Kriterien zur Empfindlichkeitsprüfung von Fluconazol im Mikrodilutionstest: Vorschlag für eine standardisierte Methode zur Testung von Sproßpilzen

In vitro susceptibilities were determined for a total of 159 clinical isolates and 12 reference strains of yeasts belonging to different Candida species including 94 Candida albicans strains, and further genera such as Cryptococcus, Trichosporon, Geotrichum and Saccharomyces. Minimum inhibitory concentration (MIC) values for fluconazole and itraconazole were assessed using a microdilution technique with the semisynthetic high resolution (HR) medium supplemented with glucose and asparagine but without sodium hydrogen carbonate (pH 7.0), according to a proposal of the working group 'Clinical Mycology' of the German Speaking Mycological Society. Fluconazole MIC values for C. albicans were between 0.125 and > or = 128 micrograms ml-1. Thus, the median of 1 microgram ml-1 showed that the overall fluconazole susceptibility was good. As expected, Candida krusei (seven strains) exhibited diminished in vitro susceptibility with MIC values for fluconazole of 8 to 128 micrograms ml-1 with a median of 64 micrograms ml-1. Some Candida kefyr strains seemed to be less susceptible against fluconazole which was indicated by a MIC90 of 64 micrograms ml-1. Surprisingly, no Candida glabrata isolate exhibited a MIC value greater than 16 micrograms ml-1. Other Candida species, Trichosporon cutaneum, Geotrichum candidum and Saccharomyces cerevisiae showed low MICs to fluconazole. In vitro susceptibility testing of itraconazole revealed that all Candida species except C. albicans, but also Trichosporon cutaneum, Geotrichum candidum, and Saccharomyces cerevisiae exhibited acceptable low MIC values against itraconazole (0.03-2 micrograms ml-1). Their MIC90 values for itraconazole were in the close range between 0.125 and 2 micrograms ml-1. MIC values between 0.125 and 2 micrograms ml-1 were obtained, even for C. krusei strains. On the other hand, the range of C. albicans MICs was between 0.0125 and > or = 16 micrograms ml-1 with MIC50 and MIC90 values of 0.125 and > or = 16 micrograms ml-1, respectively, indicating that a considerable number of yeast strains have high MICs. The comparative evaluation of different experimental conditions revealed that there exists a marked influence both of inoculum size and incubation time on the results of susceptibility testing. Therefore, for routine usage 10(2) CFU ml-1 and 18-24 h incubation time for this microdilution method with HR medium are recommended.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

In vitro susceptibility of yeasts for fluconazole and itraconazole. Evaluation of a microdilution test

Nenoff

Oswald

Haustein

1999

“…The in vitro and in vivo susceptibility of the yeasts correlates with the concentrations of fluconazole measured in the different compartments of the body Einleitung Fluconazol, ein Triazol-Antimykotikum, wird seit einigen Jahren erfolgreich in der Behandlung von Cryptococcosen und Candidosen eingesetzt. Die Wirksamkeit jeder antimykotischen Behandlung setzt voraus, daB der Wirkstoff zuverlassig und schnell an den Ort der Infektion gelangt und dort iiber eine ausreichend lange Zeit eine Konzentration aufrecht er- [42].…”

Section: Summary Fluconazole Penetrates Well Into the Tissuesunclassified

Fluconazol: Vergleich von Pharmakokinetik, Therapie und Empfindlichkeit der Sproßpilze in vitro

Wildfeuer

Laufen

Schmalreck

et al. 1996

Self Cite

Fluconazole penetrates well into the tissues and body fluids which were examined and achieves rapid equilibration between the different compartments. The pharmacokinetics of fluconazole are independent of the dose after oral or intravenous administration. This finding, together with the drug's slow elimination (t1/2 30 h) facilitate the estimation of the therapeutically effective dosage. The concentrations of fluconazole measured in blood can be extrapolated to the concentrations in tissue (lung, brain, gynecological tissues), body fluids (sputum, saliva, vaginal secretions) and exudates. The concentration of fluconazole in cerebrospinal fluid and in the vitreous humour of the eye is ca. 80% of that in blood. Fluconazole is predominantly excreted in the urine in the unchanged form, which explains the 10 to 20 fold higher concentration of the drug in urine relative to blood. Although this pharmacokinetic profile favours the use of fluconazole in mycotic infections of the urinary tract it also means that the dose of the drug may have to be adapted to lower regimens in the systemic treatment of patients with restricted kidney function. The in vitro and in vivo susceptibility of the yeasts correlates with the concentrations of fluconazole measured in the different compartments of the body.

“…DaR hierzu auch der fur die Bakteriologie bereits gut dokumentierte Etest [20] zahlt, wurde durch zahlreiche Untersuchungen aufgezeigt [9,[21][22][23][24]. Auf Basis des Testprotokolles fur den Mikrodilutionstest [25] Die Ergebnisse des Etests mit HR-Medium bestatigen vorangegangene, vergleichende Untersuchungen [16] sowie Studien mit anderen Kulturmedien [9, 21, 231, die zeigen, daB der Etest vergleichbar mit der von der AG-KMYK vorgeschlagenen Mikrodilution-Standardmethode und der auf der gleichen Grundlage beruhenden Agardilutionsmethode ist. Der Etest kann daher als Alternativmethode zur Mikrodilution oder Agardilution angesehen werden.…”

Section: Introductionunclassified

Empfindlichkeitsprüfung von Hefen gegenüber Fluconazol: Vergleich der Etest‐Methode mit der Mikrodilution und der Agardilution

Schmalreck

Kottmann

Reiser

et al. 1996

In bacteriology, the Etest has a broad field of application in bacteriology and is recently available for the antimycotics fluconazole and itraconazole. By means of the presence of gradient concentrations of the active substance on the carrier material, it is possible to obtain reproducible MICs of the antimycotic substances. The results of susceptibility testing of 326 clinical yeast isolates with the Etest were compared to those MICs obtained by microdilution and agar dilution. A 100% concordance of the MIC markers (mode-, MIC50- and MIC90-value, standard deviation of the mean log2-MIC-dilution steps) was given when compared by a +/- 1 MIC-dilution step range with microdilution and by +/- 2 MIC-dilution steps with agar dilution; species dependent all strains were within 2 x standard deviation of the individual MIC-mean of the species. By comparison of the individual MIC-values maximum differences of +/- 6 MIC-dilution steps were obtained, where 70% of all results were within +/- 2 MIC-dilution steps, and more than 92% of all strains were within +/- 3 MIC-dilution steps. The Pearson's correlation coefficients show a good agreement of the Etest with microdilution (r = 0.92) resp., agar dilution (r = 0.88) demonstrate, however, clearly insufficient correlations (r < 0.65) to the reference methods, for species with difficult to read Etest inhibition zones (e.g., Candida glabrata, Candida krusei, Candida parapsilosis). The differences between the proposed test methods recommended by the NCCLS and the working group "Clinical Mycology" of the German Speaking Mycological Society (AG-KMYK) are tabled.