Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fosfomycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1988

Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults.

The pharmacokinetics of two oral forms of fosfomycin, tromethamine (trometamol) salt and calcium salt, were studied in five young (age, 29 +/- 3 [standard deviation] years) and eight elderly (age, 72 +/- 6 years) adults. The subjects received a single 40-mg/kg (body weight) (approximately equal to 3-g) calcium fosfomycin dose and a 25-mg/kg (approximately equal to 2-g) tromethamine fosfomycin dose in fosfomycin acid form. Blood and urine samples were collected for 24 h. Antibiotic concentrations in serum and urine were measured by microbiological assay. In all subjects, the peak levels of the calcium salt in serum were two- to fourfold lower than those of the tromethamine salt (6 to 7 and 18 to 22 micrograms/ml, respectively), indicating poor intestinal absorption of the calcium form. The elimination half-life of the two oral forms was about 5 h in young adults, and the half-life was only moderately longer in elderly subjects, with large individual variations: 8.28 +/- 5.51 h for tromethamine fosfomycin and 11.80 +/- 6.86 h for calcium fosfomycin. In elderly subjects, absorption of the tromethamine salt form was not modified, but the time to peak level was delayed for the calcium salt (2.58 +/- 0.54 h versus 1.41 +/- 0.67 h in young adults). Pharmacokinetic elimination of the two forms of fosfomycin was only moderately affected in elderly subjects; we observed lower urinary elimination, about 58 versus 28% of the dose in 24-h urines for the tromethamine salt and decreased renal clearance of both forms. However, the dosages of tromethamine and calcium fosfomycin need not be adjusted for elderly subjects who have endogenous creatinine clearances above 50 ml/min per 1.73 m2.

Adult↗
PubMed1989

Relative bioavailability of fosfomycin and of trometamol after administration of single dose by oral route of fosfomycin trometamol in fasting conditions and after a meal.

The pharmacokinetics of fosfomycin and trometamol after single oral dose of fosfomycin trometamol (Z 1282) was studied in healthy volunteers in fasting conditions and immediately after standard meal. The dose was of 1.876 g (equivalent to 1.0 g of fosfomycin). The parameters considered were: serum apparent elimination half-life (t1/2), maximum serum concentration (Cmax), time to Cmax (tmax), area under the curve of the serum concentrations from time 0 (zero) to infinity (AUC0-infinity) and urinary recovery in the first 48 h. The results confirm that fosfomycin trometamol allows high bioavailability of fosfomycin. The absorption and elimination rates of fosfomycin and trometamol in the serum were similar. A statistically significant difference was found between the Cmax values of fosfomycin in the 2 experimental conditions. Means +/- SE of Cmax (micrograms/ml) were 12.1 +/- 0.6 in fasting conditions and 7.8 +/- 1.6 after a meal. Urinary recovery of the antibiotic was high in both experimental conditions. The fraction of the dose recovered (the dose being taken as equal to 1) was on the average 0.58 in the first condition and 0.52 in the second. Urinary recoveries of trometamol in the 2 different conditions were similar.

Administration, Oral↗
PubMed1985

Fosfomycin causes transient lysis in Escherichia coli strains carrying fosfomycin-resistance plasmids.

Escherichia coli cells carrying fosfomycin-resistance plasmids show high levels of resistance towards this drug. However, the plasmid-carrying strains exhibited a transient lytic phase induced by fosfomycin when grown in rich liquid media. This lytic phase was not observed if the cells were grown in liquid minimal media. Fosfomycin-induced lysis depended on the accumulation of drug inside the bacteria, presumably as a result of the saturation of the fosfomycin modification system. Growth recovery after lysis was not due to drug inactivation in the culture medium and could be explained by selection of mutants showing impaired fosfomycin transport when high concentrations of fosfomycin were used. However, there was no selection of mutants with low drug concentrations.

Bacteriolysis↗
PubMed1985

Fosfomycin-resistance plasmids determine an intracellular modification of fosfomycin.

Escherichia coli cells carrying fosfomycin-resistance plasmids modify fosfomycin intracellularly. The product of this modification (fosfomycin-derivative) differs from fosfomycin in chromatographic mobility, but the chemical nature of the modification is not yet known. Fosfomycin-derivative appears to have a cytoplasmic location and lacks antibiotic activity. The modification system can be saturated by an excess of fosfomycin in the incubation media.

