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N Diallo

Publications and source records attributed to N Diallo.

14 recordsLinked to original sources

Dracunculiasis eradication: delayed, not denied.

By the end of 1998, Asia was free of dracunculiasis (Guinea worm disease), with Pakistan, India, and Yemen having interrupted transmission in 1993, 1996, and 1997, respectively. Transmission of the disease was also interrupted in Cameroon and Senegal during 1997. Chad reported only 3 cases during 1998. Dracunculiasis is now confined to only 13 countries in Africa. The overall number of cases has been reduced by more than 97% from the 3.2 million cases estimated to have occurred in 1986 to 78,557 cases reported in 1998. Because the civil war in Sudan remains the major impediment to eradication of dracunculiasis, the interim goal is to stop all transmission outside that country by the end of 2000. The most important operational need now is for national programs to improve the frequency and quality of supervision of village-based health workers in order to enhance the sensitivity of surveillance and effectiveness of case containment.

Africa South of the Sahara↗

Antistaphylococcal activities of quinupristin/dalfopristin in vitro across platelet-fibrin matrices and in experimental endocarditis.

In-vitro and in-vivo efficacies of quinupristin/dalfopristin and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) responsible for endocarditis have been compared. The following parameters were investigated: MIC, activity across a platelet-fibrin matrix simulating cardiac vegetations, killing of bacteria on the cardiac vegetations resulting from experimental aortic valve endocarditis in an animal model, and concentrations of antibiotics in the serum and vegetations of infected rabbits. The same bacterial strain was used for all experiments. The MICs of quinupristin/dalfopristin and vancomycin were 0.25 and 1 mg/L, respectively. When tested for their ability to penetrate platelet-fibrin matrices, both drugs were bactericidal against the MRSA strain (> or = 2 log10 cfu/mL decrease in 2 h). Both drugs significantly reduced the bacterial counts in vegetations in infected rabbits. Within 12 h of intravenous administration of 20 mg/kg, concentrations of quinupristin/dalfopristin decreased from 5.3 to < 0.10 mg/L in serum and from 12.9 to < 1 mg/kg in the valve vegetations. Although the concentrations of vancomycin in the serum and the infected tissue were higher than those of quinupristin/dalfopristin, the latter combination was equally effective, perhaps because its bactericidal activity is rapid and because it can more easily penetrate the cardiac vegetations.

Animals↗

Effect of sparfloxacin on Staphylococcus aureus adhesiveness and phagocytosis.

We investigated the effect of sparfloxacin, a new broad-spectrum fluoroquinolone, on the morphology, adhesiveness and phagocytosis of a clinical isolate of Staphylococcus aureus sensitive to this compound (MIC = 0.06 mg/L). The strain was tested for its adherence to human buccal epithelial cells, measured by interference contrast microscopy, and for phagocytosis by guinea-pig peritoneal macrophages, measured by fluorescence microscopy. Accumulation of sparfloxacin by macrophages was studied by means of a velocity-gradient centrifugation technique. The S. aureus strain, grown in the presence of sub-inhibitory concentrations of sparfloxacin, exhibited an increased cell diameter and a markedly reduced capacity to adhere to buccal epithelial cells. The phagocytic capacity and activity of macrophages were greater with the treated strain than with an untreated control. A reduction in numbers of intracellular cocci was also observed 2 h after postphagocytic treatment of macrophages with sparfloxacin at 10 x MIC. This intracellular bactericidal activity may result from accumulation of sparfloxacin in macrophages, evidenced by a high ratio of cellular to extracellular concentration. It was concluded that sparfloxacin reduces adherence to epithelial cells, increases phagocytosis and facilitates the intracellular killing of S. aureus.

Animals↗

Accumulation of pefloxacin in the lower respiratory tract demonstrated by bronchoalveolar lavage.

