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PubMed1982

Tn292l, a transposon encoding fosfomycin resistance.

The determinant of resistance to fosfomycin of the Serratia marcescens plasmid pOU900 was transposed into the plasmid ColE1 and into the plasmid RP4 in the absence of the RecA function of the host. In each case, the acquisition of fosfomycin resistance was correlated with the presence of a discrete piece of DNA, uniform in size and in restriction pattern, This new, 7.5-megadalton transposable element encoding resistance to fosfomycin has been called Tn2921. A preliminary map of the transposon is presented.

Anti-Bacterial Agents↗
PubMed1975

Fosfomycin in treatment of chronic urinary tract infection.

A study was made of fosfomycin in the treatment of chronic urinary infection in 51 patients. 72% of the 67 bacteria isolated and tested in the laboratory with discs containing 50 mug of fosfomycin were found to be sensitive to the antibiotic. The majority of E. coli, Klebsiella, P. mirabilis and Ps. aeruginosa strains were sensitive to the antibiotic. Generally, 60 mg of fosfomycin/kgbody weight was administered intramuscularly 6-hourly for 7-15 days. A clinical and bacteriological cure was obtained in 39 patients (76%), and after 4-6 weeks in 31 patients (61%). Blood and urine fosfomycin levels were determined in seven patients, three with normal renal function, three with moderate renal insufficiency, and one with severe renal insufficiency. The antibiotic levels and elimination time maintained a clear relation with the degree of renal insufficiency.

Adolescent↗
PubMed1976

Fosfomycin in Osteomyelitis.

Fosfomycin was exclusively used as antibiotic treatment in 37 patients suffering from osteomyelitis, out ot which 23 were operated for sequestrectomy or fistulectomy, whereas the remaining 14 did not undergo any surgery during fosfomycin treatment. Fosfomycin was adminsitered parenterally, alone or combined with oral administration, and in some cases only orally. The dosage varied from 4 to 8 g/day for an average period of 3 weeks. After one or two treatments the results were 29 definitive cures (78%), 2 failures and 6 relapses (22%).

Adolescent↗
PubMed1977

Fosfomycin, antimicrobial activity in vitro and in vivo.

Antibacterial activities of fosfomycin were investigated both in vitro and in vivo for the purpose of comparative evaluation on its fundamental properties with other antimicrobial agents. The MIC was determined with nutrient agar (Difco) inoculated with one loopful of 1,000-fold dilution (about 10(6) cells/ml) of bacterial suspension cultured overnight in nutrient broth. This substance showed antibacterial activity to most gram-positive and gram-negative bacteria, being strongest to Enterobacteriaceae with a peak of the MIC at 1.56 mug/ml in Salmonella. It was also active against P. aeruginosa with a peak of the MIC at 6.25 mug/ml in its sensitivity distribution. Intravenous and subcutaneous fosfomycin Na salt and oral fosfomycin Ca salt were given to 5-week-old ddN strain male mice challenged with clinical isolates of P. aeruginosa, E. coli and P. mirabilis. Therapeutic effect was observed in all these test organisms. In P. aeruginosa, it was more effective than carbenicillin.

Animals↗
PubMed1977

Effect of fosfomycin on the fecal microflora of man.

Use of broad-spectrum antibiotics is known to cause changes in the intestinal microflora of man. The present study was initiated to determine the effect of oral fosfomycin calcium on several groups of microorganisms indigenous to the gut. Data from this double-blind study indicate that 2 g of fosfomycin given daily in four divided doses for 28 days increased the incidence of soft stools. No significant changes in numbers of staphylococci or Candida were observed during treatment. Although there was no significant change in total coliforms, the numbers of E. coli decreased markedly from 10(5) to 10(2) organisms/g feces. Concurrent with this decrease, the Klebsiella-Enterobacter counts increased from 10(3) to 10(6) organisms/g feces. Two weeks posttreatment the E. coli and the Klebsiella-Enterobacter counts approached pretreatment levels. These observations are similar to those reported for ampicillin. During the course of treatment when the E. coli dropped precipitously the few surviving E. coli still were suceptible to fosfomycin as determined by an agar diffusion disc test.

Anti-Bacterial Agents↗
PubMed1977

Influence of fosfomycin on intestinal disaccharidases in rats.

