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Biomedical subjects

J F Desnottes

Publications and source records attributed to J F Desnottes.

At least 37 records · Page 2Linked to original sources
PubMed1988

Spiramycin concentrations in lung tissue.

Spiramycin concentrations in lung tissue were studied in patients undergoing pulmonary surgical procedures. The first group of six patients received 500 mg spiramycin iv 16 h before surgery and 500 mg at anaesthetic induction (total 1 g). The second group of six patients received three doses of 500 mg spiramycin iv 24, 16 and 8 h before surgery, and 500 mg at anaesthetic induction (total 2 g). Samples were taken from lung tissue, pleura, fat tissue and muscle. In group 1, the mean lung tissue concentration of spiramycin was 1.15 +/- 0.14 mg/kg and 7.99 +/- 2.02 mg/kg in group 2 (P less than 0.02). The differences in concentration in pleura, fat tissue and muscle samples between treatment groups 1 and 2 were not statistically significant.

Humans↗
PubMed1988

Spiramycin uptake by alveolar macrophages.

The in-vitro and in-vivo uptake of spiramycin by human and animal alveolar macrophages was studied. In-vitro penetration was studied in guinea pig and human alveolar macrophages incubated in medium 199 at 37 degrees C containing spiramycin at various concentrations. Results were expressed as the cellular/extracellular concentration ratio (C/E). The in-vivo study was performed in patients receiving 500 or 1000 mg spiramycin every 8 h as a 1-h infusion on day 1. A single infusion was given on day 2, 2 h before serum and bronchoalveolar lavage (BAL) sampling. Spiramycin was assayed by HPLC, and by a microbiological assay. In guinea pig alveolar macrophages, the C/E ratio of spiramycin after 60 min at 37 degrees C was 20.3 +/- 6.5 when the concentration was 10 mg/l. In human alveolar macrophages, the C/E ratio was 21.3 +/- 8.7 at 5 mg/l spiramycin and 23.8 +/- 8.7 at 50 mg/l. The accumulated spiramycin was slowly released when the cells (guinea pig alveolar macrophages) were washed and re-incubated in antibiotic free medium. Spiramycin was able to penetrate the alveolar space. In BAL supernatant, spiramycin levels were about 24-fold the serum level (n = 6 patients), when the BAL/serum glucose ratios were used as the dilution estimate. Alveolar macrophage levels ranged from 17 to 210 mg/l (n = 6 patients receiving 500 mg spiramycin infusion). These results are consistent with the in-vitro data.

Animals↗
PubMed1988

Effect of spiramycin on adhesiveness and phagocytosis of gram-positive cocci.

Three strains of Staphylococcus aureus, serotype 18, Cowan I and serotype 66438, and different species of streptococci (Streptococcus pyogenes, Str, mutans, Str. sanguis and Str. faecalis) were tested for their adherence to buccal cells (as measured by interference contrast microscopy) and phagocytosis by rat polymorphonuclear leucocytes (PMNs) (as measured by fluorescence microscopy with a vital fluorochrome, acridine orange). Pretreatment of cocci with serial two-fold dilutions of spiramycin (from 1/2 to 1/1024 the MIC), increased the diameter of bacterial cells and decreased the adherence of staphylococci and streptococci to buccal cells. Exposure of streptococci to 1/4 the MIC of spiramycin led to an increase of the phagocytic capacity of PMNs. Pretreatment of PMNs with a therapeutic concentration (2 mg/l) also stimulated the phagocytosis of streptococci. Action of spiramycin on the phagocytosis of staphylococci varied according to the strain tested. Although in-vitro results cannot be directly compared with in-vivo data, it is of interest that spiramycin decreases adherence of different Gram-positive cocci and enhances phagocytic capacity of PMNs.

Bacterial Adhesion↗
PubMed1988

Pharmacokinetics of spiramycin in man.

