Determinants of fluconazole resistance and the efficacy of fluconazole and milbemycin oxim combination against Candida parapsilosis clinical isolates from Brazil and Turkey

Fluconazole-resistant Candida parapsilosis (FLZR-CP) outbreaks are a growing public health concern and have been reported in numerous countries. Patients infected with FLZR-CP isolates show fluconazole therapeutic failure and have a significantly increased mortality rate. Because fluconazole is the most widely used antifungal agent in most regions with outbreaks, it is paramount to restore its antifungal activity. Milbemycin oxim (MOX), a well-known canine endectocide, is a potent efflux pump inhibitor that significantly potentiates the activity of fluconazole against FLZR C. glabrata and C. albicans. However, the FLZ-MOX combination has not been tested against FLZR-CP isolates, nor is it known whether MOX may also potentiate the activity of echinocandins, a different class of antifungal drugs. Furthermore, the extent of involvement of efflux pumps CDR1 and MDR1 and ergosterol biosynthesis enzyme ERG11 and their link with gain-of-function (GOF) mutations in their transcription regulators (TAC1, MRR1, and UPC2) are poorly characterized among FLZR-CP isolates. We analyzed 25 C. parapsilosis isolates collected from outbreaks in Turkey and Brazil by determining the expression levels of CDR1, MDR1, and ERG11, examining the presence of potential GOF mutations in their transcriptional regulators, and assessing the antifungal activity of FLZ-MOX and micafungin-MOX against FLZR and multidrug-resistant (MDR) C. parapsilosis isolates. ERG11 was found to be universally induced by fluconazole in all isolates, while expression of MDR1 was unchanged. Whereas mutations in MRR1 and UPC2 were not detected, CDR1 was overexpressed in three Brazilian FLZR-CP isolates, which also carried a novel TAC1L518F mutation. Of these three isolates, one showed increased basal expression of CDR1, while the other two overexpressed CDR1 only in the presence of fluconazole. Interestingly, MOX showed promising antifungal activity against FLZR isolates, reducing the FLZ MIC 8- to 32-fold. However, the MOX and micafungin combination did not exert activity against an MDR C. parapsilosis isolate. Collectively, our study documents that the mechanisms underpinning FLZR are region specific, where ERG11 mutations were the sole mechanism of FLZR in Turkish FLZR-CP isolates, while simultaneous overexpression of CDR1 was observed in some Brazilian counterparts. Moreover, MOX and fluconazole showed potent synergistic activity, while the MOX-micafungin combination showed no synergy

First isolation of alternaria alternata from a dog in Turkey [Türkiye’deki bir köpekte ilk Alternaria alternata izolasyonu]

Alternaria alternata is a fungus species which can infect animals and people as well as being commonly found in nature. On the other hand, animals with Alternaria infection can infect other animals and people by spreading a high amount of fungal spores. In this work, Alternaria alternata was detected for the first time in Turkey from the skin lesions of a dog, an antifungal susceptiblity testing was carried out and treatment with itracanozole to which the agent showed susceptibility was accomplished. The aim of this work was to report the Alternaria infection in dogs in Turkey for the first time, to draw attention to the zoonotic dimension of this disease and to emphasize the importance of antifungal susceptibility tests. © 2017, Chartered Inst. of Building Services Engineers. All rights reserved

Actinomycosis osteomyelitis of the jaws: Report of four cases and a review of the literature

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. © 201

Estimated burden of serious human fungal diseases in Turkey

###EgeUn###The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological data from 1920 to 2017 and modelling previously described by the LIFE program (http://www.LIFE-worldwide.org). Among the population of Turkey (80.8 million in 2017), approximately 1 785 811 (2.21%) people are estimated to suffer from a serious fungal infection each year. The model used predicts high prevalences of allergic fungal rhinosinusitis episodes (312 994 cases) (392/100 000), of severe asthma with fungal sensitisation (42 989 cases) (53.20 cases/100 000 adults per year), of allergic bronchopulmonary aspergillosis (32 594 cases) (40.33/100 000), of fungal keratitis (26 671 cases) (33/100 000) and of chronic pulmonary aspergillosis (5890 cases) (7.29/100 000). The estimated annual incidence for invasive aspergillosis is lower (3911 cases) (4.84/100 000 annually). Among about 22.5 million women aged 15-50 years, recurrent vulvovaginal candidiasis is estimated to occur in 1 350 371 (3342/100 000) females. The burden of three superficial fungal infections was also estimated: tinea pedis (1.79 million), tinea capitis (43 900) and onychomycosis (1.73 million). Given that the modelling estimates reported in the current study might be substantially under- or overestimated, formal epidemiological and comprehensive surveillance studies are required to validate or modify these estimates. © 2018 Blackwell Verlag GmbHNational Institutes of Health National Institute of Allergy and Infectious Diseases National Institutes of Health Juvenile Diabetes Research Foundation United States of America National Institute of Allergy and Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health National Institute of Allergy and Infectious Diseases National Institutes of Health2Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States of America -- Seyedmojtaba Seyedmousavi, Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. Email: [email protected] -- S.S. is presently supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA. All the other authors declare no conflict of interests related to this publication. -

