Pharmacological properties of oral antibiotics for the treatment of uncomplicated urinary tract infections

The therapeutic management of uncomplicated bacterial urinary tract infections (UTIs) is based on short-term courses of oral antibiotics. The preferred drugs are nitrofurantoin trimethoprim-sulfamethoxazole, fosfomycin trometamol, fluoroquinolones and β-lactam agents. The choice of agent for treating uncomplicated UTIs should be based on the pharmacokinetic characteristics of the molecule so that clinical benefit is optimized and the risk of antibacterial resistance is minimized. This article discusses the general pharmacokinetic-pharmacodynamic (PK/PD) aspects of antimicrobial chemotherapy, the PK/PD characteristics of oral antimicrobial agents for the treatment of uncomplicated UTIs and the pharmacological and therapeutic strategies for limiting or preventing bacterial resistance

actual role of older oral antibiotics in the treatment of resistant urinary tract infections utis

n/

Voriconazole treatment of Candida tropicalis meningitis: persistence of (1,3)-b-D-glucan in the cerebrospinal fluid is a marker of clinical and microbiological failure

Introduction: Infections are still the most common complications of cerebral shunt procedures. Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality. Due to their uncommonness, diagnostic procedures and optimal therapy are poorly defined. We report a case of Candida tropicalis infection of ventriculo-peritoneal cerebrospinal fluid (CSF) shunt in a 49-year-old immune competent male treated with voriconazole (VOR). Methods: Microbiological and CSF markers (1,3-b-D-glucan-BDG) of fungal infection, biofilm production capacity, sensitivity of serial isolates of the pathogen, and the concentration of the antifungal drug have been monitored and related to the clinical course of this infection. Results: Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed. Conclusion: Biofilm production of the C. tropicalis isolate might have had a significant role in treatment failure. Of interest, clinical and microbiological unfavorable outcome was anticipated by persistence of BDG in CSF. Rising titers of this marker were associated with relapse of fungal infection

Sarcopenia in the elderly: from clinical aspects to therapeutic options

Sarcopenia is a major contributor to the risk of physical frailty, functional decline, poor health-related quality of life and premature death in older people. Sarcopenia can be considered a geriatric syndrome. The term sarcopenia indicates the loss of muscle mass that accompanies aging. Muscle mass declines with aging process with differences between subjects in relation to the presence of chronic diseases, to lifestyles habits (mainly diet and physical activity), to cognitive status. Sarcopenia in the elderly is associated with poor health outcomes, such as falls, disability, loss of independence, and mortality; however, it is potentially treatable if recognized and intervened early. The prevalence of sarcopenia rates between 5% and 13% in community-dwelling older people aged 65 years and over, and is higher in those 80 years and older (20-25%). The cause of sarcopenia is generally thought to be multifactorial, with environmental causes, disease triggers, inflammatory pathway activation, and a large number of cellular and biochemical abnormalities. Resistance training and amino acid supplementation are a recommended practice for the prevention of sarcopenia. The essential elements for the management of the sarcopenic patient are the recognition of a condition of frailty, an accurate multidimensional geriatric assessment, with attention to cognitive problems, mood, functional problems, living conditions, using standardized instruments. Combining exercise with some pharmacological compounds such as β- Hydroxy-β-methylbutyrate (HMB) and dietary supplements (including proteins, aminoacids and vitamin D) may exert a beneficial effect on older adults thus influencing the progress to sarcopenia. The recommended daily amount of protein is greater for older people. Vitamin D and leucine enrichment seems mandatory in order to improve muscle mass and lowerextremity function among sarcopenic older adults. There are some evidences that collagen peptides in this setting might be even superior to whey protein in promoting muscle growth and increasing the mobility

The First Spontaneous Spawning of Red Drum Sciaenops Ocellatus L. in Europe: Broodstock Management and Early Larval Stages

The present paper reports a research on reproductive parameters and larval rearing of red drum (Sciaenops ocellatus) maintained in captivity for the first time in Europe. Red drum juveniles were obtained from United States in the late 90s. In early January 2013, 40 in total male and female red drums ranging from 34 to 47 cm in length were held in a 25 m3 rectangular tank with a closed recirculating system with a water flow of 6000 L/h, located in Lesina (FG) fish farm (Southern Italy). Water temperature and salinity ranged between 21.0 and 28.8°C and from 25 to 27 g/L respectively. The fish were fed commercial feed pellet (46% protein) at 1.1% of body weight daily. Sexual maturation occurred during the natural breeding season of red drum. Approximately 43 spawns were recorded by the end of July and continuing to mid-September, with mean number of 66.5 millions of eggs collected overall on spawn period. Batch fecundity (3.325*106 ova per female) and relative fecundity (361.41 ova/g body weight) were calculated. Fertilisation rate was 30 to 80%. Larvae were hatched at a mean total length of 2.40±0.33 mm and showed a gradual increase in size of approximately 0.378 mm/day for the first 40 day after hatching (DAH). Cannibalism was observed as larger larvae preyed on smaller ones; to limit the phenomenon red drum population was selected for size at 35 DAH. Reliable information on fecundity and larval stage is essential for encouraging Sciaenops ocellatus farming also in Mediterranean countries

Simplified Equations Using Two Concentrations To Calculate Area under the Curve for Antimicrobials with Concentration-Dependent Pharmacodynamics: Daptomycin as a Motivating Example.

