Objective of the study was the investigation of vaginal yeast isolates from patients with chronically recidivist vaginal candidiasis against 8 antifungal agents with the aim of optimising the standard therapy with azole antifungal agents and assessment of alternative therapy schemes. 55 clinical isolates (Dermatology, Charité) of 40 patients were tested by microdilution according to DIN 58940-84. Species differentiation and identification was performed by Fourier-Transform Infrared Spectroscopy (FTIR). In the result Candida glabrata was the predominant causative agent for the recidivist vaginal candidiasis. MIC-mode values for C. glabrata were: fluconacole 32 micrograms/ml, itraconacole 1 microgram/ml, ketoconacole 1 microgram/ml, amphotericine B, voriconacole 0.03 microgram/ml, amphotericin B 0.5 microgram/ml, terbinafine 128 micrograms/ml, cicloproxolamine 4 micrograms/ml, 5-fluorocytosine 0.03 microgram/ml. Some strains of Patients with suboptimal introductory low doses of fluconacole showed increasing of MIC in course of therapy. Parallel resistance with itraconacole was observed in all these cases. Consecutively isolated strains could be clearly and reliably identified by FTIR. In conclusion of most importance is the initial dose adapatation of the drug used, e.g. for fluconacole 800/d p.o., when C. glabrata is the causative agent. Low dose fluconacole therapy is always unsuccessful in recurrent vaginal candidiasis and induces secondary resistance. Demonstrated high susceptibility of voriconacole, amphotericine B an 5-fluorocytosine particularly for C. glabrata may indicate of an anitmycotic therapy potential unconsidered regarding to dermatological indication up to now.

In clinical medicine mere colonization with yeasts is often hardly to be discriminated from true infection. Thus, a clear-cut separation of preventive from therapeutic use of antimycotics is not possible in practical medicine. The problem is that on the one hand one has no exact diagnosis of yeast infection, but on the other hand best therapeutic results are obtained when the drugs are given as early as possible. In comparison to the huge number of antibacterial compounds, the members of antimicrobials are limited. For prophylaxis, one can use the polyenes, such as amphotericin B and nystatin, or the azoles, such as fluconazole or itraconazole. Thereby the azoles act not only locally at the site of application but are absorbed and thus are distributed to remote sites, where the non-resorbable polyenes never arrive. Among the azoles, fluconazole has the advantage that resorption is independent from an acid pH in the stomach, whereas itraconazole resorption is variable in severely ill persons with neutralized gastric fluid. For therapeutic use systemically applied amphotericin B has certain disadvantages. Because of toxic reactions an optimal dose cannot be given; furthermore in some sites insufficient concentrations are achieved, particularly in the kidney and also in the CSF. In contrast, the azoles possess better pharmacologic and toxicologic properties. Resistance to antimycotics is principally possible but still rare, so that in practice a routine testing is not necessary. Candida glabrata as well as Candida krusei are primarily resistant to fluconazole.

The in-vitro influence of drugs on the superoxide production of human neutrophils was investigated. The superoxide production is inhibited by colchicine, g-strophanthin, propranolol, fluphenazine and stimulated by levamisole and lithium. The superoxide production is inhibited or stimulated by chloramphenicol, hydrocortisone and amphotericin B in concentration dependent manner.

400 sputa and 400 vaginal smears (each from 200 patients and 200 healthy subjects) were examined for candida. To establish "change of pathogen" and alteration of resistance, the isolated strains were differentiated and investigated for their sensitivity to amphotericin, gentian violet, Glyceromerfen, iodine, Castellani's paint, gentian violet-nystatin, nystain and BAY 5097. An attempt was also made to ascertain the germ count "suspected" of producing pathological conditions. Pathogenicity, diagnosis and therapy are discussed.

Comparative review of widely used classic and modern antimycotic agents - Polyene-group, Griseofulvin, Tolnaphthate, 5-Fluorcytosin and the new Imidazolyl-group - in view of antimycotic, pharmacocinetic and therapeutic properties.