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.

Administration, Oral↗
PubMed1977

Treatment of urinary infections with fosfomycin.

This report deals with the study made of the treatment of 45 acute, subacute and chronic urinary infections in a department of general medicine. 43 of these were infections caused by a single species of bacteria and 3 were caused by more than one species. The sensitivity test of the isolated organisms (E. coli, Proteus, Serratia, Pseudomonas, Klebsiella and S. faecalis) showed 83.33% of the strains to be senstive and 16.8% of the strains to be resistant. Nevertheless, this last group of strains, with the exception of one Pseudomonas, proved to be sensitive to the association of fosfomycin with a beta-lactamin (carbenicillin, amoxycillin) or an aminoglycoside (gentamicin, tobramycin). Of a total of 45 cases, 34 were exclusively treated with fosfomycin (2 g by the intramuscular route and 2 g by the oral route) and 11 cases were treated with a double association of fosfomycin with a beta-lactamin (carbenicillin or amoxycillin) or an aminoglycoside (gentamicin), after having studied the bactericidal activity of the association in vitro. The clinical and bacteriological results were verified 4 weeks after the conclusion of the treatment and showed that there was an eradication of the urinary infection in 34 cases (75.55%), relapses in 6 cases (13.33%) and reinfections in 5 cases (11.22%). These results would seem to be favourable with regards to hospital infections and with respect to organisms that are considered to be very little sensitive or resistant.

Acute Disease↗
PubMed1977

Acute infantile pneumonopathies treated with fosfomycin.

Reference is made to the results obtained in 24 children, from 11 months to 12 years, affected with acute pneumopathies and treated with fosfomycin with a dosage of 200 mg/kg/day. In all cases a clinical, radiological, biological and bacteriological study was carried out. At the same time, levels of fosfomycin in plasma and sputum were checked every 5 days during the course of treatment. In the 4 cases of pleurisy the level of antibiotic in the pleural liquid was also checked. The concentration of fosfomycin in the sputum gives very variable results with average values oscillating between 16.5 and 23.4% of the plasmatic level respectively at the beginning and end of treatment, a cumulative effect of the antibiotic being observed. Concentration in pleural liquid oscillates between 39 and 50%. The clinical, radiological and biological evolution has been favourable iin 21 cases, unfavourable in two cases and in one case treatment had to be suspended because of the apparition of a cutaneous necrosis. Apart from this case no notable toxic effects were observed. Children do not support intramuscular injections very well and intravenous injections often cause phlebitis.

Anti-Bacterial Agents↗
PubMed1977

Clinical bacteriological evaluation of infantile bacteriuria treated with fosfomycin.

The therapeutic action of fosfomycin has been studied in a group of 14 children, with simple and complicated infections of the urinary tract with congenital renal malformations. In the bacteriological study of the urine it was observed that the strains most frequently isolated were E. coli, Proteus sp. and Klebsiella sp. Of the 25 strains isolated 76% were sensitive to the disc of 50 mug fosfomycin and 24% moderately sensitive with a MIC of 64 and 128 mug/ml. The doses of fosfomycin used were 150 mg/kg/day in four administrations. In 13 cases it was administered orally alone and in one case orally and intramuscularly. The results have been good in 10 cases (71.4%) and bad in four cases. The antibiotic has shown good tolerance and no secondary effects have been noticed.

Administration, Oral↗
PubMed1977

Treatment of chronic suppurated otitis with fosfomycin.

A group of 24 patients with suppurated chronic processes of the medial ear have been treated with fosfomycin. All the cases were studied bacteriologically, isolating in the pus or exudates pathogenic bacterial flora, in which P. aeruginosa (40%) of the isolations) and S. aureus (23%) predominated. The sensitiveness of the strains isolated to fosfomycin was 94%. The results obtained were 21 clinical cures accompanied by the sterility of the exudates and 3 failures, which represents 87.5% success and 12.5% failures. These results are considered very satisfactory in view of the complexity and chronicity of the processes treated. It is also pointed out that fosfomycin totally lacks ototoxicity, being, therefore, a suitable antibiotic for treating chronic infectious processes of the ear.

