Clonal outbreak of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of FLZR C. parapsilosis blood isolates have not been reported in Turkey. Herein, we consecutively collected the C. parapsilosis blood isolates (n=225) from the fifth largest hospital in Turkey (2007–2019), assessed their azole susceptibility pattern using CLSI M27-A3/S4, and sequenced ERG11 for all and MRR1, TAC1, and UPC2 for selected number of C. parapsilosis isolates. The typing resolution of two widely used techniques, AFLP and microsatellite typing (MST), and the biofilm production of FLZR isolates with/without Y132F were compared. Approximately 27% of isolates were FLZR (60/225), among which 90% (54/60) harboured known mutations in Erg11, including Y132F (24/60) and Y132F+K143R (19/60). Several mutations specific to FLZR isolates were found in MRR1, TAC1, and UPC2. AFLP clustered isolates into two clusters, while MST revealed several clusters. The majority of Y132F/Y132F+K143R isolates grouped in clonal clusters, which significantly expanded throughout 2007–2019 in neonatal wards. Candida parapsilosis isolates carrying Y132F were associated with significantly higher mortality and less biofilm production relative to other FLZR isolates. Collectively, we documented the first outbreak of FLZR C. parapsilosis blood isolates in Turkey. The MRR1, TAC1, and UPC2 mutations exclusively found in FLZR isolates establishes basis for future studies, which potentially broaden our knowledge on FLZR mechanisms in C. parapsilosis. MST should be a preferred method for clonal analysis of C. parapsilosis isolates in outbreak scenarios.

The purpose of this study was to determine the prevalence of causative non-dermatophytic filamentous fungi in onychomycosis. Totally 1,222 (1,222 x 3 = 3,666) samples of nail scrapings from 1,146 patients (from 76 patients two specimens: both from finger- and toe-nails) with prediagnosis of onychomycosis sent to the Mycology Laboratory from the Clinic of Dermatology, Ege University Hospital, Izmir, Turkey, July 2001-December 2003, were prospectively studied with conventional mycological procedures. The set criteria for the diagnosis of onychomycosis due to non-dermatophytic molds were: (1) Observation of fungal elements in 15% KOH-preparations made from nail scrapings, (2) growth of the same mold in all three consecutive cultures of the specimens taken three times from the same patient with one-week intervals, (3) no growth of a dermatophyte or yeast in three consecutive cultures. As agents of onychomycosis molds were detected in 33 (9%), dermatophytes in 175 (48%), yeasts in 150 (41%), and mixed (two different fungi) in 8 (2%) patients. In cases of mold onychomycosis, 11 (33%) had finger-nail and 22 (67%) toe-nail infection; 25 (76%) were female and 8 (24%) male; and 27 (82%) were above 40 years of age. The agents of mold onychomycosis, in order of frequency, were Aspergillus niger (7), Acremonium spp. (6), Fusarium spp. (6), Ulocladium spp. (4), sterile mycelia (2), Alternaria sp. (1), Aspergillus flavus (1), Aspergillus fumigatus (1), Aspergillus terreus (1), Cladosporium sp. (1), Paecilomyces spp. (1), Scopulariopsis sp. (1) and Trichoderma sp. (1). In conclusion, this study showed that non-dermatophytic molds were responsible for nearly 10% of onychomycoses cases attending the dermatology outpatient clinic of a university hospital in Izmir, Turkey. Since molds are common contaminants in the laboratory, cultures from consecutively taken nail scrapings should be made and carefully evaluated in order to diagnose a "mold onychomycosis".

Actinomycosis osteomyelitis of the jaw bones, particularly in the maxilla, is an extremely rare disease. This report presents two cases of maxillary and two cases of mandibular actinomycosis osteomyelitis, with the diagnosis particularly based on histological procedures. The highly diversified pathogenicity of the phenomenon and the absence of solid diagnostic criteria are discussed. Laboratory challenges are emphasized, and a comprehensive overview of the entity including treatment alternatives is given along with a review of the relevant literature.

