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PubMed1988

Treatment of experimental cystitis in the rat with a single dose of fosfomycin trometamol.

The therapeutic effectiveness of a single oral dose (60 and 200 mg/kg body weight) of fosfomycin trometamol (FT), norfloxacin, trimethoprim sulfamethoxazole (Bactrim) and pipemidic acid against experimental cystitis in the rat were compared. Infections were produced with clinical isolates of Klebsiella pneumoniae, Proteus mirabilis and Escherichia coli in a total of 135 Sprague-Dawley albino rats. Oral treatment with all four drugs consistently lowered the numbers of CFU in bladder tissue, especially E. coli and P. mirabilis. Fosfomycin trometamol appeared to be as effective as norfloxacin for treatment of E. coli cystitis even thoughs its minimal inhibitory concentration (MIC) in vitro is 100 times greater than that of the quinolonic antibiotic. Fosfomycin trometamol, pipemidic acid and Bactrim were equally effective against P. mirabilis infection, but FT was less active than norfloxacin or Bactrim for treatment of K. pneumonia cystitis. In conclusion, single dose treatment with fosfomycin trometamol was effective for treatment of experimental cystitis in the rat and might, by extrapolation, be of use in clinical practice for single dose treatment of uncomplicated urinary tract infections.

Administration, Oral↗
PubMed1988

Fosfomycin versus ampicillin in the treatment of acute pyelonephritis.

In a controlled open study of 38 patients with acute pyelonephritis, treatment with fosfomycin 8 g b.i.d. was compared to treatment with ampicillin 2 g t.i.d., both for one week. The most common pathogen in both groups was Escherichia coli, susceptible to fosfomycin. However, 17% were resistant to ampicillin. The success rate was 44% in the fosfomycin treated group and 28% in the ampicillin group. The difference was not significant (p greater than 0.20). Peak concentrations of fosfomycin in serum were 395 mg/l and in tissue fluid 85 mg/l. Urine concentrations ranged from 6990 to 24,320 mg/l.

Acute Disease↗
PubMed1986

[Diffusion of fosfomycin into the human and rabbit eye (aqueous humor and vitreous body)].

The intraocular distribution of fosfomycin was studied in 32 patients undergoing cataract surgery and in 8 rabbits after experimental infection of one eye by Staphylococcus aureus. Concentrations found 1 to 6 hours after termination of a 4 g fosfomycin infusion ranged from 14 to 18.8 mg/l in the aqueous humor and 8 to 12.5 mg/l in the vitreous body. These levels are higher than the MICs for 80 to 90% of the bacteria responsible for endophthalmitis. In each rabbit, the fosfomycin concentration in the infected eye as compared to the healthy eye was increased 2.5 to 5--fold for the aqueous humor and 4.9 to 19.2--fold for the vitreous body. Fosfomycin, in association with a third generation cephalosporin (ceftriaxone) or one of the new quinolones (pefloxacin) can be recommended for the prevention or early treatment of endophthalmitis.

Adolescent↗
PubMed1987

[In vitro action of fosfomycin combined with rifampicin, pefloxacin and imipenem on staphylococci (checkerboard method in a liquid medium)].

The combined activity of fosfomycin with rifampin, pefloxacin and imipenem was investigated, by the checkerboard method performed in liquid medium, against 50 clinical isolates of staphylococci (25 Staphylococcus aureus and 25 coagulase-negative staphylococci). The combination of fosfomycin plus rifampin had an additive bacteriostatic effect and an antagonistic bactericidal effect. Fosfomycin combined with pefloxacin was found to be additive or moderately synergistic. Fosfomycin in combination with imipenem was generally highly synergistic, especially against meticillin-resistant strains; however the bactericidal effect was occasionally antagonistic.

Anti-Bacterial Agents↗
PubMed1985

[Diffusion of fosfomycin in the presence of glucose-6-phosphate from discs for antibiotic sensitivity testing].

A disc containing 50 microgram fosfomycin and 25 microgram glucose-6-phosphate (G-6-P) has been developed for fosfomycin susceptibility testing. The present study was designed to examine the influence of G-6-P on the diffusion gradient of fosfomycin in Mueller-Hinton agar. Discs containing 50 microgram 3H-fosfomycin and/or 25 microgram 14C-G-6-P were placed in the center of agar plates. Radioactivity of agar cylinders removed along the radius of the Petri plate at different times from 30 sec to 24 hours was measured. Results showed that the fosfomycin/G-6-P ratio throughout diffusion remained close to the initial ratio in the disc, suggesting that loads of both substances borne by the discs are adequate for antibiotic sensitivity testing.

