[Local hemostasis using lyophilized collagen].
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Biomedical subjects
Publications and source records attributed to R Haag.
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Intramuscular infections of mice with eight different strains of Pseudomonas aeruginosa were treated with three doses each of fosfomycin, piperacillin and azlocillin. The therapeutic response (measured as decrease in colony-forming units in the homogenized infected tissue) was compared with the 'aggregate suprainhibitory time' (the time for which the serum concentration exceeds the minimal inhibitory concentration of the infecting bacteria during the whole treatment period). The therapeutic response improved with increasing aggregate suprainhibitory time. The correlation was better for fosfomycin than for piperacillin and, especially, azlocillin.
Following a single intramuscular application of 1 g ceftizoxime, levels of the drug were determined in plasma as well as in suction blister fluid (SBF) and cantharides blister fluid (CBF). This regimen invariably led to both high and long-lasting plasma levels: 81 +/- 16 min post dose maximum plasma levels of 17.5 +/- 3.1 micrograms/ml were reached; 6 h post dose levels of 4.6 +/- 0.4 micrograms/ml were still found, i.e., 4375 and 1150 times, respectively, the MIC90% of Neisseria gonorrhoeae. The high plasma levels were parallelled by high concentrations in SBF, with peaks amounting to 8.4 +/- 1.0 micrograms/ml. Peak concentrations in CBF ranged from 8.1 to 15.7 micrograms/ml. Thus, the pharmacokinetic behavior of ceftizoxime given as a single intramuscular injection of 1 g explained the excellent clinical results of this regimen in uncomplicated gonorrhea.
40 patients were given a single, short intravenous infusion of 4 g fosfomycin over a period of five to ten minutes. In 23 patients, the contents of the gall bladder were removed intra-operatively 30-105 minutes after the fosfomycin infusion. In 17 patients who had undergone cholecystectomy eight to ten days earlier, bile was obtained via a T-drain 30, 60, 120, 240 and 360 minutes after the fosfomycin infusion. Fosfomycin concentrations of 1-196 mg/l were present in the bile which had been removed intra-operatively. No correlation was found between the concentration and the time of removal. Patients with the highest alkaline phosphatase in serum, however, had the lowest fosfomycin concentrations. In the patients with T-drains, the highest concentrations (93 mg/l) were found 30 minutes after the fosfomycin infusion. By the sixth hour the concentrations had fallen to 19 mg/l.
A transpapillary indwelling catheter was inserted to prevent stone impaction in six female patients who were suffering from choledocholithiasis. The bile withdrawn via the catheter was infected on six occasions with Escherichia coli. In one of these cases Klebsiella sp. and in another Salmonella sp. were also identified. All bacteria were sensitive to ceftizoxime (the MIC was between 0.007 and 0.06 mg/l). The bacterial counts in the bile were determined before and during treatment by means of membrane filtration. In all six cases there was a rapid decline in the colony count. The concentration of ceftizoxime in bile samples was several times higher than the MIC of ceftizoxime for the corresponding pathogens. Overall, the therapeutic results with ceftizoxime were good. Three of eight pathogens were eliminated from the bile within eight to 24 hours. In one case a change of pathogen was seen after 24 hours. Forty-eight hours after beginning treatment, four of eight pathogens had been eliminated from the bile. After 72 hours the colony count in six patients was less than 10 pathogens/ml. In two patients a change of pathogen occurred; in one patient treatment had to be stopped after the first injection because of urticaria.
Serum pharmacokinetics of 1 g ceftizoxime were studied in eight patients undergoing chronic haemodialysis. Arterial blood samples were collected at 3, 60, 120, 180 and 240 minutes and before the next dialysis 2-3 days after injection of ceftizoxime. Three minutes after injection the serum levels were 122 +/- 8.4 microgram/ml and 19.4 +/- 1.7 microgram/ml at the end of the dialysis. Mean elimination half-life under haemodialysis was 2.1 hours. Serum concentrations ranged from 4.9 to 13 microgram/ml two to three days after the haemodialysis.
