Nicolas Grégoire

Nicolas Grégoire
Université de Poitiers | UP · Pôle Biologie Santé

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92
Publications
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Publications

Publications (92)
Article
Objectives: To describe the population pharmacokinetics of temocillin administered via continuous versus intermittent infusion in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a rang...
Article
Full-text available
Resistance to colistin, one of the antibiotics of last resort against multidrug-resistant Gramnegative bacteria, is increasingly reported. Notably, MCR plasmids discovered in 2015 have now been reported worldwide in humans. To keep this antibiotic of last resort efficient, a way to tackle this mechanism seems essential. Terpene alcohols such as far...
Article
A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of residues of spiramycin, a macrolide antibiotic, and its active metabolite neospiramycin in cow's milk as well as in minor species ‘milk, goat and ewe. Spiramycin-d3 was used as internal standard for quantification of both ana...
Article
Full-text available
Introduction Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evalu...
Article
Due to the low level of resistance observed with daptomycin, this antibiotic has an important place in the treatment of severe Gram-positive infections. It is the first-in-class of the group of calcium-dependent, membrane-binding lipopeptides, and is a cyclic peptide constituted of 13 amino acids and an n-decanoyl fatty acid chain. The antibacteria...
Article
Objectives To describe the rationale for subcutaneous (SC) administration of antibiotics from available published data and to make propositions to help clinicians in daily practice. Design Narrative review. Setting and Participants Hospitalized patients, persons in long-term care facilities and ambulatory care. Methods We searched the MEDLINE/Pu...
Article
Full-text available
To assess the difference in the fate of the antibiotic colistin (COLI) after its pulmonary delivery as a powder or a solution, we developed a COLI powder and evaluated the COLI pharmacokinetic properties in rats after pulmonary administration of the powder or the solution. The amorphous COLI powder prepared by spray drying was characterized by a ma...
Article
Experiments were conducted with polymyxin B and two Klebsiella pneumonia isogenic strains (the wild-type, KP_WT and its transconjugant carrying the mobile colistin resistance gene, KP_MCR-1), to demonstrate that conducting 2 consecutive time-kill experiments, referred as sequential TK, represents a simple approach to discriminate between PK/PD mode...
Article
Thiamphenicol (TAP) is reported to be effective against many respiratory pathogens including methicillin-resistant Staphylococcus aureus (MRSA). However, its poor solubility in water remains as one of the obstacles hindering the preparation of inhalable TAP formulations. The aim of this study was to improve the dissolution rate of TAP by micronizat...
Article
Full-text available
Objectives: The goal of this study was to expand on previous reports of synergy between polymyxin B and minocycline against Acinetobacter baumannii and gain insights on the qualitative and quantitative determinants of the synergy. Methods: A semi-mechanistic PK/PD model was developed based on data from in vitro time-kill experiments data with de...
Poster
The aim of this study was to describe, by an original approach of sequential time-kill experiments, the role of MCR-1 in the development of additional adaptive resistance to polymyxins in MDR(-) http://phar.labo.univ-poitiers.fr/wp-content/uploads/sites/74/2019/04/ECCMID2019-Poster_Hariyanto_IH_P1383-FINAL.pdf
Article
Objectives: Colistin often remains the last resort antibiotic active against carbapenemase-producing Enterobacteriaceae. However, while the in vitro inoculum effect has been reported, therapeutic relevance of this phenomenon remains questioned. Methods: Ten E. coli strains were used that included the wild-type CFT073 and its transconjugant CFT07...
Article
Objectives Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported i...
Article
Full-text available
Aztreonam‐avibactam (ATM‐AVI) is a promising combination to treat serious infections caused by multidrug‐resistant (MDR) pathogens. Three distinct mechanisms of action have been previously characterized for AVI: inhibition of ATM degradation by β‐lactamases, proper bactericidal effect, and enhancement of ATM bactericidal activity. The aim of this s...
Chapter
All of the small number of studies conducted during the second half of last century to investigate the pharmacokinetics of polymyxins in animals used microbiological methods to quantify the compounds in biological fluids. Those methods generally lacked the accuracy and precision required for such investigations and, in the case of studies involving...
Article
Mycobacterium abscessus is responsible for difficult-to-treat chronic pulmonary infections in humans. Current regimens including parenteral administrations of cefoxitin (FOX) in combination with amikacin and clarithromycin raise compliance problems and are frequently associated with high failure and development of resistance. Aerosol delivery of FO...