Agar↗
PubMed1979

[General pharmacological studies on fosfomycin sodium (author's transl)].

The pharmacological effects of fosfomycin sodium, a new antibiotic agent, were studied on central nervous system, neuromuscular junction, isolated smooth muscles, blood coagulation, red blood cell resistance, body temperature, permeability of skin vessels and IgG and IgE antibody formation in laboratory animals. Fosfomycin sodium inhibited activities on the isolated smooth muscles, elevated body temperature, and increased permeability of skin vessels. Any of these actions, however, was noticeable only when it was administered in higher doses. Except for these above effects, fosfomycin sodium did not show any actions. Consequently, it can be concluded that fosfomycin sodium has no specific pharmacological actions.

Animals↗
PubMed1984

[Diffusion of fosfomycin into the cerebrospinal fluid in purulent meningitis].

Cerebrospinal fluid levels of fosfomycin were measured in 10 patients with bacterial meningitis. Fosfomycin 200 mg/kg/day was administered in three 4-hour intravenous infusions. The antibiotic was associated with amoxicillin in 9 patients and with cefotaxime in one. Cerebrospinal fluid was obtained on the 2nd and 5th days of treatment, 2 hours after the end of the infusion. The mean CSF fosfomycin levels were 31 mg/l on the 2nd day and 37.2 mg/l on the 5th day. These levels were higher than the MIC 90 for most bacteria encountered in meningitis. Fosfomycin could be used to treat some cases of bacterial meningitis, but always in association with another antibiotic.

Adult↗
PubMed1983

[Clinical studies on combination chemotherapy with fosfomycin and dibekacin in complicated urinary tract infection].

Clinical studies were performed on combination chemotherapy with Fosfomycin and Dibekacin. Sixteen patients with complicated urinary tract infections were treated with a combination of Fosfomycin (4 g/day, d.i.v.) and Dibekacin (200 mg/day, i.m.) for 5 days; and, 15 of them were clinically evaluated by criteria of UTI committee. The clinical effects proved excellent in 3 patients, good in 8 patients, and poor in 4 patients overall effective rate was 73.3%. Out of 19 strains isolated from the patients, 12 strains disappeared after the therapy. No side effect was observed in 16 cases. Clinical use of the combination chemotherapy with Fosfomycin and Dibekacin was thought to be effective and safe for patients with complicated urinary tract infections, because the combination acts not only synergistically, but also because Fosfomycin acts to protect against the nephrotoxicity induced by Dibekacin.

Adult↗
PubMed1982

[A study on the disc sensitivity test for fosfomycin (author's transl)].

Susceptibilities to fosfomycin of 216 strains of 28 bacterial species were determined by the 2-fold agar dilution method in parallel with the diameter of inhibition zone by the single-disc method, under the experimental condition establish by Kanazawa. The experiments demonstrated significant correlation between MIC by the dilution method and diameter of inhibition zone in each of conventional assay of the over-night (about 16 hours) incubation, delayed assay (about 24 hours incubation), thus confirming applicability of the single-disc assay for fosfomycin. Analysis of the data obtained by using fosfomycin disc containing 200 micrograms revealed the primary regression equation to be: D (diameter, mm) = 42.73-13.85 log MIC (microgram/ml) in conventional assay, D = 56.51-18.18 log (microgram/ml) in delayed assay, respectively. The range of variations in MICs estimated from the diameter of inhibition zone by the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution assays, as reference for the experimental errors which may be involved in the estimation of MIC of fosfomycin by the single-disc assay.

Anti-Bacterial Agents↗
PubMed1980

[Fosfomycin: animal experiments on nephrotoxicity, pharmacokinetics and therapeutic efficacy (author's transl)].

