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 91 records · Page 5Linked to original sources
PubMed1988

Effects of fosfomycin, mesna, and sodium thiosulfate on the toxicity and antitumor activity of cisplatin.

Fosfomycin and mesna were investigated in rats and mice concerning their detoxifying effects on cisplatin toxicity in comparison to sodium thiosulfate, a known protector against cisplatin nephrotoxicity. After separate i.p. injection of cisplatin and fosfomycin (500 mg/kg) or mesna (800 mg/kg) a slight increase in the 50% lethal dose of cisplatin was found in all animals. In mice sodium thiosulfate proved to be far more effective in preventing lethal toxicity and nephrotoxicity as measured by blood urea nitrogen increase. Fosfomycin and mesna were almost without influence on cisplatin treatment of L-1210 leukemia whereas their inhibition of the antitumor effect against S-180 ascites sarcoma (increase of in cisplatin dose to cure 50% of animals from 2.0 mg/kg to 3.5/4.7 mg/kg cisplatin) was similar to thiosulfate, which showed a strong inhibiting effect in the treatment of both tumors. In rats fosfomycin distinctively reduced the antitumor efficacy of cisplatin against Yoshida ascites sarcoma. Thus the concurrent injection of fosfomycin and mesna reduced both the toxicity and the antitumor activity of cisplatin. Therefore their simultaneous administration in addition to cisplatin via the same injection route should be avoided. Due to the weak detoxifying efficacy of fosfomycin and mesna they cannot be used instead of sodium thiosulfate for renal protection against cisplatin toxicity in local i.p. treatment modalities.

Animals↗
PubMed1982

[Fosfomycin concentrations in serum and bile (author's transl)].

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.

Adult↗
PubMed1990

Fosfomycin trometamol: activity in vitro against urinary tract pathogens.

The spectrum of activity of fosfomycin embraces all the common causes of uncomplicated urinary tract infection. The activity is greatly affected by the conditions of the test. Glucose, phosphates and NaCl all interfere with the activity of the drug, whereas glucose-6-phosphate has a marked potentiating effect against many strains. The activity of fosfomycin is greater at acid than at alkaline pH; inoculum density also has an effect, but this is less marked at acid pH values. Fosfomycin is rapidly bactericidal to susceptible bacteria, causing lysis within 30 min. In contrast, fosmidomycin, which also has a narrower spectrum of activity than fosfomycin, is much more slowly bactericidal. In the form of its trometamol salt, fosfomycin is well absorbed after oral administration, and is excreted in high concentration in the urine. Experiments in an in-vitro model of the treatment of bacterial cystitis suggest that concentrations of fosfomycin achievable in urine after oral administration of high doses of the trometamol salt have a marked suppressive effect on bacterial growth without favouring the emergence of resistant mutants.

Biological Availability↗
PubMed1990

Fosfomycin trometamol in a single dose versus norfloxacin for seven days in the treatment of uncomplicated urinary infections in general practice.

The efficacy and tolerability of fosfomycin trometamol in a single dose of 3 g was compared with norfloxacin 400 mg b.i.d. for seven days in the treatment of adult female patients with uncomplicated urinary infections. 158 female patients with a mean age of 30 years who presented symptoms of dysuria and frequency with documented pyuria and bacteriuria on urinalysis (greater than or equal to 10(5) cfu/ml of urine) were initially included in the study. The total number of clinically and bacteriologically evaluable patients was 111, of which 61 received fosfomycin trometamol and 50 norfloxacin. One to two days after the double blind medication schedule for seven days, 55 of 60 patients (92%) in the fosfomycin trometamol group and 48 of 50 patients (96%) in the norfloxacin group were clinically cured. 37 patients without significant bacteriuria showed a clinical cure rate of over 90% in both therapy groups. Two to three days after the single dose treatment with fosfomycin trometamol the initial infecting pathogen was eradicated in 60 of the 61 patients (98%). One to two days after a seven day treatment with norfloxacin 48 of 50 patients (96%) showed an eradication of the initial infecting pathogen. Six weeks after the start of therapy 39/60 patients (65%) and 32/49 (65%) in the fosfomycin trometamol and norfloxacin groups respectively, remained free from urinary infection. The reinfection rate in both treatment groups was approximately 25%. The relapse rate in the post treatment evaluation period of four weeks was relatively low in both therapy groups, 5/49 patients (10%) in the norfloxacin group and 3/55 patients (6%) in the fosfomycin trometamol group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Comparison of the response of Escherichia coli to fosfomycin and fosmidomycin.

