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E Despaux

Publications and source records attributed to E Despaux.

At least 19 recordsLinked to original sources

Synthesis and solution structure of the antimicrobial peptide protegrin-1.

Protegrins are members of a family of five Cys-rich, cationic antimicrobial peptides recently isolated from porcine cells. We have synthesised an 18-amino-acid peptide that corresponds to protegrin-1. After Cys oxidation, the peptide has bactericidal activity against gram-positive and gram-negative bacteria, similar to that described for the natural peptide. The solution structure of protegrin-1 was investigated by means of 1H-NMR spectroscopy in water and in (CD3)2SO, with distance-geometry and simulated-annealing calculations. The C6-C15 and C8-C13 disulfide pattern was determined on the basis of NMR-derived constraints. These two parallel disulfide bridges stabilised a beta-sheet structure which comprised two antiparallel strands (residues 5-9 and 12-16) linked by a distorted beta-turn (residues 9-12). The N-terminus and C-terminus were essentially disordered. The distribution of hydrophobic and hydrophilic residues at the peptide surface was found to be a structural feature shared with tachyplesin-1, a related peptide which displays cytolytic activity, and, to a lesser extent, with mammalian defensins. These findings led us to assume that the distribution pattern could be required for the cytolytic activity of these peptides.

Amino Acid Sequence↗

Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation.

Protegrin 1 (PG-1) is a naturally occurring cationic antimicrobial peptide that is 18 residues long, has an aminated carboxy terminus and contains two disulphide bridges. Here, we investigated the antimicrobial activity of PG-1 and three linear analogues. Then, the membrane permeabilisation induced by these peptides was studied upon Xenopus laevis oocytes by electrophysiological methods. From the results obtained, we concluded that protegrin is able to form anion channels. Moreover, it seems clear that the presence of disulphide bridges is a prerequisite for the pore formation at the membrane level and not for the antimicrobial activity.

Amino Acid Sequence↗

Concentration of teicoplanin in the serum of adults with end stage chronic renal failure undergoing treatment for infection.

We examined the adequacy of the following schedule for the administration of i.v. teicoplanin to patients with chronic renal failure: three doses of 6 mg/kg at 12 h intervals, a fourth dose 24 h later and then subsequent doses every 72 h. Eight infected patients undergoing dialysis were investigated, with serum antibiotic concentrations measured ten minutes before and one hour after administration. Mean trough concentrations were 6.9 +/- 3.1 mg/L on day two, 9.8 +/- 4.4 mg/L (day three), 9.2 +/- 4.8 mg/L (day six), 10.9 +/- 5.5 mg/L (day nine), 12.1 +/- 6.1 mg/L (day 12) and 14.8 +/- 8.0 mg/L (day 15). The proposed schedule achieved adequate trough serum teicoplanin concentrations by 48 h in six out of eight patients examined. The dosage regimen was well tolerated.

Adult↗

Comparative evaluation of blood culture using the Vital automated system and the Becton-Dickinson Septi-Chek BHI-S biphasic and Sch bottles.

A comparative study was performed using 1,168 aerobic and anaerobic blood culture pairs from 395 patients, during which 5-10 mL of blood were collected in both Septi-Chek BHI-S biphasic and Septi-Chek Sch bottles (Becton-Dickinson, Meylan, France) and Vital AER and Vital Ana bottles (bioMérieux, Marcy-l'Etoile, France). The bottles were analyzed by using a 7-day protocol for Vital and a 12-day protocol for Septi-Chek. The Vital bottles revealed negative were all subcultured at the end of the protocol. Of the 374 positive Septi-Chek bottles, only 202 bottles gave a positive subculture. Of the 245 positive Vital bottles, 223 bottles led to the isolation of a microorganism. Thirty-five septic episodes were detected by Septi-Chek compared to 38 by the Vital system (only clinically significant isolates were taken into consideration). Four septic episodes were detected by Vital only (one episode implicating coagulase-negative Staphylococcus, one Streptococcus pneumoniae, one Pseudomonas aeruginosa and one Candida albicans, involving a total of 15 bottles). One septic episode implicating Bacteroides fragilis was detected by Septi-Chek only (five bottles). Among the negative Vital bottles, only six bottles gave a positive terminal subculture. This study validates the reliability of the Vital system to detect positive blood cultures.

