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J C Pechère

Publications and source records attributed to J C Pechère.

At least 91 records · Page 5Linked to original sources
PubMed1989

In vitro effects of three new 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) on Toxoplasma gondii.

The in vitro effects of three synthetic, cis-fused, bicyclic 1,2,4-trioxanes (pentatroxane, thiahexatroxane, and hexatroxanone) against intracellular Toxoplasma gondii were studied. Unactivated peritoneal macrophages were infected with the virulent RH strain of T. gondii and exposed to the 1,2,4-trioxanes at different concentrations. The antitoxoplasmic activity of the drugs was first assessed with [3H]uracil, which is incorporated by the parasite but not the host cell. Pentatroxane and thiahexatroxane were the most active, exhibiting 90% inhibitory concentrations of 6.8 and 5.3 micrograms/ml, respectively. Furthermore, microscopic examination of the infected macrophages after treatment with pentatroxane, thiahexatroxane, and hexatroxanone at their respective 90% inhibitory concentrations confirmed the inhibition of intracellular growth of T. gondii. Their activities were comparable to those of pyrimethamine (1 micrograms/ml) and pyrimethamine (0.1 micrograms/ml) in combination with sulfadiazine (25 micrograms/ml). Pentatroxane and thiahexatroxane were also able to inhibit intracellular growth of T. gondii within nonprofessional phagocytes (HeLa cells), suggesting that the antitoxoplasmic activity was not caused by a macrophage-specific mechanism, such as macrophage activation. However, the 1,2,4-trioxanes were not active against extracellular T. gondii. Pentatroxane and thiahexatroxane are new, promising compounds that deserve further study to assess their usefulness for treating toxoplasmosis.

Animals↗
PubMed1989

Synergistic effect of quinolones and oxacillin on methicillin-resistant Staphylococcus species.

Various combinations of antistaphylococcal antimicrobial agents have been tested against 17 selected Staphylococcus isolates, including methicillin-susceptible and methicillin-resistant strains of S. aureus and coagulase-negative Staphylococcus species. With the checkerboard technique the following combinations were tested: oxacillin-ofloxacin, oxacillin-temafloxacin, oxacillin-fleroxacin, vancomycin-fleroxacin, gentamicin-fleroxacin, and rifampin-fleroxacin. Against methicillin-resistant staphylococci the combination oxacillin-quinolone tested at 35 degrees C always showed a fractional inhibitory concentration (FIC) index of less than 0.75, which is interpreted as synergistic or additive. Equal or more synergistic effects were observed at 30 degrees C. In contrast, when methicillin-susceptible Staphylococcus species were tested, the FIC for the combination oxacillin-quinolone was always 1 or 2, which is considered to be indifferent. For the other mentioned combinations the FICs were also 1 or 2. Killing kinetics showed synergistic or additive bactericidal activity for the combination oxacillin-ofloxacin against methicillin-resistant Staphylococcus species, killing 1.5 to 2.8 log10 CFU more of these per ml than did the most active drug after 24 h of incubation. This difference was not observed for methicillin-susceptible strains. In vitro evidence for the potential clinical use of quinolones in treating infections due to methicillin-resistant staphylococci in combination with a beta-lactamase-resistant penicillin is provided.

4-Quinolones↗
PubMed1989

Permeability and penicillin-binding protein alterations in Salmonella muenchen: stepwise resistance acquired during beta-lactam therapy.

A patient with Salmonella muenchen sepsis was unsuccessfully treated with ampicillin. During therapy, four strains that showed stepwise ampicillin resistance and affected other beta-lactams and unrelated antibiotics were isolated sequentially. Resistance was caused by decreased outer membrane permeability associated with diminished expression of porin OmpF. Furthermore, the most resistant isolate overproduced the PBP 3 target molecule.

Anti-Bacterial Agents↗
PubMed1989

Cellular events and intracellular survival of Campylobacter jejuni during infection of HEp-2 cells.

Invasion and intracellular survival of Campylobacter jejuni in HEp-2 cells were analyzed by transmission electron microscopy and by viable counts after killing of extracellular bacteria by gentamicin. During the first 30 min after challenge, no bacteria were seen in association with the host cell. After 1 h, campylobacters apparently attached to the cell membrane, with areas of close appositions. In these areas, an intracellular network of actin-like filaments was seen beneath the plasma membrane. Other bacteria were included into endocytic vacuoles. After 3 h, an intense lysosomal response was observed in the host cells, as determined by the presence of myelinic forms and acid phosphatase activity. After 9 h, bacteria still contained in vacuoles showed signs of degradation with a change from spiral to coccal forms. Morphological evidence of phagosome-lysosome fusion was also seen, and these observations by transmission electron microscopy correlated well with a decrease in bacteria viability 9 h after challenge, as determined from separate kinetics studies. Inhibitors of phagocytosis were observed to reduce markedly the entry of C. jejuni into the cells at concentrations which apparently did not affect bacterial viability. These results suggest that the campylobacters were successively attached to the HEp-2 cell membrane, internalized by a phagocytic-like mechanism, and digested after phagosome-lysosome fusion.

