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Biomedical subjects

F Jehl

Publications and source records attributed to F Jehl.

At least 19 recordsLinked to original sources
PubMed2002

[Urinary tract infections due to wide spectrum beta lactamase producing enterobacteriaceae].

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 producing WSBL, diagnosed in a geriatric department of internal medicine from May 1977 to April 2001, were studied retrospectively. RESULTS: Sixty-six enterobacterial urinary infections producing WSBL were diagnosed, with 53 (80%) of them acquired in the ward. They represented 1.6% of admissions and concerned 24 men and 42 women (sex ratio: 0.57), with a mean age of 87 years. Their prevalence was of 20 in the 1st year, 11 in the 2nd, 9 in the third and 26 in the 4th year. The mean duration of hospitalization of infected patients was 4.5-fold longer (90 vs. 20 days) and the mortality rate 2-fold higher (32 vs. 14%). Enterobacter aerogenes were responsible for half (46%) of the WSBL urinary infections. The skin was invaded by enterobacteria in 67% and the feces in 57% of cases. More than one third of the urinary infections treated relapsed, and digestive decontamination was only efficient in half of the patients treated. CONCLUSION: This 4-year study emphasizes the limits of antibiotherapy in eradicating WSBL-producing enterobacteria and the fact that only the strict respect of hygiene by all caregivers (isolation of patients exhibiting WSBL and washing-disinfection of the hands between each patient) limits the incidence of such infections.

Aged↗
PubMed2001

[Chronic experimental bacteremia in Yucatan micropigs].

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Acute Kidney Injury↗
PubMed2001

Evidence for a true post-beta-lactamase-inhibitor effect of clavulanic acid against Klebsiella pneumoniae and Haemophilus influenzae.

OBJECTIVE: 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. METHODS: The PLIE was investigated against one strain of Klebsiella pneumoniae and one strain of Haemophilus influenzae. A stationary-phase inoculum of about 107 colony-forming units per mL of each bacterium was pre-exposed for 2 h to clavulanic acid, either alone or in combination with amoxicillin at various concentrations. After pre-exposure, the dilution required to remove the beta-lactamase inhibitor was 1:100 or 1:1000 according to the bacterial species and their susceptibilities to clavulanic acid. Bacteria were counted hourly after drug removal, on solid agar medium. RESULTS: Control cultures exposed to amoxicillin alone after dilution, showed a delay in growth, which may be inherent to the time required to synthesize sufficient beta-lactamase after the dilution steps. Control experiments clearly distinguished the post-antibiotic effect and the growth delay from the PLIE. CONCLUSION: The PLIE could be one of several factors explaining why beta-lactam/beta-lactamase inhibitor combinations remain effective throughout the dosing interval, even if a few hours after in vivo administration, serum concentrations of beta-lactamase inhibitor fall below levels that are active in vitro.

Amoxicillin↗
PubMed2001

Ex vivo 12 h bactericidal activity of oral co-amoxiclav (1.125 g) against beta-lactamase-producing Haemophilus influenzae.

The aim of the study was to evaluate the in vitro/ex vivo bactericidal activity of a new coamoxiclav single-dose sachet formulation (1 g amoxicillin + 0.125 g clavulanic acid) against a beta-lactamase-producing strain of Haemophilus influenzae. The evaluation covered the 12 h period after antibiotic administration. Serum specimens from the 12 healthy volunteers included in the pharmacokinetic study were pooled by time point and in equal volumes. Eight of 12 pharmacokinetic sampling time points were included in the study. At time points 0.5, 0.75, 1, 1.5, 2.5, 5, 8 and 12 h post-dosing, the kinetics of bactericidal activity were determined for each of the serial dilutions. Each specimen was serially diluted from 1:2 to 1:256. The index of surviving bacteria (ISB) was subsequently determined for each pharmacokinetic time point. For all the serum samples, bactericidal activity was fast (3-6 h), marked (3-6 log(10) reduction in the initial inoculum) and sustained over the 12 h between-dosing interval. The results obtained also confirmed that the potency of the amoxicillin plus clavulanic acid combination was time dependent against the species under study and that the time interval over which the concentrations were greater than the MIC (t > MIC) was 100% for the strain under study. The data thus generated constitute an interesting prerequisite with a view to using co-amoxiclav 1.125 g in a bd oral regimen.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2000

[Comparative diffusion of fusidic acid, oxacillin, and pristinamycin in dermal interstitial fluid after repeated oral administration].

