Evaluation of the first Candida auris isolates reported from Türkiye in terms of identification by various methods and susceptibility to antifungal drugs.

PURPOSE: Candida auris is increasingly being isolated from patients all over the world. It has five clades. In this study, it was aimed to compare the results of biochemical tests obtained using different methods and the antifungal susceptibility profiles of C. auris strains isolated from the first seven cases reported in Türkiye, and evaluate whether this information could be useful as preliminary data in determining the clade of strains in centers that lack the opportunity to apply molecular methods. METHODS: Identification test results obtained using API ID 32 C, API 20C AUX, VITEK-2 YST, and MALDI-TOF MS; colony color and morphology on Chromagar Candida, CHROMagar Candida Plus media, and cornmeal-Tween 80 agar; susceptibility to antifungals were tested and compared. Antifungal susceptibility test was studied using microdilution method according to the recommendations of EUCAST. Additionally, a pilot study was conducted to investigate the value of CHROMagar Candida Plus. RESULTS: All seven strains were identified as Lachancea kluyveri with API ID 32 C, Rhodotorula glutinis; Cryptococcus neoformans with API 20 C AUX, and C. auris with both VITEK-2 YST and MALDI-TOF MS. MIC values for fluconazole were very high (≥64 mg/L) for all seven strains. It was observed that 11 (37.9%) of 29 Candida parapsilosis strains formed colonies with morphology similar to C. auris on CHROMagar Candida Plus medium, leading to false positivity. CONCLUSIONS: Although there have been many isolations of C. auris in our country in recent years, clade distribution of only a small number of strains is known yet. In this study, when the biochemical properties and antifungal susceptibility profiles of the seven strains were evaluated, it was concluded that they exhibited some characteristics compatible with clade I. It was also observed that strains 1 and 2 may belong to a different clade.

Invasive fungal rhinosinusitis by Fusarium proliferatum/annulatum in a patient with acute myeloid leukemia: A case report and review of the literature.

Antifungal prophylaxis with a mold-effective agent has led to a substantial decrease in invasive infections caused by Aspergillus spp. in the management of patients with acute myeloid leukemia undergoing induction chemotherapy. However, difficult-to-treat infections caused by other molds, such as Fusarium, Lomentospora, and Scedosporium species may still complicate the neutropenic period. Here, we present a case of a 23-year-old woman with acute myeloid leukemia who developed a breakthrough invasive fungal rhinosinusitis caused by Fusarium proliferatum/annulatum on posaconazole prophylaxis. The infection was diagnosed using clinical, microbiological, and radiological criteria and the isolate was identified using Matrix Assisted Lazer Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and sequencing. We searched Pubmed with "Fusarium proliferatum", "Fusarium annulatum", "immunosuppression AND fusariosis", "rhinosinusitis AND Fusarium proliferatum" and summarized the English literature for similar rhinosinusitis cases infected with the same pathogen.

Saprochaete/Magnusiomyces: identification, virulence factors, and antifungal susceptibility of a challenging rare yeast.

Saprochaete/Magnusiomyces is among rare yeasts which might emerge as causes of breakthrough infections and nosocomial outbreaks. Identification to the species level might be a challenge in clinical laboratories. Data on virulence factors are scarce and antifungal susceptibility testing methodology is not definite. The aim of this study was to confirm species identification of clinical Saprochaete/Magnusiomyces isolates, find out their virulence factors, and obtain antifungal minimum inhibitory concentrations with two reference methods. Of the 57 isolates included, 54 were Saprochaete capitata and four were Saprochaete clavata as identified by ID32C, MALDI-TOF MS, and sequencing. When tested using phenotypic methods, all isolates were negative for coagulase, hemolysis, acid proteinase, and phospholipase, 56.1% were positive for esterase, and 19.3% had intermediate surface hydrophobicity. All isolates formed biofilms, with 40.4% of the isolates producing more biomass than biofilm-positive reference strain Candida albicans MYA-274. Antifungal susceptibility testing needed an adjusted spectrophotometric inoculum than recommended in reference methods for Candida/Cryptococcus. In conclusion, Saprochaete/Magnusiomyces species could be identified using methods available in the clinical laboratories. Despite the disadvantages of the phenotypic methods, esterase positivity was observed for the first time. A high biomass production was observed in biofilms. The need for standardization of antifungal susceptibility testing was brought to attention.

