First case of Rhinocladiella mackenziei brain abscess in Turkey: Case report and review of the literature.

Rhinocladiella mackenziei is a highly neurotropic fungus, mainly reported from the Middle East. However, in recent years, there have been some cases from outside this region. We described an additional fatal case of R. mackenziei cerebral infection for the first time from Turkey and made a literature review of all previously reported cases. During 34 years (1988-2022), there have been 42 R. mackenziei brain abscess cases. Most patients have been reported from Saudi Arabia (n = 14, 33.3%). It is noteworthy that 40.5% of patients, including our case, were immunocompetent at initial diagnosis and mostly presented with a single lesion (n = 10, 23.8%). The most frequent comorbidities were solid organ transplant (n = 9, 21.4%), diabetes mellitus (n = 6, 14.3%), malignancy (n = 6, 14.3%) and prior surgery (n = 3, 7.1%). The most commonly used initial antifungal regimen were amphotericin B together with itraconazole (n = 9, 21.4%), combinations of lipid preparations of amphotericin B, voriconazole and/or posaconazole (n = 9, 21.4%) and amphotericin B alone (n = 8, 19%). Although both surgical procedures and antifungal medication in the majority of patients were performed, mortality rates remained high (90.4%). The area at risk of R. mackenziei cerebral abscess cases extends to other countries. Clinicians should be aware of this emerging disease and take a detailed travel history in patients with atypical and undocumented brain abscesses. Our case confirms the hypothesis that this fungus might spread more widely than previously predicted regions.

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.

Invasive Saprochaete capitata Infection in a Patient with Autosomal Recessive CARD9 Deficiency and a Review of the Literature.

PURPOSE: Autosomal recessive (AR) CARD9 deficiency is an inherited immune disorder which results in impaired innate immunity against various fungi. Superficial and invasive fungal infections, mainly caused by Candida or Trichophyton species, are the hallmark of CARD9 deficiency. Together with the increasing number of CARD9-deficient patients reported, different pathogenic fungal species have been described such as Phialophora, Exophiala, Corynespora, Aureobasidium, and Ochroconis. Saprochaete capitata is an opportunistic infectious agent in immunocompromised patients and is a common cause of invasive fungal disease in patients with hematological malignancies. In this study, we investigated the causative genetic defect in a patient with S. capitata fungal infection which disseminated to lymph nodes and common bile duct. METHODS: The identification of the isolated yeast strain was made by direct microscopic examination and confirmed by internal transcribed spacer (ITS) sequencing. We applied whole exome sequencing to search for the disease-causing mutation. Sanger sequencing was used to validate the mutation in the patient and his parents. RESULTS: S. capitata was isolated from the biopsy specimen as the causative microorganism responsible for the invasive fungal disease in the patient. Whole exome sequencing revealed a homozygous c.883C > T, (p.Q295*) mutation in CARD9, confirmed by Sanger sequencing. CONCLUSIONS: This is the first report of invasive Saprochaete infection associated with autosomal recessive (AR) CARD9 deficiency in the literature and thereby further extends the spectrum of fungal diseases seen in these patients.

Evaluation of MALDI-TOF MS for identification of nontuberculous mycobacteria isolated from clinical specimens in mycobacteria growth indicator tube medium.

Nowadays, there is a rising worldwide incidence of diseases caused by nontuberculous mycobacteria (NTM) species, especially in immunocompromised patients and those with underlying chronic pulmonary diseases. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) became a method of choice for the identification of NTM species. The aim of this study was to evaluate MALDI-TOF MS for the identification of NTM isolates compared to the PCR-restriction enzyme analysis (PRA)-hsp65 method. In this study, a total of 152 NTM strains isolated from various clinical specimens were retrospectively analysed. MALDI-TOF MS successfully identified 148 (97.4%) of the 152 NTM isolates but failed to identify four (2.6%) of them. Bruker mycobacteria library gave spectral scores higher than 2.0 for 45 (29.6%) of NTM isolates, between 1.6 and 2.0 for 98 (64.5%) of NTM isolates, and lower than 1.6 for nine (5.9%) NTM isolates. The discordant results between MALDI-TOF MS and PRA-hsp65 analysis were confirmed by sequence analysis. In conclusion, MALDI-TOF MS is a technique capable of performing accurate, rapid, cost-effective, and easy identification of NTM isolates.