Bacteria↗

Influence of arterio-venous haemofiltration on teicoplanin elimination.

The pharmacokinetics of teicoplanin infused for 30 min at a dose of 6 mg kg-1 was studied in 11 infected patients under continuous arterio-venous haemofiltration (CAVH). Serum teicoplanin levels were assayed by h.p.l.c. over 24 h. After 0.5 h, i.e. at the end of the infusion, the mean plasma concentration was 49.6 +/- 15.1 mg l-1. At the last sampling time (24 h), the mean concentration was 2.6 +/- 1.0 mg l-1. The concentration of teicoplanin was determined in the haemofiltrates. The percentage of the administered dose recovered in the haemofiltrate was low: less than 1% for seven patients, between 1.8 and 3.7% for three patients and 7% for one patient. CAVH patients should be given teicoplanin using the same dosage regimens as previously described for patients with renal impairment.

Adult↗

Detection kinetics for positive blood culture bottles by using the VITAL automated system.

The VITAL system principle is based on homogeneous fluorescence technology. During an 11-month period, a total of 19,706 blood cultures from adult patients hospitalized in various establishments of the Montpellier Teaching Hospital were collected in VITAL bottles, of which 1,939 were declared positive. Only 204 bottles (1.04%) were false positives. The 1,735 true-positive bottles were collected from 130 patients. The final visual control permitted the detection of 10 falsely negative bottles (0.05%), of which 5 contained clinically significant microorganisms from four patients. The kinetics of detection for all microorganisms showed that 66.6% were detected within 24 h, 83.1% within 48 h, 95.5% within 120 h, and 100% within 150 h. No clinical episode would have been missed had a 5-day protocol been used instead of a 7-day protocol. Among the positive bottles, 65.7% were detected by the SLOPE algorithm, 20.1% by the DELTA algorithm, and 14.2% by the THRESHOLD algorithm. This retrospective study of our results shows that a 5-day protocol is sufficient for the detection of septic episodes using the VITAL system.

Adult↗

Epidemiological study by pulsed-field gel electrophoresis of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a geriatric hospital.

Twelve cases of infections caused by extended-spectrum beta-lactamase (ESBla)-producing Klebsiella pneumoniae were reported between August 1991 and March 1993 in the Geriatric Department of the Nimes University Hospital, where these bacterial had not been previously isolated. Restriction profiles of total genomic DNAs cleaved by XbaI and SpeI were compared by pulsed-field gel electrophoresis. The strains that were tested included the 12 isolates from K. pneumoniae-infected patients, strains recovered from rectal swabs of asymptomatic patients in the same ward, and strains isolated in other hospitals in Nîmes at the same time. The restriction profiles of the 12 isolates and those recovered from asymptomatic patients in the same ward were very similar. Over a period of more than 1 year, extended-spectrum beta-lactamases were not detected in K. pneumoniae isolates with restriction patterns different from that of the epidemic strain. It seems, therefore, that there was no transfer of a plasmid or a gene coding for ESBla to strains of K. pneumoniae that were different from the epidemic strain. At the same time, ESBla-producing K. pneumoniae isolates exhibiting restriction endonuclease profiles very different from that of the epidemic strain were isolated from other hospitals in Nîmes. None of these strains caused an outbreak. Pulsed-field gel electrophoresis, which allows precise characterization of strains beyond the species level, is a useful tool for studying the ESBla-producing K. pneumoniae strains involved in nosocomial outbreaks.

Aged↗

[Ofloxacin (RU 43280). Clinical study].