OBJECTIVE: The aim of this study was to use the suction bullae technique to compare skin diffusion of 3 antibiotics commonly used for skin infections (fusidic acid, oxacillin, pristinamycin) and to estimate their potential activity at the site of skin infections. SUBJECTS AND METHODS: This comparative open study was conducted in 12 healthy volunteers using a repeated latin square experimental scheme. Antibiotic concentrations in serum and suction bullae fluid were measured by high performance liquid chromatography after 5.5 days of repeated oral administration of fusidic acid (1 g/d), oxacillin (2 g/d), and pristinamycin (2 g/d). RESULTS: Mean antibiotic concentrations in serum and interstitial fluid (suction bullae fluid) were highest for fusidic acid with a Cmax at 91.3 +/- 23.0 mg/l and 45.5 +/- 18.0 mg/l respectively (interstitial fluid/serum ratio=49 +/- 10 p. 100). For oxacillin, Cmax was 8.3 +/- 3.6 mg/l and 0.98 +/- 0.49 mg/l (ratio 13 +/- 5 p. 100). Pristinamycin concentrations were low with a Cmax at 0.51 +/- 0.40 and 0.26 +/- 0.15 mg/l (ratio 73 +/- 57 p. 100). Comparing the area under the interstitial fluid and the serum concentration-time curves showed that the best diffusion was obtained with pristinamycin (114 +/- 61 p. 100), followed by fusidic acid (57 +/- 13 p. 100) and oxacillin (48 +/- 25 p. 100). DISCUSSION: These data were used to calculate indicators of potential efficacy in the interstitial dermal fluid: inhibitor quotient (Cmax/MIC) and AUIC (ASC/MIC), indicator of the time antibiotic concentrations are maintained above the minimal inhibitor concentration (MIC). This showed that fusidic acid was potentially more active against all staphylococci. For streptococci, the observed interstitial concentrations of pristinamycin and of fusidic acid should theoretically inhibit streptococci A growth, but oxacillin was the most adapted antibiotic.

Administration, Oral↗
PubMed2000

[Bacterial growth delay in E. coli: demonstration and evaluation of the beta-lactamase post-inhibitor effect on 6 strains with different resistance phenotypes].

Six E. coli, whose phenotypes of resistance were different, were tested in vitro in order to evaluate a regrowth delay, the post beta-lactamases inhibitor effect (PLIE). This PLIE was investigated after a brief incubation in contact with clavulanic acid (CA) alone or associated with amoxicillin (AMX). After removal of the drugs used during the pre-exposure phase, the bacteria were incubated with AMX at different concentrations. The PLIE was shown not to be in association with any other regrowth delay (post-antibiotic effect or effect inherent to the technical procedures used). A PLIE was evaluated on the five intermediary or high-level beta-lactamases-producing strains. Generally, the duration of the PLIE was prolonged after the CA alone pre-exposure phase and could reach values up to 22 hours. The concentrations of AMX added in cultures previously exposed to sufficient CA concentrations were related to an extended PLIE.

Amoxicillin↗
PubMed1999

Stability and compatibility of teicoplanin in parenteral nutrition solutions used in pediatrics.

AIMS: To investigate teicoplanin added to pediatric parenteral nutrition solutions in terms of its stability, its compatibility with parenteral nutrition solution components, and its diffusion through an antibacterial filter material. METHODS: Three binary solutions with and without teicoplanin were studied. Different solution compositions and teicoplanin concentrations were used: A (98.3 +/- 8.2 mg/l), B (116.3 +/- 12.4 mg/l), and C (162.7 +/- 16.2 mg/l). Concentrations of teicoplanin and of solution components, osmolality, and pH of each solution were measured at H0, after 24 h at room temperature, after 24 h at +4 degrees C followed by 24 h at room temperature, and after 144 h at +4 degrees C followed by 24 h at room temperature (H168). Teicoplanin concentrations were also measured before and after passage of each solution through a 0.22 micro filter. RESULTS: Teicoplanin concentrations remained unchanged from H0 to H168 in solutions A (99.6 +/- 8.3 mg/l), B (116.9 +/- 12. 3 mg/l), and C (162.4+12.9 mg/l). During the H0-H168 interval, iron and methionine were the only components that showed significant decreases, which were similar in solutions without teicoplanin [iron, -6.1% (A), -6.8% (B), and -4.5% (C); methionine, -7.3% (A) and -8. 7% (B)] and in those with teicoplanin [iron, -6.2% (A), -7.1% (B), and -4.0% (C, nonsignificant); methionine, -10.5% (A) and -10.7% (B)], indicating that they were not dependent on the presence of teicoplanin. Teicoplanin levels after filtration were identical to prefiltration values in solutions A (86.4 +/- 5.0 vs 89.8 +/- 3.4 mg/l) and B (112.6 +/- 4.3 vs 115.3 +/- 9.0 mg/l) but were 10.0% lower in solution C (161.6 +/- 3.9 vs 145.4 +/- 4.0; P << 0.001). CONCLUSIONS: Teicoplanin can be added to pediatric parenteral nutrition solutions to treat central venous catheter-related infections due to teicoplanin-susceptible organisms since its concentrations and those of solution components remain stable over time.