Biological Transport↗
PubMed1986

Activity of fosfomycin and R-plasmid conferring fosfomycin resistance among some clinical bacteria isolates in Nigeria.

The in vitro activity of fosfomycin (an antibiotic that has clinically not been widely used in Nigeria) against 516 clinical bacteria isolates and the screening for the presence of R plasmid conferring resistance to fosfomycin among the test bacteria isolates were determined. In the presence of added glucose-6-phosphate (25 micrograms/ml) to the growth medium, all the isolates were inhibited at fosfomycin minimum inhibitory concentrations (MIC) of less than or equal to 32-64 micrograms/ml. Without the glucose-6-phosphate, fosfomycin had MIC75, MIC70, MIC48, and MIC20 at 64 micrograms/ml against Escherichia coli, Pseudomonas aeruginosa, Klebsiella spp., and Serratia spp., respectively, while the rest of the strains maintained about the same susceptibility as in the presence of glucose-6-phosphate. An R plasmid of about 59 megadaltons in size, conferring resistance to streptomycin, ampicillin, carbenicillin, and fosfomycin, was obtained from a Serratia liquifacens isolated in an area where fosfomycin had not been clinically used.

Bacteria↗
PubMed1978

Synergism of fosfomycin-ampicillin and fosfomycin-chloramphenicol against Salmonella and Shigella.

Ninety strains of Salmonella and 50 strains of Shigella were tested for susceptibility to fosfomycin, chloramphenicol, and ampicillin by the agar dilution method. Drug interaction between fosfomycin-ampicillin and fosfomycin-chloramphenicol was studied by the agar dilution method. The fractional inhibitory concentration was calculated. The combination of fosfomycin-ampicillin was synergistic against Salmonella in 74 cases, additive in 7, indifferent in 7, antagonistic in none, and nonevaluable in 2; against Shigella it was synergistic in 27 cases, additive in 9, indifferent in 14, and antagonistic in none. The combination of fosfomycin-chloramphenicol was synergistic against Salmonella in 56 cases, additive in 9, indifferent in 13, nonevaluable in 12, and antagonistic in none; against Shigella it was synergistic in 29 cases, additive in 10, indifferent in 9, nonevaluable in 2, and antagonistic in none. Killing curves with combinations of each antimicrobial agent showed that the cultures that had proven to be indifferent by the agar dilution method showed a bactericidal effect until h 4, with posterior regrowth of the culture after this time period. For the strains in which synergism was demonstrated, total bactericidal activity was reached at 24 h.

Ampicillin↗
PubMed1975

Experimental studies on absorption, distribution and excretion of a new antibiotic, fosfomycin. II. Absorption of oral preparations of fosfomycin calcium salt in dogs (author's transl).

To establish the best usage and dosage of fosfomycin granule and capsules which had been prepared based on our fundamental experiences as described in the first report, absorption of calcium salt contained in both preparations was evaluated using dogs as test animals. (1) Granule containing the calcium salt equivalent to 200 mg of fosfomycin free acid per g showed almost the same absorption as the bulk (fosfomycin calcium), having no disadvantage due to processing. (2) Capsules containing the calcium salt equivalent to 250 mg and 500 mg of the free acid per capsule showed slightly more retarded absorption than the bulk, probably due to some inevitable factors such as disintegration rate of capsules and dispersion rate of the calcium salt. But, once dispersed, the calcium salt in capsules was well absorbed as well as the bulk material. (3) Gastrointestinal absorption of granule and the capsule contents was almost the same. (4) Simultaneous administration of capsules and water improved the absorption efficiency. Though administration after feeding caused somewhat retarded absorption of the drug, the serum levels were rather well sustained with a slight drop but sufficiency of absorption, suggesting better clinical advantages than in the fasted animals. (5) Fosfomycin calcium salt in both preparations was well absorbed in the test animals through gastrointestinal tract as well as the bulk calcium salt, without any possible disadvantage caused by processing. In addition, the absorption efficiency was improved by giving with water or meal to the animals.