The nephrotoxicity, pharmacokinetic and therapeutic activity of fosfomycin were investigated in female wistar-rats. Measures of nephrotoxicity were urinary excretion of tubular cells and of the enzymes MDH, LDH, and GOT. Histological investigations and estimation of serum urea concentration and proteinuria were also evaluated. The doses of 500, 1000, 2000, 3000, and 5000 mg/kg/d were administered in 9 single doses with 12 hours interval. The lowest dose which induced a significantly increased tubular cell excretion was 1000 mg/kg/d and therefore in the same range as the tubulotoxic threshold doses of cephalosporins. Chemotherapy of the chronic estrogen induced pyelonephritis revealed equally favourable results for fosfomycin and cefuroxim at dosages of 2 X 150 mg/kg/d. The pharmacokinetics of fosfomycin at a single dose of 150 mg/kg/d were equivalent to those of cefuroxim. These animal experiments showed fosfomycin to be of value as a therapeutic alternative to cephalosporin antibiotics.

Animals↗
PubMed1995

[A patient with acute leukemia and meningitis caused by Staphylococcus epidermidis treated with fosfomycin].

In a 17-year-old male patient with acute lymphoblastic leukaemia, who was being treated with chemotherapy, a Staphylococcus epidermidis infection with several septicaemias developed during a period of protracted neutropenia. The patient was treated with vancomycin and fusidic acid, but blood cultures remained positive. The patient also developed staphylococcal meningitis. After the antibiotic regimen was supplemented by fosfomycin, the blood cultures became sterile. Combination treatment with vancomycin and fosfomycin was continued for two months without apparent toxicity. In individual cases of infection with multiresistant S. epidermidis fosfomycin may be included in the antibiotic regimen. This is the first report of parenteral use of fosfomycin in the Netherlands.

Adolescent↗
PubMed1997

[Sensitivity to fosfomycin of multiresistant serotype 012 Pseudomonas aeruginosa. Multicenter study].

In a multicentric study including 214 strains of Pseudomonas aeruginosa, we observed that serotype O12 is more frequently sensitive to fosfomycine than other serotypes strains (72% vs 13.2%, p < 0.000001). Time killing experiments demonstrated that combination of ceftazidime-fosfomycine and amikacine-fosfomycine have usually bactericidal and synergistic activities and could be used for the treatment of multiresistant Pa O12 infections. However, an antagonism between beta-lactams and fosfomycin in disk diffusion needs an adequate concentration of both antibiotics in the site of infection.

Aminoglycosides↗
PubMed2026

Cranberry juice potentiates sensitivity of uropathogenic Escherichia coli (UPEC) strains to fosfomycin and decreases occurrence of spontaneous resistance.

Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs). The growing prevalence of antimicrobial resistance underscores the need for alternative or complementary strategies to enhance antibiotic activity. Fosfomycin (FOS) remains a recommended first-line treatment for uncomplicated UTIs due to its broad activity and low resistance rates; however, spontaneous resistance frequently arises through mutations in bacterial transport systems. Cranberry juice is known for its anti-adhesive and anti-infective properties; however, its potential to modulate antibiotic activity remains poorly understood. Here, we show that cranberry juice markedly potentiates the antibacterial activity of FOS and limits the emergence of resistance in UPEC clinical isolates. In 72% of the 32 tested isolates, cranberry juice significantly increased FOS inhibition activities and reduced spontaneous FOS-resistant mutant frequencies by up to five orders of magnitude. Whole-genome sequencing revealed distinct mutational patterns: FOS-resistant mutants selected without cranberry juice primarily carried glpT mutations, whereas those obtained with juice harbored mutations in uhpT or associated regulatory genes. Reporter assays indicated that cranberry juice represses glpT expression while maintaining UhpT-mediated FOS uptake, thereby sustaining antibiotic entry and activity. These results demonstrate that cranberry juice alters bacterial carbohydrate transport regulation to potentiate FOS activity and suppress resistance emergence. This study provides novel evidence that a natural product can enhance FOS activity, highlighting its potential as an antibiotic adjuvant for UTI management.IMPORTANCEAntimicrobial resistance is a growing threat to public health, and new strategies are needed to preserve the activity of existing antibiotics. This study reveals that cranberry juice, a widely consumed natural product, enhances the antibacterial activity of fosfomycin against uropathogenic Escherichia coli by modulating bacterial sugar transport systems. By shifting fosfomycin uptake from GlpT- to UhpT-mediated pathways, cranberry juice both potentiates antibiotic activity and suppresses the emergence of resistant mutants. These findings provide new insight into how dietary components can influence antibiotic response, offering a promising basis for developing natural adjuvants that extend the lifespan of current antimicrobial agents.

Fosfomycin↗
PubMed1978

[In vitro effect of fosfomycin against Pseudomonas aeruginosa compared to carbenicillin, gentamycin and polymyxin B].

