Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n?=?2000), Gram-positives (n?=?403) and yeasts (n?=?132) had inhibition zone diameters for nitroxoline ≥18?mm. Except for Pseudomonas aeruginosa, nitroxoline MIC₉₀ values were ≤16?mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC₉₀ values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time–kill curves in Mueller–Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.     

Synthesis,structure, antioxidant activity,and water solubility of trolox ion conjugates

The interaction of trolox with ammonia, alkylamines of different classes, and amino derivatives of heterocyclic compounds, including nitroxyl radicals and alkaloids, led to the production of ammonium salts called ion conjugates (ICs). Five ICs were characterised by X-ray diffraction. This is the first time a wide range of ICs were made from trolox with amines, and ESI-MS data demonstrated they have the potential to generate pseudomolecular [(A^?B⁺)?+?H]⁺ ions. For all obtained trolox ICs, a significant increase (1–3 orders of magnitude) in water solubility was achieved while retaining high antioxidant activity. ICs synthesised from two biologically active fragments may be used to create polyfunctional agents with varying solubility and bioavailability.     

Extracellular vesicles released in response to respiratory exposures: implications for chronic disease

Extracellular vesicles (EV) are secreted signaling entities that enhance various pathological processes when released in response to cellular stresses. Respiratory exposures such as cigarette smoke and air pollution exert cellular stresses and are associated with an increased risk of several chronic diseases. The aim of this review was to examine the evidence that modifications in EV contribute to respiratory exposure-associated diseases. Publications were searched using PubMed and Google Scholar with the search terms (cigarette smoke OR tobacco smoke OR air pollution OR particulate matter) AND (extracellular vesicles OR exosomes OR microvesicles OR microparticles OR ectosomes). All original research articles were included and reviewed. Fifty articles were identified, most of which investigated the effect of respiratory exposures on EV release in vitro (25) and/or on circulating EV in human plasma (24). The majority of studies based their main observations on the relatively insensitive scatter-based flow cytometry of EV (29). EV induced by respiratory exposures were found to modulate inflammation (19), thrombosis (13), endothelial dysfunction (11), tissue remodeling (6), and angiogenesis (3). By influencing these processes, EV may play a key role in the development of cardiovascular diseases and chronic obstructive pulmonary disease and possibly lung cancer and allergic asthma. The current findings warrant additional research with improved methodologies to evaluate the contribution of respiratory exposure-induced EV to disease etiology, as well as their potential as biomarkers of exposure or risk and as novel targets for preventive or therapeutic strategies.     

New,Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in Patients With Head and Neck Cancer: An Exploratory Study

Background: The perioperative use of immunomodulatory nutrition formulas in patients with head and neck cancer reduces the number of postoperative infections and the length of hospital stay. Objective: An exploratory, randomized, controlled, blind, clinical trial was designed to examine the effect of the preoperative consumption of a new, immunomodulatory, oral nutrition formula in patients with head and neck cancer. Methods: Thirty‐eight patients were randomized to receive either 400 mL/d of either the new immunomodulatory formula (IF) or that commonly used in clinical practice (CF) over 10 days prior to surgery. Thirty‐three patients completed the study. Compliance, tolerance, the length of hospital stay, the incidence of infections and noninfectious complications before discharge, and the same up to 15 and 30 days after discharge were recorded. Results: The percentage of patients who developed infections before discharge was significantly lower in the IF than in the CF group (P = .013), as was the number of infections/100 patients/d (P = .035). The length of hospital stay was significantly shorter in the IF group (P = .001). Both formulas were safe and well tolerated. No other differences were detected. These results suggest preoperative consumption of the new formula to be beneficial for patients with neck and head cancer. Further trials are needed to confirm these results and to test the efficacy of the formula in patients with other conditions. Conclusion: The new formula can be safely prescribed as part of the preoperative treatment of patients with head and neck cancer and might reduce the problem of postoperative infection.     

Nuevos retos en gestión de vectores en salud pública: la mosca negra en Murcia (España)

Historically, no black fly (Diptera: Simuliidae) nuisance has been reported in the Murcia Region. Back in September 2016 the Ojós City Council has contacted the Regional Public Health General Directorate for help regarding a local insect nuisance, most probably based on mosquitoes. After sampling with a BG-sentinel 2 trap, collecting adult specimens with an entomological aspirator, and collect larvae and pupae on submerged giant cane stalks at the river, it turned out that Simulium sergenti was the insect species causing the nuisance. This species is not considered particularly anthropophilic; therefore, a low vector risk for human health was considered. However, the high fly density impaired the life quality of the people at the village. A management plan was recommended, treating the river with Bacillus thuringiensis var israelensis.