Effect of ceftazidime/avibactam plus fosfomycin combination on 30†day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study.

Introduction: The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Materials and methods: From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam ±â€Šother). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score. Results: Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam ±â€Šother). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS ≥ 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective. Conclusions: Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens.

Melissa officinalis L. Supplementation Provides Cardioprotection in a Rat Model of Experimental Autoimmune Myocarditis.

Due to existing evidence regarding antioxidant and anti-inflammatory effects of Melissa officinalis extracts (MOEs), this study was aimed at investigating the potential of ethanolic MOE to prevent the development of myocarditis and its ability to ameliorate the severity of experimental autoimmune myocarditis (EAM) by investigating MOE effects on in vivo cardiac function, structure, morphology, and oxidative stress parameters. A total of 50 7-week-old male Dark Agouti rats were enrolled in the study and randomly allocated into the following groups: CTRL, nontreated healthy rats; EAM, nontreated rats with EAM; MOE50, MOE100, and MOE200, rats with EAM treated with either 50, 100, or 200 mg/kg of MOE for 3 weeks per os. Myocarditis was induced by immunization of the rats with porcine myocardial myosin (0.5 mg) emulsion on day 0. Cardiac function and dimensions of the left ventricle (LV) were assessed via echocardiography. Additionally, the blood pressure and heart rate were measured. On day 21, rats were sacrificed and the hearts were isolated for further histopathological analyses (H/E and Picrosirius red staining). The blood samples were collected to determine oxidative stress parameters. The EAM group characteristically showed greater LV wall thickness and lower ejection fraction (50.33 ± 7.94% vs. 84.81 ± 7.74%) and fractional shortening compared to CTRL (p < 0.05). MOE significantly improved echocardiographic parameters (EF in MOE200 81.44 ± 5.51%) and also reduced inflammatory infiltrate (by 88.46%; p < 0.001) and collagen content (by 76.39%; p < 0.001) in the heart tissues, especially in the MOE200 group compared to the EAM group. In addition, MOEs induced a significant decrease of prooxidants production (O2 -, H2O2, and TBARS) and improved antioxidant defense system via increase in GSH, SOD, and CAT compared to EAM, with medium and high dose being more effective than low dose (p < 0.05). The present study suggests that ethanolic MOEs, especially in a 200 mg/kg dose, improve cardiac function and myocardial architecture, possibly via oxidative stress mitigation, thus preventing heart remodeling, development of dilated cardiomyopathy, and subsequent heart failure connected with EAM. MOEs might be considered as a potentially helpful adjuvant therapy in patients with autoimmune myocarditis.

Minocycline as heart conditioning agent in experimental type 2 diabetes mellitus - an antibacterial drug in heart protection.

Cardiovascular diseases, and among them certainly myocardial infarction, remain leading cause of death worldwide. Diabetes increases risk of occurrence as well as adverse outcome of myocardial infarction. Conditioning maneuvers are the most attractive method for alleviating both the consequences of ischemia and reperfusion. Minocycline is a tetracycline derivative which exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. The aim of this study was to assess the protective ability of preconditioning and postconditioning of isolated hearts from healthy and rats with experimentally induced type 2 diabetes with minocycline on functional recovery and redox status after ischemia and reperfusion. The hearts from healthy and diabetic rats were excised and retrogradely perfused according to the Langendorff technique. Using sensor in the left ventricle, the cardiodynamic parameters were recorded and in the samples of the coronary venous effluent oxidative stress biomarkers were analyzed. Minocycline was injected directly into the coronary vessels, in preconditioning 5 min before global ischemia, and in postconditioning during the first 5 min of reperfusion. Results of this study clearly show beneficial effects of minocycline applied both before ischemia and in the first minutes of reperfusion fashion in both healthy and diabetic rat hearts. The most prominent protective effect regarding oxidative stress is related to the decreased production of superoxide anion radical due postconditioning with minocycline in diabetic hearts. Cardiodynamic parameters were significantly improved in minocycline conditioned groups. Superoxide anion radical stands out as the most susceptible to changes induced by minocycline.

