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Biomedical subjects

G A Dette

Publications and source records attributed to G A Dette.

At least 19 recordsLinked to original sources
PubMed1989

[In vitro evaluation of lomefloxacin].

Lomefloxacin (1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4- oxoquinoline-3-carboxylic acid monohydrochloride, SC-47111) is a broad-spectrum antibiotic of the 4-quinolone group. In this comparative study the antimicrobial in-vitro activity of lomefloxacin was tested against 863 gram-negative and 415 gram-positive strains from fresh clinical isolates. As comparative agents ciprofloxacin, norfloxacin and ofloxacin were used. The minimal inhibitory concentrations were determined by means of a serial dilution with the agar-dilution procedure. Lomefloxacin showed an antibacterial efficacy comparable to other quinolones. Ciprofloxacin in general was two-fold dilutions more active. No cross-resistance with beta-lactamase producing-methicillin resistant or aminoglycoside-, tetracycline-, chloramphenicol- and co-trimoxacol-resistant strains could be found. Lomefloxacin showed in this study a broad antimicrobial activity. The clinical utilities of this new fluoroquinolone will depend on the pharmacokinetic properties and the adverse event profile.

4-Quinolones↗
PubMed1988

Serotyping, sites of isolation and resistance of Pseudomonas aeruginosa.

407 strains of pseudomonas aeruginosa form in-patients and out-patients were serotyped according to Habs' schema. 11.3% of the isolates were non-typable and among the other strains serotypes 6 and 10 were the most prevalent (20.4 and 14.0%, respectively). Type 14 was not observed. Most of the strains isolated from sputum were non-typable, whereas serotype 6 predominated in specimens from urine, wounds and ears. The susceptibility of the isolates to antipseudomonal agents was estimated: 4.7% of the isolates (mainly serotypes 2, 4, and 11) were resistant to gentamicin and among these strains parallel resistance to tobramycin and netilmicin was observed in 47.4%.

Anti-Bacterial Agents↗
PubMed1987

Comparative in vitro activity, serum binding and binding activity interactions of the macrolides A-56268, RU-28965, erythromycin and josamycin.

The minimal inhibitory concentrations of macrolide antibiotics against staphylococci, streptococci and Haemophilus influenzae were determined in vitro. A-56268 was the most active and RU-28965 was the least active of the macrolides tested. The interaction at erythromycin binding sites in serum and at alpha 1-acid glycoprotein was studied. RU-28965 exhibited the highest binding affinity. The effect of binding on antimicrobial potencies was evaluated by measurements of the first-order generation rate constants and by determination of MICs of staphylococci in broth and in human serum. The activity of each of the macrolides was lowered by serum binding, but only that of RU-28965 was dramatically decreased.

Blood Proteins↗
PubMed1987

Whole body tissue distribution of [14C]-erythromycin in the guinea pig. An autoradiographic study.

The distribution of 14C-labelled erythromycin following intravenous administration to the guinea pig has been studied by whole body autoradiographic technique. Erythromycin was quickly and extensively distributed throughout the body although penetration into some compartments like brain, spinal cord or vitreous body was limited. High radioactivity concentrations were detected in kidney, liver, lung, upper respiratory tract and in bone marrow. Lung tissue and bone marrow were characterized by delayed elimination of erythromycin. The prenetration of erythromycin into skin could be shown. 24 h after the administration of erythromycin still high amounts of radioactivity were detected in the faeces.

Animals↗
PubMed1987

Modifying effects of pH and temperature on (14C)erythromycin uptake into Staphylococcus aureus--relation to antimicrobial activity.

The uptake of (14C)erythromycin into Staphylococcus aureus was investigated by use of a rapid centrifugation method. Erythromycin uptake was saturable with time and with increasing erythromycin concentrations (apparent uptake constant Km = 6.0 x 10(-7) moles/l). Inhibitors of glycolysis, respiration and oxidative phosphorylation did not influence the uptake process but uptake was decreased by reducing temperature. Increases of erythromycin uptake, decreases of half life times of the uptake reaction and a log dose linked to enhancement of antimicrobial activity were seen with alkaline pH levels of the incubation medium. The experimental data conform well with the concept of non ionic diffusion. The high affinity of erythromycin to the intracellular ribosomal target site probably generates the driving force of uptake and the unionized antibiotic obviously represents the antimicrobially active molecular form.

Animals↗
PubMed1987

Kinetics of erythromycin uptake into Ehrlich mouse ascites tumor cells.

The uptake was studied with freshly isolated Ehrlich ascites tumor (EMAT) cells and with 14C-labelled erythromycin. Erythromycin was accumulated by EMAT cells. The uptake rates and quotes of erythromycin increased with increasing temperature and with increasing pH value (alkaline pH). The uptake was reduced by SH-group reagents, by inhibitors of electron transport and of oxidative phosphorylation and by ouabain. The uptake was saturable (Km = 6.0 X 10(-4) mol/l). The release of the accumulated erythromycin followed first order kinetics (k = 4.5 X 10(-2) min-1). The uptake and accumulation of erythromycin cannot be explained by non-ionic partition. An active uptake mechanism is suggested.