Aggressive exercise as treatment for chronic low back pain

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Genetic Diversity and Antifungal Susceptibility of Candida parapsilosis Sensu Stricto Isolated from Bloodstream Infections in Turkish Patients

PubMedID: 29725811Candida parapsilosis sensu stricto is an emerging cause of hospital-acquired Candida infections, predominantly in southern Europe, South America, and Asia. We investigated the genetic diversity and antifungal susceptibility profile of 170 independent C. parapsilosis sensu stricto strains obtained from patients with candidemia who were treated at the Ege University Hospital in Izmir, Turkey, between 2006 and 2014. The identity of each strain was confirmed via PCR amplification and digestion of the secondary alcohol dehydrogenase-encoding gene. The 24-h geometric mean minimum inhibitory concentrations of the antifungal agents, in increasing order, were as follows: posaconazole, 0.10 µg/mL; voriconazole, 0.21 µg/mL; caspofungin, 0.38 µg/mL; amphotericin B, 0.61 µg/mL; anidulafungin, 0.68 µg/mL; and fluconazole, 2.95 µg/mL. Microsatellite genotyping of the isolates (using fluorescently labeled primers and a panel of four different short-nucleotide repeat fragments) identified 25, 17, 17, and 8 different allelic genotypes at the CP6, B5, CP4, and CP1 locus, respectively. Posaconazole, caspofungin, and amphotericin B showed the greatest in vitro activity of the tested systemic azole, echinocandin, and polyene agents, respectively, and the observed antifungal susceptibility of the isolates was shown to be independent of their isolation source. We obtained a combined discriminatory power of 0.99 with a total of 130 genotypes for 170 isolates tested. Finally, microsatellite profiling analysis confirmed the presence of identical genotype between separate isolates, supporting that effective surveillance and infection-prevention programs are essential to limit the impact of C. parapsilosis sensu stricto on hospitalized patients’ health. © 2018, Springer Science+Business Media B.V., part of Springer Nature.National Institutes of Health: BG 10 RM 11C106 National Institute of Allergy and Infectious DiseasesS. Seyedmousavi (&) Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), BG 10 RM 11C106, 10 CENTER DR, 9000 Rockville Pike, Bethesda, MD 20892, USA e-mail: [email protected]

Pulmonary mucormycosis due to Lichtheimia ramosa in a patient with HIV infection.

Mucormycosis is increasingly common in patients with risk factors such as diabetes mellitus, neutropenia, and corticosteroid therapy. However, mucormycosis seems to be less common in patients with human immunodeficiency virus (HIV) infection compared to patients with other risk factors. Despite their lower virulence, Lichtheimia species should be regarded as emerging pathogens among Mucoralean fungi. We report a fatal case of pulmonary mucormycosis due to Lichtheimia ramosa in a 52-year-old man with an end-stage HIV infection. He had a cachectic appearance and his CD4 count was 8 cells/mm(3). The fungal infection was diagnosed based on a positive sputum culture with histopathologic confirmation. The fungus was resistant to caspofungin, anidulafungin, and voriconazole [minimum inhibitory concentration (MCI) >32 µg/ml], whereas the E test MIC values of itraconazole, posaconazole, and amphotericin B were 0.38, 0.38, and 0.5 µg/ml, respectively. Although intravenous drug use is the main risk factor for the development of mucormycosis in HIV-infected patients, it may also develop in patients with low CD4 count, opportunistic infections and/or additional diseases, such as Kaposi's sarcoma or severe immunodeficiency, as in our case

Evaluation of candidemia in children at a university hospital: A retrospective cohort

Background: Candidemia is a life-threatening infection in hospitalied children. This study aimed to evaluate candidemia's demographic and clinical characteristics and identify the risk factors and outcomes of Candida albicans (CA) and non-albicans Candida (NAC) spp. Methods: A retrospective cohort was designed to evaluate paediatric patients with candidemia between January 2008 and December 2020. Results: A total of 342 episodes in 311 patients were evaluated. The median age of the patients was 2.1 years (1 month–17 years and 6 months), and 59.6% were male. The prevalence of NAC (67.5%) candidemia was higher than that of CA (32.5%). The most commonly isolated Candida species was Candida parapsilosis (43.3%), followed by C. albicans (32.5%), Candida glabrata (6.1%) and Candida tropicalis (5.0%). The length of hospital stay prior to the positive culture and the total length of hospital stay were longer in the NAC group (p =.003 and p =.006). The neutrophil count was lower in the NAC group (p =.007). In the multivariate analysis, total parenteral nutrition, antifungal prophylaxis and a history of coagulase-negative staphylococci (CoNS) culture positivity in the past month were risk factors for developing candidemia due to NAC (p values were.003,.003 and.045). C. albicans and C. parapsilosis fluconazole resistance were 9.5% and 46.6%, respectively. The rates of amphotericin B resistance were 1.1% and 7.6% in C. albicans and C. parapsilosis, respectively. Mortality (14-day and 30-day) rates did not differ between the groups. Conclusions: A history of CoNS culture positivity in the past month, total parenteral nutrition, and antifungal prophylaxis increases the risk of NAC candidemia. © 2023 Wiley-VCH GmbH