Diagnostic performance and longitudinal analysis of fungal biomarkers in COVID-19 associated pulmonary aspergillosis.

Objectives: Galactomannan lateral flow assay (GM-LFA) is a reliable test for COVID-19 associated pulmonary aspergillosis (CAPA) diagnosis. We aimed to assess the diagnostic performance of GM-LFA with different case definitions, the association between the longitudinal measurements of serum GM-ELISA, GM-LFA, and the risk of death. Methods: Serum and nondirected bronchial lavage (NBL) samples were periodically collected. The sensitivity and specificity analysis for GM-LFA was done in different time periods. Longitudinal analysis was done with the joint model framework. Results: A total of 207 patients were evaluated. On the day of CAPA diagnosis, serum GM-LFA had a sensitivity of 42 % (95 % CI: 23-63) and specificity of 82 % (95 % CI: 78-84), while NBL GM-LFA had a sensitivity of 73 % (95 % CI: 45-92), specificity of 85 % (95 % CI: 76-91) for CAPA. Sensitivity decreased through the following days in both samples. Univariate joint model analysis showed that increasing GM-LFA and GM-ELISA levels were associated with increased mortality, and that effect remained same with serum GM-ELISA in multivariate joint model analysis. Conclusion: GM-LFA, particularly in NBL samples, seems to be a reliable method for CAPA diagnosis. For detecting patients with higher risk of mortality, longitudinal measurement of serum GM-ELISA can be useful.

Necrotizing pneumonia due to Aspergillus and Salmonella after immune checkpoint inhibitor treatment: An unusual case and review of the literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising new treatment for different types of cancer. The infectious complications in patients taking ICIs are rare. CASE REPORT: A 58-year-old male who received chemotherapy consisting of pembrolizumab (PD-1 inhibitor) for esophagus squamous cell carcinoma one month before was admitted to the emergency room with shortness of breath soon after fiberoptic bronchoscopy, which was done for the inspection of the lower airway. A computed tomography of the chest revealed a progressive consolidation on the right upper lobe. Salmonella group D was isolated from the bronchoalveolar lavage (BAL) fluid culture. The fungal culture of the same clinical sample yielded Aspergillus niger; furthermore, a high titer (above the cut-off values) of Aspergillus antigen was found both in the BAL fluid and serum of the patient. Despite the effective spectrum and appropriate dose of antimicrobial treatment, the patient died due to disseminated intravascular coagulopathy. CONCLUSIONS: Awareness of unusual pathogens in the etiology of pneumonia after ICI treatment may help to avoid underdiagnosis.

Necrotizing pneumonia due to Aspergillus and Salmonella after immune checkpoint inhibitor treatment: An unusual case and review of the literature / Neumonía necrotizante por Aspergillus y Salmonella tras tratamiento con un inhibidor de puntos de control inmunitario: un caso inusual y revisión de la literatura

Background: Immune checkpoint inhibitors (ICIs) are a promising new treatment for different types of cancer. The infectious complications in patients taking ICIs are rare. Case report: A 58-year-old male who received chemotherapy consisting of pembrolizumab (PD-1 inhibitor) for esophagus squamous cell carcinoma one month before was admitted to the emergency room with shortness of breath soon after fiberoptic bronchoscopy, which was done for the inspection of the lower airway. A computed tomography of the chest revealed a progressive consolidation on the right upper lobe. Salmonella group D was isolated from the bronchoalveolar lavage (BAL) fluid culture. The fungal culture of the same clinical sample yielded Aspergillus niger; furthermore, a high titer (above the cut-off values) of Aspergillus antigen was found both in the BAL fluid and serum of the patient. Despite the effective spectrum and appropriate dose of antimicrobial treatment, the patient died due to disseminated intravascular coagulopathy. Conclusions: Awareness of unusual pathogens in the etiology of pneumonia after ICI treatment may help to avoid underdiagnosis.(AU)