Adolescent↗
PubMed1977

Evaluation of fosfomycin in an intensive care unit.

Sensitivity to fosfomycin has been studied and recorded throughout a period of 12 months in the bacteriological isolations originating from this Intensive Care Unit. The 548 samples were biological products obtained from patients admitted to this unit (bronchial exudates, urine, wounds, blood, cava catheters and cerebrospinal fluid). The highest percentage of sensitivity was given by S. aureus coagulase (+), S. fecalis and E. coli (91, 89 and 84% respectively), and the least by P. aeruginosa and Providencia (33 and 8% respectively). A summary is included of 8 seriously ill patients admitted with varied septic processes, produced by germs sensitive to fosfomycin and treated with this, in 5 cases alone and in 3 cases with gentamicin and carbenicillin. Of those who were treated with fosfomycin alone: three were cured, one died on the sixth day through circulatory, respiratory and renal deficiences and the other with respiratory deficiency. Those treated with the combined antibiotics: two were cured and the other died of sepsis on the fourth day.

Adult↗
PubMed1990

General practitioner study: fosfomycin trometamol versus amoxycillin clavulanate in acute urinary tract infections.

A clinical trial comparing 5 days' treatment with amoxycillin/clavulanate (group A) and a single dose of fosfomycin trometamol (group B) is presented. The study was done in symptomatic patients presenting to their family practitioner, with the microbiological testing being carried out in a university hospital laboratory. Of 62 patients with significant bacteriuria, 29 were given amoxycillin/clavulanate and 33 fosfomycin trometamol, in a randomized fashion. Cure rates 1 week and 5 weeks after the end of treatment were 72 and 65% in group A and 85 and 81% in group B. Adverse events assessed in 141 patients were unusual (10.1% in group A and 8.3% in group B) and were mild in nature. The results of this study suggest that single-dose treatment with fosfomycin trometamol is effective and acceptable as a conventional course of amoxycillin clavulanate for the treatment of simple acute dysuria and/or frequency with infection.

Acute Disease↗
PubMed1990

Fosfomycin trometamol (Monuril) versus norfloxacin in single dose for adult female uncomplicated UTIs. Multicenter randomized, double-blind study.

The efficacy, tolerability and side effects of a 'single-dose' therapy for acute female lower UTIs in general practice with fosfomycin trometamol (3 g) or norfloxacin (800 mg) were compared in a randomized double-blind study. 89 patients were included in the trial; however, 36 (40.4%) did not present significant bacteriuria and were assessed mainly for tolerability. Of the 53, 28 patients in the fosfomycin trometamol group and 25 patients in the norfloxacin group, 21 (75%) had no bacteriuria at immediate follow-up after treatment with fosfomycin trometamol and 20 (84%) with norfloxacin. The tolerability of both drugs in single dose was absolute.

Adolescent↗
PubMed1987

The trometamol salt of fosfomycin: microbiological evaluation.

The spectrum of activity of fosfomycin and its pharmacological behaviour make it an attractive candidate for the oral treatment of uncomplicated urinary tract infection. Various factors affect the antibacterial activity so that results in different culture media vary widely. The highest activity was displayed in Eugonbroth and such results correlated well with those obtained in pooled human urine. The activity was enhanced in acid conditions such as commonly exist in infected urine. Glucose-6-phosphate potentiated the activity of fosfomycin against Escherichia coli and some other bacteria when tested in Eugonbroth (but less predictably in human urine) and the potentiating effect may be necessary in order to obtain therapeutically meaningful results in susceptibility tests. Experiments in an in vitro model of the treatment of bacterial cystitis (carried out in the absence of glucose-6-phosphate) indicated that both sensitive and 'resistant' strains of E. coli respond to concentrations of fosfomycin achievable by high-dose oral therapy with the trometamol salt. Resistance did not emerge in previously sensitive strains (or in one of the 2 'resistant' strains), providing a high peak level of antibiotic was achieved.

Culture Media↗
PubMedDate not supplied

Ocular penetration kinetics of fosfomycin administered as a one-hour infusion.