The in-vivo pulmonary disposition of pefloxacin in alveolar macrophages alveolar macrophages and in the alveolar epithelial lining fluid recovered by bronchoalveolar lavage was studied in 10 healthy volunteers. Bronchoalveolar lavage was performed either 2 or 4 h after oral intake of 800 mg of the drug. The recovered fluid was immediately centrifuged and processed for the assays. Pefloxacin was assayed by High Pressure Liquid Chromatography (HPLC) and by a microbiological method. The mean concentrations of pefloxacin assayed by HPLC were 106 +/- 11.1 mg/L in alveolar macrophages and 88.2 +/- 10 mg/L in the epithelial lining fluid, whereas the mean serum concentration was 6.67 +/- 0.47 mg/L. Therefore, pefloxacin accumulated rapidly in human alveolar macrophages. The high epithelial lining fluid concentrations may be attributed to lipophilicity of the drug and to rapid diffusion from blood, pulmonary cells and interstitium during the bronchoalveolar lavage procedure. The substantial accumulation of pefloxacin in alveolar components (alveolar macrophages and epithelial lining fluid) endorses its use in the treatment of intracellular bacterial infections such as legionellosis; for these diseases, pefloxacin represents an alternative to the macrolide antibiotics.

Adult↗

Cellular uptake and intracellular bactericidal activity of RP 59500 in murine macrophages.

RP 59500, a new antibacterial agent, is a combination of two compounds, RP 54476 and RP 57669. The uptake of radiolabelled RP 59500, i.e. a mixture containing [14C]-RP 54476 plus RP 57669 or [14C]-RP 57669 plus RP 54476, by J 774 murine macrophages was evaluated by a velocity gradient centrifugation technique. After 120 min, the ratios of cellular to extracellular concentration for RP 54476 and RP 57669 were 34 and 50, respectively. The highest intracellular accumulation of RP 59500 was observed at pH 7-7.5. RP 59500 was found to accumulate less at 4 degrees C than at 37 degrees C. The uptake of RP 59500 by dead macrophages was markedly higher than that by live macrophages. As the extracellular concentration of RP 59500 was increased, the intracellular concentration of each component rose, but not proportionally. The metabolic inhibitors sodium cyanide and potassium fluoride both decreased modestly the entry of RP 57669, but not that of RP 54476, into macrophages. After removal of the extracellular antibiotic, RP 54476 and RP 57669 were released rapidly by the cells until equilibrium was established (45% of the original intracellular RP 59500 remained in the cells after 120 min). The intracellular activity of RP 59500 was assessed by incubating macrophages containing ingested Staphylococcus aureus 209P with the drug (10 x MIC: 2.5 mg/L) at 37 degrees C and determining the number of viable cell-associated bacteria. Approximately 70% of the intracellular bacteria were killed within 120 min of incubation. Thus, RP 59500 attains a high intracellular concentration and is active against intracellular S. aureus.

Drug Combinations↗

Effect of pefloxacin on microorganism: host cell interaction.

Recent evidence indicates that certain antibiotics affect bacterial adherence and phagocyte-micro-organism interactions. These interactions are important in the early stages of bacterial pathogenesis, that is, attachment to mucosal surfaces and invasion. Among the antibiotics of interest in this field are the fluoroquinolones. Sub-MICs of pefloxacin can alter the ability of Gram-positive cocci (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative bacilli (Escherichia coli) to adhere to different eukaryotic cells (uroepithelial and buccal cells) and to fibrin-platelet matrices. The mechanism by which pefloxacin reduces adhesion is not completely understood. However in the case of Esch. coli, the inhibition of haemagglutination and adherence corresponds to: (1) a decrease in production of fimbriae; (2) changes in the composition of outer membrane proteins; and (3) an effect on partition coefficient (carried out with the PEG/dextran system) which can be attributed to changes in electric and/or hydrophobic properties of the Esch. coli surface. The first step of phagocytosis is represented by adherence of opsonized bacteria to the membrane receptors of phagocytes. Consequently, the action of pefloxacin on phagocytosis is also of importance. Pretreatment of bacteria (Staph. aureus, Ent. faecalis, Esch. coli and Legionella pneumophila) with 1/4 the MIC of pefloxacin leads to an increase in uptake of the different strains by phagocytes (polymorphonuclear leucocytes and macrophages). Exposure of the phagocytes to 10 mg/l of pefloxacin enhances phagocytosis of strains that have not been pretreated. Finally, entry of antibiotics into phagocytic cells is a prerequisite for activity against intracellular organisms. The concentration of pefloxacin by polymorphs and macrophages is high (intracellular concentration/extracellular concentration = 5-10). Such findings correlate well with the intracellular activity of pefloxacin, demonstrated with guinea pig macrophages and different bacteria (Staph. aureus, L. pneumophila).