The pharmacokinetics of spiramycin were studied after single and repeated administration by iv and oral routes. Following iv administration of a 500-mg dose in a one-hour infusion, peak serum concentrations were 1.54-3.10 mg/l. These concentrations are higher than MICs of spiramycin for various infectious agents. Eight hours after the end of infusion, the mean serum concentration was close to 0.25 mg/l. Spiramycin is rapidly and widely distributed throughout the body and achieves high ratios of tissue to serum concentrations in bucco-dental, pulmonary and prostatic tissues and skin. The distribution half-life of spiramycin was 10 min. The steady-state volume of distribution (Vdss) and the tissue distribution volume were 5.6 and 4.5 l/kg. The absolute bioavailability of spiramycin was 36% (S.D. +/- 14). Oral doses of spiramycin between 1 and 2 g resulted in linear increase in the peak serum levels and areas under the serum concentration-time curve. Spiramycin does not appear to undergo important metabolic conversion and is mainly excreted via the biliary route. Indeed, in man, the urinary excretion of active compounds represents only 7.6 to 20% of the administered dose. Spiramycin had a terminal elimination half-life of approximately 5 h. Renal clearance (144 ml/min) was much lower than non-renal clearance (887 ml/min). The total body clearance of spiramycin in young adults was 1.42 l/min (S.D. +/- 0.5) but only 0.53 l/min (S.D. +/- 14) in elderly subjects. During repeated iv administration (500 mg tid), steady state was achieved after four doses. Cmax and Cmin were 3.0 and 0.5 mg/l in young adults and 4.5 and 1.75 mg/l in elderly patients. Spiramycin's kinetics differ in several important respects from erythromycin's, notably the larger volume of distribution of spiramycin which reflects the higher tissue concentration. The reduced spiramycin clearance in elderly subjects requires further investigation.

Administration, Oral↗
PubMed1988

Effect of subminimal inhibitory concentrations of pefloxacin on the piliation and adherence of E. coli.

Several recent reports have shown that sub-lethal concentrations of antibiotics may decrease the adhesive ability of bacteria to epithelial cells; however, the mechanism by which the antimicrobial agents reduce adherence has remained unknown. The effect of sub-MICs of pefloxacin, a new broad-spectrum antibacterial quinolone, was studied on: haemagglutination, adherence, outer membrane and fimbriae of a pyelonephritogenic E. coli strain. The strain agglutinated in a mannose-resistant way human P1 but not p erythrocytes. After purification, the fractions containing outer membrane and fimbriae proteins were studied using electron microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The E. coli strain, grown in the presence of sub-MICs of pefloxacin, exhibited: (i) abnormal forms with filament formation; (ii) a markedly altered capacity of haemagglutination (human P1 erythrocytes) and adherence to uroepithelial cells. The inhibition of haemagglutination and adherence corresponded to a decrease in P-fimbriae production. These results were also associated with changes in the extraction of the outer membrane proteins of pefloxacin-treated bacteria. No major qualitative difference could be seen in outer membrane and P-fimbriae protein profiles after growth with sub-MICs of pefloxacin. This study has demonstrated that sub-lethal concentrations of pefloxacin alter piliation and the outer membrane of E. coli. These changes are associated with reduced bacterial haemagglutination and adherence.

Bacterial Adhesion↗
PubMed1987

Recovery of pefloxacin in saliva and feces and its action on oral and fecal floras of healthy volunteers.

Pefloxacin, a new fluoroquinolone, was given to 10 volunteers in single 400-mg oral doses repeated at 12-h intervals during 7 days. Serum, saliva, and feces samples were collected before and at appropriate intervals after the initiation of treatment. Drug concentrations were determined by bioassay. Qualitative and quantitative analyses of the saliva and fecal floras were performed. Mean concentrations in saliva (3.46 micrograms/ml on day 1 and 7.54 micrograms/ml on day 7) were closely related to levels in serum. High concentrations of pefloxacin were found in the feces (645 micrograms/g on day 8). No modification of oral flora was observed. In the fecal flora, members of the family Enterobacteriaceae were eliminated between days 2 and 8. The alterations in streptococci and anaerobic flora were not significant; Bacteroides fragilis was more resistant to pefloxacin after treatment. Clostridium difficile was not detected, and there was no overgrowth by yeasts. No side effects were observed.

Bacteria↗
PubMed1987

[Quinolones and phagocytosis].

