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Research Interests: Medicine and Gynecology
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Clonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of... more
Clonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its 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. In this study, we consecutively collected C. parapsilosis blood isolates ( n = 225) from the fifth largest hospital in Turkey (2007 to 2019), assessed their azole susceptibility pattern using CLSI M27-A3/S4, and sequenced ERG11 for all and MRR1 , TAC1 , and UPC2 for a selected number of C. parapsilosis isolates.
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... 2nd ed. Baltimore: Williams and Wilkins; 1998. p. 1091-93. 4) Say B, Tuncbilek E, Balci S, Muluk Z, Gogus T, Saraclar M, et al. Incidence of congenital malformations in a sample of the Turkish population. Hum Hered 1973;23:434-41. ...
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Candida türleri, infeksiyon patogenezinde rolü olan çeşitli hidrolitik enzimler salgılamaktadır. Candida türlerinin hemolitik aktivitesi konusunda yapılan çalışma sayısı azdır. Bu çalışmada, Candida türlerinin hemolitik aktivitelerinin... more
Candida türleri, infeksiyon patogenezinde rolü olan çeşitli hidrolitik enzimler salgılamaktadır. Candida türlerinin hemolitik aktivitesi konusunda yapılan çalışma sayısı azdır. Bu çalışmada, Candida türlerinin hemolitik aktivitelerinin araştırılması amaçlanmıştır. Toplam 70 ...
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BackgroundInvasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL.MethodsIFI episodes in children with... more
BackgroundInvasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL.MethodsIFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a ‘modified‐possible’ category included.ResultsA total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified‐possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8‐11.4%) overall and 23.5% (95% CI 14.5‐32.5%) for relapsed/refractory ALL. For non‐relapsed ALL, the IFI prevalence was significantly hig...
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Objectives Aspergillus fumigatus causes several diseases in humans and azole resistance in A. fumigatus strains is an important issue. The aim of this multicentre epidemiological study was to investigate the prevalence of azole resistance... more
Objectives Aspergillus fumigatus causes several diseases in humans and azole resistance in A. fumigatus strains is an important issue. The aim of this multicentre epidemiological study was to investigate the prevalence of azole resistance in clinical and environmental A. fumigatus isolates in Turkey. Methods Twenty-one centres participated in this study from 1 May 2018 to 1 October 2019. One participant from each centre was asked to collect environmental and clinical A. fumigatus isolates. Azole resistance was screened for using EUCAST agar screening methodology (EUCAST E.DEF 10.1) and was confirmed by the EUCAST E.DEF 9.3 reference microdilution method. Isolates with a phenotypic resistance pattern were sequenced for the cyp51A gene and microsatellite genotyping was used to determine the genetic relationships between the resistant strains. Results In total, resistance was found in 1.3% of the strains that were isolated from environmental samples and 3.3% of the strains that were isolated from clinical samples. Mutations in the cyp51A gene were detected in 9 (47.4%) of the 19 azole-resistant isolates, all of which were found to be TR34/L98H mutations. Microsatellite genotyping clearly differentiated the strains with the TR34/L98H mutation in the cyp51A gene from the strains with no mutation in this gene. Conclusions The rate of observed azole resistance of A. fumigatus isolates was low in this study, but the fact that more than half of the examined strains had the wild-type cyp51A gene supports the idea that other mechanisms of resistance are gradually increasing.