Taxing sugar-sweetened beverages as a policy to reduce overweight and obesity in countries of different income classifications: a systematic review.

OBJECTIVE: To evaluate the potential impact of sugar-sweetened beverage (SSB) taxes on overweight and obesity prevalence in countries of different income classifications. DESIGN: Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO number CRD42020161612). Five databases (Cochrane Library, Embase, LILACS (via Virtual Health Library) and MEDLINE (via PubMed), and Web of Science were searched, from January 2009 to December 2019. Articles that reported changes in purchases, sales, intake, body weight, BMI, overweight and/or obesity prevalence due to a tax on or price change in SSB were included. SETTING: Studies conducted in countries of different income classifications. PARTICIPANTS: The search yielded 8349 articles of which 21 met inclusion criteria. RESULTS: Among the sixteen studies selected, only two did not show that consumption, sales and purchase decreased as the price of SSB increased. In eight of the thirteen studies selected, a positive effect of an SSB tax on decreasing overweight and obesity prevalence was expected. It is estimated that a 20 % taxation on SSB would result in a greater decrease in the prevalence of overweight and obesity compared to a 10 % rate. Studies with no significant effect of taxing on sales, purchases, consumption and prevalence of obesity were from high-income countries, while significant effects of taxing on reducing purchase, consumption and/or obesity prevalence were found in studies from upper-middle- and middle-income countries. CONCLUSION: A high SSB tax might be an effective fiscal policy to decrease purchase and consumption of SSB and reduce overweight/obesity prevalence, especially if the tax were specific for beverage volume.

Solid wastes from the enzyme production as a potential biosorbent to treat colored effluents containing crystal violet dye.

Sugarcane bagasse, a largely available waste worldwide, was submitted to solid-state fermentation (SSF) using the fungus Metarhizium anisopliae, aiming to produce enzymes. The solid waste generated from SSF was tested as an alternative biosorbent to treat colored effluents containing crystal violet (CV) dye. The biosorbent, here named BW (bagasse waste), was characterized, and experimental tests were performed to verify the influence of pH and dosage on the CV biosorption. Isotherms and biosorption kinetics were performed, and the biosorption thermodynamic parameters were determined. The potential of BW was also evaluated for the treatment of a simulated textile effluent. The maximum biosorption capacity was 131.2 mg g-1 at 328 K, and the Liu was the most appropriate model to represent equilibrium data. The biosorption was spontaneous and endothermic. The use of BW in the simulated effluent showed that it is an efficient material, reaching color removal values of 85%. Therefore, the sugarcane bagasse generated from SSF can be considered a potential biosorbent to remove CV from textile effluents. This finding is relevant from the total environment viewpoint, since, at the same time, SSF generates enzymes and a solid waste, which in turn can be used as biosorbent to treat colored effluents.

Bactericidal activity of ceftobiprole combined with different antibiotics against selected Gram-positive isolates.

This study investigated the in vitro susceptibility of ceftobiprole and its potential synergistic activity in combination with other antimicrobials against 46 selected Gram-positive pathogens displaying resistance or decrease susceptibility to several drugs. The gradient-cross method was used to assess synergism between ceftobiprole and daptomycin, levofloxacin, linezolid, rifampicin and piperacillin/tazobactam. Time-kill curves were performed for seven representative isolates. Ceftobiprole MICs ranged from 0.25-6 mg/L for staphylococci; 4-≥32 mg/L for Enterococcus faecalis, and 0.38-≥32 mg/L for E. faecium. Ceftobiprole plus daptomycin was synergistic against all isolates. Ceftobiprole plus linezolid was synergistic against 4 isolates belonging to different species. Ceftobiprole plus levofloxacin was synergistic only against enterococci. In conclusion, ceftobiprole exhibited a potent in vitro antibacterial activity and exhibited synergy with daptomycin against all Gram-positive isolates, despite their antibiotic resistance phenotypes. The use of ceftobiprole in combination may provide a promising alternative therapy for the treatment of resistant Gram-positive infections.

Clusters of cyclones encircling Jupiter's poles.