The responses of Escherichia coli to fosfomycin and fosmidomycin were investigated by continuous turbidimetric monitoring of cultures exposed to the drugs and by microscopy. The activity of both agents was potentiated by glucose-6-phosphate, suggesting that they share the inducible hexose phosphate transport system in Escherichia coli, but several differences of response were also detected: the inoculum effect was much smaller with fosfomycin than with fosmidomycin; inhibition of bacterial growth occurred much more rapidly with fosfomycin than with fosmidomycin; and fosfomycin was able to induce the formation of spheroplasts much more rapidly than fosmidomycin. Stable resistance to fosfomycin and fosmidomycin was readily induced in cultures of Escherichia coli, and some resistant variants retained susceptibility (or partial suceptibility) to the other compound. These observations suggest that although fosfomycin and fosmidomycin may be transported into Escherichia coli by a similar mechanism, the intracellular target site may be different.

Chemical Phenomena↗
PubMed1997

Bactericidal effect of pefloxacin and fosfomycin against Pseudomonas aeruginosa in a rabbit endocarditis model with pharmacokinetics of pefloxacin in humans simulated in vivo.

The bactericidal activity of pefloxacin and fosfomycin alone and in combination against Pseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4 +/- 11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12-48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.

Animals↗
PubMed1993

Evaluation of disk susceptibility testing of fosfomycin tromethamine.

Fosfomycin tromethamine is an orally administered fosfomycin that may be used for single-dose therapy of uncomplicated urinary tract infections. At breakpoint concentrations [< or = 128 micrograms/ml plus 25 micrograms/ml glucose-6-phosphate (G-6-P)], fosfomycin tromethamine inhibited > 90% of the 350 bacterial isolates tested. When testing Escherichia coli, Klebsiella spp., and Enterobacter spp., we note that the performance of fosfomycin disks improved when G-6-P was added to the disks. The interpretive error rates were minimized when 200-micrograms fosfomycin disks were supplemented with either 50 or 100 micrograms G-6-P. Using < or = 128 and > or = 256 micrograms/ml as the susceptible and resistant MIC breakpoints, respectively, the regression-analysis-derived disk diffusion zone diameter breakpoints for the 200-micrograms fosfomycin disk supplemented with 50 micrograms of G-6-P are as follows: susceptible, > or = 16 mm; intermediate, 13-15 mm; and resistant, < or = 12 mm.

Bacteria↗
PubMed2005

Determination of fosfomycin in pus by capillary zone electrophoresis.

A method is described for the determination of fosfomycin in pus by capillary zone electrophoresis with reversed electroosmotic flow, and indirect UV absorbance detection. Sample pre-treatment is limited to removal of proteins and cell debris by adding the double volume of methanol, followed by vortexing for few seconds, and centrifugation at 15,000 x g for 2 min. The supernatant is directly injected into the instrument. Fosfomycin is separated from sample constituents with a background electrolyte at pH 7.25 (25 mM benzoate buffer with 0.5 mM hexadecyltrimethylammonium bromide added, adjusted to pH with tris(hydroxymethyl)-aminomethane (TRIS)). Separation is carried out in a capillary with 50 microm I.D., 64.5 cm total length, 56.0 cm to the detector, at 25 degrees C with -25 kV voltage applied. Due to the low absorbance of the analyte, indirect UV detection was performed at 254 nm using a bubble cell capillary. Sample was injected by pressure (450 mbar s). Repeatability for fosfomycin in spiked pus (from 8 or 10 consecutive injections of three different series at concentrations of 100 microg/mL of the antibiotic) was between 2.4 and 8.2% relative standard deviation (RSD). Accuracy (expressed as recovery of fosfomycin determined by three independent analysis at 10, 100 and 300 microg/mL fosfomycin added to plain pus) was between 75 and 102%. Intermediate reproducibility (n = 9 at three different days) was between 2 and 12% RSD. Limit of detection and limit of quantitation were 4.5 and 15 microg/mL, respectively. The concentration of fosfomycin in pus of patients treated with the antibiotic ranged up to 240 microg/mL. The concentration of other anionic pus constituents identified beside chloride (acetate, succinate, lactate, phosphate) ranged between 20 and 7800 microg/mL.

