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J F Desnottes

Publications and source records attributed to J F Desnottes.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and activities of pyoverdin-quinolone adducts: a prospective approach to a specific Therapy against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is particularly resistant to most all the antibiotics presently available, essentially because of the very low permeability of its outer membrane. To overcome this, we synthesized four siderophore-based antibiotics formed by two quinolones - norfloxacin and benzonaphthyridone - bound to the pyoverdin of P. aeruginosa ATCC 15692 via two types of spacer arms: one stable and the other readily hydrolyzable. From the comparison of their antibacterial properties with those of the two unbound quinolones, we reached the following conclusions: (a) The adducts inhibit Escherichia coli's gyrase showing that the dissociation of the compounds is not necessary for their activity. However, the presence of the pyoverdin moiety on the molecule decreases the inhibition activity compared to the antibiotic alone. (b) They facilitate the uptake of (55)Fe using the specific pyoverdin-mediated iron-transport system of the bacterium. No uptake was observed either with P. aeruginosa ATCC 27853, which produces a structurally different pyoverdin, or with P. aeruginosa K690, which is a mutant of P. aeruginosa ATCC 15692 lacking FpvA, the outer-membrane pyoverdin receptor. (c) MIC determinations have shown that only strains P. aeruginosa ATCC 15692 and the derived outer-membrane receptor-producing but pyoverdin-deficient P. aeruginosa IA1 mutant present higher susceptibility to the pyoverdin-quinolone adducts, whereas P. aeruginosa ATCC 27853 and K690 are much more resistant. (d) Growth inhibition by these adducts confirmed these results and showed that the adducts with the hydrolyzable spacer arm have better activity than those with the stable one and that the labile spacer arm adducts present much higher activity than the quinolones alone. These results show clearly that the penetration of the antibiotic into the cells is favored when this latter is coupled with pyoverdin: Only the strains possessing the appropriate outer-membrane receptor present higher susceptibility to the adduct. In this case the antibiotic uses the pyoverdin-mediated iron-transport system. Furthermore, better efficiency is obtained when the spacer arm is labile and favors the antibiotic release inside the cell, allowing better inhibition of gyrase.

Anti-Infective Agents↗
PubMed1999

[New targets in the field of antibacterial agents. Prospective aspects].

Even though a great number of antibiotics and antiseptic agents are available at present, these substances are often rendered ineffective by the capacity of bacteria to develop resistance to them. The importance of continuing research in this area cannot be sufficiently stressed. Of the various strategies likely to yield innovative products in the future, two can be applied not only to the search for new antibiotics, but also for finding new antiseptics. Numerous Gram-negative, as well as some Gram-positive, bacteria have efflux systems by which they excrete toxic substances, in particular, antibiotics. Because bacterial efflux pumps differ from those in eukaryotic cells, it should be possible to find inhibitors that are specific for the bacterial pumps. The colonization of biological supports by bacteria leads to the development of biofilms, which are highly resistant to both antiseptics and antibiotics. Bacteria that grow and persist within the biofilm differ metabolically from bacteria growing freely in culture. The study of the various steps in the colonization of supports might provide clues to the discovery of products that could penetrate the exopolysaccharide layer which forms the biofilm and that would be active against bacteria in this particular metabolic state.

Anti-Bacterial Agents↗
PubMed1998

Recent developments in streptogramin research.

