| 1. |
- Le, Ngai Kien, et al.
(författare)
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High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs A multi-centre point prevalence survey
- 2016
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Ingår i: Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0025-7974 .- 1536-5964. ; 95:27
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Tidskriftsartikel (refereegranskat)abstract
- There is scarce information regarding hospital-acquired infections (HAIs) among children in resource-constrained settings. This study aims to measure prevalence of HAIs in Vietnamese pediatric hospitals. Monthly point prevalence surveys (PPSs) in 6 pediatric intensive care units (ICUs) in 3 referral hospitals during 1 year. A total of 1363 cases (1143 children) were surveyed, 59.9% male, average age 11 months. Admission sources were: other hospital 49.3%, current hospital 36.5%, and community 15.3%. Reasons for admission were: infectious disease (66%), noninfectious (20.8%), and surgery/trauma (11.3%). Intubation rate was 47.8%, central venous catheter 29.4%, peripheral venous catheter 86.2%, urinary catheter 14.6%, and hemodialysis/filtration 1.7%. HAI was diagnosed in 33.1% of the cases: pneumonia (52.2%), septicemia (26.4%), surgical site infection (2%), and necrotizing enterocolitis (2%). Significant risk factors for HAI included age under 7 months, intubation and infection at admission. Microbiological findings were reported in 212 cases (43%) with 276 isolates: 50 Klebsiella pneumoniae, 46 Pseudomonas aeruginosa, and 39 Acinetobacter baumannii, with carbapenem resistance detected in 55%, 71%, and 65%, respectively. Staphylococcus aureus was cultured in 18 cases, with 81% methicillin-resistant Staphylococcus aureus. Most children (87.6%) received antibiotics, with an average of 1.6 antibiotics per case. Colistin was administered to 96 patients, 93% with HAI and 49% with culture confirmed carbapenem resistance. The high prevalence of HAI with carbapenem resistant gram-negative strains and common treatment with broad-spectrum antibiotics and colistin suggests that interventions are needed to prevent HAI and to optimize antibiotic use.
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| 2. |
- Nguyen, Phu Hai, et al.
(författare)
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Structure-Activity Relationship Study around Guanabenz Identifies Two Derivatives Retaining Antiprion Activity but Having Lost alpha 2-Adrenergic Receptor Agonistic Activity
- 2014
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 5:10, s. 1075-1082
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Tidskriftsartikel (refereegranskat)abstract
- Guanabenz (GA) is an orally active alpha 2-adrenergic agonist that has been used for many years for the treatment of hypertension. We recently described that GA is also active against both yeast and mammalian prions in an alpha 2-adrenergic receptor-independent manner. These data suggest that this side-activity of GA could be explored for the treatment of prion-based diseases and other amyloid-based disorders. In this perspective, the potent antihypertensive activity of GA happens to be an annoying side-effect that could limit its use. In order to get rid of GA agonist activity at alpha 2-adrenergic receptors, we performed a structure-activity relationship study around GA based on changes of the chlorine positions on the benzene moiety and then on the modifications of the guanidine group. Hence, we identified the two derivatives 6 and 7 that still possess a potent antiprion activity but were totally devoid of any agonist activity at alpha 2-adrenergic receptors. Similarly to GA, 6 and 7 were also able to inhibit the protein folding activity of the ribosome (PFAR) which has been suggested to be involved in prion appearance/maintenance. Therefore, these two GA derivatives are worth being considered as drug candidates.
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| 3. |
- Oumata, Nassima, et al.
(författare)
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The Toll-Like Receptor Agonist Imiquimod Is Active against Prions
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e72112-
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Tidskriftsartikel (refereegranskat)abstract
- Using a yeast-based assay, a previously unsuspected antiprion activity was found for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for clinical applications. The antiprion activity of IQ was first detected against yeast prions [PSI+] and [URE3], and then against mammalian prion both ex vivo in a cell-based assay and in vivo in a transgenic mouse model for prion diseases. In order to facilitate structure-activity relationship studies, we conducted a new synthetic pathway which provides a more efficient means of producing new IQ chemical derivatives, the activity of which was tested against both yeast and mammalian prions. The comparable antiprion activity of IQ and its chemical derivatives in the above life forms further emphasizes the conservation of prion controlling mechanisms throughout evolution. Interestingly, this study also demonstrated that the antiprion activity of IQ and IQ-derived compounds is independent from their ability to stimulate TLRs. Furthermore, we found that IQ and its active chemical derivatives inhibit the protein folding activity of the ribosome (PFAR) in vitro.
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