Administration, Oral↗
PubMed1975

[Experimental studies on absorption, distribution and excretion of fosfomycin. I. Absorption distribution and excretion of fosfomycin calcium salt (author's transl)].

In order to develop some oral drug preparations containing calcium salt of fosfomycin ((minus)-cis-1,2-epoxypropylphosphonic acid) which is a new antibiotic, the absorption, distribution and excretion were studied when it was administered orally to fasted test animals such as rats, rabbits and dogs. The results are as follows: 1) In the case of rats, the more dose size was increased, the more ratio of excretion in urine as index of gastrointestinal absorption was reduced and ratio of excretion in stools was adversely increased, which suggested a decrease in absorption efficiency. But, as absolute amount of excretion in urine became larger with dose size, it was considered that increase in dose size would serve for elevation of serum levels. 2) When the calcium salt was given to rats and rabbits in form of solution and suspension, the former was more eminent than the latter regarding to absorption efficiency, as generally known. The solution, however, needed relatively large quantity of water to solubilize the calcium salt, and it was not considered that the absorption efficiency depends on only dissolution step or dissolution rate. 3) Difference of the particle size varying from 1.50 mu(bulk particle size) and 0.64 mu(mechanical limit size) measured by Kozeny-Carman method did not affect on the absorption in rats and dogs. So it was considered that the bulk could be use directly without micronizing in manufacturing process for the oral preparations. 4) There were some differences of absorption among the animal species. Good absorption was shown in turn in rats, dogs and rabbits. These differences might depend not only on physiological factors but also anatomical differences such as length of gastrointestinal tract. 5) In rabbits high concentration was observed successively in kidney, lung, heart and so on. In any organ its level decreased similarly to the serum level, not sustaining its initial high concentration. The calcium salt did not possess any affinity to certain organs. 6) In conclusion, though some differences of gastrointestinal absorption were observed among the animal species, fosfomycin calcium salt was well absorbed without problem of micronizing the bulk particles. Moreover, it was perceived that fosfomycin calcium salt, once distributed, would not remain in particular organs, being excreted out of body.

Administration, Oral↗
PubMed1988

Molecular relationship among fosfomycin-resistant plasmids and clinical impact of fosfomycin resistance.

We have been carrying out a surveillance programme on plasmid-mediated fosfomycin resistance in our community over the last decade and have isolated and characterized several varieties of conjugative plasmids from different enterobacteriae. In this work we show that seven varieties of plasmids are related with the Inc M group, and carry the same For determinant which encodes a modifying enzyme. The comparative study on their R-phenotype, restriction analysis and DNA-DNA hybridization showed different degrees of molecular relationship among them. The spread of For-plasmids as well as the fosfomycin resistance by other mechanisms seems to be low in spite of the great For-plasmid diversity found.

DNA, Bacterial↗
PubMed1992

[Experimental study on intramaxillary injection of fosfomycin. Effects of fosfomycin on experimental acute sinusitis in rabbits].

We studied effects of intramaxillary injection of fosfomycin (FOM) on experimental sinusitis in rabbits. The experimental sinusitis was induced by intramaxillary injection of Staphylococcus aureus to rabbits for 3 successive days. 1. 0.5, 1, 3 or 5% FOM with saline as a control was instilled into the maxillary sinus and the maxillary sinus mucosa were examined macroscopically and light and electron microscopically. 3% and 5% FOM suppressed the damage of mucosa macroscopically and scanning electron microscopically. 2. After administration of 3% FOM and saline twice a week, the maxillary sinus mucosa was examined macroscopically and light and electron microscopically. The maxillary sinus injected with 3% FOM showed almost normal mucosa after 2 weeks while that injected with saline showed severe mucosal damage. S. aureus were decreased by 3% FOM injection and not found in the maxillary sinus in a week. The results indicate that intramaxillary injection of FOM is very effective in the treatment of sinusitis.

Acute Disease↗
PubMed1990

[Antibacterial activities and electron microscopic studies of imipenem in combination with fosfomycin against methicillin and fosfomycin resistant strains of Staphylococcus aureus].