Antecedentes: Los fármacos inhibidores de puntos de control inmunitario (ICI) son una nueva y prometedora opción de tratamiento para diferentes tipos de cáncer. Las complicaciones infecciosas en pacientes que toman ICI son poco frecuentes. Caso clínico: Un varón de 58 años que recibió quimioterapia con pembrolizumab (inhibidor de PD-1) para un carcinoma de células escamosas de esófago hacía un año, ingresó en Urgencias por dificultad respiratoria poco después de realizarse una broncoscopia de fibra óptica para una inspección de las vías aéreas inferiores. La tomografía computarizada de tórax reveló una consolidación progresiva en el lóbulo superior derecho. Se aisló Salmonella grupo D en el cultivo del líquido de lavado broncoalveolar (LBA). En el cultivo de hongos de la misma muestra creció Aspergillus niger; además, se detectó antígeno (por encima de los valores de corte) de Aspergillus tanto en la muestra del LBA como en el suero del paciente. A pesar del espectro eficaz y la dosis adecuada del antifúngico utilizado, el paciente falleció debido a una coagulopatía intravascular diseminada. Conclusiones: El conocimiento de patógenos inusuales en la etiología de la neumonía tras el tratamiento con ICI puede ayudar a evitar el infradiagnóstico.(AU)

Rational Design of New Monoterpene-Containing Azoles and Their Antifungal Activity.

Azole antifungals, including fluconazole, have long been the first-line antifungal agents in the fight against fungal infections. The emergence of drug-resistant strains and the associated increase in mortality from systemic mycoses has prompted the development of new agents based on azoles. We reported a synthesis of novel monoterpene-containing azoles with high antifungal activity and low cytotoxicity. These hybrids demonstrated broad-spectrum activity against all tested fungal strains, with excellent minimum inhibitory concentration (MIC) values against both fluconazole-susceptible and fluconazole-resistant strains of Candida spp. Compounds 10a and 10c with cuminyl and pinenyl fragments demonstrated up to 100 times lower MICs than fluconazole against clinical isolates. The results indicated that the monoterpene-containing azoles had much lower MICs against fluconazole-resistant clinical isolates of Candida parapsilosis than their phenyl-containing counterpart. In addition, the compounds did not exhibit cytotoxicity at active concentrations in the MTT assay, indicating potential for further development as antifungal agents.

A case-control study of the effects of Aspergillus clinical phenotypes on pulmonary functions in patients with cystic fibrosis.

INTRODUCTION: There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively. METHODS: Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up. RESULTS: Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity  (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar. CONCLUSION: Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up.

Investigating Dual-Species Candida auris and Staphylococcal Biofilm Antiseptic Challenge.

Candida auris can persistently colonize human skin, alongside a diverse bacterial microbiome. In this study we aimed to investigate the efficacy of antiseptic activities on dual-species interkingdom biofilms containing staphylococci to determine if antiseptic tolerance was negatively impacted by dual-species biofilms. Chlorhexidine, povidone iodine, and hydrogen peroxide (H2O2), were able to significantly reduce biofilm viable cell counts following exposure at 2%, 10%, and 3%, respectively. Notably, H2O2-treated biofilms were able to significantly recover and considerably repopulate following treatment. Fortunately, inter-kingdom interactions in dual-species biofilms of C. auris and staphylococci did not increase the tolerance of C. auris against antiseptics in vitro. These data indicate mixed infections are manageable with chlorhexidine and povidone iodine, but caution should be exercised in the consideration of H2O2.