Anti-Bacterial Agents↗
PubMed1999

Gastric penetration of amoxicillin in a human Helicobacter pylori-infected xenograft model.

The delivery of antibiotics into Helicobacter pylori-infected human stomachs is still poorly understood. Human embryonic gastric xenografts in nude mice have recently been proposed as a new model for the study of H. pylori infection. Using this model, we compared the penetration of amoxicillin, after intraperitoneal administration of a dose of 20 mg/kg of body weight, into the gastric mucosae of infected and uninfected xenografts. The concentrations of this drug in serum and superficial gastric mucosae were determined at 20 min and 1 and 3 h after injection. Ten mice with H. pylori-infected grafts (n = 5) or uninfected grafts (n = 5) were studied. Mucosal samples were obtained by cryomicrotomy. The concentrations in serum were similar to those obtained in the serum of humans after oral administration of 1 g of amoxicillin. The mean area under the tissue concentration-versus-time curve from 0 to 3 h obtained for mice with infected grafts was significantly higher than that obtained for the animals with uninfected grafts (P = 0.01). These results suggest that the penetration of amoxicillin into the superficial gastric mucosa may be substantially increased in the case of H. pylori infection. Thus, human xenografts in nude mice represent a new, well-standardized model for investigation of systemic delivery of drugs into H. pylori-infected gastric mucosa.

Amoxicillin↗
PubMed1999

[In vitro demonstration of a true post-beta-lactamases inhibitor effect (PLIE) of clavulanic acid on Klebsiella pneumoniae and Haemophilus influenzae].

In vivo, serum concentrations of beta-lactamase inhibitors measured during the last part of the dosing interval are below the levels associated with in vitro activity. Nevertheless, beta-lactam plus beta-lactamase inhibitor combinations remain active in vivo throughout the dosing interval. One of the many reasons for this contradiction may be the PLIE. The PLIE can be evaluated only in the light of the postantibiotic effect (PAE). Also, accurate determination of the PLIE requires a careful investigation of all bacterial regrowth delays (BRDs) inherent to the technical procedures used. The purpose of the study reported herein was to determine the true in vitro PLIE of clavulanic acid (CA) against two beta-lactamase-producing strains, a Klebsiella pneumoniae strain (amoxicillin [AMX] MIC > 256 mg/L; CA MIC = 64 mg/L; and AMX + CA MIX = 4 mg/L) and a Haemophilus influenzae strain (AMX MIC = 32 mg/L; CA > 32 mg/L; AMX-CA = 1 mg/L). For each strain, a stationary phase inoculum of 10(7) was preexposed for 2 h to either CA alone or CA + AMX in various concentrations. Dilution to 10(-2) or 10(-3) was performed to eliminate the CA and/or AMX after the preexposition phase. Hourly bacterial counts were done between 0 and 8 h and after 24 h. Control cultures exposed to AMX after dilution showed a growth delay possibly ascribable to the time needed for bacteria to produce a large enough amount of beta-lactamases. Control experiments were done to unequivocally differentiate PLIE from PAE and BRD. The true PLIE values thus obtained ranged from 0 to 4.5 h for K. pneumoniae and from 0 to 15 h for H. influenzae. For both strains, a PLIE was demonstrated after exposure to CA alone.

Amoxicillin↗
PubMed1999

[Biliary diffusion of tazocillin in man].

The objective of this study was to determine the extent of biliary excretion of tazocillin, a combination of piperacillin and tazobactam administered as an intravenous infusion in a dose of 4 g of piperacillin and 0.5 g of tazobactam. In 10 patients, piperacillin and tazobactam levels were determined in serum, main bile duct bile, gallbladder bile, and gallbladder wall specimens harvested during a cholecystectomy procedure 1 h after completion of a tazocillin infusion. In five other patients, piperacillin and tazobactam levels were determined in bile collected from a main bile duct T-tube during 12 h following a tazocillin infusion given seven days after cholecystectomy. HPLC was used to assay both compounds. Piperacillin and tazobactam levels in the intraoperative specimens were as follows: 69.1 +/- 13.8 and 9.9 +/- 1.7 micrograms/ml, respectively, in the serum; 630 +/- 133 and 11.9 +/- 2.2 micrograms/ml, respectively, in the main bile duct bile; 342 +/- 114 and 7.7 +/- 2.3 micrograms/ml, respectively, in the gallbladder bile; and 49.3 +/- 20.2 and 2.9 +/- 0.6 micrograms/g, respectively, in the gallbladder wall. In the T-tube bile specimens, peak piperacillin and tazobactam levels were 358 +/- 281 and 9.9 +/- 3.3 micrograms/ml, respectively, after 1 h; total biliary excretion over 12 hours was 28.3 +/- 18.0 mg and 1.0 +/- 0.5 mg, i.e., 0.7 +/- 0.4% and 0.2 +/- 0.1% of the dose, respectively. The levels of piperacillin and tazobactam found in bile and gallbladder wall specimens in this study suggest that tazocillin may prove valuable for the prevention and treatment of biliary infections.

