Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%.This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.     

Flare Up Reaction During Provocation Test to Glatiramer Acetate in a Patient With Allergy to Interferon Beta1a

Glatiramer acetate (GA) is a synthetic amino acid polymer, used for relapsing-remitting multiple sclerosis. The most common adverse effect of GA is a skin reaction at the injection site with a probable IgE-mediated mechanism. We report a case of a 45-year-old woman with multiple sclerosis and urticaria to interferon-β1a, who underwent a challenge test to GA. She presented itching wheals at the intradermal sites. A month later the patient repeated the test and presented the same reactions of the first test. The next day she continued the test with subcutaneous injections. One hour later she presented a flare up of the reactions appeared during the previous 2 tests. No reactions appeared at the subcutaneous injection sites. The patient also presented dyspnea. Flare-up reactions are characterized by the reactivation of previously positive reactions to intradermal or skin tests triggered by patch testing and after systemic provocation with an allergen. The phenomenon is not common to drugs. The mechanisms involved in this reaction seem to be heterogeneous and are not completely understood. To our knowledge this is the first case of allergic reaction to GA manifested as a flare-up reaction during challenge test.     

Periodontal clinical and microbiological data in desquamative gingivitis patients

Objectives

A series of patients affected by desquamative gingivitis (DG) was investigated in order to evaluate relation patterns among clinical parameters relevant to plaque-induced periodontitis, periodontal microbiological data and the presence of DG lesions.

Patients and methods

Eight oral lichen planus (OLP) and four mucous membrane pemphigoid (MMP) patients were examined. Periodontal measurements (performed at six sites per tooth on all teeth) included probing depth (PD), gingival recession (REC), clinical attachment loss (CAL) and full-mouth plaque (FMPS) and bleeding (FMBS) scores; the presence and the exact location (site by site) of DG lesions were carefully recorded. Sub-gingival plaque samples were collected and examined by means of real-time PCR for the quantitative determination of the six most important marker organisms of periodontitis. Statistically significant differences and correlation of studied variables between DG-positive and DG-negative sites were investigated in MMP and OLP cases using Mann–Whitney test (p?<?0.05) and the Spearman rank correlation coefficient, respectively.

Results

OLP gingival lesions do not significantly affect CAL, although the presence of such lesions may reduce REC and increase PD and FMPS. MMP gingival lesions significantly worsened CAL and increased REC and FMPS. In both OLP and MMP cases, no significant difference was found between DG-positive and DG-negative sites as regards the relative percentage of the investigated species on the total bacterial load. Correlations between the presence of DG lesions and clinical parameters (CAL, PD, REC) were not significant (p?<?0.05). Significant correlations were found for the presence of gingival OLP lesions and Aggregatibacter actinomycetemcomitans (AA) and for the absence of gingival MMP lesions and AA.

Conclusions

These findings are not definitive, but highlight the need for further investigations of periodontal clinical and microbiological aspects of disorders causing DG in order to clarify their potential interference with plaque-related periodontitis.     

Randomized Trial of Trimethoprim-Sulfamethoxazole versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients with AIDS

The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.     

Independent component analysis of fMRI group studies by self-organizing clustering

Independent component analysis (ICA) is a valuable technique for the multivariate data-driven analysis of functional magnetic resonance imaging (fMRI) data sets. Applications of ICA have been developed mainly for single subject studies, although different solutions for group studies have been proposed. These approaches combine data sets from multiple subjects into a single aggregate data set before ICA estimation and, thus, require some additional assumptions about the separability across subjects of group independent components. Here, we exploit the application of similarity measures and a related visual tool to study the natural self-organizing clustering of many independent components from multiple individual data sets in the subject space. Our proposed framework flexibly enables multiple criteria for the generation of group independent components and their random-effects evaluation. We present real visual activation fMRI data from two experiments, with different spatiotemporal structures, and demonstrate the validity of this framework for a blind extraction and selection of meaningful activity and functional connectivity group patterns. Our approach is either alternative or complementary to the group ICA of aggregated data sets in that it exploits commonalities across multiple subject-specific patterns, while addressing as much as possible of the intersubject variability of the measured responses. This property is particularly of interest for a blind group and subgroup pattern extraction and selection.     

Circulating monocyte chemoattractant protein-1 and early development of nephropathy in type 1 diabetes

OBJECTIVES: To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA(1c), and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA(1c) were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment. RESULTS: FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA(1c), FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA(1c) values. CONCLUSIONS: This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.