Bactericidal Activity

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Mirian Michelle Machado Depaula - One of the best experts on this subject based on the ideXlab platform.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Samarah V Harb, Nicole J Bassous, Bartolomeu C Viana
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on the combination of three different polymers polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Moreover, they were able to significantly reduce gram-positive, negative, and MRSA bacteria mainly after UV photocrosslinking (PCL:PEG:GelMa-UV). Furthermore, we performed a series of study for gaining a better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. Furthermore, the in vivo subcutaneous implantation performed in rats confirmed the biocompatibility of our designed scaffolds.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Bartolomeu C Viana, Samarah V Harb, Nicole J Bassous, Thomas J Webster, Anderson Oliveira Lobo
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Our developed scaffolds were thus able to significantly reduce gram-positive, negative, and MRSA bacteria. Furthermore, we performed a series of study for better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. In summary, we have demonstrated the design and generation of electrospun fibers with improved hydrophilicity and efficient Bactericidal Activity without the association of any antibiotics.

Andreas H Diacon - One of the best experts on this subject based on the ideXlab platform.

  • greater early Bactericidal Activity at higher rifampicin doses revealed by modeling and clinical trial simulations
    2018
    Co-Authors: Robin J Svensson, Andreas H Diacon, Elin M Svensson, Rob E Aarnoutse, Rodney Dawson, S H Gillespie, Mischka Moodley, Martin J Boeree, Ulrika S H Simonsson
    Abstract:

    Background. The currently recommended rifampicin dose (10 mg/kg) for treating tuberculosis is suboptimal. The PanACEA HIGHRIF1 trial evaluated the pharmacokinetics and early Bactericidal Activity o ...

  • phase ii dose ranging trial of the early Bactericidal Activity of pa 824
    2012
    Co-Authors: Andreas H Diacon, P R Donald, A Venter, Rodney Dawson, Kim Narunsky, Christo Van Niekerk, Jeannine Du Bois, Ngozi Erondu, Ann M Ginsberg, Piet J Becker
    Abstract:

    PA-824 is a novel nitroimidazo-oxazine under evaluation as an antituberculosis agent. A dose-ranging randomized study was conducted to evaluate the safety, tolerability, pharmacokinetics, and early Bactericidal Activity of PA-824 in drug-sensitive, sputum smear-positive adult pulmonary-tuberculosis patients to find the lowest dose giving optimal Bactericidal Activity (EBA). Fifteen patients per cohort received oral PA-824 in doses of 50 mg, 100 mg, 150 mg, or 200 mg per kg body weight per day for 14 days. Eight subjects received once-daily standard antituberculosis treatment with isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) as a positive control. The primary efficacy endpoint was the mean rate of decline in log CFU of Mycobacterium tuberculosis in sputum incubated on agar plates from serial overnight sputum collections, expressed as log10 CFU/day/ml sputum (± standard deviation). The mean 14-day EBA of HRZE was consistent with previous studies (0.177 ± 0.042), and that of PA-824 at 50 mg, 100 mg, 150 mg, and 200 mg was 0.063 ± 0.058, 0.091 ± 0.073, 0.078 ± 0.074, and 0.112 ± 0.070, respectively. Although the study was not powered for testing the difference between arms, there was a trend toward significance, indicating a lower EBA at the 50-mg dose. Serum PA-824 levels were approximately dose proportional with respect to the area under the time-concentration curve. All doses were safe and well tolerated with no dose-limiting adverse events or clinically significant QTc changes. A dose of 100 mg to 200 mg PA-824 daily appears to be safe and efficacious and will be further evaluated as a component of novel antituberculosis regimens for drug-sensitive and drug-resistant tuberculosis.

  • early Bactericidal Activity and pharmacokinetics of pa 824 in smear positive tuberculosis patients
    2010
    Co-Authors: Andreas H Diacon, P R Donald, A Venter, Rodney Dawson, M Hanekom, Kim Narunsky, Stefan J Maritz, Christo Van Niekerk, Karl Whitney, Doris J Rouse
    Abstract:

    PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis (TB) therapy. This randomized study evaluated safety, tolerability, pharmacokinetics, and extended early Bactericidal Activity of PA-824 in drug-sensitive, sputum smear-positive, adult pulmonary tuberculosis patients. Fifteen patients per cohort received 1 of 4 doses of oral PA-824: 200, 600, 1,000, or 1,200 mg per day for 14 days. Eight subjects received once daily standard antituberculosis treatment as positive control. The primary efficacy endpoint was the mean rate of change in log CFU of Mycobacterium tuberculosis in sputum incubated on agar plates from serial overnight sputum collections, expressed as log10 CFU/day/ml (± standard deviation [SD]). The drug demonstrated increases that were dose linear but less than dose proportional in serum concentrations in doses from 200 to 1,000 mg daily. Dosing of 1,200 mg gave no additional exposure compared to 1,000 mg daily. The mean daily CFU fall under standard treatment was 0.148 (±0.055), consistent with that found in previous studies. The mean daily fall under PA-824 was 0.098 (±0.072) and was equivalent for all four dosages. PA-824 appeared safe and well tolerated; the incidence of adverse events potentially related to PA-824 appeared dose related. We conclude that PA-824 demonstrated Bactericidal Activity over the dose range of 200 to 1,200 mg daily over 14 days. Because maximum efficacy was unexpectedly achieved at the lowest dosage tested, the Activity of lower dosages should now be explored.

  • the early Bactericidal Activity of anti tuberculosis drugs a literature review
    2008
    Co-Authors: P R Donald, Andreas H Diacon
    Abstract:

    Quantification of mycobacteria in sputum from pulmonary tuberculosis patients has been used to evaluate patient's response to treatment since the earliest days of anti-tuberculosis chemotherapy. More recently the early Bactericidal Activity (EBA) of anti-tuberculosis agents, measured as the fall in viable colony forming units of Myco-bacterium tuberculosis in sputum early in therapy, has been shown to be an objective, repeatable measure of the ability of an agent to kill the metabolically active bacilli found in the sputum of patients with sputum microscopy smear-positive pulmonary tuberculosis. EBA offers an opportunity to rapidly demonstrate that a new agent has a detectable anti-tuberculosis effect in a relatively small number of patients, what the most appropriate dose is to take forward to more extensive clinical trials and allows the study of the relationship between pharmacokinetics and Bactericidal Activity and toxicity of the relevant agent.

  • early Bactericidal Activity and pharmacokinetics of the diarylquinoline tmc207 in treatment of pulmonary tuberculosis
    2008
    Co-Authors: Roxana Rustomjee, Andreas H Diacon, J Allen, A Venter, C Reddy, R F Patientia, Thuli Mthiyane, T De Marez, R Van Heeswijk, R Kerstens
    Abstract:

    Tibotec Medicinal Compound 207 (TMC207) is a novel diarylquinoline with a unique mode of action that targets mycobacterial ATP synthase. TMC207 exhibits high in vitro Activity against mycobacterial strains either susceptible or resistant to all first-line and many second-line drugs, including fluoroquinolones, and has shown exceptional in vivo Activity against several mycobacterial species in different animal models. In this early Bactericidal Activity study, 75 treatment-naive patients with smear-positive pulmonary tuberculosis were randomized to once-daily oral TMC207 (25 mg, 100 mg, or 400 mg), 600 mg rifampin (RIF), or 300 mg isoniazid (INH) for 7 days. Sixteen-hour overnight sputum collected at baseline and on each treatment day was plated in serial dilutions on selective agar plates. The Bactericidal Activity was expressed as the log(10) decrease in CFU/ml sputum/day. Pharmacokinetic sampling was performed on day 7 of TMC207 administration up to 24 h postdose. The decreases in log(10) CFU counts (+/- standard deviation) from baseline to day 7 were 0.04 +/- 0.46 for 25 mg TMC207 (n = 14), 0.26 +/- 0.64 for 100 mg TMC207 (n = 14), 0.77 +/- 0.58 for 400 mg TMC207 (n = 14), 1.88 +/- 0.74 for INH (n = 11), and 1.70 +/- 0.71 for RIF (n = 14). Significant Bactericidal Activity of 400 mg TMC207 was observed from day 4 onward and was similar in magnitude to those of INH and RIF over the same period. The pharmacokinetics of TMC207 were linear across the dose range. In summary, TMC207 demonstrated Bactericidal Activity with a delayed onset and was well tolerated, and no study drug-related serious adverse events occurred.

Bartolomeu C Viana - One of the best experts on this subject based on the ideXlab platform.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Samarah V Harb, Nicole J Bassous, Bartolomeu C Viana
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on the combination of three different polymers polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Moreover, they were able to significantly reduce gram-positive, negative, and MRSA bacteria mainly after UV photocrosslinking (PCL:PEG:GelMa-UV). Furthermore, we performed a series of study for gaining a better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. Furthermore, the in vivo subcutaneous implantation performed in rats confirmed the biocompatibility of our designed scaffolds.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Bartolomeu C Viana, Samarah V Harb, Nicole J Bassous, Thomas J Webster, Anderson Oliveira Lobo
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Our developed scaffolds were thus able to significantly reduce gram-positive, negative, and MRSA bacteria. Furthermore, we performed a series of study for better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. In summary, we have demonstrated the design and generation of electrospun fibers with improved hydrophilicity and efficient Bactericidal Activity without the association of any antibiotics.

Samson Afewerki - One of the best experts on this subject based on the ideXlab platform.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Samarah V Harb, Nicole J Bassous, Bartolomeu C Viana
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on the combination of three different polymers polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Moreover, they were able to significantly reduce gram-positive, negative, and MRSA bacteria mainly after UV photocrosslinking (PCL:PEG:GelMa-UV). Furthermore, we performed a series of study for gaining a better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. Furthermore, the in vivo subcutaneous implantation performed in rats confirmed the biocompatibility of our designed scaffolds.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Bartolomeu C Viana, Samarah V Harb, Nicole J Bassous, Thomas J Webster, Anderson Oliveira Lobo
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Our developed scaffolds were thus able to significantly reduce gram-positive, negative, and MRSA bacteria. Furthermore, we performed a series of study for better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. In summary, we have demonstrated the design and generation of electrospun fibers with improved hydrophilicity and efficient Bactericidal Activity without the association of any antibiotics.

Samarah V Harb - One of the best experts on this subject based on the ideXlab platform.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Samarah V Harb, Nicole J Bassous, Bartolomeu C Viana
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on the combination of three different polymers polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Moreover, they were able to significantly reduce gram-positive, negative, and MRSA bacteria mainly after UV photocrosslinking (PCL:PEG:GelMa-UV). Furthermore, we performed a series of study for gaining a better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. Furthermore, the in vivo subcutaneous implantation performed in rats confirmed the biocompatibility of our designed scaffolds.

  • understanding the impact of crosslinked pcl peg gelma electrospun nanofibers on Bactericidal Activity
    2018
    Co-Authors: Mirian Michelle Machado Depaula, Paria Ghannadian, Samson Afewerki, Fernanda Roberta Marciano, Bartolomeu C Viana, Samarah V Harb, Nicole J Bassous, Thomas J Webster, Anderson Oliveira Lobo
    Abstract:

    Herein, we report the design of electrospun ultrathin fibers based on polycaprolactone (PCL), polyethylene glycol (PEG), and gelatin methacryloyl (GelMA), and their potential Bactericidal Activity against three different bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the morphology, chemical structure and wettability before and after UV photocrosslinking of the produced scaffolds. Results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation. Our developed scaffolds were thus able to significantly reduce gram-positive, negative, and MRSA bacteria. Furthermore, we performed a series of study for better mechanistic understanding of the scaffolds Bactericidal Activity through protein adsorption study and analysis of the reactive oxygen species (ROS) levels. In summary, we have demonstrated the design and generation of electrospun fibers with improved hydrophilicity and efficient Bactericidal Activity without the association of any antibiotics.