Thirty-two patients were treated by ofloxacin on bacteriological documented infections. They were Enterobacterias: n = 15 (MIC less than or equal to 0.06 to 0.5 microgram/ml); Pseudomonas aeruginosa and Acinetobacter: n = 1 (MIC 0.5 and 4 micrograms/ml); Staphylococcus: n = 6 (MIC less than or equal to 0.06 to 4 micrograms/ml); Pneumococcus: n = 1; Mycoplasma: n = 1; Chlamydia psittaci: n = 2; Legionella pneumophila: n = 1; Rickettsias: n = 4 (three mediterranean fevers one query fever). Ofloxacin was given orally from 400 to 800 mg per day (5 to 15 mg/kg/day). It was used alone 26 times and on 6 occasions it was associated with rifampin on 6 staphylococcal infections. On 19 cases it was used after failure or intolerance of initial therapy. Thirty times it was the first antibiotic substance used. Results were good mainly: 1) on nine pneumonitis (enterobacterias: 4; Pneumococcus: 1; Mycoplasma: 1; Chlamydia: 2; Legionella: 1) during a mean duration of twenty days; 2) urinary infections (n:7) provoked by E. coli and Enterobacter cloacae (mean duration: 20 days); 3) 4 osteo-articular-infections (mean duration: 77 days); 4) Rickettsial infections (n:4) during a mean duration of 11 days. Results are particularly noteworthy because patients treated had severe infections: 12 bacteremias, 1 endocarditis and 1 purulent meningitis. None severe adverse effect was observed.

Adolescent↗

[Pharmacokinetic and clinical investigation of amoxicillin administered intravenously in the newborn ].

Neonatal antibiotherapy involves special requirements which justify carrying out a clinical and pharmacokinetic investigation of amoxicillin. Our study concerns 34 newborn babies prone to infection divided in 3 groups: 26 newborns at gestational age; 6 hypotrophic and slightly premature newborns (age: 34 at 37 weeks); 1 highly premature baby (28 weeks, 0,9 kg). After direct IV drip of 33 mg/kg, 4 plasma concentrations analyses at time 0,5 1, 3, 8 hours, as well as an analysis of the urine from 0 to 8 hours are carried out by method of disk diffusion in nutrient agar. The main pharmacokinetics parameters are the following: half-live elimination time: 5.l4 +/- 3.43 hours; volume of distribution: 1.38 +/- 1.13 l/kg; total clearance: 0.211 +/- 0.277 l/kg/h. There is no correlation between birth weight and the parameters studied. However in the case of hypotrophic baby the volume of distribution is higher than for the child born after full gestation and may be partly correlated with the weight at birth. The same holds for clearance (correlation index of 0.66 and 0.59 respectively). The extreme variability of the pharmacokinetics parameters for newborn babies leads the authors to recommend a minimum dose of 150 mg/kg per day spread over 3 or 4 injections per day.

Amoxicillin↗

[Pseudomonas aeruginosa bacteriaemia: new clinical and therapeutic aspects ].

Fifty one cases of Pseudomonas aeruginosa bacteriaemia observed during the last 12 years are reported. Thirty five patients were over fifty years old; 92 p. cent were admitted for several days and about 50 p. cent were in post-operative period. A previous antibiotherapy and an impaired status are promotive factors. The respiratory or peritoneal origins are the most frequent. All patients were feverish; 24 have had an infectious shock which was inaugural in 12 cases. Seven pneumonitis, 3 endocarditis, one pericarditis and 2 osteitis were observed. An ecthyma gangrenosum was noted in three patients. Mortality was 70 p. cent. Comparison between recovered and died patients improved bad prognosis of old age, post operative period, neoplasic, previous organica weakness and pulmonary or peritoneal origins. Used alone, colimycin has seemed to be more effective than aminosid antibiotics; but their association with betalactamins was better. An in vitro study of the susceptibility of 100 Pseudomonas aeruginosa strains has proved the interest of piperacillin and cefsulodin; azlocillin, cefoperazone and ceftriaxone are just less effective.

Aged↗