Article
Objectives: Cefoxitin is frequently used for surgical antibiotic prophylaxis (SAP). Using microdialysis, we evaluated whether the currently recommended dosing regimen is appropriate to maintain cefoxitin subcutaneous tissue concentrations above the MIC for pathogens involved in abdominal surgical site infection. Methods: Data from eight patients u...
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Full-text available
The aim of this study was to investigate the pharmacokinetics of oseltamivir phosphate, a prodrug, and its active moiety in plasma and lung after its nebulization and intravenous administration, in rats. Only 2% of prodrug was converted into active moiety pre-systematically, attesting to a low advantage of oseltamivir phosphate nebulization suggest...
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Full-text available
Objectives: Checkerboard experiments followed by fractional inhibitory concentration (FIC) index determinations are commonly used to assess in vitro pharmacodynamic interactions between combined antibiotics, but FIC index cannot be determined in case of antibiotic/non-active compound combinations. The aim of this study was to use a simple modelling...
Article
Objectives: The objective of this study was to characterize the pharmacokinetics of unbound and total concentrations of daptomycin in infected ICU patients with various degrees of renal impairment. From these results, the probability of attaining antimicrobial efficacy and the risks of toxicity were assessed. Methods: Twenty-four ICU patients wi...
Article
Full-text available
Amikacin and gentamicin pharmacokinetic behaviors after nebulization were determined by comparing plasma and pulmonary epithelial lining fluid (ELF) concentrations in rats after intra-tracheal and intravenous administrations. ELF areas under concentrations time-curves were 874 and 162 times higher after nebulization than after IV administration for...
Article
Objectives: Optimal dosing for nebulized gentamicin is unknown. We compared the pulmonary and systemic pharmacokinetics (PK) of gentamicin following intravenous and nebulized administration in mechanically ventilated patients. Methods: Twelve critically ill male patients with ventilator-associated pneumonia received a 30 min intravenous infusion...
Article
Full-text available
Colistin is a polymyxin antibiotic used to treat patients infected with multidrug‐resistant Gram negative bacteria (MDR‐GNB). The objective of this work was to develop a whole‐body physiologically based pharmacokinetic (WB‐PBPK) model to predict tissue distribution of colistin in rat. The distribution of a drug in a tissue is commonly characterized...
Article
Full-text available
Purpose: The objective was the development of a whole-body physiologically-based pharmacokinetic (WB-PBPK) model for colistin, and its prodrug colistimethate sodium (CMS), in pigs to explore their tissue distribution, especially in kidneys. Methods: Plasma and tissue concentrations of CMS and colistin were measured after systemic administrations...
Article
An obese woman was treated with oral tedizolid 200 mg once daily for pseudoarthrosis 10 years after Roux-en-Y bypass surgery. Total plasma peak concentration was 2.12 mg/liter 3 h after intake, and area under the concentration-time curve from 0 to 24 h (AUC0-24) was 28.3 mg/liter · h. The AUC0-24/MIC ratio for unbound concentrations and for sensiti...
Article
Objectives: Optimal dosing for nebulized colistin methanesulfonate (CMS), the prodrug of colistin, is unknown. We describe the pulmonary and systemic pharmacokinetics of CMS and colistin following nebulization of 0.5 million IU (MIU) of CMS in ventilated patients. Methods: Twelve critically ill patients received 0.5 MIU of CMS administered every...
Article
In this review, we provide an updated summary on colistin pharmacokinetics and pharmacodynamics. Colistin is an old molecule that is frequently used as last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Colistin is a decapeptide administered either as a prodrug, colistin methanesulfonate (CMS), when used intrav...
Article
A comparative pharmacokinetic study was conducted in rats after intratracheal aerosolization of levofloxacin, as a solution, as immediate-release chitosan microspheres or as sustained-release PLGA microspheres. A pharmacokinetic model was constructed to model levofloxacin concentrations both in plasma and in the lung epithelial lining fluid (ELF)....
Article
The aim of this study was to determine aztreonam (ATM) membrane permeability using Calu-3 cells and its plasma and pulmonary epithelial lining fluid (ELF) pharmacokinetics in rats after intratracheal nebulization and intravenous administration (15 mg · kg-1). ATM exhibits low Calu-3 permeability (0.07 ± 0.02 × 10-6 cm · s-1), and a high area under...
Article
Full-text available
Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to disting...
