françois Jehl

CHRU de Strasbourg | CHRU strasbourg · Microbiology

Background and Objective Daptomycin has been recommended in the treatment of bone and joint infection. Previous work showed that the approved dosage of daptomycin may be insufficient to achieve optimal exposure in patients with bone and joint infection. However, those studies assumed that bone exposure was similar to steady-state daptomycin-free pl...

Data demonstrating that antibiotics administered intraoperatively in patients with surgical revision for periprosthetic joint infection achieve concentrations exceeding minimal inhibitory concentrations of the identified bacteria at the surgical site when the new implant is inserted are lacking. We prospectively included patients with periprostheti...

Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover t...

Introduction Dans la prise en charge des infections chroniques de PTH/PTG avec changement de prothèse en un temps, aucune recommandation ne précise quand l’antibiothérapie probabiliste doit couvrir les BGN en plus des cocci à gram positif (CGP). L’objectif de notre travail est de définir des critères permettant de cibler les patients nécessitant un...

The disk diffusion test is very popular but for anaerobes the main pitfalls arise from the significant variation of diameters for an individual MIC and the weak correlation observed between the MIC's values and diameters zone that generates many major and very major errors. Aims of the study without any change in the methodology and revisiting onl...

Objectives: Daptomycin has shown clinical efficacy in diabetic foot infections (DFI). However, only limited data are available on its bone penetration in this particular population. The aim of this study was to determine daptomycin bone concentrations in patients with DFI undergoing surgery after multiple daptomycin infusions and to determine bone...

Bacterial biofilms are highly recalcitrant to antibiotic therapies due to multiple tolerance mechanisms. The involvement of Pseudomonas aeruginosa in a wide range of biofilm-related infections often leads to treatment failures. Indeed, few current antimicrobial molecules are still effective on tolerant sessile cells. In contrast, studies increasing...

Cystic fibrosis (CF) patients are predisposed to chronic colonization of the major airways by Pseudomonas aeruginosa biofilms. Pulmonary infections, involving sessile bacteria, are the main cause of morbidity and mortality. As the eradication of antibiotic-resistant biofilms remains impossible, one key objective for the treatment of lung infections...

Objective: To describe the clinical presentation and 1-year follow-up of patients with bone and joint infections (BJIs) caused by Staphylococcus lugdunensis and evaluate its biofilm-forming capacities. Patients and methods: Overall, 28 patients with BJIs from VISLISI clinical trials were included. We evaluated 1-year clinical follow-up and analy...

Currently, few techniques are available for the evaluation of bacterial biofilm adhesion. These detection tools generally require time for culture and/or arduous handling steps. In this work, the Biofilm Ring Test® (BRT), a new technology, was used to estimate the biofilm formation kinetics of twenty-five strains of Pseudomonas aeruginosa , isolat...

Daptomycin exhibits excellent antibacterial activity against a wide range of Gram-positive bacteria. The on-label standard daily doses for daptomycin are 4mg/kg for skin infections and 6mg/kg for bacteraemia or right-sided endocarditis. Daptomycin bactericidal activity is predominantly concentration-dependent and by considering the values of pharma...

Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 20...

Macrophages are key-cells in the initiation, the development and the regulation of the inflammatory response to bacterial infection. Macrophages are intensively and increasingly recruited in septic joints from the early phases of infection and the infiltration is supposed to regress once efficient removal of the pathogens is obtained. The ability t...

Objectives Mupirocin is the cornerstone of decolonization regimens, a successful strategy to prevent healthcare-associated staphylococcal infections. Several recent studies have reported alarming results: (i) an extending reservoir of mupA, the ancestral mobile resistance gene, among coagulase-negative staphylococci (CoNS); (ii) the emergence of a...

Innate immunity involving antimicrobial peptides represents an integrated and highly effective system of molecular and cellular mechanisms that protects host against infections. One of the most frequent hospital-acquired pathogens, Staphylococcus aureus, capable of producing proteolytic enzymes, which can degrade the host defence agents and tissue...