The activity of fosfomycin against Pseudomonas aeruginosa (78 serotyped strains isolated from clinical specimens) is considerably more dependent on test conditions than that of carbenicillin, polymyxin B or gentamicin. Using a degree of standardization of the micro-serial dilution test and agar diffusion test (Iso-Sensitest broth and agar), which yields a high degree of correlation between the values of both techniques with carbenicillin and gentamicin, a moderate degree of correlation is obtained with fosfomycin. In regard to minimal inhibitory concentration (MIC) values in human serum and human urine, fewer "false" results are obtained in Iso-Sensitest broth than in Mueller Hinton broth and in particular glucose caseinhydrolysate broth. On the basis of MIC values in Iso-Sensitest broth P. aeruginosa is much more sensitive to polymyxin B, carbenicillin and gentamicin than to fosfomycin.

Anti-Bacterial Agents↗
PubMedDate not supplied

Influence of fosfomycin and tobramycin on vancomycin-induced nephrotoxicity.

Since combinations of fosfomycin and vancomycin or tobramycin and vancomycin could be of advantage in the therapy of staphylococcal infections, we studied renal tolerance of both combinations. The experimental animal was the rat and the parameters of nephrotoxicity were cyturia and enzymuria. The experiments showed that fosfomycin at dosages of 50 and 250 mg/kg protected against nephrotoxicity caused by vancomycin (dose: 50 mg/kg), whereas the administration of both tobramycin (dose: 2.5 mg/kg) and vancomycin (dose: 50 mg/kg) resulted in an increase of cyturia and enzymuria. However, repeated dosing of vancomycin (single dose: 50 mg/kg) led to renal accumulation when combined with fosfomycin (single dose: 250 mg/kg); renal vancomycin concentrations were lower. This study suggests similarities in the renal handling of vancomycin and aminoglycosides and demonstrates the possibility of reducing drug-associated nephrotoxicity.

Animals↗
PubMedDate not supplied

The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci.

Infections with multiresistant strains of Staphylococcus aureus and Staphylococcus epidermidis pose severe clinical problems. The drug of choice in such cases, vancomycin, is potentially ototoxic and nephrotoxic and this may give rise to additional problems in the patient. Fosfomycin has been shown to be nephroprotective when given with vancomycin and with other nephrotoxic drugs. We report the inhibitory and bactericidal activity of fosfomycin and vancomycin alone and in combination against 26 clinically relevant strains of S. aureus and 48 strains of S. epidermidis. In most instances these two drugs showed indifferent or additive effects, synergism or antagonism was only rarely observed. Assessment of the bactericidal action of the combination revealed similar effects. The combination of fosfomycin and vancomycin may, therefore, be beneficial in clinical situations where the nephrotoxic effect of vancomycin cannot be tolerated.

Drug Combinations↗
PubMed1987

Fosfomycin protects against tubulotoxicity induced by cis-diaminedichloroplatin and cyclosporin A in the rat.

The nephroprotective effect of fosfomycin against tubulotoxicity induced by cis-diaminedichloroplatin (DDP) and cyclosporin A (Cs) was studied in the rat. The parameter of nephrotoxicity was urinary tubular cell excretion. The experiments revealed that fosfomycin, given either concomitantly or in advance was able to reduce the nephrotoxic effect of DDP and Cs significantly. We conclude from these studies that fosfomycin is a broad-spectrum nephroprotective agent.

Animals↗
PubMed1988

Use of fosfomycin disks for isolation of diphtheroids.

A fosfomycin disk (200 micrograms) placed on blood agar was used to select diphtheroids from clinical specimens. All Corynebacterium type strains tested, representing ten different groups of diphtheroids, and 150 toxigenic strains of Corynebacterium diphtheriae from different outbreaks, overgrew the fosfomycin disk, while other aerobic gram-positive rods had a large inhibition zone. The method increased the rate of isolation of diphtheroids in 1267 clinical specimens fivefold, from 1.4% to 7.6%, especially when the diphtheroids were found concomitantly with other bacteria. Overgrowth of the disk by other microorganisms occurred in 11% of the samples tested, but such microorganisms could easily be distinguished by culture morphology or Gram stain. Fosfomycin disks provide a simple, highly sensitive but not very specific aid for isolation of Corynebacterium diphtheriae and diphtheroids from clinical specimens.

Corynebacterium↗