Search PubMed⌕ Search

Biomedical subjects

R Marre

Publications and source records attributed to R Marre.

At least 145 records · Page 8Linked to original sources
PubMed1980

[Fosfomycin: animal experiments on nephrotoxicity, pharmacokinetics and therapeutic efficacy (author's transl)].

The nephrotoxicity, pharmacokinetic and therapeutic activity of fosfomycin were investigated in female wistar-rats. Measures of nephrotoxicity were urinary excretion of tubular cells and of the enzymes MDH, LDH, and GOT. Histological investigations and estimation of serum urea concentration and proteinuria were also evaluated. The doses of 500, 1000, 2000, 3000, and 5000 mg/kg/d were administered in 9 single doses with 12 hours interval. The lowest dose which induced a significantly increased tubular cell excretion was 1000 mg/kg/d and therefore in the same range as the tubulotoxic threshold doses of cephalosporins. Chemotherapy of the chronic estrogen induced pyelonephritis revealed equally favourable results for fosfomycin and cefuroxim at dosages of 2 X 150 mg/kg/d. The pharmacokinetics of fosfomycin at a single dose of 150 mg/kg/d were equivalent to those of cefuroxim. These animal experiments showed fosfomycin to be of value as a therapeutic alternative to cephalosporin antibiotics.

Animals↗
PubMed1979

[Antibacterial in-vitro activity of pipemidic acid and nalidixic acid (author's transl)].

The in-vitro activity of nalidixic acid and pipemidic acid was investigated in a combined study in 450 freshly isolated bacterial strains using the agar dilution test. Gram-positive cocci were resistant to both substances except for a few pipemidic acid sensitive staphylococci. Both substances had good antibacterial activity in the gram-negative spectrum. However, the MIC values of pipemidic acid were generally clearly lower than those of nalidixic acid. Only pipemidic acid showed activity against Pseudomonas aeruginosa. Thus the in-vitro results showed that pipemidic acid has clear-cut and valuable advantages for the treatment of urinary tract infections when compared with nalidixic acid.

Anti-Bacterial Agents↗
PubMed1979

Antimicrobial agents in rats. II. Serum levels of oral cephalosporins.

Cephalexin, cephradine and 7 beta-(D-2-amino-2-[(1,4-cyclohexadienyl)-acetamido])-3-methoxy-3-cephem-4-carboxylic acid (CGP 9000) were tested for their pharmacokinetic behaviour in rats. The cephalosporin serum concentrations were determined at certain times after oral administration of 150 mg/kg by the agar-well-diffusion method. The experiments revealed that the serum levels of cephalexin and cephradine did not differe essentially from one another. They maintained maximum serum concentrations of 30 microgram/ml to 40 microgram/ml during the first hour and than declined with a half-life of 2.5 h. CGP 9000 reached peak concentrations 60 to 90 min postdose and was eliminated with a half-life of 3.5 h. The area under the curve was double as large as those of cephalexin and cephradine. This may be a reason of favourable results in experimental chemotherapy with CGP 9000.

Animals↗
PubMed1979

Investigations on the effectiveness of cefazedone in experimental E. coli pyelonephritis.

The therapeutic effectiveness of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephazolin, cephacetrile and cephalothin was compared in the test model of estradiol-induced E. coli pyelonephritis in the rat. Cefazedone and cephazolin were similar in effect. The relations between results of treatment and microbiological and pharmacokinetic characteristics of the cephalosporins tested are discussed.

Animals↗
PubMed1979

Antimicrobial agents in rats. I. Serum levels of parenteral cephalosporins.

Eleven cephalosporins were tested for their pharmacokinetic properties in rats in order to obtain a basis for experimental evaluation of their in vivo activity. The compounds were administered to female Wistar rats in i.m. doses of 150 or 50 mg/kg. The cephalosporin concentrations in rat serum were determined by the agar-well-diffusion method. Essential differences concerning the serum levels, half-life and the area under the curve could be ascertained. Low serum levels and short half-life could be reported for cephapirin, cephalotin, and cephradin, whereas cefazolin, cefazedone, and cefuroxime produced high and longer lasting serum levels. All cephalosporins were quickly absorbed, most of them were beneath the minimum detectable concentration after 6 h. It is concluded that pharmacokinetic data should be taken into consideration in conjunction with experimental chemotherapy.