The familiar axisymmetric zones and belts that characterize Jupiter's weather system at lower latitudes give way to pervasive cyclonic activity at higher latitudes. Two-dimensional turbulence in combination with the Coriolis ß-effect (that is, the large meridionally varying Coriolis force on the giant planets of the Solar System) produces alternating zonal flows. The zonal flows weaken with rising latitude so that a transition between equatorial jets and polar turbulence on Jupiter can occur. Simulations with shallow-water models of giant planets support this transition by producing both alternating flows near the equator and circumpolar cyclones near the poles. Jovian polar regions are not visible from Earth owing to Jupiter's low axial tilt, and were poorly characterized by previous missions because the trajectories of these missions did not venture far from Jupiter's equatorial plane. Here we report that visible and infrared images obtained from above each pole by the Juno spacecraft during its first five orbits reveal persistent polygonal patterns of large cyclones. In the north, eight circumpolar cyclones are observed about a single polar cyclone; in the south, one polar cyclone is encircled by five circumpolar cyclones. Cyclonic circulation is established via time-lapse imagery obtained over intervals ranging from 20 minutes to 4 hours. Although migration of cyclones towards the pole might be expected as a consequence of the Coriolis ß-effect, by which cyclonic vortices naturally drift towards the rotational pole, the configuration of the cyclones is without precedent on other planets (including Saturn's polar hexagonal features). The manner in which the cyclones persist without merging and the process by which they evolve to their current configuration are unknown.

How often are clinicians performing genital exams in children with disorders of sex development?

BACKGROUND: We sought to determine the frequency with which genital exams (GEs) are performed in children with disorders of sex development (DSD) and ambiguous genitalia (AG) during routine visits to the pediatric endocrine clinic. METHODS: Medical records of children with DSD and AG seen at one large academic center since 2007 were reviewed. Data analyzed included diagnosis, sex of rearing, age, initial or follow up visit, number of individuals present and sex of the pediatric endocrinologist. Repeated measures analysis was performed to evaluate associations between GEs and patient/physician factors. RESULTS: Eighty-two children with DSD and AG who had a total of 632 visits were identified. Sex of rearing was female in 78% and the most common diagnosis was congenital adrenal hyperplasia (CAH) (68%). GEs were performed in 35.6% of visits. GEs were more likely in patients with male sex of rearing (odds ratio [OR] 17.81, p=0.006), during initial vs. follow-up visits (OR 5.99, p=0.012), and when the examining endocrinologist was female (OR 3.71, p=0.014). As patients aged, GEs were less likely (OR 0.76, p<0.0001). CONCLUSIONS: GEs were performed in approximately one-third of clinic visits in children with DSD and AG. Male sex of rearing, initial visits and female pediatric endocrinologist were associated with more frequent GEs.

Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis.

Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens.

Proteinuria in Children: Evaluation and Differential Diagnosis.

Although proteinuria is usually benign in the form of transient or orthostatic proteinuria, persistent proteinuria may be associated with more serious renal diseases. Proteinuria may be an independent risk factor for the progression of chronic kidney disease in children. Mechanisms of proteinuria can be categorized as glomerular, tubular, secretory, or overflow. A history, a physical examination, and laboratory tests help determine the cause. Transient (functional) proteinuria is temporary. It can occur with fever, exercise, stress, or cold exposure, and it resolves when the inciting factor is removed. Orthostatic proteinuria is the most common type in children, especially in adolescent males. It is a benign condition without clinical significance. Persistent proteinuria can be glomerular or tubulointerstitial in origin. The urine dipstick test is the most widely used screening method. Although a 24-hour urine protein excretion test is usually recommended for quantitation of the amount of protein excreted in the urine, it may be impractical in children. A spot, first-morning urine test for a protein-to-creatinine or protein-to-osmolality ratio is a reliable substitute. Treatment of proteinuria should be directed at the underlying cause. Patients with active urinary sediments, hematuria, hypertension, hypocomplementemia, renal insufficiency with depressed glomerular filtration rate, or signs and symptoms suggestive of vasculitic disease may require referral to a pediatric nephrologist and a renal biopsy.