Enterococcus faecalis (E. faecalis) has become a major leading cause of nosocomial endocarditis. Treatment of such infections remains problematic and new therapeutic options are needed. Nine E. faecalis strains were tested: six obtained from patients presenting endocarditis, one with isolated bacteremia, and two reference strains. Antibiotics inclu...

L’abaissement des concentrations critiques des bêtalactamines a contribué à optimiser leur utilisation. Cela est particulièrement patent pour le couple céphalosporines de troisième et quatrième génération — aztréonam/entérobactéries productrices de bêtalactamases à spectre élargi. L’interprétation phénotypique, qui a prévalu jusqu’en 2011, obligean...

To evaluate the efficacy of intravitreal administration of linezolid (LZD) in a rabbit model of Staphylococcus aureus endophthalmitis. Of 40 rabbits studied, 36 of them received 10(2) colony-forming units (CFU) of S. aureus in their right eye before being randomly assigned to the following groups: four groups of 8 animals received 24 hours after th...

Staphylococcus aureus is a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria,...

Antibiotics pharmacodynamics are descriptive of the bactericidal activity of these drugs or their ability to prevent from the emergence of resistant mutants, in vitro and in vivo. This paper describes the terms of the bactericidal activity of the major families of antibiotics. The pertinent parameters are defined for each family, and the pre-requis...

The pharmacokinetics of linezolid (LZD) was investigated in rabbit eyes after single and multiple oral administrations. Pharmacology Laboratory, University Hospital of Strasbourg, Strasbourg, France. Twelve New Zealand rabbits were divided into 2 groups: an oral dose of 120 mg (35 mg/kg) was administrated in group 1 (n=6), and a multiple-dose proto...

To prospectively evaluate in vivo noninvasive monitoring of antibiotic therapy in experimental infectious arthritis by imaging macrophages by using magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles. The institutional review committee on animal care approved the experimental protocol. Unilateral...

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The objective of our study was to prospectively evaluate macrophage imaging using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI to depict bacterial knee infection in an experimental rabbit model. Unilateral knee infection was induced by intraarticular injection of Staphylococcus aureus in eight rabbits. The contralateral knees were u...

Vitek-2™ AIX versus Vitek-2™ PC have different rules for phenotypic interpretation. The aim of this study is to ensure that the raw results determined by these two versions of Vitek-2™ allow biologists to conclude to the same resistance phenotype, but also to evaluate their own phenotypic interpretation system (advanced expert system). A total of 2...

To evaluate ocular penetration of topically applied linezolid, a new antibiotic agent targeted against gram-positive organisms. Laboratory of Pharmacology, University Hospital of Strasbourg, Strasbourg, France. New Zealand White rabbits were divided into 3 equal groups. One drop of 50 microL (2 mg/mL) linezolid was administrated in Group 1. In Grou...

Posaconazole is a recent triazole antifungal agent currently available in an oral suspension. It is approved in the treatment of various refractory invasive fungal diseases and for prophylaxis in high-risk patients. This review presents the published clinical pharmacokinetic data of posaconazole. Aspects regarding absorption, distribution, eliminat...

This review presents the published data regarding the molecular determinants (enzymes, transporters, orphan nuclear receptors) of fluoroquinolones pharmacokinetics in humans. The clinical impact of these determinants (drug disposition, drug-drug interactions) is also discussed.

To evaluate macrophage imaging using the ability of superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) to differentiate infectious vertebral osteomyelitis and degenerative disk-related inflammatory endplates. The in vivo demonstration of the different distribution of macrophages in those two disorders may allow a more accurate cha...

The recent experimental and clinical data on betalactams pharmacodynamics confirm that the continuous infusion is the best way of administration of these antibiotics. They show a time-dependant bactericidal activity and thus, the key-parameter predictive of their activity is the percent of time that serum concentrations are above the MIC (T > MIC)...

The purpose of this study was to prospectively evaluate USPIO-enhanced MR imaging for the differentiation of vertebral infectious osteomyelitis and sterile inflammation. Vertebral osteomyelitis and sterile vertebral inflammation were induced in two groups of six rabbits each. MRI examinations were performed including unenhanced and gadolinium-enhan...