Fluoroquinolones as pefloxacin (PEF), ciprofloxacin (CIP), ofloxacin (OFL), norfloxacin (NOR) and enoxacin (ENO), are able to interfere with phagocyte-bacteria interaction. Active forms of PEF, CIP and OFL are concentrated in macrophages (MA) and polymorphonuclear leukocytes (PMN). These molecules appear to be free in MA cytoplasm and their release is rapid after withdrawal of extracellular antibiotic. Pretreatment of different species of bacteria (Enterobacteriaceae, S. aureus) with sub-CMIs of CIP and PEF, leads to morphologic modifications of bacteria and increases their engulfment by PMNs. Pretreatment of PMNs with therapeutic concentrations of PEF, NOR and ENO, but not CIP, increases phagocytic capacity and/or chemiluminescence. S. aureus pretreatment with sub-CMIs of CIP enhances intracellular killing. Adding of PEF after L. pneumophila phagocytosis by MA, involves a significant intracellular killing even after withdrawal of the extracellular drug. These different properties could explain good therapeutic results in severe infection treatment when the antibacterial activity of an antibiotic is not really sufficient to cure the infectious disease.

Animals↗
PubMed1987

Effects of subinhibitory concentrations of pefloxacin on the adherence of Staphylococcus aureus to human cells.

The adherence of bacterial strains to eukaryotic cells can be influenced by subinhibitory concentrations of antibiotics. The effect of sub- and infra-MICs of pefloxacin, a new broad-spectrum antibacterial quinolone, on the adherence of Staphylococcus aureus to human buccal cells, was studied. Six S. aureus strains belonging to several serotypes and all sensitive to pefloxacin were pretreated with serial twofold dilutions of the drug (from 1/2 to 1/1024 the MIC). After the adhesion test, 100 buccal cells were counted in randomly chosen microscopic fields using a Nomarski interference microscope and attachment was measured as the percentage of cells with at least 50 or more adhering bacteria. Sub-MICs (1/2 and 1/4 the MIC) of pefloxacin increased the diameter of the six staphylococci. All of the strains, grown in the presence of pefloxacin, exhibited a markedly altered capacity for adhesion to buccal cells. The highest significant decrease was observed for 1/2 to 1/8 the MIC, although infra-MICs such as 1/1024 the MIC also decreased the attachment of S. aureus to buccal cells. These results were compared with those obtained with other antibiotics active against S. aureus.

Anti-Bacterial Agents↗
PubMed1986

Effects of pefloxacin on phagocytosis function of rat macrophages and polymorphonuclear leucocytes.

The influence of pefloxacin on polymorphonuclear leucocytes (PMN) and alveolar macrophages (AM) phagocytosis and microbicidal activity was studied. Phagocytes were collected from Sprague-Dawley rats, mixed with pefloxacin at different concentrations (1, 10, 100 mg/l) and a yeast phagocytosis assay was performed. Three parameters were measured, the phagocytic capacity (number of live and dead yeast/100 cells), the phagocytic activity (number of cells containing 2 or more yeast/100 cells) and the microbicidal activity or % killed (Formula: see text) Both low and high concentrations of pefloxacin increased significantly the phagocytic capacity and activity of AM and PMN. The increase of the AM phagocytic capacity and activity seen with increasing levels of extracellular pefloxacin was not statistically significant. Pefloxacin showed no adverse effect on the microbicidal activity of AM and PMN.

Animals↗
PubMed1986

[Effects of subinhibitory concentrations of pefloxacine on hemolysin production and adherence of urinary Escherichia coli].

The in vitro effect of subinhibitory concentrations of pefloxacin on E. coli's production of hemolysin and adherence to eucaryotic cells was studied. Six uropathogenic E. coli strains, with mannose-resistant and/or mannose-sensitive adhesins were tested. All strains produced an alpha-hemolysin and were susceptible to pefloxacin (0.125 less than or equal to MIC less than or equal to 0.250 mg/l). The effect on hemolysin production was studied using microtitration plates to determine the concentration inhibiting 50% of E. coli's hemolytic activity. The inhibition of adhesion was tested following adhesion of E. coli to uroepithelial cells. Sub-MICs of pefloxacin strongly inhibited the production of alpha-hemolysin and adhesion of E. coli regardless of adhesin type. A correlation between the inhibition of hemolysin production and the inhibition of adhesion to uroepithelial cells was found for four E. coli strains.

Bacterial Adhesion↗
PubMed1981

Experimental retrograde pyelonephritis and cystitis induced in rabbits by a group D Streptococcus sp.: serum antibody assay by a hemagglutination test.