Methicillin-resistant Staphylococcus aureus infections: A review of the currently available treatment options.

This review is the result of discussions that took place at the 5th MRSA Working Group Consensus Meeting and explores the possible treatment options available for different types of infections due to methicillin-resistant Staphylococcus aureus (MRSA), focusing on those antibiotics that could represent a valid alternative to vancomycin. In fact, whilst vancomycin remains a viable option, its therapy is moving towards individualised dosing. Other drugs, such as the new lipoglycopeptides (oritavancin, dalbavancin and telavancin) and fifth-generation cephalosporins (ceftaroline and ceftobiprole), are showing good in vitro potency and in vivo efficacy, especially for patients infected with micro-organisms with higher vancomycin minimum inhibitory concentrations (MICs). Tedizolid is an attractive agent for use both in hospital and community settings, but the post-marketing data will better clarify its potential. Daptomycin and linezolid have shown non-inferiority to vancomycin in the treatment of MRSA bacteraemia and non-inferiority/superiority to vancomycin in the treatment of hospital-acquired pneumonia. Thus, several options are available, but more data from clinical practice, especially for invasive infections, are needed to assign specific roles to each antibiotic and to definitely include them in the new antibacterial armamentarium.

Effects of competition and cooperation interaction between agents on networks in the presence of a market capacity.

A network effect is introduced taking into account competition, cooperation, and mixed-type interaction among agents along a generalized Verhulst-Lotka-Volterra model. It is also argued that the presence of a market capacity undoubtedly enforces a definite limit on the agent's size growth. The state stability of triadic agents, i.e., the most basic network plaquette, is investigated analytically for possible scenarios, through a fixed-point analysis. It is discovered that: (i) market demand is only satisfied for full competition when one agent monopolizes the market; (ii) growth of agent size is encouraged in full cooperation; (iii) collaboration among agents to compete against one single agent may result in the disappearance of this single agent out of the market; and (iv) cooperating with two rivals may become a growth strategy for an intelligent agent.

Pathological Gambling in Parkinson's disease patients: Dopaminergic medication or personality traits fault?

Impulse control disorders (ICDs) are clinically relevant in Parkinson disease (PD) patients, with an established association with PD medication. Aim of our study was to study whether the increased frequency of pathological gambling (PG), reported in subgroups of PD patients, is related to specific personality tracts additional to dopaminergic medications. Thirty-seven PD patients with a personal history of PG where enrolled. Twenty one PD patients, matched for disease and dopaminergic therapy, never experiencing PG, were enrolled as controls. All subjects were tested with the Minnesota Multiphasic Inventory Personality scales (MMPI-2). Our data showed that PD group with PG exhibited significantly higher mean values of the three validity scales in comparison to the non-PG-PD group, demonstrating an higher tendency to lie. Content scales showed a significant increase of cynicism and bizarre ideation scales score in the PG-PD group, not exhibiting pathological values at the validity scales, (p: 0.02) in comparison to non-PG PD patients. According to our results, PG seems to be associated with precise personality tracts. Personality profiles of cluster A personality disturbances - Axys 2 according with DSM-5 TR (paranoid type) at MMPI-2 might be a warning index helpful in selecting dopaminergic treatment, to avoid subsequent ICDs appearance.

In vivo development of daptomycin resistance in vancomycin-susceptible methicillin-resistant Staphylococcus aureus severe infections previously treated with glycopeptides.