PURPOSE To prospectively evaluate USPIO enhanced MR imaging for the differentiation of vertebral infectious osteomyelitis and sterile inflammation METHOD AND MATERIALS Infectious vertebral osteomyelitis and sterile vertebral inflammation were induced in two groups of 6 rabbits. MRI examinations were performed in the 12 rabbits twice a week includi...

Most studies show a trend toward a beneficial or at least neutral effect of associating corticosteroids and antibiotics. However, caution must be taken, with various factors considered: the type, virulence, and size of the inoculum, and the treatment chosen. Early intravitreal administration of 400 microg of dexamethasone seems to be beneficial in...

Objective: To investigate the pharmacodynamic disposition of two recently developed β-lactam antibiotics, meropenem and cefpirome, in the Yucatan micropig model, and to compare the bactericidal activity of these drugs against bacteria in this in vitro/ex vivo micropig model after administration by both intermittent injection and continuous infusion...

Background: Achieving high trough of glycopeptides is recommended in MRSA bacteremia since minimum inhibitory concentration (MIC) ≥ 2 mg/l is associated with therapeutic failure. But whether increasing PIQ lead to better outcome has not been evaluated. Methods: We conducted a prospective observational study between 1/10/2003 and 1/4/2006 in adult p...

La majorité des études conclut au rôle bénéfique ou neutre de l’adjonction de corticoïdes au traitement antibiotique habituel. Ces conclusions ne peuvent pourtant pas être généralisées et doivent tenir compte de nombreux facteurs parmi lesquels le type de bactérie, sa virulence, la taille de l’inoculum, de même que du schéma thérapeutique adopté. L...

The aims of this study were to characterize MRI features in percutaneously inoculated spondylodiscitis rabbit models, to evaluate MRI for non-invasive diagnosis, and to assess the incremental information brought by the use of gadolinium-enhanced MR sequences. Under fluoroscopic control, lumbar discs of 12 New Zealand White adult rabbits were inject...

To prospectively evaluate ultrasmall superparamagnetic iron oxide (USPIO) magnetic resonance (MR) imaging for the depiction of macrophages in infected areas of an experimental rabbit vertebral osteomyelitis model. Lumbar vertebral osteomyelitis was induced in 10 rabbits with intradiscal injection of bacteria in a vertebral disk (test level) versus...

Objectifs Les objectifs de notre étude ont été de préciser les anomalies en IRM de la spondylodiscite d’inoculation percutanée dans le modèle expérimental du lapin, d’évaluer la valeur diagnostique de la méthode non invasive qu’est l’IRM et de préciser les informations supplémentaires apportées par l’utilisation des séquences après injection de gad...

Problematique La CMI moyenne des glycopeptides pour Staphylococcus aureus augmente progressivement depuis plusieurs annees et est un facteur de risque de mortalite dans les BSARM lorsqu’elle est ≥ 2 mg/l. Objectif de l’etude Evaluer l’impact des associations d’antibiotiques et du taux serique de glycopeptide sur la mortalite globale en cas de BSARM...

Between 1st January 2005 and 31st December 2005, 232 strains of Streptococcus pneumoniae were collected in the Alsace county from participating laboratories (one from university hospital, 7 from general hospitals and 12 private laboratories) to assess their susceptibility to penicillin and evaluated serogroups of strains. The coordinating centre pe...

This review focuses on the published data regarding the molecular determinants (enzymes, transporters, orphan nuclear receptors) of Catharanthus (vinca) alkaloids pharmacokinetics in humans. The clinical impact of these determinants (drug disposition, drug-drug interactions) is also discussed.

The purpose of the present work was to evaluate the intra-tonsillar concentrations of roxithromycin (ROX), clarithromycin (CLR) and 14-OH-CLR at steady state in children, and then to compare them with their respective MICs against group A Streptococci. It was a monocenter, pharmacokinetic study in children hospitalized for a tonsillectomy and recei...

