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Biomedical subjects

R Marre

Publications and source records attributed to R Marre.

At least 127 records · Page 7Linked to original sources
PubMed1986

[Ciprofloxacin and cefotaxim: pharmacokinetic and therapeutic effectiveness in E. coli pyelonephritis in rats].

Ciprofloxacin was tested in the acute and chronic experimental E.coli pyelonephritis in rats. Its therapeutic efficacy was compared with that of cefotaxime. In the acute pyelonephritis increasing doses resulted in increasing elimination of bacteria from the kidneys. Ciprofloxacin and cefotaxime showed no difference in the efficiency in therapy of the acute pyelonephritis. In chronic pyelonephritis ciprofloxacin proved to be more effective than cefotaxime in spite of identical in vitro activity. Pharmacokinetic data showed that ciprofloxacin was eliminated more slowly than cefotaxime. The long serum half-life and the high volume of distribution could be responsible for the high therapeutic efficacy and could outweigh the disadvantage of metabolic instability.

Acute Disease↗
PubMed1985

Renal tolerance of imipenem/cilastatin and other beta-lactam antibiotics in rats.

Imipenem is inactivated by the renal dehydropeptidase I, which can be inhibited by cilastatin. Therefore, both compounds are administered in combination. According to the manufacturers, they are not nephrotoxic in rats. 70 female Wistar rats (n = 10/test series) were treated over five days at dosage intervals of 12 hours with intraperitoneal injections (injection volume: 10 ml/200 g body weight) of isotonic 0.9% NaCl, cilastatin (1000 mg/kg/day), imipenem (500 and 1000 mg/kg/day), cilastatin + imipenem (500 or 1000 mg/kg/day each) and cefsulodin (1000 mg/kg/day). The nocturnal excretion of renal tubular cells was determined. Furthermore, three rats in each test were treated intraperitoneally with 150 mg/kg imipenem or with the combination of imipenem and cilastatin (150 mg/kg each). Imipenem concentrations were measured over four hours in the blood of the tail vein. Commencing on the second day of study, cilastatin, imipenem and the combination of both substances induced significant surplus excretion of tubular cells compared to the control group. The tubulotoxic effects of imipenem and imipenem + cilastatin in combination were dose-dependent. The toxic effects of imipenem, imipenem + cilastatin and cefsulodin did not significantly differ. Cilastatin prolonged the half-life of imipenem in the blood from 0.4 to 0.9 h and increased the AUC of imipenem from 156 to 325 mg/l/h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The therapeutic response of cephalosporin-treated E. coli pyelonephritis of the rat, in relation to variations of the infection model.

In the E. coli pyelonephritis, induced in female Wistar rats by retrograde infection (high pressure reflux), we investigated the influence of 1) the time of commencement of therapy, 2) the renal bacterial counts, i.e. the inflammatory activity of the pyelonephritis after endovesical instillation of cultures with different bacterial concentrations, and 3) the level of infection resistance of the experimental animal strain on the therapeutic response of the model infection with single doses of cefoxitin (150 mg/ml) and cefotaxime (5 mg/ml). Early commencement of therapy post inoculation was therapeutically advantageous provided the intrarenal multiplication of the infective organisms was not delayed or the initial bacterial concentrations were not too high. The mild form of pyelonephritis with lower renal bacterial concentrations and poor inflammatory activity after endovesical instillation of a low inoculum (10(4) cfu/ml) was less amenable to treatment than the inflammatory active pyelonephritis with high renal bacterial counts, using a high inoculum (10(7) cfu/ml). High renal bacterial counts after retrograde inoculation of an E. coli culture of 10(8) cfu/ml resulted in significant reduction of bacterial counts 48, 72 and 96 h post infectionem, with i.m. application of cefoxitin 12 h prior. For Wistar rat strain Bor:WIST, which showed a stronger infection resistance with lower renal bacterial concentrations and a stronger tendency to spontaneous healing, application of a single dose of cefotaxime (5 mg/ml) was therapeutically ineffective, whereas, in contrast, with Han: WIST rats the acute phase of E. coli pyelonephritis could be treated effectively.

Animals↗
PubMed1985

Bactericidal activity and induction of cell volume alterations of cephalosporins in Escherichia coli.