Animals↗
PubMed1979

[Animal studies on nephrotoxicity of seven aminoglycoside antibiotics during long-term treatment (author's transl)].

In studies on female Wistar rats (n = 133) the nephrotoxicity and kidney concentrations of amikacin, butirosin, gentamicin, kanamycin, bekanamycin, sisomicin, and tobramycin were examined during four weeks therapy and four weeks convalescence. Maximum doses recommended for human therapy were administered i.m. at 12-h intervals. For evaulation of the tubulotoxic effect the excretion rates of tubular cells were determined daily. At weekly intervals animals were sacrificed for determination of the kidney aminoglycoside concentration, which was assayed microbiologically. The application of all aminoglycosides resulted in an increase of excreted tubular cells, but the extent and course of cell excretion varied for the different aminoglycosides. An initial peak after different periods of therapy and later on a decrease of cell excretion was found for all aminoglycosides. These periods of high and low loss of tubular cells corresponded to aminoglycoside accumulation and saturation in the kidneys. During the first week of treatment only gentamicin was tolerated without signs of renal damage. Initially the nephrotoxic effect was strongest for bekanamycin, but at the end of the first week kanamycin and sisomicin produced similar distinct side effects. Thereafter the highest cell excretion rates were continuously caused by sisomicin.

Aminoglycosides↗
PubMed1979

[Netilmicin and tobramycin: comparative evaluation of pharmacokinetics, nephrotoxicity, and therapeutic efficacy in animal studies (author's transl)].

Pharmacokinetics, nephrotoxicity, and therapeutic efficacy of (2S-cis)-4-O-[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]-2-deoxy-6-O-[3-deoxy-4-C-methyl-3-(methyl-amino)-beta-L-arabinopyranosyl]-N1-ethyl-D-streptamine sulfate (netilmicin) and tobramycin were investigated in rats. The excretion rates of tubular cells and of the urinary enzyme malic dehydrogenase served as parameter of nephrotoxicity. Both compounds were, similar to other aminoglycosides, tubulotoxic within the range of dosages used for human therapy. Netilmicin, however, produced less renal damage than did tobramycin in all dosages applied. Pharmacokinetic studies revealed lower renal concentrations of netilmicin after repetitive administration. Experimental chemotherapy of the chronic E. coli pyelonephritis in rats with both aminoglycosides resulted in a significant reduction of the renal bacterial counts. In spite of approximately identical serum concentration curves and in vitro activity, especially the low dosage of netilmicin led to more favourable therapeutic results than equal doses of tobramycin. These animal experiments suggest higher renal tolerance and efficacy of netilmicin.

Animals↗
PubMed1978

[Comparative susceptibility testing to sulfamethoxazole and trimethoprim by agar diffusion test on different media (author's transl)].

14 lots of 6 different commercial media for susceptibility testing were compared by agar diffusion test with 161 bacterial strains. The result "resistant" to sulfamethoxazole, trimethoprim, or co-trimoxazole varied in wide limits between the media. The lot employed by the "Work-Group on Resistance" of the Paul Ehrlich Society is of limited value for testing of the investigated drugs.

Culture Media↗
PubMedDate not supplied

Animal studies on the reduction of aminoglycoside-induced nephrotoxicity by D-glucaro-1,5-lactam.

We studied the effect of D-glucaro-1,5-lactam on aminoglycoside-induced nephrotoxicity in rats. Parameters of nephrotoxicity were urinary excretion of tubule cells and malate dehydrogenase. When given in appropriate doses, either i. m. or via an oral tube, D-glucaro-1,5-lactam significantly reduced the excretion of cells and enzymes during the administration of gentamicin, tobramycin, dibekacin, netilmicin and ribostamycin. It did not impair the therapeutic efficacy of ribostamycin in the experimental treatment of acute pyelonephritis in rats. The protective effect of D-glucaro-1,5-lactam could be ascribed to its inhibition of beta-glucuronidase, an enzyme which is located in renal lysosomes and which is activated by aminoglycosides.

