Porazdelitev minimalnih inhibitornih koncentracij antimikotikov za medicinsko pomembne glive

Martini Keber, Lara (author), Matos, Tadeja (mentor)

Glivne okužbe so na našem geografskem območju oportunistične narave in se najpogosteje pojavljajo pri imunokomprimitiranih posameznikih. Z razvojem novih antimikotikov in vedno večjega interesa ter potreb po teh zdravilih se razvija tudi testiranje občutljivosti gliv za antimikotike. Poznamo referenčne metode in več oblik komercialno dostopnih metod za testiranje občutljivosti. V magistrski nalogi smo želeli opredeliti razporeditev minimalnih inhibitornih koncentracij (MIK) antimikotikov za medicinsko pomembne glive, ki so bile izolirane iz kliničnih vzorcev v Laboratoriju za glivične infekcije na Inštitutu za mikrobiologijo in imunologijo Medicinske fakultete Univerze v Ljubljani (IMI MF UL). Te smo primerjali s porazdelitvami MIK iz podatkovne baze Evropske komisije za testiranje antimikrobne občutljivosti (EUCAST), ki so bili pridobljeni z referenčno mikrodilucijsko metodo. V analizo smo vključili 27 različnih medicinsko pomembnih gliv. Podatke o MIK smo pridobili z metodo gradient difuzije, ki so bili v veliki večini že v bazi informacijskega sistema IMI (MBL), deloma pa smo opravili še dodatna testiranja za novejše antimikotike ali redkejše izolate. Rezultate MIK smo primerjali s podatki, pridobljenimi z referenčno metodo mikrodilucije, opredeljeno s strani EUCAST. Kjer je bilo možno, smo opredelili zgornjo mejo divjega tipa (angl. wild-type upper limit, wtUL). Ugotovili smo, da se vrednosti MIK z obema metodama za Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, Aspergillus flavus, Aspergillus fumigatus in Aspergillus niger v več kot 95 % skladata, če upoštevamo razpon dveh redčitvenih stopenj. Ugotovili smo, da imajo vse redkeje osamljene glive kvasovke wtUL za flukonazol višjo (80 %) ali enako (20 %) epidemiološki razmejitveni vrednosti (angl. epidemiological cut-off value, ECOFF) Candida albicans. Vrednosti wtUL za izavukonazol za najpogosteje izolirane glive iz skupine Mucorales in ECOFF A. fumigatus so bile skladne, medtem ko je bil wtUL za posakonazol dve in štiri redčitvene stopnje višji za za Mucor spp. in Rhizopus spp.

• Language: Slovenian
• Keywords: antimikotiki, minimalna inhibitorna koncentracija, glive, epidemiološka razmejitvena vrednost, zgornja meja divjega tipa, gradient difuzija
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: BF - Biotechnical Faculty
• Place of publishing: Ljubljana
• Publisher: [L. Martini Keber]
• Year: 2022
• PID: 20.500.12556/RUL-143552
• UDC: 579.24:615.282
• COBISS.SI-ID: 135351811
• Publication date in RUL: 25.12.2022

Secondary language

• Language: English
• Title: Distribution of minimal inhibitory concentrations of antifungal compounds for medically relevant fungi

Abstract

Fungal infections are opportunistic in our geographic area and most often occur in immunocompromised individuals. With the development of new antifungals and the ever-increasing interest and need for these drugs, antifungal sensitivity testing is also developing. We are familiar with reference methods and several forms of commercially available sensitivity testing methods. In this Master's thesis we wanted to define the distribution of minimum inhibitory concentrations (MIC) of antifungals for medically important fungi, which were isolated from clinical samples in the Laboratory for Fungal Infections at the Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana (IMI MF UL). These were compared with MIC distributions from the European Commission Antimicrobial Susceptibility Testing (EUCAST) database, which were obtained using the reference microdilution method. We included 27 different medically important fungi in the analysis. We obtained data on MIC using the gradient diffusion method, the vast majority of which were already in the database of the IMI information system (MBL), if there was no data available, we performed additional testing for newer antifungals or rarer isolates. MIC results were compared with data obtained using the reference microdilution method defined by EUCAST. Where possible, we defined the wild-type upper limit (wtUL). We found that the MIC values with both methods for Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, Aspergillus flavus, Aspergillus fumigatus and Aspergillus niger agree in more than 95 % if we consider a range of two two-fold dilutions. We found that all of the less common yeast isolates had fluconazole wtUL higher (80 %) or equal (20 %) to the epidemiological cut-off value (ECOFF) of Candida albicans. The wtUL values for isavuconazole for the most frequently isolated fungi from the Mucorales group and ECOFF of A. fumigatus were consistent, while the wtUL for posaconazole was two and four two-fold dilutions higher than for Mucor spp. and Rhizopus spp..

• Keywords: antimycotics, minimum inhibitory concentration, fungi, epidemiological cut-off value, wild-type upper limit, gradient diffusion