Two-year analysis of Clostridium difficile ribotypes associated with increased severity.

BACKGROUND: Certain Clostridium difficile ribotypes have been associated with complex disease phenotypes including recurrence and increased severity, especially the well-described hypervirulent RT027. This study aimed to determine the pattern of ribotypes causing infection and the association, if any, with severity. METHODS: All faecal samples submitted to a large diagnostic laboratory for C. difficile testing between 2011 and 2013 were subject to routine testing and culture. All C. difficile isolates were ribotyped, and associated clinical and demographic patient data were retrieved and linked to ribotyping data. RESULTS: In total, 86 distinct ribotypes were identified from 705 isolates of C. difficile. RT002 and RT015 were the most prevalent (22.5%, N=159). Only five isolates (0.7%) were hypervirulent RT027. Ninety of 450 (20%) patients with clinical information available died within 30 days of C. difficile isolation. RT220, one of the 10 most common ribotypes, was associated with elevated median C-reactive protein and significantly increased 30-day all-cause mortality compared with RT002 and RT015, and with all other ribotypes found in the study. CONCLUSIONS: A wide range of C. difficile ribotypes were responsible for C. difficile infection presentations. Although C. difficile-associated mortality has reduced in recent years, expansion of lineages associated with increased severity could herald increases in future mortality. Enhanced surveillance for emerging lineages such as RT220 that are associated with more severe disease is required, with genomic approaches to dissect pathogenicity.

Antibiotic sensitivity of bacteria associated with community-acquired urinary tract infection in Britain.

Twelve laboratories in different parts of Britain each supplied approximately 80 consecutive urinary bacterial isolates from community patients. All strains were identified by a central laboratory, where sensitivity to a variety of orally administered antimicrobials was determined by microtitre broth dilution. 65.1% of isolates were Escherichia coli, 23.4% 'coliforms' other than E. coli, 4.6% Proteus and Morganella spp., 1.8% Pseudomonas spp., 2.4% enterococci, 0.7% group B streptococci, 1.5% coagulase-negative staphylococci and 0.5% Staphylococcus aureus. Using previously published breakpoint sensitivity values, 98.9% of all isolates were found to be sensitive to norfloxacin and to ciprofloxacin, 95.7% to co-amoxiclav, 86.8% to nitrofurantoin, 77.4% to cephalexin, 75.6% to trimethoprim, 75.0% to cephradine and 51.7% to amoxycillin. There were some differences in sensitivities between centres, particularly those of the cephalosporins. Using standard breakpoints, submitting laboratories were found to overestimate sensitivity to nitrofurantoin and to underestimate sensitivity to the quinolones and to co-amoxiclav; there was considerable overestimation of sensitivity to cephalosporins.

False-positive Mycobacterium avium-intracellulare cultures with the Bactec 460 TB system.

Isolation of Mycobacterium avium-intracellulare from a number of specimens cultured with the Bactec 460 TB system was suspected to be due to carry-over contamination. The analysis of culture records and of the typing results confirmed this hypothesis. The problem seems to have been eliminated after replacement of the needle heater and increase of the needle temperature. We recommend that a number of precautions should be taken to reduce the risk of reporting false positive mycobacterial cultures.

Pharmacology of UK-38485 (dazmegrel), a specific inhibitor of thromboxane A2 synthetase.

Thromboxane A2 (TXA2) synthesis in rabbit and human platelet rich plasma (PRP) was inhibited in a dose-dependent manner by UK-38485 (dazmegrel) when the PRP was aggregated with collagen, arachidonic acid and ADP. The level of inhibition was time-dependent. That is, the dose-response curves shifted to lower concentrations with increasing incubation times with UK-38485 prior to addition of aggregation agents. Following bolus intravenous injections of UK-38485 in rabbits, the elimination from serum fitted a 3-exponential curve. The terminal elimination phase had a half-life of 69.8 +/- 3.8 min. Oral treatment of rabbits with UK-38485 for 2 weeks showed that animals with serum concentrations of 0.358 +/- 0.091 microgram/ml of the inhibitor had TXA2 synthesis inhibited in serum by 83.8 +/- 7.1%. This corresponded to animals which were treated with 20 mg/kg/day of the inhibitor.

Suppression of foam cell lesions in hypercholesterolemic rabbits by inhibition of thromboxane A2 synthesis.

Hypercholesterolemia induces adhesion of blood-borne monocytes to vascular endothelium and their subsequent migration into the intima, where foam cell lesions subsequently develop. The regulating mechanisms for the adhesion and migration are unclear. In this study, a specific thromboxane A2 (TXA2) synthetase inhibitor, UK-38485, was used to treat rabbits fed an atherogenic diet to determine whether inhibition of TXA2, the major metabolite of arachidonic acid in monocytes, affects lesion development. Rabbits were fed a diet supplemented with 2% cholesterol and 8% peanut oil for 12 weeks with or without UK-38485 at a dosage that maintained 80% to 90% inhibition of TXA2 formation in serum. The treatment with UK-38485 had no effect on total serum cholesterol. Both the treated and untreated groups developed subpopulations of high and low responders with respect to the extent of lesion coverage, forming a bimodal distribution. The treatment with UK-38485 significantly (p less than 0.001) reduced the percentage of the thoracic aorta covered by lesions when treated low responders (5.3 +/- 1.0%, n = 12) were compared to untreated low responders (23.6 +/- 2.9%, n = 12). However, UK-38485 had no effect when treated high responders (76.3%, n = 3) were compared to untreated high responders (72.0%, n = 12). Lesion coverage was not correlated with serum cholesterol levels. Stimulation of isolated rabbit monocytes in autologous plasma with 0.66 mM arachidonic acid in the presence of increasing concentrations of UK-38485 caused a dose-dependent inhibition of TXA2 and a concurrent increase in prostaglandin E2 (PGE2).(ABSTRACT TRUNCATED AT 250 WORDS)