Experimental models of urinary tract infection caused by a group D Streptococcus sp. in rabbits are described: retrograde pyelonephritis was induced by injecting 10(9) group D streptococci into the renal pelvis and obstructing the ureter by ligature for 24 h; cystitis was induced by injecting 5.10(9) group D streptococci through a transurethral catheter. The animals were observed for 3 months. Microbiological data from the urine and from the renal parenchyma were well correlated in 12 of 14 animals. A hemagglutination test for titration of serum antibodies in these infected rabbits is described. Before the beginning of experimentation, hemagglutination titers for all animals were below 160. During experimentation, titers for rabbits with cystitis were always below 640; in those with pyelonephritis, the highest titer was much greater than 640. These results show a positive correlation between serum antibody levels and the localization of urinary tract infection.

Animals↗
PubMed1981

[Interest of humoral antibodies assay for diagnosis and survey of urinary tract infections by gram negative bacilli and streptococcus D in children (author's transl)].

The assay of humoral antibodies during urinary tract infections of children is performed by passive haemagglutination. In gram negative bacilli infections (176 children) the antigens are derived from the patients' bacteria. For streptococcus D infections the antigen is a phenol extract, specifically tested and used for all streptococcus D urinary tract infections (40 children). The humoral antibodies assay is of first interest to distinguish between high urinary tract infections with renal parenchym bacterial involvement and low urinary tract infections. In high urinary tract infections the antibodies are significantly elevated and almost surely indicate renal infection for a 1/2 560 titre; they raise both in gram negative bacteria and in streptococcus D infections. There is however a difference in a rather higher number of cases of streptococcus D infections where it is impossible of connect high sera titres and clinical symptoms of pyelonephritis, contrary to gram negative bacilli infections. It seems to be due to aetiological differences in urinary tract infections by streptococcus D, which are more often secondary infections, during severe urologic diseases. In such cases the symptomatology of infections is less typical than in E. Coli urinary tract infections. Another interest is the capacity of survey by this method. Three kinds of courses of antibody titres are observed: the first is a clean break of titre lower than 1/160 after three months; the second is the continuance of the same high levels over three months; the third is continuance of high significative level after a first incomplete fall. In the last two cases it is highly probable that a pyelonephritis processes is engaged. This may be useful for treatment and survey of children with urologic diseases.

Antibodies, Bacterial↗
PubMed1980

[Classes of antibody and complement coating bacteria in the urinary tract infections of the child].

Urine specimens from 88 children with urinary tract infections were tested by direct immunofluorescence for the presence of antibody coated bacteria and were positive. They were further tested to determine the classes of antibody complexed with the bacteria: 75% were coated with IgA, 62% with IgG and 9% with IgM. In 47 children, C1q, C3 and C4 coated bacteria were also studied: negative results were found in 30 children and positive in 17. The ACB test may be positive without any IgG present; therefore it must be used a antihuman globulin and not only a antihuman IgG.

Adolescent↗
PubMed1978

[Localization of urinary tract infection in children by immunofluorescent study of bacteriuria and measurement of humoral antibodies].

In 62 children presenting with a urinary infection, the immuno-fluorescent (I.F.) study of immunoglobulins fixed on the cell wall of urinary bacteria was performed jointly with the titration of serum antibodies towards the same bacteria. This study revealed that: 1. There was a correlation between I.F. and serodiagnosis in 82% of the cases. 2. There was a correlation between the localization of the urinary tract infection, as assessed by the classical biochemical means, and the results of I.F. and antibody measurements. Positivity of either I.F. or serodiagnosis, or of both tests, is significantly related with upper urinary tract infection wheras the negativity of the two tests is observed, at the exception of children under 1 year of age, in lower urinary tract infection. 3. There was a correlation between the site of infection and the results of I.F. and antibody measurements. In upper urinary tract infections, either I.F. or serological tests, or both are positive, whereas in lower urinary tract infections both tests are negative, except in children under the age of 1 year.

Adolescent↗
PubMed1977

[Serodiagnosis of gram-negative urinary infections (author's transl)].

The authors recall the interest of serodiagnosis of urinary infection in children for the diagnosis of pyelonephritis and supervision during treatment. They then give details of the technic of estimation of specific antibodies for Gram negative bacilli isolated during past and present infections.

Bacterial Infections↗