Animals↗
PubMed1986

The binding protein of erythromycin in human serum.

Erythromycin binding to human serum albumin and to alpha 1-acid glycoprotein was measured under conditions of binding equilibrium. At therapeutical concentrations of erythromycin the binding to albumin is not saturable. The fraction of total erythromycin bound to alpha 1-acid glycoprotein is proportionally related to the protein concentration and is bound to a single class of binding sites with an apparent association constant Ka = 0.16 X 10(6) M-1 (38 degrees). About one mole of erythromycin is bound per mole of alpha 1-acid glycoprotein. The binding affinity can be enhanced and vice versa lowered by increasing the concentrations of NaCl and urea, respectively. The semilogarithmic plot of bound/free ratios vs log concentration of NaCl or urea exhibits linear relationships. Erythromycin binding can be competitively inhibited by mersalyl (Ki = 11-16 microM) but not by other SH-reagents or by neuraminidase treatment. A marked reduction of erythromycin binding to alpha 1-acid glycoprotein is seen with dithiothreitol. alpha 1-acid glycoprotein is the main erythromycin binding protein in human serum.

Binding Sites↗
PubMed1986

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections.

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms.

Adult↗
PubMed1986

Kinetics of erythromycin uptake and release by human lymphocytes and polymorphonuclear leucocytes.

The uptake of 14C-labelled erythromycin by human lymphocytes and polymorphonuclear leucocytes was studied. Erythromycin was concentrated by the cells. The amount of accumulated erythromycin was correlated with the cell count and was found to increase with alkaline pH and with increasing temperature of the incubation medium. The uptake of erythromycin could be reduced by compounds which inhibit cell respiration, glycolysis and (Na+-K+)membrane ATPase. Furthermore, the uptake was saturable and followed Michaelis-Menten kinetics (Km = 0.7 and 1.6 mM for lymphocytes and polymorphonuclear leucocytes, respectively). The intracellular concentrations cannot be explained by the principle of non ionic diffusion. It is suggested that erythromycin is actively transported via the nucleoside transport system. The accumulated erythromycin was rapidly released when the cells were washed and re-incubated in antibiotic-free medium. Probably, no strong intracellular binding takes place.

Erythromycin↗
PubMed1985

Impact of injectable cephalosporins on the gastrointestinal microflora: observations in healthy volunteers and hospitalized patients.

A disturbed microbiological ecosystem of the gut flora is frequently seen as a consequence of antibiotic therapy. Because this impact on the physiological balance is known to be causative for severe nosocomial infections and is mainly seen with antibiotics that are massively excreted via the bile (e.g. broadspectrum penicillins, ceftriaxone and cefoperazone), we investigated cefotaxime (CTX), cefotiam (CTM), cefmenoxime (CMX), ceftazidime (CAZ), ceftizoxime (CZX) and cefazolin + netilmicin (CEZ + NTL) in healthy volunteers. The respective daily i.v. doses, days of medication and numbers of volunteers were: CTX 3 g, 1 d, n = 8; CTM 6 g, 3 d, n = 15; CMX 4 g, 3 d, n = 15; CAZ 4 g, 1 d, n = 8; CZX 4 g, 1 d, n = 8; CEZ + NTL 2 X 3 g + 1 X 3 mg/kg/day, 4 d, n = 15. CTX was also investigated in 11 selected hospitalized patients. One or two stool specimens were taken before, during and several days after medication. The microorganisms were also tested for ampicillin and CEZ resistance on selective media. Ampicillin and CEZ resistance was much higher in hospitalized patients than in volunteers (mainly Proteus and Serratia sp.): 90% vs. 42% and 63.6% vs. 43%, respectively. CTX did not affect the anaerobes (Bacteroides sp. and lactobacilli) that are antagonistic to clostridia and Candida. No selection of strains resistant to ampicillin or CEZ occurred. In hospitalized patients, the level of resistance to these drugs was lower after treatment than before.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗
PubMed1983

The current state of cephalosporin antibiotics: microbiological aspects.

An increasing number of new cephalosporins continue to become available in the clinic so that the clinician requires something akin to Ariadne's thread to work through the labyrinth of confusing names and product claims. The parenteral cephalosporins may be grouped on the basis of structure, antimicrobial activity and metabolic stability as follows: 1. cephacetrile, cephalothin, cefapirin; 2. cefotaxime; 3. cephaloridine, cefazedone, cefazolin, cefotiam; 4. cefamandole, cefoperazone, cefsulodin, cefuroxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, lamoxactam. Groups 2 and 4 contain the most interesting compounds in terms of their biological activity and therapeutic significance. Even carbenicillin-resistant strains of Pseudomonas aeruginosa are inhibited by one of the recent broad-spectrum cephalosporins. In the clinic, minor differences between the highly active cephalosporins are not likely to be of therapeutic significance.