Abscess↗
PubMed2001

[Correlation between sensitivity to fosfomycin and the presence of penicillinase PSE-1 in Pseudomonas aeruginosa].

A prospective survey was carried out during three three-weeks periods in May, October 1997 and October 1998 in 13 teaching hospitals. All non-repetitive isolates of P. aeruginosa collected were subject to serotypage and determination of the inhibiting minimal concentrations for ticarcillin, piperacillin, piperacillin + tazobactam, ceftazidime, imipenem, amikacin, ciprofloxacin and fosfomycin. Identification of the betalactamases and quantification of the cephalosporinase were done for the strains intermediate or resistant to ticarcillin. The most frequent serotypes were O: 6 (17%), O: 11 (13%), O: 1 (10%) and O: 12 (9%). Serotype O: 12 was the least susceptible to antibiotics except for fosfomycin. Whatever the serotype, 76% of P. aeruginosa strains with bla PSE-1 are susceptible to fosfomycin, when only 29.8% of non bla PSE-1 producing strains were susceptible to this antibiotic. Integron encoding bla PSE-1 could be implicated in susceptibility to fosfomycin of P. aeruginosa strains. The associations fosfomycin + imipenem or fosfomycin + ceftazidime could be proposed in case of infections due to P. aeruginosa O: 12.

Anti-Bacterial Agents↗
PubMed1998

Effects of fosfomycin and imipenem/cilastatin on nephrotoxicity and renal excretion of vancomycin in rats.

PURPOSE: The effects of fosfomycin and imipenem/cilastatin on the nephrotoxicity of vancomycin were studied in rats, and those on the renal handling of vancomycin were also investigated in perfused kidneys. METHODS: The protective effects of fosfomycin and imipenem/cilastatin on vancomycin nephrotoxicity were evaluated by increases in plasma concentration of creatinine and urea nitrogen in rats. The urinary excretion of vancomycin was measured and analyzed kinetically in the perfused rat kidney. RESULTS: The nephrotoxicity induced by vancomycin (500 mg/kg, i.v.) was inhibited almost completely by co-administration of fosfomycin or imipenem/cilastatin. In the perfused rat kidney, the excretion ratio of vancomycin was less than those of p-aminohippurate and cimetidine, and greater than that of arbekacin, suggesting the secretion and reabsorption of vancomycin in renal tubules. The tissue/perfusate ratios of unbound vancomycin were not significantly changed by co-treatment with fosfomycin or imipenem/cilastatin. Imipenem/cilastatin significantly decreased the excretion ratio of vancomycin. Fosfomycin also decreased vancomycin excretion ratio, although this effect was not significant. CONCLUSIONS: The renal handling of vancomycin was different from those of organic anions and cations and an aminoglycoside antibiotic. The protective effects of fosfomycin and imipenem/cilastatin against the nephrotoxicity of vancomycin might be partly due to the change in renal handling of vancomycin, probably in its tubular secretion/ reabsorption, in rats.

Animals↗
PubMed1991

The dynamics of intraperitoneal growth and elimination of Escherichia coli and Bacteroides fragilis in porcine faecal peritonitis treated with fosfomycin.