Acid Phosphatase↗
PubMed1989

Emergence of resistance in gram-negative bacilli during beta-lactam therapy: a challenge for the future.

The means by which gram-negative bacilli can resist newer beta-lactam antibiotics are reviewed. A first situation is generated by mutants which produce great amounts of a chromosomal cephalosporinase. These cells are present (frequency: 10(-4) to 10(-7] within bacterial populations such as Enterobacter cloacae, and multiply after selection during therapy by third-generation cephalosporins or monobactams. A second problem arose by 1985, with the sudden development of plasmid-mediated beta-lactamases markedly active against third-generation cephalosporins. Some recent molecules, such as penems, are not affected by the two mechanisms mentioned above but remain exposed to other resistance problems. Notably Pseudomonas aeruginosa strains can develop resistance during therapy by imipenem thanks to specific alterations of the bacterial outer membrane. As a consequence of these resistance difficulties, new interpretations for susceptibility testing and new therapeutic approaches should be considered.

Anti-Bacterial Agents↗
PubMed1988

Effect of mucin on Campylobacter jejuni association and invasion on HEp-2 cells.

We report the development of an in vitro assay using HEp-2 cell monolayers in which cell association of five C. jejuni strains and E. coli K12 C600 were tested under different experimental conditions. Both total cell associated colony forming units (CFU) and the CFU protected from gentamicin killing (i.e. internalized bacteria) were determined. Pretreatment of HEp-2 cells with mucin (100 micrograms/ml) enhanced internalization of four fresh isolates of C. jejuni by 3.2 to 20.7-fold, depending on the strain, but not internalization of C. jejuni K105 (a stock culture) or E. coli C600. Mucin also increased the total number of cell associated C. jejuni fresh isolates by 2 to 3.4-fold, the four strains yielding similar results. We conclude from these studies that mucin, which has been shown to be a prerequisite of intestinal colonization by C. jejuni, also promotes infectivity.

Campylobacter fetus↗
PubMed1988

Activity of A-56268 (TE-031), a new macrolide, against Toxoplasma gondii in mice.

The activity of A-56268 (TE-031), a new macrolide, was tested in a murine model of acute toxoplasmosis. All control animals died in 8 +/- 1 days, while all mice treated with nine daily doses of A-56268 at 300 mg/kg, administered by gavage, survived. Moreover, 41.6% of the surviving mice were free from cerebral infection with Toxoplasma gondii, as assessed by brain subpassage. A-56268 is active against T. gondii in vivo, but further studies are needed to determine its usefulness in the treatment of human toxoplasmosis.

Animals↗
PubMed1988

Activity of spiramycin against Toxoplasma gondii in vitro, in experimental infections and in human infection.

The in-vitro, experimental and clinical activities of spiramycin against Toxoplasma gondii have been reviewed. In mammalian cells infected by T. gondii as in various experimental models, spiramycin definitively exerts an inhibitory antitoxoplasmic effect which, clinically, seems useful for preventing congenital toxoplasma infection during pregnancy or for reducing the inflammation in toxoplasmic chorioretinitis. However, spiramycin does not kill the parasite efficiently, and cannot be recommended for eradicating the most severe forms of toxoplasmosis.

Animals↗
PubMed1988

In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [CP-62,993], and A-56268) on Toxoplasma gondii.

The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with [3H]uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

Animals↗
PubMed1988

Effect of a single dose of cefotaxime or ceftriaxone on human faecal flora. A double-blind study.