The purpose of the present work was to evaluate the intra-tonsillar concentrations of roxithromycin (ROX), clarithromycin (CLR) and 14-OH-CLR at steady state in children, and then to compare them with their respective MICs against group A Streptococci. It was a monocenter, pharmacokinetic study in children hospitalized for a tonsillectomy and recei...

Linezolid, a new antistaphylococcal agent for oral or intravenous administration is active against Staphylococcus aureus with limited sensitivity to glycopeptides. The purpose of the present work was to compare data in the literature with practical clinical experience with the use of linezolid for lung infections in adult cystic fibrosis patients w...

Introduction Linezolid, a new antistaphylococcal agent for oral or intravenous administration is active against Staphylococcus aureus with limited sensitivity to glycopeptides. The purpose of the present work was to compare data in the literature with practical clinical experience with the use of linezolid for lung infections in adult cystic fibros...

The authors had for aim to assess, the incidence of symptomatic bacteriuria and the level of antibiotic resistance in bacteria identified in long-term care facilities (LTC). Symptomatic bacteriuria cases were prospectively collected, during 9 months in the two LTC of the Strasbourg French Teaching Hospital (196 beds). One hundred and eleven bacteri...

This review presents the published clinical pharmacokinetic data for the antifungal agent voriconazole. Aspects regarding absorption, tissue distribution, elimination and kinetic interactions are also discussed.

In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to...

Among the numerous parameters that describe the pharmacokinetics of an antibiotic, those inherent to the distribution are among the most important. Several factors may influence the distribution, among which the physico-chemical properties of the antibiotic, and its interactions with plasma and tissues protein matrix play a significant role. The di...

Among the numerous parameters that describe the pharmacokinetics of an antibiotic, those inherent to the distribution are among the most important. Several factors may influence the distribution, among which the physico-chemical properties of the antibiotic, and its interactions with plasma and tissues protein matrix play a significant role. The di...

Background: Problems with the dissemination of guidelines are frequently cited as a major reason for failure to influence clinical practice.We report the results of a time-series impact study of online antibiotic (AB) guidelines on the quality of prescribing for pneumonia in a teaching psychiatric hospital comprising 410 adult beds.Methods: The int...

This review presents the clinical pharmacokinetics of the marketed therapeutic monoclonal antibodies used in oncology. Aspects regarding absorption, tissue distribution, elimination as well as factors influencing pharmacokinetics, pharmacodynamics and kinetic interactions are also discussed.

Background There is virtually no information in the medical literature on the quality of antibiotic prescribing in mental healthcare setting. We report the results of an antibiotic utilization review focused on pneumonia in a university-affiliated psychiatric hospital comprising 410 adult beds.Methods We implemented a computerized system for declar...

Trough serum teicoplanin concentrations were compared in healthy adults following intravenous administration of one of two regimens: (i) 12 mg/kg of body weight every 12 h for 3 doses and then 15 mg/kg every 48 h for 4 doses (n = 16 subjects) or (ii) 6 mg/kg every 12 h for 2 doses and then 6 mg/kg every 24 h for 9 doses (n = 8 subjects). The mean +...

A capillary electrophoresis method with direct UV detection was developed for the determination of fosmidomycin, a promising new anti-malarial drug, in human serum and urine. Optimization of the separation parameters resulted in a buffer system adjusted to pH 10.8 containing a cationic reagent and an organic modifier. Under these conditions, the mi...

The elimination from the blood of any drug and especially of an antibiotic is defined by its elimination half-life. The length of this half-life is then essential for the establishment of the dosing regimen in an antibacterial therapy, concomitantly with tissue diffusion, bactericidal activity, toxicity, and potential post-antibiotic effect.The len...

The elimination from the blood of any drug and especially of an antibiotic is defined by its elimination half-life. The length of this half-life is then essential for the establishment of the dosing regimen in an antibacterial therapy, concomitantly with tissue diffusion, bactericidal activity, toxicity, and potential post-antibiotic effect. The le...