Aminoglycosides↗
PubMedDate not supplied

Influence of fosfomycin and tobramycin on vancomycin-induced nephrotoxicity.

Since combinations of fosfomycin and vancomycin or tobramycin and vancomycin could be of advantage in the therapy of staphylococcal infections, we studied renal tolerance of both combinations. The experimental animal was the rat and the parameters of nephrotoxicity were cyturia and enzymuria. The experiments showed that fosfomycin at dosages of 50 and 250 mg/kg protected against nephrotoxicity caused by vancomycin (dose: 50 mg/kg), whereas the administration of both tobramycin (dose: 2.5 mg/kg) and vancomycin (dose: 50 mg/kg) resulted in an increase of cyturia and enzymuria. However, repeated dosing of vancomycin (single dose: 50 mg/kg) led to renal accumulation when combined with fosfomycin (single dose: 250 mg/kg); renal vancomycin concentrations were lower. This study suggests similarities in the renal handling of vancomycin and aminoglycosides and demonstrates the possibility of reducing drug-associated nephrotoxicity.

Animals↗
PubMedDate not supplied

The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci.

Infections with multiresistant strains of Staphylococcus aureus and Staphylococcus epidermidis pose severe clinical problems. The drug of choice in such cases, vancomycin, is potentially ototoxic and nephrotoxic and this may give rise to additional problems in the patient. Fosfomycin has been shown to be nephroprotective when given with vancomycin and with other nephrotoxic drugs. We report the inhibitory and bactericidal activity of fosfomycin and vancomycin alone and in combination against 26 clinically relevant strains of S. aureus and 48 strains of S. epidermidis. In most instances these two drugs showed indifferent or additive effects, synergism or antagonism was only rarely observed. Assessment of the bactericidal action of the combination revealed similar effects. The combination of fosfomycin and vancomycin may, therefore, be beneficial in clinical situations where the nephrotoxic effect of vancomycin cannot be tolerated.

Drug Combinations↗
PubMedDate not supplied

Comparative in vitro activities of amoxicillin-clavulanate, ampicillin-sulbactam and piperacillin-tazobactam against strains of Escherichia coli and proteus mirabilis harbouring known beta-lactamases.

Strains of Escherichia coli (N = 124) and Proteus mirabilis (N = 29) harboring known beta-lactamases were analyzed as to their susceptibility to ampicillin, amoxicillin, and piperacillin alone and in combination with sulbactam, clavulanate, and tazobactam. With TEM 1-producing E. coli, a correlation between specific beta-lactamase activity and the MIC of piperacillin and ampicillin-sulbactam was observed. These strains also showed significant differences in susceptibilities to the various combinations, suggesting that, at least in strains resistant to one combination, several beta-lactam/beta-lactamase inhibitor combinations should be tested in the laboratory. All combinations tested enhanced the activity of the beta-lactam towards TEM 1-producing E. coli, piperacillin-tazobactam being the most active. The drugs were less active to OXA 1 enzymes; solely with piperacillin-tazobactam 90% of strains were within the therapeutic range of the drug. Sulbactam acted synergistically to chromosomally encoded beta-lactamases, whereas amoxicillin-clavulanate was inactive. Piperacillin and piperacillin-tazobactam inhibited all strains producing chromosomally encoded beta-lactamases at concentrations within the therapeutic range of the drugs. In contrast, TEM 2 of P. mirabilis was not sensitive to ampicillin-sulbactam, but to the other combinations; here again piperacillin-tazobactam was the most active.

Amoxicillin↗
PubMedDate not supplied

Relationship between the bactericidal and bacteriolytic activity of cephalosporins and changes in the cell volumes of Escherichia coli cultures.