Bile↗
PubMed1998

Analysis of recent antimicrobial agents in human biological fluids by high-performance liquid chromatography.

Our previous review on the liquid chromatographic (LC) analysis of anti-bacterial agents was published in 1990 in a special issue of the Journal of Chromatography. Eight years later, some new agents have been registered and numerous other are under clinical experiment. In spite of therapeutic problems encountered with certain bacterial pathogens, the development of novel drug candidates has slowed partially due to the need for identification of new bacterial targets and the cost of the research. The present overview updates the LC methods for the quantitations of recent antimicrobial agents (marketed and in clinical development) in human biological fluids. Consideration has been given to procedures permitting the determination of isomers and metabolites as well as methods regarding tissue extracts or liquid sampled from physiological sanctuaries. LC methods are available for the quantitation of almost all registered or investigated recent anti-infective drugs and some are applicable in routine practice. Nevertheless, few techniques have been validated for the determination in tissue extracts limiting the development of penetration studies.

Anti-Bacterial Agents↗
PubMed1998

Synthesis and antimicrobial activity of coumarin 7-substituted cephalosporins and sulfones.

Some coumarin 7-substituted cephalosporins and related sulfones were prepared and an antimicrobial assay was performed. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) carried out on cephalosporins showed a potential activity of some of the synthesized compounds against Gram-positive microorganisms. The tests performed on the corresponding sulfones showed no significant activity, neither as antimicrobial agents nor as inhibitors of beta-lactamase. An association of sulfone 6a with ampicillin was observed to inhibit Gram-positive microorganisms with a lower MIC than for ampicillin alone.

Cephalosporins↗
PubMed1997

Capillary electrophoresis for pharmacokinetic studies.

Different analytical techniques involving capillary electrophoresis for the determination of drugs and metabolites in biological fluids are described. Pharmacokinetic studies carried out using capillary electrophoresis are presented, as well as the in vitro metabolism investigations. The advantages and the limitations of capillary electrophoresis for pharmacokinetic studies are discussed.

Animals↗
PubMed1997

High-performance liquid chromatographic assay for cefepime in serum.

A simple, rapid, specific and sensitive high-performance liquid chromatographic method was developed for the determination of cefepime 1-[[(6R, 7R)-7-[2-(2-amino-4-thiazolyl) glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo- [4.2.0]oct-2-en-3-yl]methyl]-1-methylpyrrolidinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) in human serum. Separation was achieved on a reversed-phase Ultrasphere XL-ODS column (75 x 4.6 mm I.D.). The mobile phase was 7% acetonitrile in 20 mM ammonium acetate (pH 4). Cefepime eluted in the range of 1.8-2.2 min. Detection was by UV absorbance at 254 nm. The lower limit of quantitation of cefepime in plasma was 0.5 microgram/ml. The average absolute recovery was 106.2 +/- 2.1%. The linear range was from 0.1 to 50 micrograms/ml, with a correlation coefficient greater than 0.999. The within-day C.V.s for human samples were 4.9 and 2.3% for 1 and 50 micrograms/ml, respectively. The between-day C.V.s for human serum samples were 14.5, 7.4 and 6.7 for 1, 25 and 50 micrograms/ml, respectively. Cefepime was found to be unstable in serum at room temperature. For delayed assay, samples must be stored at -80 degrees C.

Animals↗
PubMed1997

Bactericidal effect of pefloxacin and fosfomycin against Pseudomonas aeruginosa in a rabbit endocarditis model with pharmacokinetics of pefloxacin in humans simulated in vivo.

The bactericidal activity of pefloxacin and fosfomycin alone and in combination against Pseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4 +/- 11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12-48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.

Animals↗
PubMed1997

Gastric diffusion of antibiotics used against Helicobacter pylori.

Only a few pharmacological studies have been carried out on men and guinea pigs to determine the gastric diffusion of antibiotics, which are active against Helicobacter pylori. The results of these studies have been analysed in considering the physicochemical nature, the mode of administration, the way of gastric diffusion (topic and/or systemic) and the pharmacological interactions. The correlation of these pharmacokinetic results with those obtained in clinical trials is difficult because of the heterogeneity of the pharmacological and pharmacodynamic data. The absence of a convenient and suitable animal or in vitro study model renders further standardized pharmacokinetic studies in infected man and at steady state necessary.

Animals↗