UNLABELLED: Imipenem (IPM) and fosfomycin (FOM) have been reported to possess a synergistic relationship in their activities against both methicillin (DMPPC)-susceptible and -resistant strains of Staphylococcus aureus. However it was not concluded whether these antibacterial activities were bacteriostatic or bactericidal. The purpose of this report is to elucidate this point clearly. Activities of the 2 antibiotics against 15 strains S. aureus resistant to both DMPPC and FOM were investigated by means of the killing-curve method and electron microscopic studies. MICs of DMPPC and FOM against these strains determined using the agar dilution method were greater than or equal to 50 micrograms/ml and MICs of IPM by the broth dilution method ranged from 12.5 to 50 micrograms/ml. The killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth: 1. FOM 25 micrograms/ml, 2. FOM 25 micrograms/ml + IMP 1/2 MIC, 3. IPM 1MIC, 4. FOM 25 micrograms/ml + IPM 1 MIC and 5. FOM 25 micrograms/ml + IPM 2MIC. Morphological changes produced in 1 strain by 2 of the combinations, 2. FOM 25 micrograms/ml + IPM 1/2 MIC and 4. FOM 25 micrograms/ml + IPM 1MIC, were observed using scanning and transmission electron microscopy. The following results were obtained; (1) The synergistic effects were found in 6/15 strains (40%) and no antagonistic effect was found. (2) Electron microscopic observation showed that IPM in combination with FOM caused lysis of the cells. CONCLUSIONS: IPM in combination with FOM produced bactericidal and bacteriolytic effects on DMPPC-resistant S. aureus (MRSA). This combination therapy should be evaluated for FOM resistant MRSA infections.

Bacteriolysis↗
PubMed1990

Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives.

The pharmacokinetic comparison of phosphonic acid derivatives is based upon a survey of available literature on the whole group of compounds and on our own studies on fosfomycin. All three clinically used compounds, fosfomycin, fosmidomycin, and alafosfalin, are available for both oral and parenteral administration. The highest bioavailability is observed for the trometamol derivative of fosfomycin (37-44%); the calcium salt of fosfomycin is 2-2.5 times less absorbed and fosmidomycin has a bioavailability of 20-30%. The peak serum concentration of fosfomycin when given as the trometamol salt is about 2 times higher than the one reached with fosfomycin calcium or fosmidomycin. Urine recovery of unchanged drug is comparable after intravenous doses of fosfomycin and fosmidomycin, 80-95%, whereas the figure is only 10-20% for alafosfalin because it is extensively metabolized. After oral administration, urine recovery is highest for fosfomycin trometamol, 35-60%, compared to approximately 25% (range 18-29%) for fosfomycin calcium, 26% for fosmidomycin, and 6-17% for alafosfalin. The serum half-life of fosfomycin is 2-4 h (higher, up to 5.5 h, for some formulations of the calcium salt), 1.5-2.0 h for fosmidomycin, and about 1 h for alafosfalin. Thus, among available phosphonic acid derivatives and formulations, the trometamol derivative of fosfomycin has the most favourable characteristics. This applies to both bioavailability and urinary recovery, while at the same time the medium long half-life renders moderate fluctuation of concentrations whereby longer dosage intervals are possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

[The transport mechanism of antibiotics using microvillous membrane vesicles (placental transport of fosfomycin)].

Using the rapid filtration technique, the uptake of fosfomycin into microvillous membrane vesicles isolated from human term placental trophoblast was investigated. The microvillous membrane vesicles exhibited the uptake of fosfomycin into an osmotically reactive intravesicular space and it was indicated that the uptake of fosfomycin by microvillous membrane vesicles represented transport into membrane vesicles. The uptake of fosfomycin by microvillous membrane vesicles was not dependent on the Na+ electrochemical gradient or membrane potential. The initial uptake of fosfomycin by microvillous membrane vesicles did not exhibit saturation kinetics with respect to fosfomycin concentration, and increased linearly as the fosfomycin concentration increased. These results indicated that fosfomycin was transported across the microvillous membrane by simple diffusion. L-alanine, L-valine, L-lysine, inorganic phosphate or D-glucose did not inhibit the uptake of fosfomycin into microvillous membrane vesicles. On the other hand, fosfomycin did not inhibit the uptake of L-alanine, L-valine, L-lysine inorganic phosphate or D-glucose into microvillous membrane vesicles. These results revealed that fosfomycin did not affect the placental transport activity of other nutrients.

Biological Transport↗