The bactericidal effect of cefoxitin and cefotaxime in relation to concentration and exposure time, as demonstrated by the killing curve diagrams of Escherichia coli cultures, was compared with the degree of bacteriolysis and the cell volume increase measured by the coulter counter-channel analyser system. Human plasma ultrafiltrate was used as the growth medium. Cefoxitin has a higher bactericidal activity than cefotaxime. With increasing concentrations the bactericidal efficacy of cefoxitin increases more rapidly in the lower range of concentrations (2-10 mg/l) than in the higher range (10-40 mg/l). In contrast, the bactericidal effect of cefotaxime in the range 0.06-1.2 mg/l is virtually constant and can only be increased by high levels (10-40 mg/l). The morphometric effect of cefoxitin on E. coli cultures, as demonstrated by volume distribution curves, is characterized by intensive and rapidly appearing bacteriolysis 20 min after exposure to the antibiotic without a preceding increase in bacterial cell volume. Higher concentrations result in an earlier onset of bacteriolysis. In contrast, the application of cefotaxime reveals a massive increase in bacterial cell volume (more than five-fold) with a delayed (greater than 2 h) onset of bacteriolysis. High cefotaxime concentrations reduce the extent of bacterial cell volume increase, associated with an earlier and more intensive onset of bacteriolysis. With both cephalosporins, the bacterial cell alterations are particularly dependent on the exposure time. There is evidently a close correlation between bactericidal and bacteriolytic activity. This is valid both for the two cephalosporins and generally for the concentration-activity relationships.

Blood↗
PubMedDate not supplied

Diagnostic value of bronchoalveolar lavage in patients with opportunistic and nonopportunistic bacterial pneumonia.

In 29 patients with community-acquired pneumonia, 24 patients with hospital-acquired pneumonia and 35 patients with pneumonia in the immunocompromised host the diagnostic value of bronchoalveolar lavage (BAL) with quantitative bacterial and fungal cultures was studied; 32 patients with noninfectious pulmonary diseases and 14 healthy volunteers served as controls. An infectious etiology could be established in 81% of the pneumonia patients without differences between the three groups; significant infection was associated with colony counts of > or = 10(4) cfu/ml. Prior antibiotic therapy lowered the yield of BAL culture only in community-acquired pneumonia (94% vs 55% positive cultures in untreated vs pretreated patients, p < 0.02). Furthermore the culture results were related to the radiographic extension of pulmonary infiltrates (92% positive cultures in multilobar vs 54% in lobar or segmental infiltrates, p < 0.001). Therapeutic consequences of BAL were shown by resistance of the isolated organisms to predefined empiric treatment regimens in 41% community-acquired pneumonia, 43% pneumonia in the immunocompromised host and 67% hospital-acquired pneumonia patients.

Adult↗
PubMedDate not supplied

Ochrobactrum anthropi bacteremia: report of four cases and short review.

Ochrobactrum anthropi, formerly "Achromobacter" CDC group Vd, is a nonfermentative, nonfastidious gram-negative bacillus, that only recently has been given attention as a potential human pathogen. Over a 2-year period, we observed four patients with multiple blood cultures that were positive for the organism. The patients had acute leukemia as underlying disease, and presented with clinical and microbiologic features consistent with catheter-related bacteremia. In three of the patients the infection initially appeared to be unrelated to chemotherapy-associated profound neutropenia and occurred early after, or was the reason for, hospital admission. The antimicrobial susceptibility of the isolates varied: unlike previously reported cases, resistance in some of our isolates included aminoglycosides, newer fluoroquinolones, and trimethoprim-sulfamethoxazole. Despite in vitro susceptibility to imipenem in initial isolates, treatment of two patients with this agent obviously failed to eradicate the organism, and the patients either relapsed with bacteremia shortly after discontinuation of treatment or remained persistently febrile and bacteremic. O. anthropi appears to be increasingly recognized as a human opportunist pathogen associated with intravascular catheters and unpredictable multiple antibiotic resistance.

Adult↗
PubMedDate not supplied

Teicoplanin: 10 years of clinical experience.

The teichomycin antibiotics have been discovered and chemically purified in the late 1970s. Teicoplanin, one of the major derivatives of this group, has been introduced into clinical use in 1984. In Germany, teicoplanin was licensed in 1988 and now ranks among the antimicrobial agents most frequently used in intensive care units. Due to its reduced rate of side effects compared to vancomycin, its longer serum half-life and a simplified mode of application, teicoplanin has become the glycopeptide of choice in many hospitals. The present review summarizes in vitro activity data, pharmacokinetics, and clinical experience with teicoplanin, with special consideration of currently recommended doses and serum levels.

Clinical Trials as Topic↗