Our aim was to describe the clinical and microbiological features of four cases of severe vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) infections in which the vancomycin non-susceptibility development and daptomycin resistance occurred under therapy with teicoplanin (three cases) and daptomycin switched to vancomycin (one case). Clinical data were retrospectively reviewed. On nine clinical epidemiologically unrelated daptomycin-susceptible (DAP-S) and daptomycin-resistant (DAP-R) MRSA, we performed: (i) DAP-VAN-TEC-CFX-RIF minimum inhibitory concentrations (MICs); (ii) glycopeptide resistance detection (GRD) by δ-hemolysis; (iii) glycopeptide population analysis; (iv) molecular characterization by PFGE-MLST-SCCmec-agr-typing; (v) rpoB and mprF single nucleotide polymorphisms (SNPs); (vi) dltA-mprF-atl-sceD expression by real-time quantitative polymerase chain reaction (qPCR). Three out of the four patients did not survive despite salvage treatment; two died with active MRSA infection and one died because of Stenotrophomonas maltophilia sepsis. The fourth patient, in which a reversion to a DAP-S phenotype occurred, survived with daptomycin plus trimethoprim/sulfamethoxazole and oxacillin treatment, and endovascular device removal. Daptomycin resistance development was preceded by a stable heterogeneous vancomycin-intermediate S. aureus (hVISA) or VISA phenotype acquisition, while in one case, daptomycin resistance was preceded by an unstable daptomycin heteroresistance (hDAP) behavior reverting to DAP-S during vancomycin plus rifampin therapy followed by high doses of daptomycin. All DAP-R strains showed hVISA or DAP-R traits, including mutations and/or up-regulation of genes involved in cell wall turnover and cell membrane perturbation. In our study, daptomycin resistance arose during glycopeptide therapy. The emergence of DAP-R isolates was preceded by a stable VISA or hVISA phenotype or by instability reverting to a DAP-S heteroresistant phenotype. Daptomycin, as first-line therapy for the treatment of severe MRSA infections, should be used at optimal dosage combined with other agents such as beta-lactams, to prevent daptomycin resistance occurrence.

Antifungal coatings by caspofungin immobilization onto biomaterials surfaces via a plasma polymer interlayer.

Not only bacteria but also fungal pathogens, particularly Candida species, can lead to biofilm infections on biomedical devices. By covalent grafting of the antifungal drug caspofungin, which targets the fungal cell wall, onto solid biomaterials, a surface layer can be created that might be able to provide long-term protection against fungal biofilm formation. Plasma polymerization of propionaldehyde (propanal) was used to deposit a thin (∼20 nm) interfacial bonding layer bearing aldehyde surface groups that can react with amine groups of caspofungin to form covalent interfacial bonds for immobilization. Surface analyses by x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the intended grafting and uniformity of the coatings, and durability upon extended washing. Testing for fungal cell attachment and ensuing biofilm formation showed that caspofungin retained activity when covalently bound onto surfaces, disrupting colonizing Candida cells. Mammalian cytotoxicity studies using human primary fibroblasts indicated that the caspofungin-grafted surfaces were selective in eliminating fungal cells while allowing attachment and spreading of mammalian cells. These in vitro data suggest promise for use as antifungal coatings, for example, on catheters, and the use of a plasma polymer interlayer enables facile transfer of the coating method onto a wide variety of biomaterials and biomedical devices.

Streptococcus salivarius 24SMB administered by nasal spray for the prevention of acute otitis media in otitis-prone children.

This paper reports the results of the first study in which Streptococcus salivarius 24SMB, a safe α-haemolytic strain capable of producing bacteriocin-like substances with significant activity against acute otitis media (AOM) pathogens, was intranasally administered in an attempt to reduce the risk of new episodes of AOM in otitis-prone children. In this prospective, randomized, double-blind, placebo-controlled study, 100 children aged 1-5 years with histories of recurrent AOM were randomized 1:1 to receive an intranasal S. salivarius 24SMB or placebo twice daily for 5 days each month for 3 consecutive months. Fifty treated children and 47 who received placebo who were compliant with study protocol were followed monthly for 6 months. The number of children who did not experience any AOM was higher among the children treated with the S. salivarius 24SMB preparation than among those in the placebo group (30.0 vs 14.9%; p = 0.076). Moreover, the number of children who received antibiotics during the study period was lower among the children treated with S. salivarius 24 SMB than among those who received placebo (70 vs 83.0%; p = 0.13). Compared with the children who were not colonized by S. salivarius 24SMB after treatment, the number of colonized children who experienced any AOM was significantly lower (42.8 vs 13.6%; p = 0.03). Similar results were observed when the children treated with antibiotics for AOM were analysed (67.8 vs 95.5%; p = 0.029). This study revealed the ability of intranasally administered S. salivarius 24SMB to reduce the risk of AOM in otitis-prone children.

