| 1. |
- Pham, Thi Anh Mai, et al.
(författare)
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Evaluation of screening algorithms to detect rectal colonization with carbapenemase-producing Enterobacterales in a resource-limited setting
- 2024
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Ingår i: JAC - Antimicrobial Resistance. - : OXFORD UNIV PRESS. - 2632-1823. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources.Methods A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR).Results Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases.Conclusions These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible.
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| 2. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 3. |
- Vu, Thi Huyen, et al.
(författare)
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Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:12
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC50) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.
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| 4. |
- Vu, Thi Thanh Huyen
(författare)
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Anti-diabetic effect of gynostemma pentaphyllum tea in type 2 diabetes
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes mellitus (T2D) is a major non-communicable disease and an important health burden worldwide, especially in the developing countries including Vietnam. Gynostemma pentaphyllum has been widely used in Vietnam as a herbal medicine for the prevention and treatment of T2D but the mechanism related to its effects is unknown. This thesis aims to evaluate the anti-diabetic effect and safety of GP extract (tea) in T2D patients and to investigate the major mechanisms of action of GP in T2D patients and in Goto-Kakizaki (GK) rats. The medication was provided as GP tea (dose 6g/day). The studies were implemented on newly diagnosed T2D patients to investigate the anti-diabetic effect of GP tea (Paper I), the effect of GP tea as add-on therapy with sulfonylurea (SU) (Paper II), and the effect of GP tea on insulin sensitivity (Paper III). Effects of GP tea on glucose tolerance and hepatic glucose output (HGO) were studied in GK rats (Paper IV). There was a randomized, placebo-controlled, double blind design for Papers I, II and IV, and a cross-over design for Paper III. Significant anti-diabetic effects and improved insulin sensitivity of GP tea were clearly demonstrated in Paper I. After 12 weeks of treatment, fasting plasma glucose (FPG) levels decreased 3.0 ± 1.8 mmol/l in the GP group, compared to a decrease of 0.6 ± 2.2 mmol/l in the control group (p < 0.01). HbA1C levels decreased approximately 2%-units in the GP group, compared to 0.2%-unit in the controls (p < 0.001). Changes in Homeostasis Model Assessment-Insulin Resistance between baseline and the 12th week indicated that insulin resistance decreased significantly in the GP group (-2.1 ± 3.0) compared with that (+1.1 ± 3.3) in the control group (p < 0.05). As add-on therapy to SU, GP tea further improved glycemic control and this improvement was sustained over 12 weeks (Paper II). After 4 weeks of SU treatment, FPG and HbA1C decreased significantly (p < 0.001). FPG was further reduced after add-on therapy by 2.9 ± 1.7 and 0.9 ± 0.6 mmol/l in the GP and control groups, respectively (p < 0.001). HbA1C levels decreased approximately 2%-units in the add-on GP group compared to 0.7%-units in the controls (p < 0.001). Furthermore, there were potential benefits of maintaining low-dose SU without symptoms of hypoglycemia. The biosecurity of GP tea was suggested clinically, since no hepatotoxicity, nephrotoxicity or other adverse effects were observed in the trials. The GP tea exerted anti-diabetic effects by improving insulin sensitivity, as demonstrated in the placebo-controlled cross-over study using the somatostatin-insulin-glucose infusion test (SIGIT) (Paper III). FPG and steady-state plasma glucose (SIGIT mean) were lower after GP treatment, compared to placebo treatment (p < 0.001). These glycometabolic improvements were achieved without any major change of circulating insulin levels. Finally, oral administration of GP tea for three weeks to GK rats exerted anti-diabetic effects by reducing plasma glucose (PG) levels and suppressing HGO levels significantly (Paper IV). The PG levels decreased from 9.8 ± 0.6 to 6.8 ± 0.4 mmol/L (p = 0.027) in GP- treated rats, whereas PG levels were not significantly decreased in the placebo rats. Glucose tolerance, assessed by an intra-peritoneal glucose tolerance test, was significantly improved in GP-treated rats, compared to placebo-treated group (areas under the glucose curves, AUCs, from 0 to 120 min were 1150 ± 200 vs. 1761 ± 87 mmol/L; p = 0.013). The glucose response in an intra-peritoneal pyruvate tolerance test was significantly lower in the GP group, indicating suppression of gluconeogenesis by GP treatment. In liver perfusions, the AUCs for HGO during 18 min (0-18 min) were significantly decreased in GP-treated rats, compared with control rats (302.8 ± 36.5 vs. 423.5 ± 44.7 μmol, p < 0.05). Three-week GP treatment significantly reduced hepatic glycogen content, but not glycogen synthase activity (p < 0.007), compared to the placebo group. Our studies indicate that GP tea improves glucose tolerance and FPG, most likely by increasing insulin sensitivity and suppressing HGO. GP tea could offer an alternative to the addition of other oral medications in the treatment of T2D patients in Vietnam.
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