Role of Vitamin D, ACE2 and the Proteases as TMPRSS2 and Furin on SARS-CoV-2 Pathogenesis and COVID-19 Severity.

BACKGROUND: COVID-19, the 21st century pandemic disease caused by SARS-CoV-2, has shown a wide clinical spectrum ranging from asymptomatic to deadly serious pneumonia. OBJECTIVE: In our study, the relationship between the pathogenesis and clinical severity of COVID-19 and vitamin D, ACE2, Furin and TMPRSS2 was investigated. METHODS: Serum 25(OH)D, 1,25(OH)2D and ACE2 protein were measured in 85 COVID-19 cases, divided into 5 groups, according to disease severity, from asymptomatic to severe and including a healthy control group. Expression levels of ACE2, VDR, TMPRSS2 and Furin mRNAs in PBMC were also measured. The relationship of the parameters within each group, the severity of the disease and the effect on the patients' fate were investigated. RESULTS: Statistically significant differences were found between the severity of COVID-19 and all study parameters, except for serum 25(OH)D. A strong negative correlation was found between serum ACE2 protein, 1,25(OH)2D, and ACE2 mRNA, and disease severity, length of hospital stay and death/survival rate. Vitamin D deficiency increased the death risk by 5.6-fold (95% CI 0.75-41.47), and the levels of 1,25(OH)2D lower than 1 ng/mL increased the risk of death by 3.8-fold (95% CI 1.07-13.30). CONCLUSION: This study suggests that vitamin D supplementation could be beneficial in the treatment and/or prevention of COVID-19.

Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure.

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.

[In vitro activity of fosfomycin trometamol in the treatment of Escherichia coli related uncomplicated urinary tract infections]. / Escherichia coli nedenli komplike olmamis üriner sistem enfeksiyonlarinda fosfomisin trometamolün in vitro etkinligi.

Although in certain countries in Europe fosfomycin trometamol (FT) has been used for many years, in Turkey FT has become available in recent years. FT has a broad-spectrum activity against most of gram-positive and gram-negative bacteria. In this study, we aimed to evaluate the effect of FT, a new alternative antimicrobial agent in the treatment of patients with Escherichia coli related uncomplicated lower urinary tract infection (UTI). For this purpose, between May 2007-July 2008, FT susceptibility of 771 nonduplicate E. coli strains, isolated from urine samples of patients with uncomplicated lower UTI (bacteria > or = 10(5) cfu/mL), was determined by disk diffusion method according to Clinical and Laboratory Standarts Institute (CLSI) criteria. Simultaneously, extended-spectrum beta-lactamase (ESBL) detection was performed by double disk synergy test in all isolates. Among all E. coli isolates, FT resistance rate was 0.4% (3/771) and ESBL positivity was 19.5% (150/771). The rates of ESBL producing strains isolated from inpatients and outpatients were 34.1% (70/205) and 14.1% (80/566), respectively, and the difference was found statistically significant (p = 0.0001). Although resistance to FT was not detected in non-ESBL producing E. coli isolates (n = 621), FT resistance rate was 2% (3/150) in ESBL producers. As far as the current literature was concerned this was the largest scale study investigating the activity of FT in Turkey. Resistance to antimicrobials that had been used frequently as therapeutic options for the treatment of E. coli related UTIs, has been increasing. In the present study high susceptibility rates to FT was determined for urinary E. coli isolates. In conclusion, these data suggest that FT may be a good alternative for the treatment of uncomplicated UTIs as a first line antimicrobial agent.