A screening study for COVID-19-associated pulmonary aspergillosis in critically ill patients during the third wave of the pandemic.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been reported as an important cause of mortality in critically ill patients with an incidence rate ranging from 5% to 35% during the first and second pandemic waves. OBJECTIVES: We aimed to evaluate the incidence, risk factors for CAPA by a screening protocol and outcome in the critically ill patients during the third wave of the pandemic. PATIENTS/METHODS: This prospective cohort study was conducted in two intensive care units (ICU) designated for patients with COVID-19 in a tertiary care university hospital between 18 November 2020 and 24 April 2021. SARS-CoV-2 PCR-positive adult patients admitted to the ICU with respiratory failure were included in the study. Serum and respiratory samples were collected periodically from ICU admission up to CAPA diagnosis, patient discharge or death. ECMM/ISHAM consensus criteria were used to diagnose and classify CAPA cases. RESULTS: A total of 302 patients were admitted to the two ICUs during the study period, and 213 were included in the study. CAPA was diagnosed in 43 (20.1%) patients (12.2% probable, 7.9% possible). In regression analysis, male sex, higher SOFA scores at ICU admission, invasive mechanical ventilation and longer ICU stay were significantly associated with CAPA development. Overall ICU mortality rate was higher significantly in CAPA group compared to those with no CAPA (67.4% vs 29.4%, p < .001). CONCLUSIONS: One fifth of critically ill patients in COVID-19 ICUs developed CAPA, and this was associated with a high mortality.

Frequency of azole resistance in clinical and environmental strains of Aspergillus fumigatus in Turkey: a multicentre study.

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.

[Mycoses due to Rare Moulds in Our Country: A Systematic Review]. / Ülkemizde Nadir Küf Mantarlarina Bagli Mikozlar: Sistematik bir Derleme.

An increase is observed in the frequency and diversity of fungal infections in the world and in our country. Improving the quality of patient care in infections due to rare moulds depends on early diagnosis and appropriate treatment. Raising awareness about these infections will facilitate taking the necessary steps for diagnosis and treatment in similar cases. In addition to 165 cases out of 96 studies included in this review article, 28 studies reporting rare mould isolation with limited case information were examined. The number of studies reporting cases that meet the criteria has increased over the years. The most frequently reported mould was Fusarium spp. (n= 74), followed by Scedosporium/Pseudallescheria spp. (n= 20). In 25 of the cases, dematiaceous fungi were isolated. Eye (n= 44), skin/soft tissue (n= 35), disseminated (n= 34) peritoneum (n= 13), respiratory tract (n= 13), sinus (n= 12), central nervous system (n= 10), nail (n= 3) and urinary system (n= 1) involvement was detected in the cases. Two cases due to Scedosporium apiospermum and Fonsecaea pedrosoi started locally but spread over time. Among eye involvements, two outbreak reports in which Fusarium spp. was the causative agent drew attention. Of the patients with disseminated involvement, only two who developed Exophiala dermatitidis infection did not have any conditions affecting the immune system. In all peritoneal infections, the patient had a peritoneal catheter (12 for continuous ambulatory peritoneal dialysis and one for drainage). In seven out of 10 cases with central nervous system involvement, dematiaceous fungi were isolated. Appropriate diagnosis and treatment of cases due to rare mould infections can be improved by providing knowledge on the subject in the world and in our country. In these infections where treatment success is limited, correct identification of the causative agent and application of appropriate treatment provides an advantage for clinical success. In this review article, publications from Turkey in Pubmed, Scopus and TR Directory records were searched based on The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) rules and the situation of rare mould infections in our country have been discussed.

The Emergence of Echinocandin-Resistant Candida glabrata Exhibiting High MICs and Related FKS Mutations in Turkey.