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Script for simulation with model 2. (MMD)
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Script for simulation with model 5. (MMD)
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Script for simulation with model 6. (MMD)
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Script for estimation with model 1. (CTL)
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Parameter settings for estimation with model 1. (CSV)
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Results for estimation in dynamic conditions. (XLS)
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Parameter settings for estimation with model 2. (CSV)
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Script for estimation with model 4. (CTL)
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Parameter settings for estimation with model 5. (CSV)
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Parameter settings for estimation with model 6. (CSV)
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Script for simulation with model 4. (MMD)
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Script for estimation with model 3. (CTL)
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Parameter settings for estimation with model 3. (CSV)
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Script for estimation with model 6. (CTL)
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Script for simulation with model 1. (MMD)
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Script for simulation with model 3. (MMD)
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Script for estimation with model 2. (CTL)
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Parameter settings for estimation with model 4. (CSV)
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Script for estimation with model 5. (CTL)
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Results for estimation in static conditions. (XLS)
Article
Colistin is increasingly used as a last option for the treatment of severe infections due to Gram negative bacteria, in critically ill patients requiring intermittent haemodialysis (HD) for acute renal failure. Our objective was to characterize the pharmacokinetics (PK) of colistin and its prodrug colistin methanesulphonate (CMS) in this population...
Article
Full-text available
Background: Amitriptyline (AMI) is a lipophilic, tricyclic antidepressant with analgesic properties that could potentially be used for epidural (EPI) analgesia. However, no pharmacokinetic data are available for AMI in spinal spaces. The objective of this study was to evaluate the spinal disposition and intrathecal (IT) bioavailability of AMI afte...
Article
The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin...
Article
We have improved the aerodynamic properties of pyrazinamide loaded large porous particles (PZA-LPPs) designed for pulmonary delivery. To overcome the segregation of the different components occurring during the spray drying process and to obtain homogeneous LPPs, spray drying parameters were modified to decrease the drying speed. As a result, good...
Article
Colistin is an old antibiotic that has recently gained a considerable renew of interest for the treatment of pulmonary infections due to Multi Drug Resistant Gram-negative bacteria. Nebulization seems promising for this application but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS), but differences between intrapul...
Article
Full-text available
Colistin is an old antibiotic that has recently gained a considerable renew of interest as the last line defense therapy against Multi Drug Resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowl...
Article
Full-text available
The aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs): ciprofloxacin (CIP), moxifloxacin (MXF) and grepafloxacin (GRX) after nebulization in rats. Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4 and 6h after FQ intravenous administration and nebulization to estimate epithelial lining flui...
Article
Full-text available
The aim of this study was to determine biopharmaceutical charcateristics of tobramycin (TOB) after nebulization in rats. TOB was administered by intravenous (IV) bolus and intra-tracheal nebulization (3mg.kg(-1)) and concentrations were determined in plasma and epithelial lining fluid (ELF) by LC-MS/MS. TOB ELF over plasma area under the curve (AUC...
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Full-text available
Central nervous system (CNS) antibiotic distribution was described mainly from cerebrospinal fluid data, and only few data exist on brain extracellular fluid concentrations. The aim of this study was to describe brain distribution of cefotaxime (2 g/8 h) by microdialysis in patients with acute brain injury who were treated for a lung infection. Mic...
Article
Colistin is a re-emerging old antibiotic that is used as a salvage treatment against multidrug-resistant Gramnegative infections. Because it is administrated as an inactive prodrug, colistin methanesulfonate (CMS) that undergoes rapid hydrolyze to colistin, pharmacokinetic studies using biological assays are unreliable. With the recent development...
Article
A rifampicin-hydroxypropyl-beta-cyclodextrin (RIF-HPCD) complex solution and two RIF-loaded PLGA microspheres with slow or fast release rates were nebulized into the rat lungs for a comparative biopharmaceutical evaluation. A pharmacokinetic model was applied to model systemic RIF concentrations and to predict the RIF concentrations in the lung epi...
Article
Full-text available
Colistin appears more and more frequently as a last line defense therapy against nosocomial infections due to multi-resistant Gram-negative bacteria (8).…
Article
Full-text available
The aim of this study was to determine the penetration of doripenem administered intravenously into the rabbit aqueous and vitreous humors. Nineteen New Zealand White rabbits received a 20-mg dose of doripenem intravenously over 60 min. Specimens of aqueous humor, vitreous humor, and blood were obtained 30 min (n = 5), 1 h (n = 5), 2 h (n = 5), and...