The bactericidal efficacy of cefuroxime and cephacetril on Escherichia coli cultures was measured by killing curves. Simultaneously bacterial cell volumes were analysed by electronic particle counting using a Coulter Counter Channelanalyser system in order to study the relationship between bactericidal activity and bacterial cell volume alterations. Various concentrations (2-120 mg/l cefuroxime and 16-120 mg/l cephacetril) and different exposure times (over a time period of 12 h) were used. Growth medium was human plasma ultrafiltrate. The bactericidal activity of cefuroxime, as measured by the rate of killing of the E. coli culture, was independent of the concentration and constant in the range 4-120 mg/l. The characteristic cefuroxime-induced change in bacterial cell volume was a marked volume increase up to a maximum of 5-fold after 160-200 min exposure with a low-grade bacteriolysis following. The cefuroxime-induced bacterial volume changes were, in accordance with the bactericidal testing, almost independent of the concentration. In contrast, the killing curves for cephacetril strongly depended on the drug concentration. However, this effect was short-lived and regrowth of the E. coli culture followed. The typical cephacetril-induced volume distribution curves were also highly concentration-dependent. With increasing drug levels bacterial cell volume increased up to 20-fold, and regrowth of a persisting bacterial population occurred at lower antibiotic concentrations. Bacteriolysis started earlier than with cefuroxime. The relationship between loss of viability and cell volume increase was more marked with cefuroxime than with cephacetril.

Autoanalysis↗
PubMed1985

Habekacin: nephrotoxicity, pharmacokinetics and prophylactic efficacy in rats.

1-N[(S)-4-amino-2-hydroxybutyryl]-kanamycin B (habekacin), a new aminoglycoside antibiotic found in 1973 was tested for its nephrotoxicity, pharmacokinetics and prophylactic efficacy in 351 female rats. Increased urinary elimination of tubule cells and malate dehydrogenase (MDH) demonstrated tubulotoxicity even at the minimal dosage of 2.5 mg/kg/d. At high dosages (100 or 50 mg/kg/d) habekacin produced more tubule damage than dibekacin. At lower dosages (20, 10 or 5 mg/kg/d) both aminoglycosides showed similar effects. Additionally, possible glomerular lesions were found at high dosages (100 mg/kg/d) as indicated by proteinuria, CAF (cellulose acetate foil)-electrophoresis of the urinary protein and raised albumin/globulin ratio. - Pharmacological studies revealed serum concentrations similar to dibekacin, in renal tissue, however, the concentrations of habekacin were much higher than those of dibekacin. - In experimental E. coli pyelonephritis, 9 single doses of habekacin or dibekacin (5 mg/kg) given prophylactically reduced the bacterial counts significantly; a single dose of the antibiotics (5 mg/kg) was slightly effective.

Aminoglycosides↗
PubMed1985

Nocardial infection in a renal transplant recipient--a case report.

Report is given about a 50 year old renal transplant recipient who developed signs of a severe pneumonia 37 days post transplantation. The diagnosis following chest X-ray and physical examination was multifocal nodular pneumonia of unknown origin in an immunosuppressed patient. Although a varying antibiotic chemotherapy was administered at high doses he died 4 weeks later without identification of the infective agent. Post-mortem and microbiological examinations revealed a systemic suppurative infection caused by Nocardia asteroides. Percutaneous or open lung biopsy within the first 10 days after onset of clinical symptoms has to be recommended to secure the diagnosis and treatment with sulphonamides.

Abscess↗
PubMed1984

Standardization of a model of E. coli-pyelonephritis in rats.

The validity of preclinical testing of antibiotics in animal experiments is highly dependent on the quality and, especially, the standardizability of the infection model. Some of the factors associated with standardization of the acute phases of infection are demonstrated for experimental pyelonephritis in female albino Wistar rats after transuretheral infection. The renal bacterial count and infection rate are correlated to the volume and bacterial concentration of the instilled E. coli suspension. Strains of albino Wistar rats from different breeding institutions show differing resistance to the infection. E. coli pyelonephritis establishes more easily in female Wistar rats of strain Han: WIST than in strain Bor: WIST. Following dissection of the animals, the infected kidneys can be stored for at least 4 weeks at -30 degrees C or in liquid nitrogen, because the bacterial counts remain constant. However, in frozen renal homogenates the bacterial counts fall rapidly. During the first 4 post-infection days the bacterial content of the kidneys is relatively constant. The period 30-72 h post infection is especially suitable for therapeutic studies.

Animals↗
PubMed1984

Analysis of cephalosporin-induced changes in the volume distribution of Escherichia coli cultures by an electronic counter-channelanalyser.