The frequency of invasive fungal infections shows a rising trend as well as a high morbidity and mortality. Among the causative agents, a shift toward the non-albicans Candida species including Candida glabrata species complex is being observed in several centers. Echinocandin resistance is increasingly published; however, isolates presenting with an in vitro resistance have not yet been reported from Turkey. We, herein, report the first FKS mutant and phenotypically echinocandin-resistant C. glabrata clinical strains from a single center in Turkey. In a 43-year-old female patient, several enterocutaneous fistulae developed after a long term hospitalization period and several complicated surgeries. She eventually required parenteral nutrition via a tunneled central venous catheter (CVC). Following a number of bacteremic and fungemic episodes as well as intensive antimicrobial interventions (including fluconazole, caspofungin and anidulafungin), a CVC-related candidemia caused by C. glabrata was detected. The isolated strain yielded high minimum inhibitory concentration (MIC) values for echinocandins and was categorized as resistant. A resistance-related mutation was detected in FKS2 HS1 (D666V). Blood cultures remained negative after the removal of the CVC and treatment with caspofungin and high-dose fluconazole. Following this first case, two additional C. glabrata strains with high echinocandin MICs were isolated from the urine cultures of two unrelated patients from different wards with different mutations in FKS2 HS1 (S663P and delF659). Our findings indicate that routine antifungal susceptibility testing is crucial and underlines the need for attention for the increasing trend of acquired echinocandin resistance in C. glabrata.

Implementation of Pharmacist-Driven Antifungal Stewardship Program in a Tertiary Care Hospital.

Antifungal stewardship (AFS) is recommended to reduce the inappropriate use of antifungal drugs. In this study, the role of AFS in providing appropriate antifungal therapy was evaluated. This study included three periods, consisting of observation, feedback/education, and daily AFS activities. In the observation period, the use of systemic antifungals was evaluated for a baseline measurement of appropriateness. In the second period, monthly meetings were organized to provide feedback and education to physicians regarding antifungal therapy and the rate of adherence to the clinical guidelines. In the final period, a clinical pharmacist participated in daily ward rounds to evaluate the appropriateness of the antifungal therapy. A scoring system for appropriateness was used for comparison between the three periods. Four hundred eighteen episodes of antifungal therapy were evaluated. Baseline demographics of patients were similar in all three periods for age, gender, and the number of comorbidities. The indications for antifungal use were for prophylaxis in 22.7%, Candida infections in 58.6%, and invasive mold infections in 18.7%. During the third period, 157 (78.9%) recommendations were made and 151 (96.2%) were accepted. The overall appropriateness of antifungal use increased significantly for prophylaxis (30.8%, 17.9%, and 46.3%; P = 0.046) and treatment of fungal diseases (27.8%, 32.4%, and 71.9%; P < 0.001) between the first, second, and third periods, respectively. The 30-day mortality was not significantly changed between the three periods (19%, 15.6%, and 27.5%; P = 0.050). Appropriateness in antifungal therapy can be augmented by the integration of an AFS program. A team-based evaluation of fungal infections and assessment of patients by a clinical pharmacist with a therapeutic perspective may help to increase the quality of antifungal therapy.

Species distribution, azole resistance and related molecular mechanisms in invasive Candida parapsilosis complex isolates: Increase in fluconazole resistance in 21 years.

BACKGROUND: Candida parapsilosis complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among C. parapsilosis complex were reported from various centres. OBJECTIVES: Aim of this study was to identify invasive C. parapsilosis complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre. METHODS: Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the SADH gene and confirmed with ITS sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of ERG11 and MRR1 genes were analysed for fluconazole non-susceptible isolates. RESULTS: A total of 283 isolates from 181 patients were tested for azole susceptibility. All were C. parapsilosis sensu stricto, except one C. orthopsilosis. All three azoles were effective against 213 of the isolates from 135 patients, including one C. orthopsilosis. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole-resistant isolates were detected in 2004, increase was evident after 2011. In ERG11, Y132F mutation was the most common among fluconazole non-susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated. CONCLUSIONS: Rising azole resistance rates in C. parapsilosis sensu stricto isolates particularly after 2011 were of concern. The well-known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.

