Objectives: Invasive Candida infections pose a major public health problem worldwide and is a major cause of nosocomial bloodstream infection. Our aim was to assess dynamics in incidence, species distribution and antifungal susceptibility of candidemia episodes in Jerusalem, to better understand the epidemiology of invasive isolates and to better direct therapy. Methods: We analyzed the incidence dynamics, species distribution and susceptibility pattern of 899 candidemia episodes during 2005–2016 in Jerusalem. Results: The overall incidence of candidemia was relatively low of 0.62 per 1,000 admissions. Candida albicans was the leading pathogen (39.4%); however, there was a shift toward non-albicans species, with Candida glabrata predominating among them (40%). As expected, more than one-third of candidemias occurred in intensive care units. However, the distribution between species varied and Candida tropicalis was the leading pathogen in hematology-oncology patients. The susceptibility of isolates to antifungals remained stable throughout the years. Only a minority of Candida albicans isolates were non-susceptible to fluconazole (3.3%), however, an unexpectedly high resistance rate (37.8%) was observed in Candida parapsilosis isolates. We found an alarming rate of caspofungin resistance in Candida glabrata (33.6%) and Candida krusei (67%); this may reflect misclassification of resistance by the E-test method. Conclusions: This is the first comprehensive candidemia analysis in the Jerusalem area that should serve as a basis for decision-making regarding appropriate antifungal treatment in the hospital setting. The exceptional high resistance rate amongst Candida parapsilosis emphasizes the importance of antifungal susceptibility monitoring in medical centers serving large urban areas to better direct appropriate treatment.

Streptococcus mutans is a cariogenic bacterium in the oral cavity involved in plaque formation and dental caries. The endocannabinoid anandamide (AEA), a naturally occurring bioactive lipid, has been shown to have anti-bacterial and anti-biofilm activities against Staphylococcus aureus. We aimed here to study its effects on S. mutans viability, biofilm formation and extracellular polysaccharide substance (EPS) production. S. mutans were cultivated in the absence or presence of various concentrations of AEA, and the planktonic growth was followed by changes in optical density (OD) and colony-forming units (CFU). The resulting biofilms were examined by MTT metabolic assay, Crystal Violet (CV) staining, spinning disk confocal microscopy (SDCM) and high-resolution scanning electron microscopy (HR-SEM). The EPS production was determined by Congo Red and fluorescent dextran staining. Membrane potential and membrane permeability were determined by diethyloxacarbocyanine iodide (DiOC2(3)) and SYTO 9/propidium iodide (PI) staining, respectively, using flow cytometry. We observed that AEA was bactericidal to S. mutans at 12.5 µg/mL and prevented biofilm formation at the same concentration. AEA reduced the biofilm thickness and biomass with concomitant reduction in total EPS production, although there was a net increase in EPS per bacterium. Preformed biofilms were significantly affected at 50 µg/mL AEA. We further show that AEA increased the membrane permeability and induced membrane hyperpolarization of these bacteria. AEA caused S. mutans to become elongated at the minimum inhibitory concentration (MIC). Gene expression studies showed a significant increase in the cell division gene ftsZ. The concentrations of AEA needed for the anti-bacterial effects were below the cytotoxic concentration for normal Vero epithelial cells. Altogether, our data show that AEA has anti-bacterial and anti-biofilm activities against S. mutans and may have a potential role in preventing biofilms as a therapeutic measure.

Background: The association between Body Mass Index (BMI) and clinical outcomes following sepsis continues to be debated. We aimed to investigate the relationship between BMI and in-hospital clinical course and mortality in patients hospitalized with bacteremic sepsis using real-world data. Methods: A sampled cohort of patients hospitalized with bacteremic sepsis between October 2015 and December 2016 was identified in the National Inpatient Sample (NIS) database. In-hospital mortality and length of stay were defined as the relevant outcomes. Patients were divided into 6 BMI (kg/m²) subgroups; (1) underweight ≤ 19, (2) normal-weight 20–25, (3) over-weight 26–30, (4) obese I 31–35, (5) obese II 36–39, and (6) obese stage III ≥ 40. A multivariable logistic regression model was used to find predictors of mortality, and a linear regression model was used to find predictors of an extended length of stay (LOS). Results: An estimated total of 90,760 hospitalizations for bacteremic sepsis across the U.S. were analyzed. The data showed a reverse-J-shaped relationship between BMI and study population outcomes, with the underweight patients (BMI ≤ 19 kg/m²) suffering from higher mortality and longer LOS as did the normal-weight patients (BMI 20–25 kg/m²) when compared to the higher BMI groups. The seemingly protective effect of a higher BMI diminished in the highest BMI group (BMI ≥ 40 kg/m²). In the multivariable regression model, BMI subgroups of ≤19 kg/m² and ≥40 kg/m² were found to be independent predictors of mortality. Conclusions: A reverse-J-shaped relationship between BMI and mortality was documented, confirming the “obesity paradox” in the real-world setting in patients hospitalized for sepsis and bacteremia.

We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone.