scholarly journals Effect of Ertapenem Protein Binding on Killing of Bacteria

2004 ◽  
Vol 48 (9) ◽  
pp. 3419-3424 ◽  
Author(s):  
David E. Nix ◽  
Kathryn R. Matthias ◽  
Emily C. Ferguson
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Protein Binding ◽  
Human Serum ◽  
High Performance ◽  
Enterobacter Cloacae ◽  
Free Drug ◽  
Drug Concentrations ◽  
Kill Rate ◽  
Total Concentrations

ABSTRACT The effect of protein binding on the antimicrobial activity of ertapenem was evaluated using the bacterial kill rate and concentration-response studies. Various proportions of human serum were utilized to determine the total and free-drug concentrations using a validated high-performance liquid chromatography assay. The MICs and kill curves were determined for test isolates of Enterobacter cloacae and Staphylococcus aureus at various percentages of human serum. The killing of bacteria was analyzed in relation to the free and total concentrations of ertapenem at various proportions of human serum. It was determined that unbound ertapenem was responsible for the antimicrobial activity against the test isolates.

scholarly journals Analysis of aristolochlic acids and evaluation of antibacterial activity of Aristolochia clematitis L.

2019 ◽  
Vol 70 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Gergely Sámuel Bartha ◽  
Gergő Tóth ◽  
Péter Horváth ◽  
Eszter Kiss ◽  
Nóra Papp ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Antimicrobial Effect ◽  
Aristolochic Acids ◽  
Microdilution Method ◽  
Stem Leaf ◽  
Ethyl Acetate Extracts

Introduction Several Aristolochia species were used as medicinal herb across Europe and in recent years, their antimicrobial activity has also been investigated. Materials and methods In this study, A. clematitis was selected to evaluate the aristolochic acids I and II (AA I and AA II) concentrations and the antimicrobial activity of methanol, hexane, butanol, and ethyl acetate extracts of the root, stem, leaf, root, and fruit. AA I and AA II contents were measured by a validated high-performance liquid chromatography–ultraviolet method. Results Each fraction of the plant contained AA I and AA II and the root was found to have the highest contents of AA I (1.09%) and AA II (0.7454%). The minimum inhibitory concentrations of all extracts were determined by standard microdilution method. The fruit’s extracts showed the most efficient antimicrobial effect against both methicillin sensitive and resistant Staphylococcus aureus strains. Conclusion Correlation between the AA I and AA II concentrations and the antimicrobial effect was not found.

Kinetics of protein binding determine rates of uptake of drugs by brain

1986 ◽  
Vol 251 (6) ◽  
pp. R1212-R1220 ◽  
Author(s):  
P. J. Robinson ◽  
S. I. Rapoport
Keyword(s):  
Protein Binding ◽  
Rate Constants ◽  
Plasma Proteins ◽  
Numerical Solutions ◽  
Free Drug ◽  
Arterial Blood ◽  
Drug Concentrations ◽  
Analytical Expressions ◽  
Kinetics Of ◽  
The Brain

A mathematical model describing the kinetics of binding and release of substances by plasma proteins is presented. The effects of protein binding on the uptake of substances such as drugs from the capillary network of the brain are discussed. The model assumes equilibration between bound and free forms of drug in arterial blood and incorporates the on-off rate constants for the drug-protein complex and rate constants for passage of free drug across the blood-brain barrier and for drug metabolism in the brain. Regional cerebral blood flow and the related capillary transit time are important parameters in the model. Analytical expressions for bound and free drug concentrations and for the net extraction of drug are derived where practicable, and numerical solutions also are presented. Effects of changes in the total drug and protein concentrations in the plasma are discussed with special reference to the uptake of bilirubin by the brain.

High performance liquid chromatography methods for studying protein binding of aluminium in human serum in the absence and in the presence of desferrioxamine

1990 ◽  
Vol 189 (1) ◽  
pp. 69-79 ◽  
Author(s):  
J.Ignacio García Alonso ◽  
Angeles López García ◽  
Juan Pérez Parajón ◽  
Elisa Blanco González ◽  
Alfredo Sanz Medel ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Protein Binding ◽  
Human Serum ◽  
High Performance

scholarly journals Pharmacokinetic-Pharmacodynamic Relationships Describing the Efficacy of Oritavancin in Patients with Staphylococcus aureus Bacteremia

2006 ◽  
Vol 50 (3) ◽  
pp. 994-1000 ◽  
Author(s):  
Sujata M. Bhavnani ◽  
Julie A. Passarell ◽  
Joel S. Owen ◽  
Jeffrey S. Loutit ◽  
Steven B. Porter ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Odds Ratio ◽  
Regression Tree ◽  
Bloodstream Infections ◽  
Free Drug ◽  
Classification And Regression Tree ◽  
Population Pharmacokinetic ◽  
Dose Selection ◽  
Staphylococcus Aureus Bacteremia ◽  
Drug Concentrations

ABSTRACT Bloodstream infections due to antimicrobial-resistant Staphylococcus aureus occur with increasing frequency and represent an important cause of morbidity and mortality. To date, the evaluation of pharmacokinetic-pharmacodynamic relationships for efficacy among patients with bacteremia has been limited. The objectives of these analyses were to evaluate relationships between microbiological and clinical responses for patients with S. aureus bacteremia and exposures for oritavancin, a novel bactericidal glycopeptide in development. Bayesian oritavancin exposure predictions, following treatment with 5, 6.5, 8, or 10 mg/kg of body weight/day, were derived using a validated population pharmacokinetic model for 55 patients with S. aureus bacteremia. Using classification and regression tree analysis, a breakpoint of the percentage of the dosing interval duration for which free-drug concentrations were above the MIC (free-drug % time > MIC) of 22% was identified for microbiological response; the probabilities of success greater than or equal to and less than this value were 93% and 76%, respectively. Using logistic regression, a relationship was found between microbiological response and free-drug % time > MIC (odds ratio = 4.42, P = 0.09, and odds ratio = 8.84, P = 0.05, when one patient, a medical outlier, was excluded). A similar relationship was found for clinical response. These results will be valuable in supporting dose selection of oritavancin for patients with S. aureus bacteremia.

scholarly journals Comparison of the Activity of a Human Simulated, High-Dose, Prolonged Infusion of Meropenem against Klebsiella pneumoniae Producing the KPC Carbapenemase versus That against Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

2009 ◽  
Vol 54 (2) ◽  
pp. 804-810 ◽  
Author(s):  
Catharine C. Bulik ◽  
Henry Christensen ◽  
Peng Li ◽  
Christina A. Sutherland ◽  
David P. Nicolau ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
High Performance ◽  
Resistance Mechanisms ◽  
Free Drug ◽  
Pharmacodynamic Model ◽  
High Dose ◽  
Prolonged Infusion ◽  
Drug Concentrations

ABSTRACT We have previously demonstrated that a high-dose, prolonged-infusion meropenem regimen (2 g every 8 h [q8h]; 3-hour infusion) can achieve 40% free drug concentration above the MIC against Pseudomonas aeruginosa with MICs of ≤16 μg/ml. The objective of this experiment was to compare the efficacy of this high-dose, prolonged-infusion regimen against carbapenemase-producing Klebsiella pneumoniae isolates with the efficacy against P. aeruginosa isolates having similar meropenem MICs. An in vitro pharmacodynamic model was used to simulate human serum concentrations. Eleven genotypically confirmed K. pneumoniae carbapenemase (KPC)-producing isolates and six clinical P. aeruginosa isolates were tested for 24 h, and time-kill curves were constructed. High-performance liquid chromatography (HPLC) was used to verify meropenem concentrations in each experiment. Meropenem achieved a rapid ≥3 log CFU reduction against all KPC isolates within 6 h, followed by regrowth in all but two isolates. The targeted %fT>MIC (percent time that free drug concentrations remain above the MIC) exposure was achieved against both of these KPC isolates (100% fT>MIC versus MIC = 2 μg/ml, 75% fT>MIC versus MIC = 8 μg/ml). Against KPC isolates with MICs of 8 and 16 μg/ml that did regrow, actual meropenem exposures were significantly lower than targeted due to rapid in vitro hydrolysis, whereby targeted %fT>MIC was reduced with each subsequent dosing. In contrast, a ≥3 log CFU reduction was maintained over 24 h for all Pseudomonas isolates with meropenem MICs of 8 and 16 μg/ml. Although KPC and P. aeruginosa isolates may share similar meropenem MICs, the differing resistance mechanisms produce discordant responses to a high-dose, prolonged infusion of meropenem. Thus, predicting the efficacy of an antimicrobial regimen based on MIC may not be a valid assumption for KPC-producing organisms.

Chemical Composition and Antimicrobial Activity of Salvia x jamensis Essential Oil

2012 ◽  
Vol 7 (9) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Daniele Fraternale ◽  
Guido Flamini ◽  
Angela Bisio ◽  
Maria Cristina Albertini ◽  
Donata Ricci
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Chemical Composition ◽  
Essential Oil ◽  
Bacillus Cereus ◽  
Enterobacter Cloacae ◽  
Caryophyllene Oxide ◽  
First Report

This is the first report about the composition of the essential oil of Salvia x jamensis. The major compounds identified by GC-MS were β-caryophyllene (14.8 %), β-pinene (6.8 %), caryophyllene oxide (6.0 %), δ-cadinene (5.5 %), α-pinene (5.2 %) and spatulenol (5.2 %). The oil showed antimicrobial activity against three Gram (+) bacteria: Bacillus cereus, Staphylococcus aureus, and S. epidermidis, and three Candida strains: C. albicans, C. glabrata and C. tropicalis, while it was inactive against three Gram (-) bacteria: Pseudomonas aeruginosa, Escherichia coli and Enterobacter cloacae.

The First Report on Pharmacokinetic/Pharmacodynamic Study of Trimethoprim/Sulfamethoxazole against Staphylococcus aureus with a Neutropenic Murine Thigh Infection Model

Chemotherapy ◽  
2019 ◽  
Vol 64 (5-6) ◽  
pp. 224-232
Author(s):  
Mao Hagihara ◽  
Hideo Kato ◽  
Shinya Uchida ◽  
Rieko Yamashita ◽  
Shimako Tanaka ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Plasma Concentrations ◽  
Fixed Ratio ◽  
Infection Model ◽  
Healthcare Settings ◽  
Single Dosage

Introduction: With an increase in the incidence of Staphylococcus aureus infections in the healthcare settings and in the community, trimethoprim/sulfamethoxazole (TMP/SMX) has been suggested as a convenient treatment option. However, the appropriate dosage regimen of TMP/SMX is unclear. Objective: This study aimed to examine the pharmacokinetics/pharmacodynamics (PK/PD) of TMP/SMX against S. aureus using a neutropenic murine thigh infection model. Methods: Five S. aureus isolates with TMP/SMX (1:5 fixed ratio) minimum inhibitory concentrations (MICs) of 0.032–64 μg/mL were tested. The antimicrobial efficacy of TMP/SMX (1–689 mg/kg/day: dose shown as SMX dosage) was calculated as the change in bacterial density after 24 h of treatment. The plasma concentrations of TMP/SMX were detected using high-performance liquid chromatography. Results: After TMP/SMX single dose (130 mg/kg), the half-life, area under the blood concentration curve (AUC0–∞), and the protein binding ratio of SMX were 1.5 h, 718.2 μg h/mL, and 73.0 ± 8.3%, respectively. The free AUC/MIC and free %time (%T) above the MIC of SMX were better correlated with the in vivo antimicrobial activity than Cmax/MIC (free AUC/MIC, R2 = 0.69; free %T > MIC, R2 = 0.71; free Cmax/MIC, R2 = 0.53). The distributed doses (2–3 times per day) of TMP/SMX (130, 260, and 390 mg/kg/day) showed higher antimicrobial activity than the single dosage. However, TMP/SMX did not show its antimicrobial activity at <100% free %T > MIC. Conclusions: The TMP/SMX treatment demonstrated that the free AUC/MIC of SMX was the better predictor of the PK/PD index of TMP/SMX.

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