[Changing Trends in Isolation Frequencies and Species of Clinical Fungal Strains: What Do the 12-years (2008-2019) Mycology Laboratory Data Tell About?] / Enfeksiyon Etkeni Mantarlarin Zamana Göre Siklik ve Tür Dagilimlarindaki Degisimler: 12 Yillik (2008-2019) Mikoloji Laboratuvari Verileri Ne Söylüyor?

The frequency and variety of infections caused by fungi are increasing. However, changes and intercenter and regional differences are observed in the distribution of fungal species over the years. It is important to update the epidemiological data in order to enable early and appropriate treatment. In this retrospective study, the number of fungi isolated from clinical samples, their distribution at the genus/ species level and the variations over the years in Hacettepe University hospital which is a regional center for patients at risk of fungal infection were investigated. For this purpose, laboratory records from 2008- 2019 were examined and 21813 fungal strains isolated from 19636 clinical samples were detected. When the first (2008-2013) and second (2014-2019) six-year periods were compared, a 2.5 fold increase was observed in the number of specimens yielding fungal growth (first period; n= 5620, second period; n= 14016). Fungi were most frequently isolated from urine (45.0%), lower respiratory tract (30.7%) and blood (6.8%) samples. Mould isolation rate in all samples increased significantly in the second six-year period (from 8.3% to 10.6%, p≤ 0.001). As expected, the most frequent yeast was Candida albicans (57.0%) and mould was Aspergillus fumigatus complex (50.4%). In the second six-year period, isolation of C.albicans (59.3% to 56.0%, p≤ 0.001) among yeasts and A.fumigatus complex (58.1% to 48.0%, p≤ 0.001) among moulds decreased significantly. In urine specimens, most common fungi were C.albicans (49.8%), Candida glabrata complex (15.6%), Candida tropicalis (8.9%) and Candida kefyr (7.5%). In lower respiratory tract specimens, the most common mould was A.fumigatus complex (51.2%), which has decreased from 63.7% in the first six years to 47.1% in the second period (p≤ 0.001). Over the same period, other Aspergillus species (from 25.5% to 34.1%, p= 0.002) and non-Aspergillus moulds (from 36.3% to 52.9%, p≤ 0.001) were increased. In blood samples, C.albicans (44.4%), Candida parapsilosis complex (21.5%) and C.glabrata complex (13.0%) were the most frequent species. In the second six-year period, the frequency of C.albicans decreased from 47.3% to 42.2% (p= 0.059) and the frequency of C.glabrata complex increased from 9.5% to 15.5% (p≤ 0.001) when compared to the first period. For the sterile specimens other than blood, the most common species were C.albicans (37.8%), C.glabrata complex (9.1%) and C.parapsilosis complex (4.7%). However, the number of fungal isolates and the distribution of the species showed great variation over the years. In our center, a substantial increase in the number of fungal strains isolated from the clinical specimens were observed over a 12-years period. In addition and similar to previously published reports, the increase of strains belonging to species with decreased antifungal susceptibility and/or species with unknown susceptibility were detected. The use of local data is required in order to implement early and appropriate antifungal treatment because of inter-center and regional differences observed in epidemiological trends regarding the distributions of fungal genera and species. Surveillance studies to be conducted with the participation of large and sufficient numbers of centers in our country, as we have done for our center, will also contribute to approaches regarding the management of fungal infections by revealing the epidemiological data in a comprehensive manner.

[A Rare Yeast: Cases of Rhodotorula mucilaginosa Infection Followed Up in a Tertiary University Hospital]. / Nadir Etken Bir Maya: Üçüncü Basamak Üniversite Hastanesinde Izlenen Rhodotorula mucilaginosa Enfeksiyonu Olgulari.