The effect of cefotaxime and ceftriaxone on faecal flora was investigated in women undergoing routine vaginal or abdominal hysterectomy. Three groups of 9 patients received, in a double-blind fashion and just before surgery, cefotaxime 2g intravenously, ceftriaxone 2g intravenously or no antibiotic (controls). Stools were collected before prophylaxis (sample 1) and after surgery (samples 2 and 3). The only alteration after cefotaxime was a decrease of non-fastidious aerobic Gram-negative flora in sample 2. The same effect was more pronounced after ceftriaxone (p less than 0.01) which, in addition, increased yeast colonies (p less than 0.05) in sample 2. In sample 3, more resistant (MIC greater than 32 mg/L) aerobic and anaerobic bacteria were found after ceftriaxone (log10 median 7.5 and 9.0, respectively) than after cefotaxime (4.2 and 6.0) or in controls (4.4 and 6.6) [p less than 0.01 in each case]. Group D streptococci and Gram-positive cocci remained unchanged in the 3 groups. Clostridium difficile cytotoxin assays were negative. The effects on faecal flora were more pronounced after ceftriaxone.

Bacteria, Aerobic↗
PubMed1988

Emergence of resistance during beta-lactam therapy of gram-negative infections. Bacterial mechanisms and medical responses.

Some Gram-negative, non-fastidious bacilli, although classified as susceptible by conventional susceptibility testing methods, become resistant during therapy with the newer beta-lactam compounds. Emergence of resistance results primarily from the selection of resistant clones pre-existing within the susceptible bacterial populations. Most of the resistant clones produce large amounts of beta-lactamases which inhibit the beta-lactam antibiotics by hydrolysis, rather than by binding. In addition, resistant clones can limit the penetration of beta-lactam molecules through the outer membrane by a decreased expression of their porins. Less commonly, when beta-lactamase activity together with alteration of the permeability barrier does not prevent the access of the antibiotic molecules to their target, altered penicillin-binding proteins (PBPs) can produce resistance. However, the risk of resistance emerging during therapy varies with the beta-lactam drug administered. Some compounds such as cefpirome, BMY 28142, SCH 34343, or imipenem appear to be associated with a low risk. In addition, emergence of resistance can be reduced by using higher dosages of beta-lactam agents, or by combining them with other drugs such as aminoglycosides or quinolones.

Animals↗
PubMed1987

Development of beta-lactam-resistant Enterobacter cloacae in mice.

We compared the ability of four newer beta-lactam compounds to produce resistance in an experimental model of Enterobacter cloacae infection. Mice infected intraperitoneally developed resistance depending on antibiotic treatment and the dose given. Percentages of mice in which resistance was observed were as follows: 100% after ceftriaxone (50 mg/kg, two doses); 87% after ceftriaxone (50 mg/kg, one dose); 35% after ceftriaxone (500 mg/kg, one dose); and 21% after carumonam (25 mg/kg, two doses). No resistance occurred after therapy with either BMY 28142 (25 mg/kg, two doses) or Sch 34343 (50 mg/kg, two doses). Heterogeneous resistance to beta-lactams among the cells within a given Enterobacter population accounted for these differences. The minimal concentration inhibiting the growth of the preexisting resistant variants, together with the antibiotic concentrations obtained in the peritoneal fluid, were associated with further emergence of resistance in the mouse treated with this antibiotic.

Animals↗
PubMed1987

Efficacy of different dosing schedules of tobramycin for treating a murine Klebsiella pneumoniae bronchopneumonia.

The efficacy of different dosing schedules of tobramycin for treating a murine Klebsiella bronchopneumonia was compared. Therapeutic efficacy depended upon dosing intervals. In mice treated for four days with a daily dose of 48 mg/kg, dosing intervals of 4 and 8 h allowed cure of 10/10 animals, whereas dosing intervals of 12 and 24 h yielded survival rates of only 6/10 (P less than 0.05) and 2/10 (P less than 0.01) respectively. Although observed in vitro, a post-antibiotic effect of tobramycin against K. pneumoniae was unlikely in vivo since residual concentrations of tobramycin were found in the lung tissue 12 h after dosing, when efficacy starts to decrease. Efficacy also depended to some extent upon the duration of therapy.

Animals↗
PubMed1987

Activity of roxithromycin against Toxoplasma gondii in murine models.

Investigations into the activity of roxithromycin against murine toxoplasma infections are reviewed. Roxithromycin is an active drug against murine toxoplasmosis after intraperitoneal challenge with the RH strain of Toxoplasma gondii. Roxithromycin protected 100% of mice after five daily doses of 540 mg per kg administered by gavage. The cure rate after treatment of peritoneal infections seemed to be related to the length of the therapy. Roxithromycin also decreased the number of toxoplasma cysts, after intracerebral infection with the C56 strain and showed synergistic activity when combined with gamma interferon. Thus, roxithromycin could be a worthwhile alternative to current therapy against toxoplasma infections. Clinical studies on its activity and safety, especially in pregnancy, are warranted.