P-glycoprotein is a transmembrane protein involved in drug transport in humans. The gene MDR1 or ABCB1 encoding P-glycoprotein exhibits genetic polymorphism associated with variations of expression of the protein. We review the role of genetic polymorphism in MDR1 in influencing clinical pharmacokinetics of drugs. Finaly, the potential implications...

Bacterial endophthalmitis is a serious complication of ocular surgery and of eye trauma; the leading causative organisms are Staphylococcus aureus strains. Tissue damage is due both to the host inflammatory response and to toxin synthesis by bacteria. Systemic treatment remains difficult because most antibiotics show poor ocular penetration. Moxifl...

Vinorelbine has been shown to be metabolised by CYP3A4 in vitro. To evaluate the impact of CYP3A in the disposition of vinorelbine in vivo, we compared the kinetics of the alkaloid given intravenously alone and combined with rifampin, a potent CYP3A inducer, in the micropig. Four healthy Yucatan micropigs, about 20 kg, received a first infusion of...

The main pharmacokinetic characteristics of teicoplanin and vancomycin are reviewed in this article, particularly the peak and trough serum concentrations obtained according to the various dosage regimen used for both antibiotics. Half-lives are around 10 h (vancomycin) and 100 h (teicoplanin), and the respective protein binding rates are about 50%...

Objectives – The authors wanted to assess the pharmacokinetic/pharmacodynamic parameters of Augmentin® in its pediatric formulation by measuring amoxicillin and clavulanic acid concentration in blood and middle ear fluid.Methods – A multicenter, open pharmacokinetic study, randomized in 5 groups according to sampling time was made on 36 children tr...

Objectives – The authors wanted to assess the pharmacokinetic/pharmacodynamic parameters of Augmentin® in its pediatric formulation by measuring amoxicillin and clavulanic acid concentration in blood and middle ear fluid.Methods – A multicenter, open pharmacokinetic study, randomized in 5 groups according to sampling time was made on 36 children tr...

Objective. – We had for aim to investigate the efficacy of an amoxicillin-clavulanic acid treatment, corresponding to human doses, in E. coli bacteremia producing intermediate level beta-lactamase, in a Yucatan micro pig model.Methods. – We developed an experimental bacteremia model in 15 micro pigs, using one intravenous injection of 4.8 × 109 CFU...

The objective of the present study was to investigate the potential bactericidal activity of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli strains and to elucidate the extent to which enzyme production affects the activity. Six adult Yucatan miniature pigs received a single intravenous dose of 1.1 g of amoxicillin-clavul...

We present a phase I study of a 5-fluorouracil (5FU) and folinic acid combination given at high doses in weekly continuous infusions. The aim of the study was to determine the maximal tolerated dose of 5FU and the encountered toxicities. 5FU was given as a weekly 24 hr continuous infusion at doses between 1.8 and 2.7 g/m 2 . 600 mg/m 2 of calcium f...

In 1995, the emergence of extended-spectrum producing E. aerogenes was noted within various wards of the Strasbourg University Hospital.Objective – Extended-spectrum betalactamases-producing bacteria were then studied because of their therapeutical, ecological, and economical implications for hospitals.Patients and methods – In 1999, we undertook a...

In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sin...

The aim of this study was to specify the characteristics of enterobacterial urinary infections producing wide spectrum beta-lactamase (WSBL) and the management strategies for these patients infected in geriatric wards. The prevalence, bacteriological characteristics and treatment regimens of enterobacterial urinary infections producing WSBL, diagno...

Objectives The aim of this study was to specify the characteristics of enterobacterial urinary infections producing wide spectrum beta-lactamase (WSBL) and the management strategies for these patients infected in geriatric wards, Methods The prevalence, bacteriological characteristics and treatment regimens of enterobacterial urinary infections pro...

The purpose of this study was to investigate and characterize in vitro the post-beta-lactamase inhibitor effect (PLIE) of clavulanic acid against two beta-lactamase-producing species of bacteria. The PLIE was investigated against one strain of Klebsiella pneumoniae and one strain of Haemophilus influenzae. A stationary-phase inoculum of about 107 c...