The effects of several antimicrobial agents are predicted by the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC). Peak (C(p)) and trough (C(t)) concentrations are often measured clinically as surrogates of AUC because actual computation of AUC from 1 or 2 samples requires sophisticated mathematical methods. Given that the effects of daptomycin are predicted by AUC/MIC, our objective was to compare simple equation calculated AUC based on C(p) and C(t) to model integrated AUC. A standard population pharmacokinetic model was used to simulate 5,000 daptomycin concentration-time profiles after 5 doses of 6 mg/kg of body weight/day (0.5-h infusions). The AUC for the 24-h period was computed by integration and by equations with 110 C(p)-C(t) combination pairs. The C(p) time points were in 15-min increments between 0.5 h and 3 h and C(t) in 15-min increments within an hour of the end of the dosing interval for each dose. The precision and bias of the calculated AUC relative to the integrated AUC were determined to identify C(p)-C(t) pairs associated with the lowest bias and highest precision. The equations were further validated using two daptomycin concentration-time data sets from healthy volunteers and critically ill patients. The precision and bias of calculated AUC were based primarily on C(p), and use of a daptomycin C(p) 1.5 h to 3 h from the start of infusion was associated with a bias of <10% and an R(2) of >0.95. Data from the healthy volunteers and critically ill patients also demonstrated declining bias with use of C(p) ≥1.5 h from the start of infusion with relatively good precision. Simplified equations using a daptomycin C(p) approximately 2 h from the start of infusion and a C(t) within an hour of the end of the dosing interval should yield precise and unbiased estimates of daptomycin AUC

Increasing the stocking density in Paracentrotus lividus larviculture: Effects on survival and metamorphosis rates

The development of sustainable methods for sea urchin juvenile production is currently constrained by high mortality rates during larval growth and the high costs of larval rearing systems management. With the aim of developing a method for the production of juveniles of the purple sea urchin Paracentrotus lividus in a medium-scale recirculating system, the present study focused on the effects of high stocking densities on larval growth. Plutei larvae were reared at three different densities (up to 7 ind/ml) in a semi-static culture system. Larval survival and metamorphosis success were evaluated in order to identify the most effective density range. The highest metamorphosis rates (80%-95%) were obtained at 4 and 7 larvae/ml. These results are comparable with (and in some cases higher than) those reported for the same species at much lower larval densities. In conclusion, the rearing conditions tested here show for the first time that a significantly higher (4 ind/ml) stocking density than those of traditional P. lividus rearing methods (based on large volumes and low densities) can be adopted, thus supporting the feasibility of an increase in the final output of competent larvae with no increase in rearing volumes

Drug repositioning: auranofin as a prospective antimicrobial agent for the treatment of severe staphylococcal infections

Auranofin, (AF), a gold(I) complex in clinical use for the therapy of rheumatoid arthritis, is reported here to produce remarkable bactericidal effects in vitro against Staphylococcus sp. Noticeably, a similar antimicrobial action and potency are also noticed toward a few methicillin-resistant Staphylococcus aureus strains but not toward Escherichia coli. The time and concentration dependencies of the antimicrobial actions of AF have been characterized through recording time kill curves, and a concentration dependent profile highlighted. Overall, the present results point out that auranofin might be quickly and successfully repurposed for the treatment of severe bacterial infections due to resistant Staphylococci

The Gene Targeting Approach of Small Fragment Homologous Replacement (SFHR) Alters the Expression Patterns of DNA Repair and Cell Cycle Control Genes

Cellular responses and molecular mechanisms activated by exogenous DNA that invades cells are only partially understood. This limits the practical use of gene targeting strategies. Small fragment homologous replacement (SFHR) uses a small exogenous wild-type DNA fragment to restore the endogenous wild-type sequence; unfortunately, this mechanism has a low frequency of correction. In this study, we used a mouse embryonic fibroblast cell line with a stably integrated mutated gene for enhanced green fluorescence protein. The restoration of a wild-type sequence can be detected by flow cytometry analysis. We quantitatively analyzed the expression of 84 DNA repair genes and 84 cell cycle control genes. Peculiar temporal gene expression patterns were observed for both pathways. Different DNA repair pathways, not only homologous recombination, as well as the three main cell cycle checkpoints appeared to mediate the cellular response. Eighteen genes were selected as highly significant target/effectors of SFHR. We identified a wide interconnection between SFHR, DNA repair, and cell cycle control. Our results increase the knowledge of the molecular mechanisms involved in cell invasion by exogenous DNA and SFHR. Specific molecular targets of both the cell cycle and DNA repair machineries were selected for manipulation to enhance the practical application of SFHR

TECHNICAL AND ECONOMICAL FEASIBILITY OF SEABASS FRY PRODUCTION ACCORDING TO ORGANIC TECHNIQUES

Over the past few years, consumers have been increasing their awareness about environmental, health and safety concerns and they have been gradually changing their habits in favor of organic food. In aquaculture sector, the most recent legislative framework regarding the organic production in Europe is the Commission Regulation (EC) 710/2009, where chapter for aquaculture animals include requirement for animal welfare conditions in husbandry and maximum stocking densities. In Italy, only ten farms are involved in the supply of certified organic fish and only some pilot projects were carried out for organic farming of different species. Therefore, the purpose of this research was to define or verify the principal standards for organic seabass farming, evaluating technical feasibility and production costs, comparing them with conventional production. This study contains the first considerations about organic production and its relative costs for sea bass fry, one of the most reared species of the country. Conversion to organic production naturally involves additional costs concerning the conversion process itself, the production of a new type of product and the lower output. In fact, results have shown that certification and feed costs represented the most significant difference between conventional and organic production. Finally, the current market situation is characterized by a low demand, an inadequately product differentiation from conventional (domestic or foreign) ones, a legislation still in progress, an unstructured and lower offer of organic products which does not allow to consider organic aquaculture as an activity that today can assure adequate profitability for the most part of Italian aquaculture firms