The kinetics of intraperitoneal killing of proliferating bacteria was studied in pigs given fosfomycin. Eight animals were given intra-abdominal injection of Escherichia coli and Bacteroides fragilis (10(9) cfu of each species) mixed in sterile faces. Three hours later, half of the animals received an intravenous dose of 1 g fosfomycin (0.05 g/kg). Host defences rapidly decreased the density of E. coli in all animals in the first hour. After 2h, growth of E. coli started and continued throughout the experiment in pigs not receiving fosfomycin. B. fragilis was slowly eliminated in the first 5 6 h, then numbers increased in all animals. Fosfomycin caused a reduction in E. coli density, by 10(2.19) +/- 0.29 (mean +/- S.E.M.) cfu/ml, or more than 150 times within 1 h, while the concentration of B. fragilis was unaltered. After 10 h the difference in E. coli density between fosfomycin treated and untreated animals was 10(4.96) cfu/ml (P less than 0.01). Fosfomycin eradicated E. coli in faecal peritonitis but not B. fragilis, which is resistant in vitro. There was a prolonged elimination of the drug from peritoneal exudate in pigs infected with bacteria in sterile faeces compared to the elimination in uninfected pigs or pigs infected only with bacteria.

Animals↗
PubMed2006

Immunomodulatory effects of fosfomycin in an endotoxin model in human blood.

OBJECTIVES: Although a wide range of therapeutic strategies have been developed to improve the outcome of severe sepsis, a convincing reduction in mortality is lacking. Recently, increasing attention has been paid to immunomodulatory effects of antimicrobials. This study set out to explore the immunomodulatory effects of fosfomycin, a broad-spectrum antibiotic frequently used in septic patients, at the protein and molecular levels in vitro. METHODS: Whole blood from 11 healthy volunteers was incubated with 50 pg/mL endotoxin and 100 microg/mL fosfomycin or physiological sodium chloride for 4 h. Real-time RT-PCR was performed for various pro- and anti-inflammatory cytokines. Concentrations of tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in the supernatant were measured using a commercially available ELISA. RESULTS: Incubation of human leucocytes with endotoxin increased messenger RNA (mRNA) levels of cytokines several thousand fold compared with baseline. The addition of fosfomycin significantly inhibited mRNA levels of pro-inflammatory cytokines such as IL-1-alpha, IL-6 and TNF-alpha after 2 h (P < 0.01), while no significant reduction was observed for the anti-inflammatory cytokines IL-4, IL-10 and IL-13 (P = 0.26). At the protein level, the concentrations of IL-6 and TNF-alpha increased approximately 3000- and 600-fold after 4 h of incubation with lipopolysaccharide as compared with baseline, respectively. Addition of fosfomycin significantly reduced cytokine levels by 56% and 73% for IL-6 and TNF-alpha, respectively. CONCLUSIONS: Fosfomycin extensively decreased mRNA levels and release of pro-inflammatory cytokines in human blood. The broad antimicrobial coverage of fosfomycin and its immunosuppressive effects could be clinically useful in patients with sepsis.

Anti-Bacterial Agents↗
PubMed1999

Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum.

OBJECTIVES: This study investigates the effect of fosfomycin on the tumoricidal efficacy of cisplatinum. STUDY DESIGN: Prospective study utilizing the FaDu squamous cell carcinoma cell line and a nude mouse tumor xenograft model. METHODS: Tumor cell growth was assessed in vitro in the presence of cisplatinum and/or fosfomycin utilizing the MTT assay. An optimal cisplatinum dose and dosing schedule was established in a nude mouse tumor xenograft model of squamous cell carcinoma. Using this model, fosfomycin was tested at three dosages and tumor growth monitored over 4 weeks. RESULTS: Mice treated with cisplatinum and fosfomycin had smaller tumors than those treated with cisplatinum alone (P<.01). CONCLUSIONS: This study is the first demonstration that fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum in vivo. This suggests that fosfomycin may be useful in preventing cisplatinum-induced ototoxicity and nephrotoxicity in humans without altering the tumor response rate.

Animals↗
PubMed1984

Synergistic activities of combinations of beta-lactams, fosfomycin, and tobramycin against Pseudomonas aeruginosa.