Bacteria↗
PubMed1983

Comparative study of fosfomycin activity in Mueller-Hinton media and in tissues.

Fosfomycin utilizes two uptake systems as ways of entry into microorganisms: the L-a-glycerophosphate and the hexose phosphate transport system. The latter is inducible by glucose-6-phosphate. The relationship between glucose-6-phosphate (concentration range 0-100 mg/l) and the susceptibility of Staphylococcus aureus was studied in Mueller-Hinton broth. An almost maximal enhancement of fosfomycin activity was found at 25 mg/l glucose-6-phosphate. Fosfomycin activity against Staph. aureus, Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Klebsiella spp., Serratia spp., and Pseudomonas aeruginosa was studied by use of the broth and the agar dilution method, in the presence and absence of glucose-6-phosphate (25 mg/l). The minimum inhibitory concentrations (MICs) of fosfomycin against Staph. aureus Streptococcus faecalis, E. coli, Ent. cloacae, Pr. mirabilis, and Ps. aeruginosa were estimated in particle free supernatants of 25% tissue homogenates (liver, kidney, lung, heart) and in parallel in Mueller-Hinton broth. With few exceptions the MICs in Mueller-Hinton broth (with glucose-6-phosphate) were similar to those found in tissues (no glucose-6-phosphate added).

Animals↗
PubMed1983

Cefotetan: antimicrobial activity in-vitro compared with that of cefotaxime.

The antimicrobial activity of cefotetan and cefotaxime were compared in vitro against 547 strains of aerobes and 24 strains of Bacteroides fragilis. The strains were recent clinical isolates from 20 hospitals. Cefotetan was found to exhibit an activity two- to fourfold lower than that of cefotaxime against most of the enterobacteriaceae. About half the number of Enterobacter aerogenes and Enterobacter cloacae strains resistant to cefotetan were resistant also to cefotaxime. Cefotetan was more active than cefotaxime against most of the strains of Proteus vulgaris. In contrast to cefotaxime which was moderately active, cefotetan was inactive against Pseudomonas aeruginosa. Cefotetan had limited activity against Staphylococcus aureus and Streptococcus faecalis was resistant to both cefotetan and cefotaxime. Bact. fragilis was inhibited more effectively by cefotetan than by cefotaxime. Depending on the species tested, the activity of cefotetan was influenced significantly by the inoculum size in some cases. Different test media did not affect the results.

Anti-Bacterial Agents↗
PubMed1982

Erythromycin binding to human serum.

Erythromycin binding to human serum was measured under conditions of binding equilibrium. The binding is sensitive to pH changes, decreasing at acid pH. Over a great range of serum dilution, the bound fraction is semilogarithmically related to serum concentration. Binding is shown to be completely reversible. With increasing erythromycin concentration a specific part of binding is saturable and specifically displaceable by erythromycin is specifically bound to a single class of noninteracting binding sites with an apparent dissociation constant Kd = 5.9 microM (38 degrees C). The kinetic and thermodynamic parameters at 25 degrees are: Kd = 8.4 microM, delta H degrees = +4.4 X 10(3) cal per mole, delta G degrees = 6.9 X 10(3) cal per mole, delta S degrees = +38 e.u.

Blood Proteins↗
PubMed1982

[Binding, distribution and efficacy of erythromycin (author's transl)].

The significance of the binding of antibiotics in humans in still a controversial question. In principle, only free, unbound antibiotic is considered to be diffusible and biologically active. With unimpaired measurements and a binding balance within the normal therapeutic concentration range, the free portion of erythromycin in the human serum is found to depend significantly on the total concentration of erythromycin. For example, for concentrations of 1, 16 and 24 mg/l, approx. 74%, 54% and 46% are bound (+38 degrees C). binding is temperature-dependent and decreases with decreasing temperature. At +4 degrees C, 44% of 1 mg/l and 30% of 16 mg/l are bound. These binding characteristics are based in part on the properties of erythromycin's major binding partner in the serum - acidic alpha1-glycoprotein. Albumin only contributes slightly to the overall binding and is not concentration-dependent in the therapeutic range, i.e. it cannot be saturated. Binding phenomena have a decisive influence on the distribution of an antibiotic within an organism. In the case of erythromycin, the tissue levels in nearly every organ are higher, sometimes considerably higher, than the corresponding serum levels. We have shown the binding of erythromycin to cytosol and particle fractions in certain organs and compared this to the binding in the serum. The antibacterial principle regarding the efficacy of erythromycin is also based primarily on a binding reaction which maintains the concentration gradient for the intake of erythromycin in microorganisms. The kinetics ofintake (microorganism) are compared to those of binding (macroorganism) and referred to the minimum inhibitory concentration.

Erythromycin↗
PubMed1979

The role of sialic acid in 5-HT binding to synaptic membranes.

The high affinity binding of [14C]5-HT to nerve ending membranes isolated from rat brain is not affected by neuraminidase treatment. The specificity of ligand receptor interaction was demonstrated by displacement studies with tryptamine derivatives, noradrenaline, and acetylcholine.

Animals↗