摘要:

In order to determine the liquor concentration of fosfomycin, we chose 27 patients who were suffering from meningitis with different etiology. According to route, type of administration and doses employed, we classified the patients into five groups. Blood samples were taken from the patients 1 h after concluding the administration of the antibiotic and 2 h after the CSF sample. The concentration of fosfomycin in the serum and the CSF were then determined in the laboratory. In order to evaluate the results we divided our cases into three groups according to the state of their meningeal inflammation. In the first group of patients with active meningitis, we obtained an average concentration of fosfomycin in the serum of 65.20 μg/ml and in the CSF of 10.88 μg/ml. In the second group of patients with meningitis in the remission stage, the concentration of fosfomycin in the serum was 83.58 μg/ml and in the CSF it was 9.63 μg/ml. In the third group of patients with their meningitis cured, the concentration of fosfomycin in the serum was 66.45 μg/ml and in the CSF it was 4.95 μg/ml. On the basis of the concentrations obtained and with regard to the sensitivity in vitro, we concluded that fosfomycin can be useful in the treatment of meningitis caused by Pneumococcus,Staphylococcus,E. coli and other gram-negative ba

ISSN:0009-3157    

DOI:10.1159/000222045

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

This report deals with the results of a study that was made on the passage of fosfomycin into the CSF in 22 children with meningitis (11 parotideal meningitis and 11 meningococcal meningitis). The plasma and liquor levels of fosfomycin were determined in the acute phase of the illness and after the normalization of the CSF, with the object of studying the passage of the antibiotic through the blood-brain barrier in the presence and absence of meningeal inflammation. A greater permeability of the meninges was found to exist when they were in an inflammatory state and there seems to be a certain accumulative effect in the CSF when the fosfomycin is administered by intravenous perfusion. The concentrations that were obtained in the CSF were not high enough to justify the exclusive use of fosfomycin in the treatment of meningitis. Nevertheless, considering its wide antibacterial spectrum, its MIC against different microbial species and its lack of toxicity, we believe that fosfomycin can be of use when associated with other antibiotics in the treatment of meningitis caused by S. aureus, D. pneumoniae, H. influenzae, E. coli, P. mirabillis and S. marcescens.

ISSN:0009-3157    

DOI:10.1159/000222046

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

The following parameters were considered in studying 43 subjects under treatment for urinary infections with different degrees of renal insufficiency: the maximum blood concentrations, the plasmatic half-life, and the urinary concentrations of fosfomycin as a function of the plasma creatinine of the subject treated. The curve of the average maximum blood concentrations show a parabola-like increase, the plasmatic half-life followed the same tendency, while the curve of the average urinary concentrations presented an exponential decrease. The urinary concentrations were, nevertheless, always higher than 100 μg/ml regardless of the degree of renal insufficiency and even in the subjects who had a very high plasma creatinine. Given its absence of renal and systemic toxicity, the daily dosage of fosfomycin could remain unchanged regardless of the degree of insuffiziency

ISSN:0009-3157    

DOI:10.1159/000222047

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

After the parenteral injection of 1 g sodium salt of fosfomycin the serum levels of the antibiotic are detected in a series of eight adult patients with different degrees of chronic renal insufficiencies four of them submitted to periodical dialysis. The results obtained reveal that the levels as well as the time of elimination of fosfomycin maintain an obvious relation to the degree of renal insufficiency in the patients.

ISSN:0009-3157    

DOI:10.1159/000222048

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

The sensitivity to fosfomycin which is found in organisms that are frequently found in urinary infections and the lack of toxicity of this antibiotic were the reasons for which we tested fosfomycin on patients who were subjected to periodic hemodialysis. We were interested in studying (1) if fosfomycin was dialyzable, and (2) its therapeutic pattern in these patients. We selected a group of 27 patients from our programme of periodic hemodialysis who spend 18 h each week in three sessions with an RSP Travenol artificial kidney, using Ultra Flo II as the dialytic unit. They were all free of infection and had not received any antibiotics for 40 days before the test was carried out. They were administered 1 or 2 g of fosfomycin by the intravenous route at the time of beginning the dialysis. Blood samples and samples from the dialytic bath were taken before administering the fosfomycin, and ½, 3 and 6 hours after administering it. Our results show that fosfomycin is 70–80% dialyzed by the membranes of the artificial kidney and that during the hemodialysis, given the clearance which the di-alyzing membrane makes of the antibiotic, the usual doses of fosfomycin should not be altered. No side effects were observed in any of the patien

ISSN:0009-3157    

DOI:10.1159/000222049

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

A study was made of the elimination of fosfomycin by the membrane of the artificial kidney in 10 patients with hemodialysis and a creatinine clearance of less than 5 ml/min. To do so we determined the half-life, the dialysance, the percentage of total loss and the percentage of loss by the artificial kidney. We reached the conclusion that fosfomycin is heavily dialyzed (D = 64 ml/min), it is entirely eliminated by the kidneys and its half-life is therefore affected very little (an increase of only about 30 min is produced). All of this leads to a practical schema by which the entire initial dose should be replenished at the end of each dialysis.