Phenotypic Investigation of Virulence Factors, Susceptibility to Ceragenins, and the Impact of Biofilm Formation on Drug Efficacy in Candida auris Isolates from Türkiye.

Candida auris has emerged as a significant fungal threat due to its rapid worldwide spread since its first appearance, along with its potential for antimicrobial resistance and virulence properties. This study was designed to examine virulence characteristics, the efficacy of ceragenins, and biofilm-derived drug resistance in seven C. auris strains isolated from Turkish intensive care patients. It was observed that none of the tested strains exhibited proteinase or hemolysis activity; however, they demonstrated weak phospholipase and esterase activity. In addition, all strains were identified as having moderate to strong biofilm formation characteristics. Upon determining the minimum inhibitory concentrations (MIC) of ceragenins, it was discovered that CSA-138 exhibited the highest effectiveness with a MIC range of 1-0.5 µg/mL, followed by CSA-131 with a MIC of 1 µg/mL. Also, antimicrobial agents destroyed mature biofilms at high concentrations (40-1280 µg/mL). The investigation revealed that the strains isolated from Türkiye displayed weak exoenzyme activities. Notably, the ceragenins exhibited effectiveness against these strains, suggesting their potential as a viable treatment option.

Evaluation of Candida species and antifungal susceptibilities among children with invasive candidiasis.

AIM: Non-albicans Candida species and resistant microorganisms have been more commonly isolated in invasive candidiasis in recent years. The aim of this study was to evaluate the distrubution of Candida spp and antifungal resistance in our clinic. MATERIAL AND METHODS: Fifty-four Candida isolates and antifungal susceptibility results obtained from patients diagnosed as having invasive candidiasis between December 2012 and June 2016 were included. Clinical and laboratory data were retrospectively analyzed. E-test method was used in order to determine antifungal susceptibilities of Candida spp for amphotericin B, fluconazole, voriconazole, ketoconazole, itraconazole, anidulafungin, caspofungin, and flucytosine. RESULTS: The clinical diagnoses of the patients were candidemia (n=27, 50%), catheter-related blood stream infection (n=1, 1.8%), urinary tract infection (n=13, 24%), surgical site infection (n=4, 7.4%), intraabdominal infection (n=3, 5.5%), empyema (n=2, 3.7%), and pneumonia (n=4, 7.4%). The most common isolated agent was C. albicans (n=27, 50%) and the others were C. parapsilosis (n=13, 24%), C. tropicalis (n=6, 11.1%), C. glabrata (n=3, 5.6%), C. lusitaniae (n=2, 3.7%), and unspecified Candida spp. (n=3, 5.6%). Fluconazole resistance was 7.4% among all isolates. Resistance against itraconazole, ketoconazole, anidulafungin, voriconazole and caspofungin were 33.3%, 12.5%, 11.1%, 5%, and 2.5%, respectively. Isolates presented intermediate resistance against itraconazole (41.7%), voriconazole (5.6%), and amphotericin B (3.7%) to varying extents. All of the isolates were susceptible to flucytosine. CONCLUSIONS: In our clinic, C. albicans and non-albicans Candida species were equally distributed and antifungal susceptibilities against major antifungal agents such as fluconazole, amphotericin B, and caspofungin were found considerably high.

Isolation of nontuberculous mycobacteria from hospital waters in Turkey.

Nontuberculous mycobacteria (NTM) are ubiquitous in hot and cold water distribution systems. With molecular typing methods it was shown that water can be the source of colonization and infection with NTM. The aim of our study was the investigation of NTM in hot and cold water samples taken from various departments of two hospitals in Istanbul, Turkey. Totally, 160 water samples were examined. The temperature, pH, and free chlorine levels of water samples were measured between 10-41 °C, 6.78-7.98 and <0.3-0.5 mg/L, respectively. NTM were detected in 33 (20.6%) samples. Totally 20 (60.6%), 10 (30.3%) and 3 (9.1%) isolates were identified as Mycobacterium lentiflavum, Mycobacterium gordonae, and Mycobacterium peregrinum, respectively. M. lentiflavum, which was the most frequently isolated NTM, is characterized by multiple resistance to antimycobacterial drugs. Although no infections with this mycobacterium were reported from our country so far, preventive measures may be considered in patients under immunosuppression. Because no significant correlations were found among the presence of NTM or species distribution and water temperature, pH or free chlorine levels, other factors need to be investigated.