The demonstration of morphological alterations of the bacterial cell together with bactericidal kinetics are of value for the description of the antibacterial activity of beta-lactam antibiotics. One of the indicators of antibiotic effect on bacterial morphology is the change in bacterial cell volume. This can be demonstrated graphically and numerically by means of electronic cell counting and volume distribution analysis using the Coulter Counter-Channelanalyser system connected to a computer. After registration of the distribution of the relative volume of the Escherichia coli population, the mean cell volume was calculated. The latter parameter increased more than 6 fold with increasing cefotaxim-exposure times. The onset of the delayed (2 h after cefotaxim administration) bacteriolytic effect was reorganized by the appearance of small cell breakdown particles and quantified by counting. In order to demonstrate the therapeutic process graphically the distribution curves were transformed to a common scale. Since a complete storage of the data per sample is performed normally within one minute, the Coulter Counter-Channelanalyser technique can be carried out simultaneously with the bactericidal kinetic experiment. The data demonstrate the speed and intensity of the morphological cell alterations induced by the beta-lactam antibiotic.

Bacteriological Techniques↗
PubMed1984

Different mechanisms of TEM-1 and Oxa-1 mediated resistance to piperacillin in E. coli.

Clinical isolates of Oxa-1 and TEM-1 producing strains of E. coli were studied. Susceptibility to piperacillin was determined by the agar and broth dilution procedure, and beta-lactam hydrolysis rates measured by the iodometric method. The beta-lactamases were identified by isoelectric focusing. Our data on TEM-1 producing strains showed a statistically significant correlation between the MIC, if determined by the agar dilution test, and the specific beta-lactamase activity. The majority of Oxa-1 producing E. coli was resistant to piperacillin although the inactivation rate of piperacillin was usually low. Cell wall permeability of TEM-1 producing strains of E. coli to piperacillin was below the lower limit of detectability, but preincubation of the E. coli strains in piperacillin containing broth led to increased cell wall permeability. Bactericidal kinetics of an Oxa-1 and TEM-1 E. coli were studied. It revealed that regrowth of the Oxa-1 strain in piperacillin containing broth was associated with a 25% decrease of piperacillin concentrations without the formation of degradation products, suggesting binding of piperacillin to bacterial cells. The TEM-1 plasmid bearing strain inactivated piperacillin, and the degradation products (penicilloate) could be detected.

Bacteriolysis↗
PubMed1984

Renal tolerance and pharmacokinetics of vancomycin in rats.

The nephrotoxicity, as measured by urinary cell and enzyme excretion, of vancomycin was studied in rats. The lowest daily iv dose inducing significantly increased cell elimination was 25 mg/kg. Im administration caused less effects probably due to incomplete absorption from the im injection site, since im dosages of 100 mg/kg daily led to lower renal tissue concentrations than the same doses given iv. Nephrotoxicity of vancomycin increased when combined with tobramycin and was reduced when combined with D-glucaro-1.5-lactam, a beta-glucuronidase inhibitor. Vancomycin accumulated in renal tissue during repeated administration.

Animals↗
PubMed1983

Ceftazidime, ceftizoxime, cefotaxime and HR 221 in experimental chronic Escherichia coli pyelonephritis in rats.

The therapeutic efficacy and pharmacokinetics of the cephalosporins ceftazidime, ceftizoxime, cefotaxime and HR 221 were studied in animal experiments. The animal model used was experimental estrogen-induced or non-induced chronic Escherichia coli pyelonephritis in rats. The animals were treated with 5 mg cephalosporin/kg twice daily for one week. Each of the cephalosporins tested led to a significant decrease in renal bacterial counts, in spite of the low doses given. Ceftazidime was significantly more active than HR 221 in both experimental models, although the serum levels of HR 221 were higher and were maintained for a longer period of time than those of ceftazidime. Differences in pharmacokinetic properties (influenced by metabolic stability and protein binding) could be the reason for the differences in therapeutic activity, since the in vitro antimicrobial activity of each of the cephalosporins tested was very similar against the test strain.

Animals↗
PubMed1982

Characterization of the beta-lactamases of six species of Legionella.

