[Doxycycline therapy in practice].
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Biomedical subjects
Publications and source records attributed to H Knothe.
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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.
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Amikacin-, tobramycin-, gentamicin- as well as carbenicillin-resistance has been found to be transducible, in various combinations of spectra both with the phage F 116 propagated on an Amikacin-resistant wild-type strain of Pseudomonas aeruginosa (No. BE 11) and with the phage AP 19 isolated from a different Amikacin-resistant strain (No. 578). Both strains were found to transfer Amikacin-resistance genes presumably by conjugation thus possessing an R plasmid coding for multiple antibiotic resistance. Evidence is presented that classical as well as wild-type phages may acquire and transmit antibiotic resistance genes among pseudomonads. This is particularly significant in view of the importance to preserve Amikacin as an effective reserve antibiotic for treatment of poly-resistant infections including those caused by P. aeruginosa.
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The antibacterial activity of a new jelly for burns and wounds with the components tyrothricin, 8-hydroxyquinoline, fomocaine and diphenhydramine (Herit) is described. The biological availability of tyrothricin and 8-hydroxyquinoline from the gel is in accordance with minimum inhibitor concentrations (MIC). Against strains of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans the jelly was most effective.
In a series of Pseudomonas aeruginosa strains resistant to gentamicin, tobramycin, amikacin and/or netilmicin (Knothe and Krcméry, 1979), wild-type phage lysates could be prepared and two of them were studied more in detail. Both lysates were shown to mediate transfer of gentamicin, amikacin and carbenicillin resistance by direct selection. In some instances also fertility function (tra) could be demonstrated in transductants by further cycles of transfer. It could be speculated that, once such wild-type phages from resistant or toxinogenic strains are liberated into the hospital environment, they could mediate these and other properties to P. aeruginosa strains in that environment.
Excretion of Salmonellae in two groups of outpatients with Salmonellae is discussed. In one group of 51 adults, a total of 30 different serotypes were isolated. These patients were treated with lactulose and after four weeks the organisms had been eliminated in 68.6%. In a group of 23 adults receiving no treatment whatsoever, 56.5% were still excreting the organism after four weeks. Of the 64 in-patients studied, 37 received various antibiotics, 14 lactulose and in 13 only the symptoms were treated. The length of the excretion period was longer for the group receiving antibiotics (four weeks after onset of illness 67.8% were still excreting the organism). Treatment with lactulose, however, resulted in a shorter period of excretion for these patients. Special aspects of the various groups - e.g. age structure, pattern of infecting organisms - are reported in detail.
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To nine cystic fibrosis patients with chronic bronchopulmonary infection of severely damaged lungs invaded by Pseudomonas aeruginosa, eleven courses of prolonged tobramycin treatment (5 mg/kg/day) for four to 16 weeks were administered. Pulmonary symptoms improved and a better quality of life was achieved in all but one patient. Objective parameters (chest X-ray, pulmonary function tests) changed to a lesser extent. In only one patient was Pseudomonas eradicated from the sputum but reappeared after discontinuation of therapy. In the rest of the patients Pseudomonas was significantly suppressed or replaced by other pathogens. Four patients showed rises of antibody titres to Candida and two to Aspergillus fumigatus. No nephrotoxic side effects were observed, but vestibular function was reversibly impaired in one patient without corresponding clinical symptoms. No bacterial resistance to tobramycin was observed during therapy.
After the administration of various antimicrobial agents for chemotherapeutic purposes a general change in the intestinal flora of the patient is often observed. In contrast, the combination trimethoprim-sulphonamide causes in most cases a strong selective decrease in the number of Enterobacteriaceae organisms for treatment periods as long as four to 12 weeks. The results correspond to clinical experience with trimethoprim-sulphonamide therapy in urinary tract infection where reinfections with resistant organisms are the exception.