Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Pediatric Patients During Extracorporeal Membrane Oxygenation: A Systematic Review.

PURPOSE: Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exist for antimicrobial dosing adjustments in patients requiring extracorporeal membrane oxygenation (ECMO) therapy, particularly in the pediatric population. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill neonates and children requiring ECMO therapy. METHODS: Medline, EMBASE, Global Health and All EBM Reviews databases were queried. Grey literature was examined. All clinical studies reporting PK/PD parameters of antimicrobials in critically ill pediatric patients treated with ECMO were included, except for case reports and congress abstracts. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently extract data and evaluate the methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK reporting guidelines. Patient and study characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Broad dosing recommendations were formulated based on the available data for specific antimicrobials. RESULTS: Twenty-nine clinical studies were included; most were observational and uncontrolled. Patient characteristics and co-treatments were often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the drugs and population studied. It was only possible to formulate dosing recommendations for a few antimicrobials given the paucity of data, its overall low quality and heterogeneity in reporting. CONCLUSION: Limited data exists on the PK/PD of antimicrobials during ECMO therapy in the pediatric population. Rigorously designed population PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring this therapeutic modality. The use of therapeutic drug monitoring for antimicrobials in pediatric patients on ECMO should be encouraged to optimize dosing. TRIAL REGISTRY: PROSPERO registration number: CRD42018099992 (Registered: July 24th 2018).

The anti-inflammatory activity of the compounds isolated from Dichroa febrifuga leaves.

Dichroa febrifuga Lour. is a traditional medicinal herb that has been applied in the treatment of malaria and some other infectious diseases. Studies recently have focused on the anti-inflammation of the extracts of Dichroa febrifuga Lour. although there have not many reports about which compounds play the essential role. Therefore, in this study, we isolated hydrangenoside C (1), isoarborinol (2), and methyl 1,3,4,6-tetra-O-acetyl-fructofuranoside (3) from the leaves of Dichroa febrifuga. Subsequently, the anti-inflammatory property of 1-3 was assessed using an in vivo assay of edema mouse model which was induced by carrageenan. Out of the three, 2 inhibited the edema effectively and dose-dependently, similarly to diclofenac while there was no obvious activity observed in 1 and 3. The in silico results demonstrated that 2 enables binding to 5-LOX and PLA2 via generating h-bonds. This is the first study to mention the anti-inflammation of 2 in Dichroa febrifuga Lour., and would be a contribution to further studies to elucidate the promising bioactivities of this compound.

Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Adults During Extracorporeal Membrane Oxygenation: A Systematic Review.

PURPOSE: Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for antimicrobial dosing adjustments in patients requiring extracorporporeal membrane oxygenation (ECMO) therapy. A systematic review was conducted to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill adult patients requiring ECMO. METHODS: Medline, EMBASE, Global Health, and All EBM Reviews databases were searched. Grey literature was examined. All studies reporting PK/PD parameters of antimicrobials in critically ill adults treated with ECMO were included, except for case reports and congress abstracts. Ex vivo studies were included. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently abstract data and evaluate methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK guidelines. Patients' and studies' characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Dosing recommendations were formulated based on data from controlled studies. RESULTS: Thirty-two clinical studies were included; most were observational and uncontrolled. Fourteen ex vivo studies were analysed. Information on patient characteristics and co-treatments was often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the studied drugs. Few dosing recommendations could be formulated given the lack of good quality data. CONCLUSION: Limited data exist on the PK/PD of antimicrobials during ECMO therapy. Rigorously designed and well powered populational PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring ECMO support. PROSPERO REGISTRATION NUMBER: CRD42018099992 (Registered: July 24th 2018).

Antioxidant and Antimicrobial Activities of the Extracts from Different Garcinia Species.

BACKGROUND: Garcinia is a large genus which has promising bioactivities. However, the properties of many Garcinia species have not been investigated thoroughly. AIM: To determine the antioxidant and antimicrobial capabilities of the extracts from different Garcinia species. Methodology. Six Garcinia species, including Garcinia fusca, Garcinia hopii, Garcinia planchonii, Garcinia nigrolineata, Garcinia gaudichaudii, and Garcinia tinctoria were extracted using n-hexane, ethyl acetate, and methanol, producing n-hexane extract (HE), ethyl acetate extract (EAE), and methanol extract (ME). After that, the total polyphenol content was evaluated using Folin-Ciocalteu assay. DPPH, hydroxyl radical scavenging, and total antioxidant capacity assays were performed to test the antioxidant activity. Subsequently, the antimicrobial activities against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains were assessed using Kirby Bauer and the broth microdilution methods. RESULTS: Many Garcinia extracts contained high total polyphenol content consisting of ME of G. hopii ad G. tinctoria, and EAE of G. planchonii and G. tinctoria. The EAE of G. tinctoria showed effective antioxidant capacity (IC50 = 1.5 µg/mL). Additionally, the EAE of G. gaudichaudii was effective against Gram-positive bacteria with minimal inhibition concentration (MIC) of 15.625-25 µg/mL whereas ME of G. planchonii was effective against both Gram-positive bacteria (MIC = 160 µg/mL) and Gram-negative bacteria (MIC = 75 µg/mL). CONCLUSION: Several extracts of Garcinia species demonstrated valuable antioxidant and antimicrobial properties.