A disc loading of 50 microgram fosfomycin + 50 microgram glucose-6-phosphate is recommended for disc susceptibility testing. Regression analyses for the correlation of the diameter of inhibition zones with the MIC result in the following equations. For Pseudomonas aeruginosa x = -0.15 y + 16.67 and for Enterobacteriacae plus gram-positive cocci x = -0.34 y + 19.55 (x = log2MIC + 9; y = diameter of inhibition zone in mm). The correlation coefficients are r = -0.9219 and -0.8627 respectively. The analysis yield the following zone diameter interpretive standards. For Pseudomonas aeruginosa less than 12 mm resistant, greater than or equal to 25 mm susceptible, and for Enterobacteriaceae plus gram-positive cocci less than 14 mm resistant, greater than or equal to 20 mm susceptible.
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NMRI-mice were infected in the posterior of the thigh muscles of the right hind leg by injecting one of two isogenic strains of E. coli, one of which was passaged from mouse to mouse for 20 years [mouse-pathogenic (MP) strain], whereas the other was transferred on agar slants only for the same period of time (lab strain). Both strains cause persistent infections only if given as undiluted overnight culture, the MP-strain seeming slightly more virulent. Injection of lower numbers of bacteria results in a corresponding decrease of bacterial cell counts in the animals' thighs. The elimination of the bacteria seems to be all the more rapid the smaller the inoculum. If the infection was administered in mucin suspension, the MP-strain multiplies in the host tissue to a greater degree than the lab strain, irrespectively of the dose injected. The number of cells per muscle reaches a maximum level of about 10(9) even after injecting 10(2) cells of the MP-strain in mucin. To reach the same level, 10(5) cells of the lab strain are needed. Four days after infection, the bacteria start to die off in those animals originally receiving the lower infection doses. Possible reasons are discussed.
The oral protozoa frequency has been studied in 300 patients consulting for oral problems. Entamoeba gingivalis has been isolated more frequently in culture than Trichomonas tenax (50.7% against 28%). The age range which showed the highest frequency in protozoa was the 30-34 year old group for the amoeba and the 45-54 year old group for the flagellae. The endemia increased progressively in relation to the OHIS index. Trichomonas tenax is three times more frequent in case of deep periodontal diseases whereas, Entamoeba gingivalis reached its highest frequency in the case of gingivitis. The pathogenic potentials of these protozoa have been discussed in the light of these correlations and some therapeutical arguments.
Effective doses of fosfomycin against 17 strains of bacteria were determined in therapeutic experiments using infected mice. The peak serum levels obtained after administration of these doses were compared with the minimum inhibitory concentrations determined in vitro. Reasonable minimum inhibitory concentrations were obtained only with Mueller-Hinton agar containing glucose-6-phosphate: 1. Correlation of in vivo and in vitro efficacy is much better in comparison with the use of media without glucose-6-phosphate. 2. Minimum inhibitory concentrations below the levels obtained after therapeutic doses were found only in Mueller-Hinton agar containing glucose-6-phosphate. 3. Minimum inhibitory concentrations are better reproducible when determined on solid media than in broth.
Lately, reports about bensylpenicillin-resistant meningococci have been made in Germany which ensued the presentation of results regarding MIC determinations of 82 strains freshly isolated from carriers. The geometric mean of all MIC values amounts to 0.026 mu/ml which value never exceeds 0.06 mu/ml which is why further spreading of benzylpenicillin-resistant meningococci does not appear to be likely as yet.
The chloramphenicol resistance of some flavobacteria was investigated comparatively. This resistance can be explained either by acetylation of chloramphenicol to O-acetylchloramphenicol via constitutively formed acetyltransferases, followed by cometabolic degradation (strain CB 60), or by limited uptake and total degradation (strain CB 6) by inducible enzymes or by other mechanisms (F. devorans). The mechanisms of resistance, CM-acetylation, CM-degradation and limited uptake are discussed.
The determination of the antibacterial activity of fosfomycin in vitro is most suitably carried out in serial dilution tests on Mueller-Hinton agar. In this, the reproducibility of the minimal inhibitory concentrations (MIC) is the best and is the least dependent on the size of the inoculum. In addition, there is no "skip-tube" effect with this method of determination. The reproducibility of the MIC values increases for several bacterial species on addition of glucose-6-phosphate and at the same time the inhibitory values are lower. If human urine is used as the nutrient medium, the inhibitory values of fosfomycin increase for many species. The action of the antibiotic is not reduced on addition of human blood to the Mueller-Hinton agar.
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