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Purpose: The aim of this study was to report a case of fungal keratitis with subsequent corneal perforation after corneal collagen cross-linking (CXL) treatment performed for keratoconus. Case Report: A 20-year-old woman presented with... more
Purpose: The aim of this study was to report a case of fungal keratitis with subsequent corneal perforation after corneal collagen cross-linking (CXL) treatment performed for keratoconus. Case Report: A 20-year-old woman presented with redness and discharge in the left eye. She had a history of bilateral CXL procedure performed for keratoconus elsewhere 4 days earlier. The visual acuity was hand motion in the left eye. Slit-lamp examination revealed extended corneal melting with surrounding infiltrates. The patient was hospitalized, and corneal epithelial scraping samples were sent for microbiological assessment. In the meantime, empirical antibiotic therapy (fortified topical antibiotics: vancomycin 50 mg/mL, ceftazidime 50 mg/mL, and fluconazole 2 mg/mL q1 hour) was initiated. In direct microscopy of the corneal scraping, septate hyaline fungal hyphae were detected and topical fluconazole was switched to topical voriconazole (10 mg/mL). Three days after hospitalization, corneal melting progressed to perforation and corneal suturing with 10-0 monofilament was performed to reform the anterior chamber. Complete resolution of keratitis with residual scarring was noticed in 2 weeks. Three months later, penetrating keratoplasty was performed to obtain better visual acuity. Conclusions: CXL with riboflavin has become a common procedure to prevent keratoconus progression by strengthening the biomechanical specialties of the cornea. Although the treatment itself has been used in the management of microbial keratitis and related corneal melting, fungal keratitis and corneal perforation after a CXL procedure for keratoconus might also be detected. Clinicians should be aware of this rare but devastating complication of CXL treatment and start prompt treatment when suspected.
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Small colony variants (SCVs) are relatively common among some bacterial species and are associated with poor prognosis and recalcitrant infections. Similarly,Candida glabrata– a major intracellular fungal pathogen – produces small and... more
Small colony variants (SCVs) are relatively common among some bacterial species and are associated with poor prognosis and recalcitrant infections. Similarly,Candida glabrata– a major intracellular fungal pathogen – produces small and slow-growing respiratory-deficient colonies, termed “petite.” Despite reports of clinical petiteC.glabratastrains, our understanding of petite behavior in the host remains obscure. Moreover, controversies exist regarding in-host petite fitness and its clinical relevance. Herein, we employed whole-genome sequencing (WGS), dual-RNAseq, and extensiveex vivoandin vivostudies to fill this knowledge gap. WGS identified multiple petite-specific mutations in nuclear and mitochondrially-encoded genes. Consistent with dual-RNAseq data, petiteC.glabratacells did not replicate inside host macrophages and were outcompeted by their non-petite parents in macrophages and in gut colonization and systemic infection mouse models. The intracellular petites showed hallmark...
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Objectives Although perceived as a rare clinical entity, recent studies have noted the emergence of MDR C. parapsilosis (MDR-Cp) isolates from single patients (resistant to both azole and echinocandins). We previously reported a case... more
Objectives Although perceived as a rare clinical entity, recent studies have noted the emergence of MDR C. parapsilosis (MDR-Cp) isolates from single patients (resistant to both azole and echinocandins). We previously reported a case series of MDR-Cp isolates carrying a novel FKS1R658G mutation. Herein, we identified an echinocandin-naive patient infected with MDR-Cp a few months after the previously described isolates. WGS and CRISPR-Cas9 editing were used to explore the origin of the new MDR-Cp isolates, and to determine if the novel mutation confers echinocandin resistance. Methods WGS was applied to assess the clonality of these isolates and CRISPR-Cas9 editing and a Galleria mellonella model were used to examine whether FKS1R658G confers echinocandin resistance. Results Fluconazole treatment failed, and the patient was successfully treated with liposomal amphotericin B (LAMB). WGS proved that all historical and novel MDR-Cp strains were clonal and distant from the fluconazole-r...
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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... more
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 patient...