Anti-Inflammatory and Antimicrobial Activities of Compounds Isolated from Distichochlamys benenica.

Distichochlamys benenica is a native black ginger that grows in Vietnam. In point of fact, there is limitation of available information in the literature making mention of the chemical constituents and bioactive properties of this plant. This study is aimed at isolating trans-o-coumaric acid (1), trans-cinnamic acid (2), and borneol (3) from the rhizomes of D. benenica Q.B.Nguyen & Skornick and evaluate the anti-inflammatory and antimicrobial activities of 1-3 using the carrageenan paw edema model and the dilution broth method, respectively. This revealed that 1 was as effective as diclofenac in reducing the intensity of the edema development. The in silico research showed that the activity of 1 might be derived from inhibiting COX-2 by generating h-bonds at the positions of Arg 120, Tyr 355, and Arg 513 residues. The antimicrobial activities against Gram-positive strains (Staphylococcus aureus and Bacillus subtilis) were comparable, with the minimum inhibitory concentrations ranging from 1.52 to 3.37 mM. This is the first study of the bioactivity of compounds isolated from D. benenica Q.B.Nguyen & Skornick. Our results suggest that 1 may be a nature-derived compound which demonstrates the anti-inflammatory properties and inhibit the proliferation of several Gram-positive bacteria.

Thrombotic Microangiopathy in a Pregnant Woman With Kidney Transplantation: A Case Report.

BACKGROUND: The differential diagnosis of thrombotic microangiopathy (TMA) in pregnancy includes common conditions, such as preeclampsia. In women with kidney transplantation, additional causes of TMA must be considered. CASE: A 22-year-old primigravid woman with a transplanted kidney presented with fetal growth restriction, hypertension, acute kidney injury, and hemolysis at 28 weeks gestation. While her clinical presentation was initially consistent with preeclampsia, hemolysis persisted beyond 1 week postpartum. Diagnoses of TMA associated with tacrolimus and antibody-mediated rejection were considered. An elevated tacrolimus level likely contributed to her TMA and a decrease in dosage improved her clinical picture and laboratory markers. CONCLUSION: We report the case of a pregnant kidney transplant recipient with TMA. A multidisciplinary approach is required to optimize the maternal health outcomes in this complex population.

Vernolide-A and Vernodaline: Sesquiterpene Lactones with Cytotoxicity against Cancer.

Vernolide-A and vernodaline are sesquiterpene lactones isolated from genera of Vernonia. Vernolide-A and vernodaline have shown promising therapeutic properties, including antibacterial, antihelminth, and antioxidant activities. Recently, the anticancer properties of these sesquiterpene lactones have been investigated with the elucidation of effects on cell proliferation, metastasis, angiogenesis, and apoptosis. The antiproliferation and antimetastatic activities arise from targeting extracellular signal-regulated kinase 1 (ERK-1), extracellular signal-regulated kinase 2 (ERK-2), nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase 2 (MMP-2), and matrix metalloproteinase 9 (MMP9). The induction of apoptosis is due to the enhancement of caspase 9, caspase 3, while inhibition of Bcl-2 and Bcl-xL results in the release of cytochrome c into the cytosol. The activity of vernolide-A and vernodaline is hypothesized to be due to thiol reactivity through the α-methylene-γ-lactone group of sesquiterpene lactones. This review will give a brief summary of the anticancer activity of vernolide-A and vernodaline and provide information on the underlying molecular mechanisms.

Effects of palladium on the optical and hydrogen sensing characteristics of Pd-doped ZnO nanoparticles.

The effect of palladium doping of zinc oxide nanoparticles on the photoluminescence (PL) properties and hydrogen sensing characteristics of gas sensors is investigated. The PL intensity shows that the carrier dynamics coincides with the buildup of the Pd-related green emission. The comparison between the deep level emission and the gas sensing response characteristics allows us to suggest that the dissociation of hydrogen takes place at PdZn-vacancies ([Pd (2+)(4d(9))]). The design of this sensor allows for a continuous monitoring in the range of 0-100% LEL H2 concentration with high sensitivity and selectivity.