ISSN:0009-3157    

DOI:10.1159/000222050

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

A study was made of the blood levels, half-life and elimination of fosfomycin in two groups of underweight infants during the 1st to 3rd days of life and after 3–4 weeks. The test dose was 50 mg/kg i.v., administered in a single dose. The times at which the blood was controlled were 5 min, 1, 3, 6, 9 and 24 h; and 0–24 h for the urine. All samples were evaluated by the microbiological method of diffusion in plate. The results obtained indicate that the elimination of fosfomycin after 24 h is slower and occurs in smaller quantities in the group of infants 1–3 days old than in the group of 3- to 4-week-old infants, the half-life of the antibiotic being 7 and 4.9 h, respect

ISSN:0009-3157    

DOI:10.1159/000222051

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

The influence of orally administered fosfomycin on intestinal disaccharidases in albino rats was studied. The enzymes were evaluated in a homogenate of the intestinal mucosa, using the method of Sols and de la Fuente which is based on the colored reaction of the glucose that is freed by the disaccharidases from disaccharides with a glucose-oxidase-peroxidase reagent and a chromogen (Glucostat). The results obtained in animals treated with a daily dose of 1 g/kg fosfomycin for 6 consecutive days are compared with the corresponding results of animals that received 1 ml/day of saline solution during the same period. Our conclusion was that fosfomycin has no effect on the intestinal disaccharidases in rats.

ISSN:0009-3157    

DOI:10.1159/000222052

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

The effect of fosfomycin on the thrombocytal aggregation induced by ADP was studied. Plasma rich in thrombocytes was used. It was obtained from blood donors. Fosfomycin was used in concentrations of 1.3 X 10–3; 1.3 X 10–2, and 1.3 X 10–1 m and the ADP in concentrations of 1.17, 2.34 and 3.51 X 10–6 m. Two experimental groups were used: the first group was made up of five experiments, with an incubation time for the fosfomycin with the thrombocytes of 2 min; the second experimental group was made up of five experiments whose incubation times were 5 and 10 min. Fosfomycin inhibits the thrombocytal aggregation which is induced by ADP. This inhibition (1) is larger, the smaller the concentration of ADP, (2) for a single concentration of ADP it is proportional to the concentration of fosfomycin that is used, and (3) there are no significant differences according to the time of incubation. This thrombocytal anti-aggregating activity is related to the presence of a phosphonic group in the molecule of fos

ISSN:0009-3157    

DOI:10.1159/000222053

出版商:S. Karger AG    

年代:1977

数据来源: Karger

摘要:

The Japan Research Committee of Fosfomycin was organized in the fall of 1972 to promote the basic and clinical studies on fosfomycin. First of all, a subcommittee of fosfomycin consisting of a limited number of members was organized to establish the methods of determination on its antibacterial activity and its concentration in the biological fluid, and the most applicable methods were devised. The clinical trials on its oral form in a small scale were commenced from spring in 1973, and then gradually expanded to almost all of Japan. The clinical trials on its parenteral intravenous form were also undertaken from the latter half of 1973. The basic and clinical results obtained from hospitals and institutes almost all over Japan, to which members of the above Committee belong, were presented by speakers under a hot discussion in two symposia which were held by the Japan Society of Chemotherapy; one on its oral form in June 1974, and another on its parenteral form in December 1974.1 served as chairman in both of the symposia. The clinical results of fosfomycin in Japan which were mainly collected in both symposia are described below. Its antibacterial activity, and absorption and excretion will be presented elsewhere in this volume. Clinical results of its oral form: Dosage forms of fosfomycin-Ca salt, capsule and granules, were prepared for its clinical trials. It resulted effective in about 76% of 1,200 patients with infection due to gram-positive or gram-negative (Pseudomonas, Salmonella, Escherichiacoli, etc.) bacteria in several fields. As far as rates of efficacy were concerned, it was more effective in surgical, urological, ophthalmic and some other fields than in internal and pediatric ones. Fosfomycin was given in a dose of 2–3 g/day for adults or 100–130 mg/kg for infants and children in most cases. Furthermore, it can be favorably mentioned that fosfomycin was proved to be effective in salmonellosis and resistant shigellosis by a certain research group specialized in the therapy of infectious enteritis. Clinical results of its parenteral form: Sterilized bulk material of fosfomycin-Na salt was prepared in a vial for clinical use. Similarly as in the case of oral form, it was applied to about 500 patients with several infections. It resulted effective in about 68% of them. This percentage was not so high because of the higher frequency of application to severe patients or patients with underlying disease. Fosfomycin was intravenously administered by one shot or drip infusion in a dose of 2–4 g/day for adults, or 100–250 mg/kg for infants and children in most cases. Adverse reactions: In oral form, the incidence of adverse reactions was about 10% but most of them were slight gastrointestinal disorders. In an extremely small number of patients a rise of SGOT and/or SGPT was observed. In parenteral form, the incidence of adverse reactions was a little higher, being about 17% including a rise of SGOT and/or SGPT, vascular pain, nausea, and vomiting, etc. Some influences on the heart were reported at an earlier stage of clinical studies on its parenteral form, but no abnormality on heart function was confirmed by animal experiments and phase I trial with healthy volunteers. Controlled trials in comparison with other antibiotics are now in progress. A part of comparative data with cephalexin in skin and urological infections will be pr

ISSN:0009-3157    

DOI:10.1159/000222054

出版商:S. Karger AG    

年代:1977

数据来源: Karger