Comparison of ß-1-3-D-Glucan and Candida Mannan Biomarker Assays with Serological Tests for the Diagnosis of Candidemia.

Invasive candidiasis, including bloodstream infection (candidemia), encompasses the most severe forms of Candida infection. Several species-specific and non-specific serological assays are commercially available to aid in diagnosis. This study compared the performance of five such biomarker assays. Serum samples from 14 patients with proven or probable invasive candidiasis, and from 10 control patients, were included in the analysis. A total of 50 serum samples were tested using C. albicans germ tube antibody (CAGTA) assay (Vircell), C. albicans IgM, C. albicans IgG and Candida mannan assays (Dynamiker Biotechnology). Among these samples, the ß-1-3-D-glucan (BDG) assay (Fungitell), a laboratory standard for the diagnosis of invasive candidiasis, was positive in 20 (40%), intermediate in five (10%) and negative in 25 (50%). In cases of proven or probable candidemia, the sensitivity and specificity of the BDG assay was 86% and 80%, respectively; the Candida mannan assay, 14% and 86%; the CAGTA test, 57% and 60%; the C. albicans IgM assay, 71% and 60%; and C. albicans IgG assay 29% and 90%. In 4/8 (50%) cases with multiple serum samples, C. albicans IgM was positive sooner than BDG. Thus, when used as a rule-out test for invasive candidiasis, our data suggest that the C. albicans IgM assay may assist antifungal stewardship (over serum BDG).

Staphylococcus aureus strains exhibit heterogenous tolerance to direct cold atmospheric plasma therapy.

The global clinical and socioeconomic impact of chronic wounds is substantial. The main difficulty that clinicians face during the treatment of chronic wounds is the risk of infection at the wound site. Infected wounds arise from an accumulation of microbial aggregates in the wound bed, leading to the formation of polymicrobial biofilms that can be largely resistant to antibiotic therapy. Therefore, it is essential for studies to identify novel therapeutics to alleviate biofilm infections. One innovative technique is the use of cold atmospheric plasma (CAP) which has been shown to possess promising antimicrobial and immunomodulatory properties. Here, different clinically relevant biofilm models will be treated with cold atmospheric plasma to assess its efficacy and killing effects. Biofilm viability was assessed using live dead qPCR, and morphological changes associated with CAP evaluated using scanning electron microscopy (SEM). Results indicated that CAP was effective against Candida albicans and Pseudomonas aeruginosa, both as mono-species biofilms and when grown in a triadic model system. CAP also significantly reduced viability in the nosocomial pathogen, Candida auris. Staphylococcus aureus Newman exhibited a level of tolerance to CAP therapy, both when grown alone or in the triadic model when grown alongside C. albicans and P. aeruginosa. However, this degree of tolerance exhibited by S. aureus was strain dependent. At a microscopic level, biofilm treatment led to subtle changes in morphology in the susceptible biofilms, with evidence of cellular deflation and shrinkage. Taken together, these results indicate a promising application of direct CAP therapy in combatting wound and skin-related biofilm infections, although biofilm composition may affect the treatment efficacy.

Screening the Tocriscreen™ bioactive compound library in search for inhibitors of Candida biofilm formation.

Biofilms formed by Candida species present a significant clinical problem due to the ineffectiveness of many conventional antifungal agents, in particular the azole class. We urgently require new and clinically approved antifungal agents quickly for treatment of critically ill patients. To improve efficiency in antifungal drug development, we utilized a library of 1280 biologically active molecules within the Tocriscreen 2.0 Micro library. Candida auris NCPF 8973 and Candida albicans SC5314 were initially screened for biofilm inhibitory activity using metabolic and biomass quantitative assessment methods, followed up by targeted evaluation of five selected hits. The initial screening (80% metabolic inhibition rate) revealed that there was 90 and 87 hits (approx. 7%) for C. albicans and C. auris, respectively. Additionally, all five compounds selected from the initial hits exhibited a biofilm inhibition effect against several key Candida species tested, including C. glabrata and C. krusei. Toyocamycin displayed the most potent activity at concentrations as low as 0.5 µg/mL, though was limited to inhibition. Darapladib demonstrated an efficacy for biofilm inhibition and treatment at a concentration range from 8 to 32 µg/mL and from 16 to 256 µg/mL, respectively. Combinational testing with conventional antifungals against C. albicans strains demonstrated a range of synergies for planktonic cells, and notably an anti-biofilm synergy for darapladib and caspofungin. Together, these data provide new insights into antifungal management possibilities for Candida biofilms.

Effect of the Unfilled Space Size of the Abutment Screw Access Hole on the Extruded Excess Cement and Retention of Single Implant Zirconia Crowns.

