The major virulence factors of Clostridium difficile are toxins A and B. These toxins are encoded by tcdA and tcdB genes, which form a pathogenicity locus (PaLoc) together with three additional genes that have been implicated in regulation (tcdR and tcdC) and secretion (tcdE). To date, the PaLoc has always been found in the same location and is replaced in non-toxigenic strains by a highly conserved 75/115 bp non-coding region. Here, we show new types of C. difficile pathogenicity loci through the genome analysis of three atypical clinical strains and describe for the first time a variant strain producing only toxin A (A+B−). Importantly, we found that the PaLoc integration sites of these three strains are located in the genome far from the usual single known PaLoc integration site. These findings allowed us to propose a new model of PaLoc evolution in which two “Mono-Toxin PaLoc” sites are merged to generate a single “Bi-Toxin PaLoc”.
As in humans, feline HCM is characterized by marked phenotypic variability with several breed-dependent features regarding epidemiology, LV geometric patterns, and clinical course (ie, age at diagnosis, 1st cardiac event, and cause of death).
Clostridium difficile causes antibiotic-associated diarrhoea and pseudomembranous colitis. The main virulence factors of C. difficile are the toxins A (TcdA) and B (TcdB). A third toxin, called binary toxin (CDT), can be detected in 17% to 23% of strains, but its role in human disease has not been clearly defined. We report six independent cases of patients with diarrhoea suspected of having C. difficile infection due to strains from toxinotype XI/PCR ribotype 033 or 033-like, an unusual toxinotype/PCR ribotype positive for CDT but negative for TcdA and TcdB. Four patients were considered truly infected by clinicians and were specifically treated with oral metronidazole. One of the cases was identified during a prevalence study of A−B−CDT+ strains. In this study, we screened a French collection of 220 nontoxigenic strains and found only one (0.5%) toxinotype XI/PCR ribotype 033 or 033-like strain. The description of such strains raises the question of the role of binary toxin as a virulence factor and could have implications for laboratory diagnostics that currently rarely include testing for binary toxin.
BackgroundFurosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half‐life and a higher bioavailability.Objectives(1) To demonstrate that torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint “spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening.”AnimalsA total of 366 dogs with CHF attributable to DMVD.MethodsAnalysis of 2 prospective randomized single‐blinded reference‐controlled trials was performed. Dogs orally received either torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population.ResultsTorasemide was noninferior to furosemide (P
torasemide − P
furosemide = +7%; 95% CI [−8%; +22%] and P
torasemide − P
furosemide = +1%; 95% CI [−12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10–0.69 mg/kg/d) was associated with a 2‐fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27–0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70–6.30 mg/kg q12h).Conclusions and Clinical ImportanceTorasemide q24h is an effective oral diuretic in dogs with CHF.
Most dogs and cats with isolated VSDs had a long survival time; few had clinical signs at diagnosis, and none with follow-up developed clinical signs after diagnosis.
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