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Biomedical subjects

H Knothe

Publications and source records attributed to H Knothe.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

[Enterocolitis caused by Clostridium difficile. Analysis of 15 cases in adults].

Each of 48 patients with suspected Clostridium difficile enterocolitis after treatment with antibiotics underwent a faecal test in which a Clostridium difficile culture was set up and a cytotoxin test carried out. The detection of Clostridium difficile was positive in 15 cases. Diarrhoea with varying severity was present in all patients, most frequently after medication with the newer cephalosporins. Nine patients also underwent rectoscopy: a typical pseudo-membranous colitis was seen only in 5 of these and a "non-specific" enterocolitis in only 4. Management in 12 patients involved discontinuance of the antibiotic followed by oral vancomycin therapy for an average of 7 days. A female patient suffered a recurrence but responded to a repeat application of vancomycin. The possibility of Clostridium difficile enterocolitis should always be kept in mind when diarrhoea with unclear aetiology occurs during antibiotic therapy. The cytotoxin test and culture identification of Clostridium difficile are suitable routine methods for confirming the diagnosis. In severe cases, treatment should commence without waiting for the microbiological results.

Adult↗

[Respiratory tract infections--clinical results with ofloxacin].

In an open clinical trial, out-patients with respiratory tract infections were given 200 mg ofloxacin b. i. d. orally. 36 had acute bronchitis and pneumonia was diagnosed in 44. The average duration of therapy was nine days for bronchitis and 12 days for pneumonia. In the sputum of bronchitis patients, Haemophilus influenzae (n = 25), Streptococcus pneumoniae (n = 18), Branhamella catarrhalis (n = 2) and Pasteurella multocida (n = 1) were isolated. 17 H. influenzae and 12 S. pneumoniae were eliminated. All 20 S. pneumoniae strains isolated from patients with pneumonia were eliminated. A cure or improvement of clinical symptoms was seen in 32 of 36 cases of bronchitis and in 33 of 44 cases of pneumonia treated with ofloxacin.

Adult↗

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↗

Qualitative and quantitative aspects of beta-lactamase production as mechanisms of beta-lactam resistance in a survey of clinical isolates from faecal samples.

A study has been conducted to identify the beta-lactamases most likely to contribute to beta-lactam resistance in clinical populations and to investigate their interactions with cefuroxime and newer cephalosporins. A total of 217 ampicillin-resistant, Gram-negative isolates from faecal samples of healthy volunteers in Germany, South America and Amman were investigated. Such strains represent the 'gene pool' from which infections might arise. Escherichia coli was the prevalent species (59.9%) followed by Klebsiella spp. (20.3%) and Enterobacter cloacae (12.0%). At least 56.7% and possibly as high as 64.5% of strains owed their principal beta-lactamase activity to enzymes mediated by R-plasmids. The most prevalent R-plasmid mediated beta-lactamase was TEM-1 which was produced by 109 strains. The beta-lactamase activity of strains producing only a chromosomal enzyme was often markedly higher than that of strains also producing an R-plasmid mediated enzyme. The qualitative and quantitative aspects of beta-lactamase production were investigated in cell free and whole cell tests and this confirmed the superior broad spectrum beta-lactamase resistance of ceftazidime over other new cephalosporins.

Anti-Bacterial Agents↗