PURPOSE: To evaluate in vitro the effect of the size of the unfilled space of the abutment screw access hole on the amount of extruded excess cement and the retention of zirconia copings. MATERIALS AND METHODS: Twelve dental implant replicas were attached to the corresponding abutments and embedded in acrylic resin blocks. A total of 36 CAD/CAM zirconia copings were fabricated by one technician using the standard technique. Abutments were divided into group I: the entire screw access channel was completely filled (nonspaced); group II: 1-mm-spaced; and group III: 2-mm-spaced. The copings were air-abraded and temporarily cemented under constant load of 60 N for 10 minutes. The excess cement was calculated as the difference between the post-cementation and post-excess-removal weights using a digital scale. Retention test was performed by a universal testing machine at a 0.5 mm/min crosshead speed. The ultimate force and tensile strength required for separation were recorded. One-way ANOVA and Tukey's test were used for statistical analysis at p ˂ 0.05. RESULTS: The average amount of extruded cement in groups 1, 2, and 3 was 33.48 ± 1.55, 23.05 ± 5.48, and 15.58 ± 5.98 mg, respectively. Multiple comparisons showed significant differences in the amount of extruded excess cement between the three groups (p ˂ 0.001). The maximum load at decementation in groups 1, 2, and 3 was 98.8, 87.5, and 88.6 N, respectively. Groups 1, 2, and 3 separated at 6.90 ± 1.2, 6.12 ± 0.7, and 6.21 ± 0.9 MPa, respectively, with no significant differences between them. CONCLUSIONS: The amount of extruded excess cement was reduced by more than half when a 2-mm space of the screw access hole was left unfilled in comparison to the nonspaced counterpart. The retention of zirconia copings was not affected by the reported technique.

Draft Genome Sequence of Candida pseudohaemulonii Isolated from the Blood of a Neutropenic Patient.

Candida pseudohaemulonii is phylogenetically close to the C. haemulonii complex and exhibits resistance to amphotericin B and azole agents. We report here the draft genome sequence of C. pseudohaemulonii UZ153_17 isolated from the blood culture of a neutropenic patient. The draft genome is 3,532,003,666 bp in length, with 579,838 reads, 130 contigs, and a G+C content of 47.15%.

Influence of space size of abutment screw access channel on the amount of extruded excess cement and marginal accuracy of cement-retained single implant restorations.

STATEMENT OF PROBLEM: The detrimental effect of extruded excess cement on peri-implant tissue has been well documented. Although several techniques have been proposed to reduce this effect by decreasing the amount of extruded cement, how the space size of the abutment screw access channel (SAC) affects the amount of extruded cement and marginal accuracy is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effect of the size of the unfilled space of the abutment SAC on the amount of extruded excess cement and the marginal accuracy of zirconia copings. MATERIAL AND METHODS: Twelve implant replicas and corresponding standard abutments were attached and embedded in acrylic resin blocks. Computer-aided design and computer-aided manufacturing (CAD-CAM) zirconia copings with a uniform 30-µm cement space were fabricated by 1 dental technician using the standard method. The copings were temporarily cemented 3 times at different sizes of the left space of the SAC as follows: the nonspaced group (NS), in which the entire SAC was completely filled, the 1-mm-spaced group (1MMS), and the 2-mm-spaced group (2MMS). Abutments and crowns were ultrasonically cleaned, steam cleaned, and air-dried. The excess cement was collected and weighed. To measure the marginal accuracy, 20 measurements were made every 18 degrees along the coping margin at ×300 magnification and compared with the pre-cementation readings. One-way ANOVA was calculated to determine whether the amount of extruded excess cement differed among the 3 groups, and the Tukey test was applied for multiple comparisons (α=.05). RESULTS: The mean weights (mg) of extruded excess cement were NS (33.53 ±1.5), 1MMS (22.97 ±5.4), and 2MMS (15.17 ±5.9). Multiple comparisons showed significant differences in the amount of extruded excess cement among the 3 test groups (P<.001). The mean marginal discrepancy (µm) of the pre-cemented group (29.5 ±8.2) was significantly different (P<.01) from that of the NS (72.3 ±13.7), the 1MMS (70.1 ±19), and the 2MMS group (70.1 ±18.8). No significant differences were found in marginal accuracy among the 3 test groups (P=.942). CONCLUSIONS: Within the limitations of this in vitro study, leaving a 2-mm space in the SAC reduced the amount of extruded excess cement by 55% in comparison with the nonspaced abutments. However, no effect was found on the marginal accuracy of zirconia copings.

First Two Cases of Fungal Infections Associated with Multi-drug Resistant Yeast, Fereydounia khargensis.

The number of new fungal pathogens is increasing due to growing population of immunocompromised patients and advanced identification techniques. Fereydounia khargensis is a yeast and was first described in 2014 from environmental samples. As far as we know, this is the first report of human infections associated with F. khargensis. The yeasts were isolated from blood of a HIV-positive patient and pleural fluid of chronic renal failure patient. Amplification and sequencing of the internal transcribed spacer and the large subunit regions confirmed the identity of the isolates. Both isolates showed multi-drug resistance to antifungal agents tested.