The effects of antibiotic combinations against Pseudomonas aeruginosa infections frequently found in hospitalized patients were investigated. By means of an agar plate dilution checkerboard method, combinations of piperacillin-fosfomycin, cefoperazone-fosfomycin, and cefsulodin-fosfomycin were synergistic against 80.0, 85.0, and 82.6% of the strains tested. The mean fractional inhibitory concentration indices of piperacillin-fosfomycin, cefoperazone-fosfomycin, and cefsulodin-fosfomycin were 0.48, 0.42, and 0.46, respectively. The synergistic activities of these combinations were enhanced by the addition of a small amount of tobramycin, 0.25 micrograms/ml.

Anti-Bacterial Agents↗
PubMed2003

Biological costs and mechanisms of fosfomycin resistance in Escherichia coli.

Fosfomycin is a cell wall inhibitor used mainly for the treatment of uncomplicated lower urinary tract infections. As shown here, resistance to fosfomycin develops rapidly in Escherichia coli under experimental conditions, but in spite of the relatively high mutation rate in vitro, resistance in clinical isolates is rare. To examine this apparent contradiction, we mathematically modeled the probability of resistance development in the bladder during treatment. The modeling showed that during a typical episode of urinary tract infection, the probability of resistance development was high (>10(-2)). However, if resistance was associated with a reduction in growth rate, the probability of resistance development rapidly decreased. To examine if fosfomycin resistance causes a reduced growth rate, we isolated in vitro and in vivo a set of resistant strains. We determined their resistance mechanisms and examined the effect of the different resistance mutations on bacterial growth in the absence and presence of fosfomycin. The types of mutations found in vitro and in vivo were partly different. Resistance in the mutants isolated in vitro was caused by ptsI, cyaA, glpT, uhpA/T, and unknown mutations, whereas no cyaA or ptsI mutants could be found in vivo. All mutations caused a decreased growth rate both in laboratory medium and in urine, irrespective of the absence or presence of fosfomycin. According to the mathematical model, the reduced growth rate of the resistant strains will prevent them from establishing in the bladder, which could explain why fosfomycin resistance remains rare in clinical isolates.

Anti-Bacterial Agents↗
PubMed1977

A study of the levels of fosfomycin in the cerebrospinal fluid in adult meningitis.

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 mug/ml and in the CSF of 10.88 mug/ml. In the second group of patients with meningitis in the remission stage, the concentration of fosfomycin in the serum was 83.58 mug/ml and in the CSF it was 9.63 mug/ml. In the third group of patients with their meningitis cured, the concentration of fosfomycin in the serum was 66.45 mug/ml and in the CSF it was 4.95 mug/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 bacilli.

Administration, Oral↗
PubMed1977

Effect of fosfomycin on the thrombocytal aggregation induced by ADP.

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 fosfomycin.

Adenosine Diphosphate↗
PubMed1977

Fosfomycin in pneumococcal meningitis.

A study has been made of 12 patients with pneumococcal meningitis with ages ranging from 12 months to 59 years. In all cases pneumococcus was isolated in the cerebrospinal fluid (CSF). Seventeen pneumococci were studied for their sensitivity to fosfomycin, ampicillin and gentamicin, including their MIC. All were sensitive to fosfomycin and ampicillin and 7 to gentamicin. On the other hand there has also been made a study of the interaction between fosfomycin plus ampicillin and fosfomycin plus gentamicin. The concentration of antibiotics in plasma and CSF had been determined. The association of fosfomycin to penicillin or ampicillin was also studied in some cases, depending on whether the patient was younger or older than 2 years, and in other cases, the association of fosfomycin with gentamicin. The concentrations of antibiotics in the CSF varied according to the stage of evolution of the meningitis. As regards clinical results, 10 cures and 2 failures have been obtained. The pneumococcus was eradicated from the CSF in all cases, including the two failures, in the control carried out 2-3 days after beginning of treatment, the rest of the analytical data of the CSF became normal within 5 and 17 days treatment.

Adult↗