Rhodotorula species are yeasts that are common in the environment,but are not frequently encountered as an infectious agent in humans. Rhodotorula mucilaginosa, Rhodotorula glutinis and Rhodotorula minuta are the species that cause disease in humans. Although its isolation from mucosa is doubtful in terms of the presence of true infection, it is more frequently encountered in daily practice due to the increasing number of invasive procedures, immune system deficiencies caused by immunosuppressive drugs and diseases. R.mucilaginosa growth isolated from various clinical samples between 2000 and 2018 in a tertiary university hospital was presented in this case report. The first case was an 82-year-old man with chronic lung disease, hypertension, congestive heart failure and acute leukemia causing severe immunosuppression. Use of broad spectrum antibiotics, history of immunosuppressive therapy, presence of jugular catheter were the risk factors in this patient. R.mucilaginosa was isolated from blood culture while the patient was receiving fluconazole treatment for Candida albicans grown in urine culture and the patient died before starting the treatment. The second case was a 34-year-old female patient with congenital heart disease. Discharge was observed at the intracardiac defibrillator site of the patient, a temporary pacemaker was inserted, and she used broad spectrum antibiotics for a long time. When the yeast growth was reported in the blood culture, caspofungin treatment was initiated. Although the treatment was switched to amphotericin B lipid complex after the culture result was reported as R.mucilaginosa, the patient died after 12 hours. The third case was a 70-year-old woman with hypertension, dementia, diabetes mellitus and rheumatoid arthritis admitted to the intensive care unit due to cerebrovascular accident. She received different immunosuppressive treatments and had invasive procedures. R.mucilaginosa was isolated from the blood culture taken from the patient's catheter, and there was no growth in the blood culture obtained from the peripheral vein. Anidulafungin was started empirically, which was changed to amphotericin B lipid complex after the identification of the yeast. The patient died for various reasons 10 days after the antifungal treatment was stopped. Our last case was a 55-year-old woman with metastatic ovarian cancer and secondary ascites. Broad-spectrum multiple antibiotics were used and invasive procedures were performed. R.mucilaginosa and C.albicans were isolated from the urine of the patient who had a urinary catheter. No growth was detected from urine after changing the urinary catheter. Therefore, growths were evaluated as colonization, and fluconazole was administered for C.albicans due to the high risk of invasive infection. The patient was lost for different reasons. The development and diversity of the treatment methods lead to the emergence of some opportunistic infectious agents that were not observed previously. Rhodotorula species are one of the rare agents that have increased over the years. Rhodotorula species should be considered as the cause of an infection if no clinical response is obtained after echinocandin and/or fluconazole treatment in patients with long-term immunosuppression and invasive procedures. Data on clinical pictures, treatment responses, follow-up and treatment results of this rare yeast are still limited. This case series was presented to draw attention to the risk factors related to R.mucilaginosa infection/colonization, clinical characteristics of the patients, follow-up results and treatment options and to contribute to the literature.

Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis

Background/aim: Cystic fibrosis is an autosomal recessive disease with a defect in mucociliary activity that is characterized by recurrent pulmonary infections. Bacterial agents frequently implicated in airway colonization are Haemophilus influenzae, Staphylococcus spp., and Pseudomonas spp. Fungal isolation from sputum is common in adults. However, growth of fungal agent only in sputum culture in patients with cystic fibrosis is insufficient for the diagnosis of fungal diseases. There is limited data about the clinical significance of fungal isolation in sputum cultures. The aim of the study was to investigate the clinical outcomes andsignificance of fungal isolation from sputum samples in adult CF. Materials and methods: This retrospective study included patients who have been admitted between October 2017 and January 2019 in an adult cystic fibrosis unit. Patients were grouped according to fungal pathogenicity as; fungal disease group, colonization group, and nonisolated group. The data of the last one year, including demographics, clinical data, laboratory, treatment modalities, results of cultured bacteria and fungus from sputum samples, respiratory function parameters, frequency of exacerbation, and hospitalizationwere compared between groups. Results: A total of 330 sputum samples from 88 adult patients with CF were collected. Patients were divided into 3 groups, the fungal disease group (n = 10, 11.4%), colonization group (n = 49, 55.7%), and nonisolated group (n = 29, 32.9%). Presence of pulmonary exacerbation, number of admissions to emergency department, and the number of positive cultures for bacteria from sputum were higher in the fungal disease group (p = 0.03, p = 0.01 and p < 0.001). The fungal disease group had higher rate of antibiotics by parenteral routethan other groups (p = 0.001) whereas lung functions were similar. Use of nutritional supplementation and parenteral antibiotherapy were the factors associated with elevated risk of fungal isolation. Conclusion: Frequent use of parenteral antibiotics and use of nutritional supplementation were found to be independent risk factors for fungal isolation from sputum in adult CF.