Animals↗
PubMed1987

Contribution of beta-lactamase hydrolysis and outer membrane permeability to ceftriaxone resistance in Enterobacter cloacae.

Mechanisms of ceftriaxone resistance were examined in Enterobacter cloacae. Clones were selected from four strains: susceptible (S), resistant (R1), selected by plating on ceftriaxone-containing agar, and highly resistant (R2), selected in ceftriaxone-treated mice infected with S clones. According to 14C-labeled beta-lactam binding assays, ceftriaxone resistance was not associated with altered target proteins. R1 and R2 clones stably produced 50 to 1,500 times more beta-lactamase than S clones; this production increased after cefoxitin induction in all S and some R1 clones. Experiments conducted with strain 218 suggested that ceftriaxone resistance involved beta-lactamase hydrolysis. Half-lives for the beta-lactamase-beta-lactam complexes at 37 degrees C were 0.4 and 2.2 min for ceftriaxone and Sch 34343, a drug not affected by the resistance, respectively; in chromatography experiments, 218 intact R1 cells (2 x 10(9) to 3 x 10(9) CFU) suspended in ceftriaxone-containing buffer (2 micrograms/ml) hydrolyzed 80% of the antibiotic in 30 min. Three observations also suggested decreased permeability in some clones, (i) Most of the R1 and R2 clones showed decreased expression of outer membrane proteins of 37,000 to 38,000 molecular weight (37K to 38K proteins) by electrophoresis, often associated with increased amounts of 42K protein. (ii) [14C]Sch 34343 labeling of intact cells proceeded more slowly in 218 R2 (with altered 37K to 38K proteins) than in 218 R1 (without this alteration), a difference persisting after competition with unlabeled cloxacillin. Delays in binding were not caused by different enzymatic activities, since 218 R1 and 218 R2 produce, in similar amounts, beta-lactamases undistinguishable in isoelectric point and Km of cephaloridine. (iii) Intact cells from 218 R2 hydrolyzed ceftriaxone more slowly (20% in 30 min) than did those from 218 R1. In 218 R1, beta-lactamase overproduction was responsible for a 15- to 200-fold increase in the MIC's of ceftriaxone, ceftazidime, carbenicillin, piperacillin, moxalactam, aztreonam, carumonam, and BMY 28142. Imipenem and Sch 34343 were not affected; an additional three- to fivefold increase in the MIC's of these antibiotics (with the exception of piperacillin, imipenem, Sch 34343), seen with 218 R2, was associated with decreased permeability.

Anti-Bacterial Agents↗
PubMed1987

Resistance occurring after fluoroquinolone therapy of experimental Pseudomonas aeruginosa peritonitis.

Resistance emerging after fluoroquinolone therapy was investigated in a murine model of Pseudomonas aeruginosa infection. Mice were infected intraperitoneally by one of six strains and treated with pefloxacin or ciprofloxacin. In mice challenged with a low inoculum (1.6 X 10(5) CFU), no resistance occurred. With a higher inoculum (1.5 X 10(8) CFU) and after a single dose of antibiotic, posttherapy (PT1) strains with decreased susceptibility to quinolones (4- to 32-fold less) were isolated at a variable rate. The presence of talcum (125 mg) in the peritoneal cavity increased the risk of resistance after therapy. Pefloxacin (25 or 200 mg/kg) and ciprofloxacin (25 mg/kg) yielded similar resistance rates (61 to 77%), but ciprofloxacin (10 mg/kg) produced more resistance (83%) than did ciprofloxacin (50 mg/kg) (44%) (P less than 0.02). Combined with a quinolone, ceftazidime (P less than 0.001) or amikacin (P less than 0.01), but not piperacillin, reduced the emergence of resistance. After several doses of ciprofloxacin, it was found that 25-mg/kg doses every 12 h produced more resistance than did 25-mg/kg doses every 8 h or 50-mg/kg doses every 12 h. Compared with the preceding experiments using parent strains, ciprofloxacin and pefloxacin were less efficient in killing bacteria in mice infected with PT1 strains. Moreover, in one of these mice, a highly resistant PT2 strain (64-fold MIC increase for the quinolones) emerged. Besides increased MICs of the quinolones, there was a two- to eightfold increase in imipenem MIC for all PT1 and PT2 strains without alteration of other beta-lactam and aminoglycoside susceptibility. Some PT1 strains also showed a decreased susceptibility to trimethoprim and chloramphenicol. During therapy with a quinolone, resistance can emerge rapidly, especially when there is a large number of bacteria or a foreign body present. This risk may depend on the dosing schedule and may be reduced by combined therapy.

Animals↗