The beta-lactamases of six Legionella species were characterized by isoelectric focusing, gel filtration, and substrate profiles. Fifteen strains of L. bozemanii, L. dumoffii, L. gormanii, L. longbeachae, and L. pneumophila produced beta-lactamases active against nitrocefin. L. micdadei enzymes previously reported to be beta-lactamase negative caused a very slow pH-dependent breakdown of nitrocefin and degraded penicillin G at high substrate concentrations. The bioassay revealed predominantly penicillinase activity for all species except L. micdadei, which had no activity in this assay. The apparent molecular weights of enzymes of L. bozemanii, L. gormanii, and L. pneumophila were in the range of 15,000 to 32,000, and those of L. micdadei and L. longbeachae were greater than 250,000. The isoelectric focusing of extracts of Legionella strains in polyacrylamide gels showed beta-lactamase types specific for species (L. bozemanii, L. gormanii, and L. pneumophila) and serotype (L. pneumophila). It demonstrated four different beta-lactamase types in L. pneumophila and revealed close relationships among L. pneumophila serotypes 1, 3, and 6. L. pneumophila enzymes formed band patterns only in polyacrylamide gels containing 6 M urea, whereas L. dumoffii and L. longbeachae enzymes did not form bands in any of the gels. None of the band patterns resembled those of known plasmid-mediated beta-lactamases. These experiments suggest that isoelectric focusing of chromosomal beta-lactamases may be a valuable tool for taxonomic studies.

Kinetics↗
PubMed1981

[Chemotherapy with fosfomycin, cefoxitin, and cefotaxime in experimental E. coli-pleuropneumonia (author's transl)].

Two models of pneumonia--the experimental E. coli-pleuropneumonia and "intrapulmonary" E. coli-pneumonia--were employed in these studies. Only fosfomycin was effective in both models even at the low dosage of 100 mg/kg/d. The comparative drugs cefotaxime and cefoxitin, however, were not able to reduce the bacteria in both lungs even at very high dosages of 900 mg/kg and 300 mg/kg per day respectively over 6 days.

Animals↗
PubMed1981

[Animal experiments on the nephrotoxicity, pharmacokinetics and therapeutic efficacy of dibekacin].

Nephrotoxicity, pharmacokinetics, and therapeutic efficacy of 3',4'-dideoxykanamycin (dibekacin), a semisynthetic aminoglycoside, were evaluated in rats. As with other aminoglycosides, therapy with dibekacin led to an increased urinary cell and malic-dehydrogenase excretion. The lowest dose resulting in an increased urinary cell excretion was 2.5 mg/kg/d. Serum levels of dibekacin after i.m. injection of 5 mg/kg were similar to those of other aminoglycosides. The kidneys accumulated high amounts of dibekacin, and eliminated it with a half-life of about 7 days. After repetitive dosing a distinct tendency to accumulation (highest renal concentration: 330 microgram/g) could be detected. Experimental chemotherapy of the chronic estrogen induced pyelonephritis revealed that dibekacin and sisomicin fed to significant reductions of renal bacterial counts at a dosage of 2 x 5 mg/kg/d for 7 days. A dosage of 2 x 2.5 mg/kg/d diminished the effectiveness of dibekacin distinctly, that of sisomicin only slightly.

Animals↗
PubMed1981

[Animal studies on ribostamycin (author's transl)].

Nephrotoxicity, pharmacokinetics, and therapeutic efficacy of ribostamycin were evaluated in rats. Measures of nephrotoxicity were urinary excretion of tubular cells and malate dehydrogenase. The i.v. injections of ribostamycin lead to the same tubular cell excretion values as the i.m. injections. Parallel administration of D-glucaro-delta-lactam reduced the nephrotoxic effect of ribostamycin significantly. The lowest dose which leads to a significantly increased loss of tubular cells was 20 mg/kg/d and was distinctly above that of gentamicin, indicating a lower nephrotoxicity. This corresponded to lower renal ribostamycin concentrations after a single dose administration as well as after 9 times repeated dosing. In chemotherapy of the acute pyelonephritis of the rat ribostamycin was inferior to gentamicin at dosages of 2.5 or 5 mg/kg.

Animals↗
PubMed1980

Age-dependent nephrotoxicity and the pharmacokinetics of gentamicin in rats.

The pharmacokinetics and nephrotoxicity of gentamicin were studied in female Wistar rats of different ages. I.m. administration of 5 mg of gentamicin/kg revealed that young rats (90 g) had lower peak serum levels and a prolonged elimination half-life, when compared with adult animals. After repeated injections, renal gentamicin concentrations were continuously lower in young rats during the entire experiment until the 20th day after the last dose. Nephrotoxicity, as measured by urinary excretion rates of tubular cells and malic dehydrogenase, was most pronounced in the old rats (260 g) and distinctly less in the 210 g animals. The young rats reacted with a slight but not significant increase in cellular and enzyme excretion. Since one cause of nephrotoxicity can be assumed to be intrarenal accumulation of gentamicin, it may be concluded that a deficient ability to concentrate aminoglycosides in the kidneys resulted in decreased nephrotoxic potential of gentamicin in the young rats.

Age Factors↗