Expect the unexpected: fungemia caused by uncommon Candida species in a Turkish University Hospital.

Fungemia caused by uncommon Candida species (UCS) (other than C.albicans, C.glabrata, C.parapsilosis, C.tropicalis, C.krusei) is a rare but emerging threat with their potential to exhibit reduced susceptibility or resistance to antifungal agents. We identified 25 patients with UCS fungemia (9 C.kefyr, 8 C.lusitaniae, 4 C.dubliniensis, 2 C.guilliermondii, 1 C.pelliculosa, 1 C.rugosa) through January 2011 and August 2018. Echinocandins were the most common administered agents, followed by fluconazole. Overall mortality was 44%. Echinocandins and voriconazole showed sufficient activity against all tested isolates. High fluconazole MICs among C.guilliermondii, C.pelliculosa, and C.rugosa were determined. MIC value of C.pelliculosa was above the epidemiological cut-off proposed for fluconazole.

Diverse clinical characteristics of Aspergillus growth in patients with cystic fibrosis.

BACKGROUND AND OBJECTIVES: Patients with cystic fibrosis (CF) have a varying spectrum of clinically significant Aspergillus disease in addition to allergic bronchopulmonary aspergillosis (ABPA). Here we aimed to review the different clinical phenotypes related with Aspergillus growth on the airway culture of patients with CF, we also aimed to investigate the effect of Aspergillus growth on lung function tests. METHOD: The medical records of 100 patients with CF who had Aspergillus growth on airway culture within the period of April 2001 and June 2016 were retrospectively analyzed. Age, gender, symptoms, physical examination findings, pulmonary function tests, the diagnosis of ABPA, and airway culture results were recorded for every visit. Patients with Aspergillus growth on airway cultures were classified into different groups as ABPA, Aspergillus sensitization, Aspergillus colonization and Aspergillus bronchitis. RESULTS: Medical records of 83 patients and 147 sputum cultures were attained from 100 patients. The mean age of the patients was 17.6±7.6 years and the mean age of the first Aspergillus growth in sputum culture was 12.5±6.7 years. At first isolation, Aspergillus fumigatus SC was the most common Aspergillus SC in sputum (76.3%) and 14.5% of these patients required hospitalization. Aspergillus sensitization was diagnosed in 3.6% (n= 3) of the patients. Aspergillus colonization was diagnosed in 18.1% (n= 15) of all patients and led to a decline in FEV1%, FVC% and FEF25-75% which was not statistically significant, furthermore. ABPA was detected in 9.6% (n= 8) of all patients and led to a statistically significant decline in FEV1% (p= 0.02); nonsignificant decline in FVC% and FEF25-75%. Aspergillus bronchitis was detected in 43.4% (n= 36) of all patients and led to nonsignificant decline in FEV1%, FVC% and FEF25-75%. CONCLUSION: ABPA is recognized as the most common Aspergillus associated disorder in CF patients and is related to deteriorated pulmonary function tests; however Aspergillus colonization and bronchitis may also be associated with worsening lung function.