The streptogramins are a class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally, but the therapeutic use of the natural compounds is limited because they do not dissolve in water. New semisynthetic derivatives, in particular the injectable streptogramin quinupristin/dalfopristin, offer promise for treating the rising number of infections that are caused by multiply resistant bacteria. The streptogramins consist of two structurally unrelated compounds, group A and group B. The group A compounds are polyunsaturated macrolactones: the group B compounds are cyclic hexadepsipeptides. Modifications of the group B components have been mainly performed on the 3-hydroxypicolinoyl, the 4-dimethylaminophenylalanine and the 4-oxo pipecolinic residues. Semi-synthesis on this third residue led to the water-soluble derivative quinupristin. Water-soluble group A derivatives were obtained by Michael addition of aminothiols to the dehydroproline ring of pristinamycin IIA. Followed by oxidation of the intermediate sulfide into the sulfone derivatives (i.e., dalfopristin). Water-soluble derivatives (both group A and group B) can now be obtained at the industrial scale. Modified group B compounds are now also being produced by mutasynthesis, via disruption of the papA gene. Mutasynthesis has proved particularly useful for producing PIB, the group B component of the oral streptogramin RPR 106972. The streptogramins inhibit bacterial growth by disrupting the translation of mRNA into protein. Both the group A and group B compounds bind to the peptidyltransferase domain of the bacterial ribosome. The group A compounds interfere with the elongation of the polypeptide chain by preventing the binding of aa-tRNA to the ribosome and the formation of peptide bonds, while the B compounds stimulate the dissociation of the peptidyl-tRNA and may also interfere with the release of the completed polypeptide by blocking its access to the channel through which it normally leaves the ribosome. The synergy between the group A and group B compounds appears to result from an enhanced affinity of the group B compounds for the ribosome. Apparently, the group A compound induces a conformational change such that B compound binds with greater affinity. The natural streptogramins are produced as mixtures of the group A and B compounds, the combination of which is a more potent antibacterial agent than either type of compound alone. Whereas the type A or type B compound alone has, in vitro and in animal models of infection, a moderate bacteriostatic activity, the combination of the two has strong bacteriostatic activity and often bactericidal activity. Minimal inhibitory concentrations of quinupristin/dalfopristin range from 0.20 to 1 mg/l for Streptococcus pneumonae, from 0.25 to 2 mg/l for Staphylococcus aureus and from 0.50 to 4 for Enterococcus faecium, the principal target organisms of this drug. Quinupristin/dalfopristin also has activity against mycoplasmas, Neisseria gonorrhoeae, Haemophilus influenz, Legionella spp. and Moraxella catarrhalis. Bacteria develop resistance to the streptogramms by ribosomal modification, by producing inactivating enzymes, or by causing an efflux of the antibiotic. Dimethylation of an adenine residue in rRNA, a reaction that is catalyzed by a methylase encoded by the erm gene class, affects the binding of group B compounds (as well as the macrolides and lincosamides; hence, MLSB resistance), but group A and B compounds usually maintain their synergy and their bactericidal effect against MLSB-resistant strains. erm genes are widespread both geographically and throughout numerous bacterial genera. Several types of enzymes (acetyltransferases, hydrolases) have been identified that inactivate the group A or the group B compounds. Genes involved in streptogramin efflux have so far been found only in staphylococci, particularly in coagulase-negative species

Animals↗
PubMed1997

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↗
PubMed1997

In-vitro bactericidal activity of quinupristin/dalfopristin against adherent Staphylococcus aureus.

A simple in-vitro assay was developed to test antibiotics for bactericidal activity against Staphylococcus aureus adhering to an artificial biomaterial. The activity of the semisynthetic injectable streptogramin quinupristin/dalfopristin combination was evaluated with this assay and compared with that of vancomycin. Fibronectin-coated nylon membranes were used to mimic implanted biomaterial. To obtain adherent bacteria, 400 microL of a suspension of S. aureus strain Wood (5 x 10(6) cfu/mL) were placed for 1.5 h at 37 degrees C in contact with the membranes. After elimination of non-adherent bacteria by successive rinses, membranes were exposed to antibacterial agents at concentrations of 5, 10 and 50 x MIC. Drug-free controls were also prepared. After various incubation times, bacteria on both treated and control membranes were removed by sonication and subcultured on to agar medium. After incubation, the number of cfu on treated membranes was compared with that on t0 control membranes. The criterion for bactericidal activity was a 99.9% reduction of the t0 control inoculum. Under these experimental conditions, both quinupristin/dalfopristin and vancomycin, at concentrations achievable in blood (6.25 and 20 mg/L, respectively), demonstrated a potent bactericidal activity against S. aureus adhering to a support. The bactericidal effect of quinupristin/dalfopristin was more rapid than that of vancomycin. Quinupristin/dalfopristin may therefore be a useful alternative to vancomycin in the treatment of implant-associated S. aureus infections.