Bacterial Adhesion↗

[Comparative study of intramacrophagic penetration and action on phagocytosis of a macrolide (spiramycin) and a fluoroquinolone (pefloxacin)].

Antibiotic-phagocyte interaction is an important parameter involved in the elimination process of intracellular bacteria. The aim of the present study was to compare, using the same model, the phagocytic uptake and the intracellular activity of a macrolide and a quinolone. Accumulation of spiramycin and pefloxacin by guinea pig peritoneal macrophages (GPpM) was studied by means of a velocity-gradient centrifugation technique and expression of the ratio of the cellular concentration of antibiotic to the extracellular concentration (IC-EC). Three aspects of Staphylococcus aureus (209-P) phagocytosis were studied: 1) the phagocytic capacity (PC), mean number of ingested cocci by GpPM; 2) the phagocytic activity (PA), percentage of phagocyting GpPM with at least one bacterium; 3) the number of intracellular viable bacteria (IVB). Phagocytic capacity and phagocytic activity were determined by fluorescence microscopy using S. aureus stained with acridine orange. Intracellular viable bacteria were quantified by standard colony counts (CFU). The ratios of intracellular to extracellular concentration of pefloxacin and spiramycin are respectively 9 and 23. Pretreatment of guinea-pig peritoneal macrophages with 10 mg/l of each antibiotic does not modify phagocytic capacity and phagocytic activity, but lead to a decrease of intracellular viable bacteria. S. aureus pretreatment with 1/4 the MIC of each antibiotic increased phagocytic capacity and phagocytic activity and decrease intracellular viable bacteria (especially spiramycin).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effect of sub-inhibitory concentrations of cefixime on the morphology, hemagglutination and adhesiveness of urinary strains of Escherichia coli].

The treatment of urinary tract infections is one of the indications of cefixime, a new oral cephem. The aim of the present work was to study the in vitro effect of cefixime sub- and infra-MICs on the morphology, haemagglutination and adhesiveness to epithelial cells of three uropathogenic Escherichia coli strains pretreated with sub-MICs (1/2 to 1/64 the MIC) of cefixime during growth phase (37 degrees C for 18 h). This treatment led to morphological alterations of the bacteria with filament formation. The E. coli strains showed different haemagglutination profiles (MS; MS-MR; MR). In the presence of cefixime sub-MICs (1/2 to 1/32 the MIC), MR E. coli showed a markedly altered capacity for haemagglutination (using guinea pig, human P1 and p erythrocytes). Adhesiveness was studied with human buccal cells for MS adhesins and human urothelial cells for MR adhesins. A significant decrease of adherence (70-90 per cent) was observed after pretreatment of E. coli strains with cefixime (up to 1/32 the MIC). Compared with other antibiotics active against E. coli, such as nalidixic acid, norfloxacin and ampicillin, the effect of 1/8 the MIC of cefixime on adhesiveness, was more pronounced. These results demonstrate that sub-MICs of cefixime induce a marked reduction in adhesiveness of E. coli. This property might potentiate the effectiveness of cefixime in the treatment of urinary tract infections due to E. coli.

Animals↗

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↗

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↗

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↗

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↗

[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↗