Dermatophytes include fungal species that infect humans, as well as those that also infect other animals or only grow in the environment. The dermatophyte species Trichophyton rubrum is a frequent cause of skin infection in immunocompetent individuals. While members of the T. rubrum species complex have been further categorized based on various morphologies, their population structure and ability to undergo sexual reproduction are not well understood. In this study, we analyze a large set of T. rubrum and T. interdigitale isolates to examine mating types, evidence of mating, and genetic variation. We find that nearly all isolates of T. rubrum are of a single mating type, and that incubation with T. rubrum “morphotype” megninii isolates of the other mating type failed to induce sexual development. While the region around the mating type locus is characterized by a higher frequency of SNPs compared to other genomic regions, we find that the population is remarkably clonal, with highly conserved gene content, low levels of variation, and little evidence of recombination. These results support a model of recent transition to asexual growth when this species specialized to growth on human hosts.

Candida tropicalis is the fourth leading cause of candidemia in Turkey. Although C. tropicalis isolates from 1997 to 2017 were characterized as fully susceptible to antifungals, the increasing global prevalence of azole-non-susceptible (ANS) C. tropicalis and the association between high fluconazole tolerance (HFT) and fluconazole therapeutic failure (FTF) prompted us to re-evaluate azole susceptibility of C. tropicalis in Turkey. In this study, 161 C. tropicalis blood isolates from seven clinical centers were identified by ITS rDNA sequencing, genotyped by multilocus microsatellite typing, and tested for susceptibility to five azoles, two echinocandins, and amphotericin B (AMB); antifungal resistance mechanisms were assessed by sequencing of ERG11 and FKS1 genes. The results indicated that C. tropicalis isolates, which belonged to 125 genotypes grouped into 11 clusters, were fully susceptible to echinocandins and AMB; however, 18.6% of them had the ANS phenotype but only two carried the ANS-conferring mutation (Y132F). HFT was recorded in 52 isolates, 10 of which were also ANS. Large proportions of patients infected with ANS and HFT isolates (89 and 40.7%, respectively) showed FTF. Patients infected with azole-susceptible or ANS isolates did not differ in mortality, which, however, was significantly lower for those infected with HFT isolates ( P = 0.007). There were significant differences in mortality ( P = 0.02), ANS ( P = 0.012), and HFT ( P = 0.007) among genotype clusters. The alarming increase in the prevalence of C. tropicalis blood isolates with ANS and HFT in Turkey and the notable FTF rate should be a matter of public health concern.

By careful engineering of the rheological properties, in-situ thermosensitive gel formulations of econazole nitrate were prepared and were shown to be efficacious in the treatment of vaginal candidiasis.

Background Candida glabrata is the third leading cause of candidaemia in Turkey; however, the data regarding antifungal resistance mechanisms and genotypic diversity in association with their clinical implication are limited. Objectives To assess genotypic diversity, antifungal susceptibility and mechanisms of drug resistance of C glabrata blood isolates and their association with patients' outcome in a retrospective multicentre study. Patients/Methods Isolates from 107 patients were identified by ITS sequencing and analysed by multilocus microsatellite typing, antifungal susceptibility testing, and sequencing of PDR1 and FKS1/2 hotspots (HSs). Results Candida glabrata prevalence in Ege University Hospital was twofold higher in 2014‐2019 than in 2005‐2014. Six of the analysed isolates had fluconazole MICs ≥ 32 µg/mL; of them, five harboured unique PDR1 mutations. Although echinocandin resistance was not detected, three isolates had mutations in HS1‐Fks1 (S629T, n = 1) and HS1‐Fks2 (S663P, n = 2); one of the latter was also fluconazole‐resistant. All patients infected with isolates carrying HS‐FKS mutations and/or demonstrating fluconazole MIC ≥ 32 µg/mL (except one without clinical data) showed therapeutic failure (TF) with echinocandin and fluconazole; seven such isolates were collected in Ege (n = 4) and Gulhane (n = 3) hospitals and six detected recently. Among 34 identified genotypes, none were associated with mortality or enriched for fluconazole‐resistant isolates. Conclusion Antifungal susceptibility testing should be supplemented with HS‐FKS sequencing to predict TF for echinocandins, whereas fluconazole MIC ≥ 32 µg/mL may predict TF. Recent emergence of C glabrata isolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey.

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.