Colonization, safety, and tolerability study of the Streptococcus salivarius 24SMBc nasal spray for its application in upper respiratory tract infections.

Streptococcus salivarius, a non-pathogenic species and the predominant colonizer of the oral microbiota, finds a wide application in the prevention of upper respiratory tract infections, also reducing the frequency of their main pathogens. In this pilot study, the primary objective was to evaluate the safety and tolerability of a nasal spray, S. salivarius 24SMBc, as a medical device in a clinical study involving 20 healthy adult subjects. The secondary aim was to determine the ability of colonization assessed by molecular fingerprinting. Twenty healthy adult subjects, aged between 30 and 54 years, without a medical history of recurrent otitis media, were enrolled. All patient characteristics fulfilled the inclusion criteria. All subjects were treated daily for 3 days with the nasal spray containing S. salivarius 24SMBc at a concentration of 5 × 10(9) colony-forming units (CFU)/ml. The persistence of S. salivarius in the nasopharynx was investigated by the antagonism test and random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). The tolerability and safety were clinically assessed by clinical examinations during treatment. Our results demonstrate the capability of S. salivarius 24SMBc to colonize the rhinopharynx tissues in 95% of subjects and persist in 55% of them after 6 days from the last dose of the formulation, maintaining a concentration of 10(5) CFU/ml. The treatment was well tolerated by all healthy patients and no adverse effects were found. The topical application of streptococcal probiotics is a relatively undeveloped field but is becoming an attractive approach for both prevention and therapy, especially for pediatric age patients. S. salivarius 24SMBc possess characteristics making this strain suitable for use in bacteriotherapy.

Surface coatings with covalently attached caspofungin are effective in eliminating fungal pathogens.

In this work we have prepared surface coatings formulated with the antifungal drug caspofungin, an approved pharmaceutical lipopeptide compound of the echinocandin drug class. Our hypothesis was to test whether an antifungal drug with a known cell-wall disrupting effect could be irreversibly tethered to surface coatings and kill (on contact) biofilm-forming fungal human pathogens from Candida spp. The first aim of the study was to use surface analysis to prove that the chemical binding to the surface polymer interlayer was through specific and irreversible bonds (covalent) and not due to non-specific adsorption through weak forces that could be later reversed (physisorption). Secondly, we quantified the antifungal nature of these coatings in a biological assay showing excellent killing against C. albicans and C. tropicalis and moderate killing against C. glabrata and C. parapsilosis. We concluded that caspofungin retains antifungal activity even when it is irreversibly immobilized on a surface, providing a new insight into its mechanism of action. Thus, surface coatings that have echinocandins permanently bound will be useful in preventing the establishment of fungal biofilms on materials.

Seasonal and perennial allergic conjunctivitis.

Seasonal and perennial allergic conjunctivitis are IgE-mediated, hypersensitivity conditions characterized by ocular pruritus, epiphora, and hyperemia. Proper diagnosis is usually made clinically based on history and physical examination. Diagnostic procedures are rarely necessary. Non-pharmacological measures, such as environmental modification and proper eye care, should be considered for all patients with allergic conjunctivitis. Pharmacological interventions may also be required. Milder cases can be treated with short-term topical ophthalmic therapy such as a decongestant/ antihistamine combination, a mast cell stabilizer, or a multi-action agent. Moderate to severe cases may require longer usage of the above agents and/or the addition of an oral antihistamine. Refractory cases may necessitate the use of topical ophthalmic corticosteroids and topical NSAIDs. Immunotherapy, whether via the subcutaneous route or the intranasal route, should be considered in the treatment of persistent severe cases refractory to conventional treatment. Despite all the available therapeutic agents, there continues to be a constant need to discover more effective ways to treat seasonal and perennial allergic conjunctivitis. This article also discusses recent patents related to the field.