Anti-Bacterial Agents↗
PubMed1997

Glycosylated flavones as selective inhibitors of topoisomerase IV.

Three flavonoids which promoted Escherichia coli topoisomerase IV-dependent DNA cleavage were isolated from cottonseed flour and identified as quercetin 3-O-beta-D-glucose-[1,6]-O-alpha-L-rhamnose (rutin), quercetin 3-O-beta-D-galactose-[1,6]-O-alpha-L-rhamnose, and quercetin 3-O-beta-D-glucose (isoquercitrin). The most active one (rutin) also inhibited topoisomerase IV-dependent decatenation activity (50% inhibitory concentration, 64 microg/ml) and induced the SOS response of a permeable E. coli strain. Derivatives of quercetin glycosylated at position C-3 were shown to induce two site-specific DNA cleavages of pBR322 DNA, which were mapped by DNA sequence analysis to the gene encoding resistance to tetracycline. Cleavage at these sites was hardly detectable in cleavage reactions with quercetin or fluoroquinolones. None of the three flavonoids isolated from cottonseeds had any stimulatory activity on E. coli DNA gyrase-dependent or calf thymus topoisomerase II-dependent DNA cleavage, and they were therefore specific to topoisomerase IV. These results show that selective inhibitors of topoisomerase IV can be derived from the flavone structure. This is the first report on a DNA topoisomerase inhibitor specific for topoisomerase IV.

Base Sequence↗
PubMed1996

New targets and strategies for the development of antibacterial agents.

The increasing incidence of bacterial drug-resistance is stimulating the development of strategies targeting previously unexploited mechanisms of antibiotic action. Combinatorial chemistry, which generates molecularly diverse compounds, target-directed strategies, and high-throughput screens are being used to detect potential antibacterial agents. Bacterial DNA replication and cell division are the targets of new screening methods, as are membrane proteins, particularly those constituting efflux pumps; two-component signalling systems are also being targeted. Secondary-screening methods are being developed to find antibiotics that destroy slowly growing or resting bacteria, and to evaluate whether new antibiotics will be active against intracellular bacteria.

Anti-Bacterial Agents↗
PubMed1995

Bactericidal activity and kinetics of RP 59500 in a mouse model of Staphylococcus aureus septicaemia.

The bactericidal activity of RP 59500, a semisynthetic streptogramin, was compared with that of vancomycin against Staphylococcus aureus. This activity was evaluated in vitro by the kill curve method and in vivo using a model of mouse septicaemia. In vitro, RP 59500 (MIC = 0.12 mg/L) was more rapidly bactericidal against S. aureus IP 8203 than was vancomycin (MIC = 1 mg/L). In vivo, RP 59500 (120 mg/kg) was bactericidal against staphylococci in the blood of infected mice 1 h after administration, an effect which lasted for up to 7 h, whereas vancomycin at the same dose was bactericidal only 4 h after administration. The serum concentrations of vancomycin were higher than those of RP 59500 for at least 4 h after administration, and the Cmax and AUC of vancomycin were 4.8 and 8.3 times higher, respectively, than those of RP 59500 (Cmax = 13.2 mg/L; AUC0(-1) = 15.2 mg/L/h), although the agents had similar elimination half-lives (about 0.5 h). RP 59500 was also administered to mice as a fractionated dose (30 mg/kg x 4, 40 mg/kg x 3, 60 mg/kg x 2). The onset of its bactericidal effect was delayed by fractionating the dose, but the suppression of bacteria in the blood was prolonged.

Animals↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

Influence of sub-inhibitory concentrations of antibacterials on the surface properties and adhesion of Escherichia coli.

