Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lyells syndrome also called Toxic epidermal necrolysis is the extreme form of idiosyncratic drug reaction that is called Steven Johnsons Syndrome: The condition results in an extensive loss of the skin with mucous membrane involvement. Lyells syndrome has been induced by many agents. The commonest agent in the literature being sulphonamides. However, in our search of the medical literature there was no report of dihydroarthemisinin as a cause of Lyells syndrome. We report three patients seen at two tertiary health institutions with Lyells syndrome after treatment for malaria with dihydroarthemisinin. This resulted from administration of dihydroarthemisinin with chloroquine in two patients and dihydroarthemisinin with Amodiaquine in one patient. The first patient was a seven year old child who developed 90% cutaneous involvement and died from hemorrhagic shock. The second was a 28 old female that developed a 76% body surface involvement and died from septicemia. The third patient was a pregnant 37 year old woman that developed 52% body involvement and died from septic shock. In these patients the earliest symptoms were not recognized and there was considerable delay before referral. In view of the recent WHO recommendation ofArthemisinin Combination Treatment (ACT) for malaria, we expect more cases of Steven Johnson Syndrome and Lyells syndrome from ACT treatment. The aim of this report is to raise the awareness of clinicians to this potentially fatal complication.
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PMID:Severe idiosyncratic drug reaction (Lyells syndrome) after ingesting dihydroartemisinin. 1976 82

Septic shock carries substantial morbidity and mortality. The failure of many promising therapies during late-phase clinical trials prompted calls for alternative trial designs. We describe an innovative trial evaluating selepressin, a novel selective vasopressin V1a receptor agonist, for adults with septic shock. SEPSIS-ACT (Selepressin Evaluation Programme for Sepsis-induced Shock-Adaptive Clinical Trial) is a blinded, randomized, placebo-controlled, two-part, adaptive phase 2b/3 trial, evaluating up to four selepressin dosing strategies. The primary outcome is pressor- and ventilator-free days, with a value of zero assigned for death within 30 days. We calculate Bayesian probabilities of final trial success to guide interim decision-making. Part 1 (dose-finding) has an adaptive sample size based on response-adaptive randomization and prespecified rules to determine stopping for futility or selection of the best dosing regimen for Part 2. Part 2 (confirmation) randomizes a minimum of 1,000 patients equally to the selected dosing regimen or placebo. The final estimate of treatment effect compares all selepressin-treated patients with all placebo-treated patients. The sample size of 1,800 provides 91% power to detect an increase of 1.5 pressor- and ventilator-free days with a reduction in mortality of 1.5%. The trial received a Special Protocol Assessment agreement from the U.S. Food and Drug Administration Center for Drug Evaluation and Research and is underway in Europe and the United States. SEPSIS-ACT is an innovative trial that addresses both optimal dose and confirmation of benefit, accelerating the evaluation of selepressin while mitigating risks to patients and sponsor through use of response-adaptive randomization, a novel registration endpoint, prespecified futility stopping rules, and a large sample size. Clinical Trial registered with www.clinicaltrials.gov (NCT02508649).
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PMID:Rationale and Design of an Adaptive Phase 2b/3 Clinical Trial of Selepressin for Adults in Septic Shock. Selepressin Evaluation Programme for Sepsis-induced Shock-Adaptive Clinical Trial. 2938 15

From 1st January to 31st December 2015, 31 Australian institutions participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2015 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 1,009 unique episodes of bacteraemia investigated, 95.4% were caused by either E. faecalis (55.7%) or E. faecium (39.6%). Ampicillin resistance was detected in 0.2% of E. faecalis and in 86.0% of E. faecium. Vancomycin non-susceptibility was reported in 0.4% and 50.1% of E. faecalis and E. faecium respectively. Overall 56.2% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 61.0% harboured vanB genes and 36.8% vanA genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 49 multilocus sequence types (STs) of which 85.6% of isolates were classified into 11 major STs containing five or more isolates. All major STs belong to clonal cluster 17, a major hospital-adapted polyclonal E. faecium cluster. Four of the five predominant STs (ST796, ST555, ST203, and ST80) were found across most regions of Australia. The second most predominant clone was non-typable by multilocus sequence typing and found only in NSW and the ACT. Overall 73.9% of isolates belonging to the five predominant STs harboured vanA or vanB genes. In conclusion, the AESOP 2015 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium which have limited treatment options.
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PMID:Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme(AESOP) Annual Report 2015. 3062 5

From 1st January to 31st December 2016, 32 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2016 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the E. faecium isolates. Of the 1,058 unique episodes of bacteraemia investigated, 95.2% were caused by either E. faecalis (56.2%) or E. faecium (39.0%) Ampicillin resistance was detected in 0.2% of E. faecalis and in 91.5% of E. faecium. Vancomycin non-susceptibility was reported in 0.3% and 47.7% of E. faecalis and E. faecium respectively. Overall, 49.3% of E. faecium harboured vanA or vanB genes. For the vanA/B positive E. faecium isolates, 55.2% harboured vanB genes and 42.8% vanA genes, 2% harboured vanA and vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is significantly higher than that seen in most European countries. E. faecium consisted of 48 multilocus sequence types (STs) of which 90.2% of isolates were classified into 13 major STs containing 5 or more isolates. All major STs belong to clonal cluster (C) 17, a major hospital-adapted polyclonal E. faecium cluster. Four of the 6 predominant STs (ST17, ST796, ST80 and ST203) were found across most regions of Australia. The most predominant clone ST1421 (previously known as M-type 1) does not have a pstS housekeeping gene and was found in NSW, the ACT and Victoria. This clone was first described in ASSOP 2015. Overall 74% of isolates belonging to the 6 predominant STs harboured vanA or vanB genes. The AESOP 2016 has shown enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA or vanB E. faecium which have limited treatment options.
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PMID:Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme (AESOP) Annual Report 2016. 3063 59