The penetration of fosfomycin in aqueous humour was studied in 21 patients who were to undergo cataract surgery. All patients received 4 grams of fosfomycin as an infusion lasting one hour. Concentrations of the drug in aqueous humour were measured 1, 2, 4, 6 and 12 hours after the start of infusion. Drug concentrations in aqueous humour and serum were measured by HPCE (High Performance Capillary Electrophoresis). The aqueous humour concentration at one hour was 11.46 mg/l +/- 2.12. Peak concentration was 14.63 mg/l +/- 5.54, reached two hours after the infusion. Concentrations were high until 6 hours and remained significant at 12 hours. These results confirm the excellent diffusion of fosfomycin in aqueous humour, with high levels at 12 hours. They justify its use in intraocular infections, by infusions repeated every eight hours, to maintain concentrations above the MIC 90 for organisms usually susceptible to the drug.

Adolescent↗
PubMed1982

Mode of protective action of fosfomycin against dibekacin-induced nephrotoxicity in the dehydrated rats.

We studied the mechanism on protective effect of fosfomycin against experimental nephrotoxicity induced by dibekacin. In order to simplify an experimental model, the dehydrated Wistar rats were used, because a single injection of dibekacin at 30 mg/kg induced acute renal failure in the dehydrated rats, characterized by alteration of urinalytic parameters and BUN values, and retarded elimination of dibekacin from blood. When the rats were administered simultaneously with fosfomycin at 120 mg/kg, the rate of elimination was restored almost to normal, accompanied with improvement of the nephrotoxic parameters. However, markedly accelerated elimination over normal one was not observed, indicating that the improved elimination was not the reason of protection but a result of normal kidney function. On the other hand, fosfomycin protected the proximal tubular lysosomes from the injury of aminoglycoside, as evidenced a) in vivo by suppression of myeloid body formation and protection of lysosomal membrane integrity of the rats treated with dibekacin, and b) in vitro by dose-dependent protection of the lysosomal membrane integrity of the kidney cells. A study of structure-protective activity relation revealed that phosphonate anion possessing an epoxy function was important for protection, and that the mechanism of protection differed from the antibacterial mechanism.

Animals↗
PubMed1999

[Pathogenecity of fosfomycin-resistant strains isolated from Escherichia coli].

Two fosfomycin-resistant strains, FRC14 (parent strain, Escherichia coli [E.coli] c73-18) and FRK104 (parent strain, E. coli O124), were isolated from spleens before the bacterial disappearance, after inoculating the parent strains intraperitoneally into mice and treating them with a single oral dose of fosfomycin. The resistant strains were successfully isolated by a replica method from a mass of sensitive cells of respective parent. To elucidate the pathogenesis of the resistant strains, their characteristics were investigated. The MIC of fosfomycin for FRC14 was 25 micrograms/ml (4 times the MIC for the parent) and that for FRK104 was 100 micrograms/ml (8 times the MIC for the parent). The strain FRC14 showed a defective utilization of sn-glycerol 3-phosphate (G3P), but utilization of other carbohydrates was similar to that of the parent strain. Thus, the strain FRC14 seemed to be a glpT mutant. The strain FRK104 did not use variety of carbohydrates including G3P, but used glucose 6-phosphate. The utilization of G3P was recovered in the presence of cAMP. Thus, the strain FRK104 seemed to be a ptsI mutant. These resistant strains were diminished their killing activity for mice in comparison to that of the each parent strain when they were inoculated intraperitoneally. The cell number of FRC14 decreased or disappeared in blood and spleen in mice, while that of the parent increased. The strain FRK104 diminished its ability of producing keratoconjuctivitis in guinea pigs in comparison to that of the parent strain.

Animals↗
PubMedDate not supplied

Gas chromatographic analysis of fosfomycin in plasma for pharmacokinetic analysis.

An efficient method for gas chromatographic analysis of fosfomycin in plasma was developed for preliminary investigations of the bioavailability in poultry of 3 commercial complexes of fosfomycin: a levorotatory Ca(-) salt, a racemic Ca(+/-) salt, and a tromethamine (THAM) salt. The method was used to determine whether the less expensive racemic mixture would provide equivalent levels of fosfomycin in blood as the pure Ca(-) form and the THAM salt. The THAM salt, a more expensive product to market, was thought to have the greatest bioavailability. The assay is selective, sensitive, and applicable to pharmacokinetic analysis.

Animals↗