The effect of sub-inhibitory concentrations of antibacterials, including quinolones, on the surface properties of a uropathogenic strain of Escherichia coli was examined. The effect on the charge and hydrophobicity of the cell surface was assessed by means of partition between two aqueous phases, polyethylene glycol and dextran. Antibiotics at 1/8 x MIC inhibited adhesion to uroepithelial cells, and induced an increase in bacterial charge and hydrophobicity. Inhibition of adhesion correlated with increased charge, but not with hydrophobicity. The influence of magnesium on the inhibition of adhesion by sub-MICs of pefloxacin was also investigated. Loss of the anti-adhesive property of pefloxacin was observed with increasing magnesium concentrations, suggesting that quinolones should be free from magnesium to induce an inhibition of adhesion. Examination by electron microscopy showed a disappearance of fimbriae following treatment of E. coli cells with 1/8 x MIC of pefloxacin.

Anti-Bacterial Agents↗
PubMed1992

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↗
PubMed1991

Effect of oral spiramycin on the faecal and oral bacteria in human volunteers.

Six healthy adult volunteers were treated with 1 g of oral spiramycin twice daily for five days, and their oral and faecal microbial flora were studied. Mean saliva and serum concentrations of the antibiotic never exceeded 2.1 +/- 1.1 mg/l. The number of volunteers whose oral cavity was colonized by Enterobacteriaceae, group D streptococci, staphylococci, and fungi remained unchanged following treatment. The mean count of anaerobic faecal bacteria was 10.3 +/- 0.6 log10 cfu/g initially. This did not change significantly during the treatment, nor did the composition of the predominant anaerobic flora. Mean counts of group D streptococci were 1000 times lower than those of anaerobes before treatment, and also remained unchanged during therapy. No overgrowth of fungi, staphylococci, or Pseudomonas aeruginosa was observed. No significant modifications occurred in the mean total count of faecal Enterobacteriaceae (7.9 +/- 0.4 versus 7.4 +/- 1.0 log10 cfu/g of faeces before and during treatment respectively). However, faecal concentrations of highly spiramycin-resistant Enterobacteriaceae (MIC greater than or equal to 512 mg/l) increased from 4.8 +/- 1.2 to 7.0 +/- 1.8 log10 cfu/g during treatment. The MIC50 value of spiramycin for anaerobes, Enterobacteriaceae, and group D streptococci were 0.125, 64, and 0.5 mg/l respectively before treatment, and these increased to 1024, 512 and 1024 mg/l respectively during treatment. This was attributed to the rise in the faecal concentrations of spiramycin, which reached 689 +/- 48 micrograms/g of faeces on the fifth day of treatment. These concentrations decreased rapidly on cessation of treatment.

Administration, Oral↗
PubMed1990

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↗
PubMed1990

Cellular uptake, localization and activity of fluoroquinolones in uninfected and infected macrophages.

Pefloxacin, like other fluoroquinolones, accumulates in macrophages and several other types of nucleated cells (but not in erythrocytes). Upon fractionation of macrophage homogenates by isopycnic centrifugation in sucrose gradients, fluoroquinolones are not found associated with any specific cellular structure. We have compared the activities of pefloxacin and roxithromycin against intracellular Staphylococcus aureus in mouse J774 macrophages. Pefloxacin was significantly more active for equivalent intracellular drug concentrations (i.e. expressed by reference to the respective MICs of the drugs as determined in broth), suggesting differences in intracellular availability and/or capacity of the drugs to express their activity in the intracellular environment. The difference was enhanced by incubating the cells in acidic medium. We have also examined the cellular pharmacokinetics and intracellular distribution of pefloxacin in uninfected and Legionella pneumophila infected guinea pig macrophages. In contrast to uninfected cells from which pefloxacin was quickly released, macrophages infected with legionella retained approximately 20-30% of the accumulated pefloxacin after a 60-min wash-out. Cell fractionation studies indicated that the drug remaining in cells was associated with components of high buoyant density. These fractions also contained [3H] if cells had been incubated with [3H] labelled legionella (by in-vitro exposure to [3H]-thymidine, before phagocytosis). These results suggest that part of the intracellular pefloxacin becomes associated with legionella, or with legionella-containing cytoplasmic structures.

Animals↗
PubMed1990

[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↗
PubMed1989

[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↗