Early inflammation precedes cardiac fibrosis and heart failure in desmoglein 2 murine model of arrhythmogenic cardiomyopathy.

The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in Dsg2-null (Dsg2-/-) hearts at postnatal day 14 (2 weeks) that were absent in the fibrotic heart of adult mice (10 weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression.

A survey of rotational use of biocides in hospital pharmacy aseptic units.

A postal survey of biocide rotation in UK hospital pharmacy aseptic units was carried out. Seventy per cent of respondents stated that biocides were rotated, most frequently in areas outside critical work zones. High-level disinfection was employed when 'aseptic' conditions were required. Decisions on frequency of rotation were most often based on in-house validation or consultation with colleagues. Toxicity and corrosiveness were the criteria rated most important in a rotation policy. Microbiological monitoring was carried out most frequently in critical work zones but less often for handwashing. Most QC hospital pharmacists supported rotation and would prefer a standard period for all applications (monthly). Guidelines need to be clarified to assist staff in decisions regarding biocide rotation.

Resistance to antibiotics and biocides among non-fermenting Gram-negative bacteria.

OBJECTIVE: To investigate the antibiotic and biocide susceptibilities of clinical isolates of rarely encountered Gram-negative, non-fermenting bacteria. METHODS: Thirty Gram-negative non-fermenting bacterial strains were isolated from blood cultures of oncology patients. These were studied for their resistance to 11 antibiotics. Their susceptibilities to seven biocides used in hospitals were also examined. RESULTS: Isolates of Stenotrophomonas maltophilia and Ochrobactrum anthropi were generally resistant to at least five of the antibiotics, whereas isolates of Comamonas acidivorans, Flavobacterium oryzihabitans, Aeromonas hydrophila, Sphingobacterium spiritivorum, Acinetobacter junii and Acinetobacter lwoffi were generally sensitive to at least nine of the antibiotics. Trovafloxacin and trimethoprim-sulfamethoxazole were the most effective antibacterial agents tested, with 0% and 7%, respectively, of isolates being resistant, whereas 63% of isolates were resistant to aztreonam. Some isolates, sensitive to meropenem and/or ceftazidime in vitro, possessed very high MBC/MIC ratios for these beta-lactams. Two out of three biocides used in hospital pharmacies showed lethal activity towards all strains tested when used at less than one-third of their recommended in-use concentration. Proceine 40 failed to give a 5 log reduction in bacterial cell number for the isolates tested when used at its "in-use" concentration. A concentration of > 500 mg/L chlorhexidine was required to achieve a 5 log reduction for the same isolates. CONCLUSIONS: We have examined the antibiotic susceptibilities of non-fermenting Gram-negative bacterial strains isolated from immunocompromised patients. Despite being sensitive to certain antibiotics in vitro, some isolates were still able to cause serious bacteremia. We have also reported for the first time the susceptibilities of non-fermenting Gram-negative bacteria to common biocides used in hospital infection control, and have shown that some strains are able to persist at the "in-use" concentration of particular biocides. It is therefore important to study further this particular group of organisms, and, in particular, to examine whether there exists a link between resistance to antibiotics and resistance to biocides.