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While being the third leading cause of candidemia worldwide, numerous studies have shown severe clonal outbreaks due to fluconazole-resistant (FLCR) Candida parapsilosis isolates associated with fluconazole therapeutic failure (FTF) with... more
While being the third leading cause of candidemia worldwide, numerous studies have shown severe clonal outbreaks due to fluconazole-resistant (FLCR) Candida parapsilosis isolates associated with fluconazole therapeutic failure (FTF) with enhanced mortality. More recently, multidrug resistant (MDR) C. parapsilosis blood isolates have also been identified that are resistant to both azole and echinocandin drugs. Amphotericin B (AMB) resistance is rarely reported among C. parapsilosis isolates and proper management of bloodstream infections due to FLZR and MDR isolates requires prompt action at the time of outbreak. Therefore, using a well-established Galleria mellonella model, we assessed whether (a) laboratory-based findings on azole or echinocandin (micafungin) resistance in C. parapsilosis lead to therapeutic failure, (b) LAMB could serve as an efficient salvage treatment option, and (c) distinct mutations in ERG11 impact mortality. Our in vivo data confirm fluconazole inefficacy ag...
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Onychomycosis in childhood is reported to be unusual. The aim of this study was to determine the prevalence of onychomycosis in primary school children and to make comparison between different socioeconomic status in the rural and urban... more
Onychomycosis in childhood is reported to be unusual. The aim of this study was to determine the prevalence of onychomycosis in primary school children and to make comparison between different socioeconomic status in the rural and urban areas of the city. Hand and foot nails of 23235 children aged 7-14 were examined. Onychomycosis was suspected and nail scrapings for mycological examination were taken in 116 of them. Hyphae or spores were seen in 41 (0.18%) by direct microscopic examination, and mycological cultures were positive in 24 (0.1%) of them. Toenails were affected in all of the fungal culture positive cases. Trichosporon spp, Trichophyton rubrum, Candida albicans and Candida glabrata grew in 11, 6, 5 and 2 of the cultures respectively. Onychomycosis prevalence was significantly higher in the children living in the rural areas (p = 0.016) [Odds ratio = 3.43 (%95 CI 1.11<OR<11.84)], and onychomycosis was more frequent in boys than girls (p = 0.001) [(Odds ratio = 5.85 (1.66<OR<24.61)].
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Objectives: To report the outcomes of therapeutic corneal transplant for managing fungal keratitis that is refractory to medical treatment. Materials and Methods: Retrospective data analyses of the medical records was performed on 17... more
Objectives: To report the outcomes of therapeutic corneal transplant for managing fungal keratitis that is refractory to medical treatment. Materials and Methods: Retrospective data analyses of the medical records was performed on 17 patients who underwent a therapeutic corneal transplant for severe culture-proven fungal keratitis between October 2006 and August 2013. We evaluated demographics, fungal organism type, surgical data, recurrence presentation, disease course, follow-up, and graft status. Results: Mean patient age was 53.2 years (range, 33-81 y). The male/female ratio was 12/5. All patients had positive microscopic evaluation and positive culture results for fungal infection. The most common fungal agent was Fusarium sp. (35%). Nine patients reported a history of injury to the cornea and/or contact with plant material or soil. The mean best-corrected visual acuity at the initial visit was 2.45 logMAR unit (range, 0.52-3.10 logMAR unit). The mean follow-up was 14 months (r...
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Background Echinocandin resistance rarely occurs in clinical Candida parapsilosis isolates and the underlying mechanism is unknown. Objectives To determine the prevalence of echinocandin resistance and the underlying mechanism for a large... more
Background Echinocandin resistance rarely occurs in clinical Candida parapsilosis isolates and the underlying mechanism is unknown. Objectives To determine the prevalence of echinocandin resistance and the underlying mechanism for a large collection of C. parapsilosis blood isolates and to determine whether the echinocandin-resistant isolates were clonally related. Methods C. parapsilosis blood isolates (n = 213) were subjected to antifungal susceptibility testing (CLSI M27), for micafungin, anidulafungin, amphotericin B and, if appropriate, caspofungin. Hotspot (HS) 1 and HS2 of FKS1 were sequenced for all isolates (n = 213) and microsatellite typing was performed for echinocandin-resistant isolates. Results All isolates were susceptible to amphotericin B and two isolates were intermediate to anidulafungin (MIC = 4 mg/L), while micafungin resistance was noted in four isolates (MIC >8 mg/L); three of which were also fluconazole resistant and therefore were MDR. Interestingly, mic...