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PubMed1985

A multicenter, randomized parallel double-blind study comparing three antibiotics, cephemic-cofosfolactamine, fosfomycin and cephalexin, in the treatment of systemic infections.

In the present multicenter, randomized and double-blind study, performed on 127 hospitalized patients, we compared the effects of three antibiotics (cephemic cofosfolactamine, cephalexin and fosfomycin) in the treatment of acute or recurrent systemic infections. Results show that the percentage of recoveries of clinical symptoms and of bacterial eradications were significantly higher, and associated with a lower rate of side effects in the patients treated by cephemic cofosfolactamine than in those treated by cephalexin or fosfomycin.

Anti-Bacterial Agents↗
PubMed1979

Ultrastructure and viability of E. coli treated fosfomycin.

In concentrations of 6 microgram/ml Fosfomycin acted bactericidal against E. coli ATCC 10536. The sensitivity of E. coli was evaluated by turbidity measurement (Table 1) and by counting colony forming units (CFU) (Table 2). Thus the bactericidal action began at different times in respect to the concentration and the method of documentation: turbidity fell 30-120 min after the administration of 6 microgram/ml and 10-30 min after 60 microgram/ml; CFU were reduced 10-30 min after 6 microgram/ml and 3-10 min after 60 microgram/ml. Before the cytoplasm and DNA-region were disorganized with reduced electron density, some elongated (up to more than 20 micron) cells occurred (Fig. 1,2). More prominent alterations in shape and ultrastructure were obvious 120 min after 6 microgram/ml (Fig. 5) and after 30 min when 60 microgram Fosfomycin per ml were administered (Fig. 3, 4), i.e. considerably later than the reduction of reproductivity.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Epidemiological aspects relating to the determination of fosfomycin sensitivity: results of a study on 300 strains isolated in a hospital milieu in Turin].

The AA. evaluated the sensitivity to Fosfomycin and to other commonly used antibiotics of 105 bacterial strains isolated from hospital environment and 195 from pathological materials. They also studied the problem of bacterial resistence to Fosfomycin considering the frequency of "inner colonies" and of bacterial cross-resistance to other antibiotics.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Fosfomycin. I. Antimicrobial action in vitro].

The results obtained from the test of the in vitro activity of Fosfomycin by a concentration of 104 bacteria/ml and by Nutrient Broth with 5% defibrinated blood, have shown that the drug has a capacity of action on both Gram-negative and Gram-positive germs, also on beta-lactamase producing bacteria. Fosfomycin is a bactericidal antibiotic. infact the M.I.C. values are simjlar to M.B.C. values.

Anti-Bacterial Agents↗
PubMed1984

[Pharmacokinetics and clinical studies of fosfomycin in bile duct infections].

Serum and bile levels of fosfomycin sodium (FOM-Na) were evaluated and the pharmacokinetic parameters were estimated in 10 patients with various forms of biliary drainage (PTCD or T-tube). Clinical trials of FOM-Na were also performed in another 11 patients with bile duct infections and the clinical efficacy was estimated. Mean serum level of FOM-Na after drip infusion of 2 g fosfomycin sodium was 145.43 micrograms/ml at 1 hour, meanwhile bile level was 31.49 micrograms/ml at 2 hours. Serum level of FOM-Na was interpreted by the pharmacokinetic analysis after the damping GAUSS-NEWTON method using the one-compartment open model and bile level of FOM-Na by the damping GAUSS-NEWTON method and deconvolution method. Mean Vd was 12.16 L/body and half-time of serum level was 1.75 hours. Lag-time of bile level was 0.9 hour, Tmax 2.01 hours. The clinical efficacy of FOM-Na was determined excellent without any adverse effect. FOM-Na was remarkably effective in 91% of the patients. Hence, the first choice of FOM-Na against bile duct infections could be recommended.

Aged↗
PubMed1981

[Clinical experience with fosfomycin in urinary tract infections (author's transl)].

Fosfomycin, an antibiotic from a new class of substances, has a bactericidal action against a broad spectrum of gram-positive and gram-negative organisms. The efficacy of fosfomycin in urinary tract infections was investigated with a dose of 15 g/day. 52 urological patients with obstructive and non-obstructive infections of the urinary tract were accepted for the study. The therapeutic success was convincing: 91% of the pathogens were eliminated from the urine, the urine was free from organisms in 84% of the patients after the treatment. 93% were clinically symptomless. The effects against Pseudomonas was very good: 8 of 9 strains present were eliminated. Unpleasant gastrointestinal side effects occurred which were dependent on the rate of infusion and usually became tolerable at a slower rate.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Effects of subinhibiting concentrations of fosfomycin on the ultrastructure of E. coli K 126].

In the present paper we have evaluated the ultrastructural effects of fosfomycin on E. coli K 126, after different exposure times with subinhibitory concentrations (1/2 MIC). After 3 hrs, the antibiotic acts on bacterial morphology. Population shows some elongated forms and lysed cells with abnormal divisions. At 6 hrs, on the other hand, the bacteria appear intact, though they present cytoplasmic disorganization and cell wall particularly undulated. In the presence of fosfomycin, the cells tend to clump together.

Anti-Bacterial Agents↗
PubMed1982

[The value of fosfomycin].

After description of the most important properties of fosfomycin including pharmacokinetics, antibacterial activity and hitherto got clinical experiences the determinations of the resistance on frequent clinical pathogenic agents are reported. They were performed in the diffusion test in a platelet content of 20 micrograms with admixture of glucose-6-phosphate. High sensitivity rates showed E. coli, P. mirabilis, hemophiliacs and above all Staph. aureus, but also a large part of the Klebsiella and the Pseudomonas strains could be classified as sensitive. Streptococci, pneumococci and enterococci mostly proved as resistant. Thus, in an oral therapy the spectre is smaller than in a highly dosed parenteral supply. Nevertheless, fosfomycin in the two forms of application is to be regarded as an enrichment of the therapeutic possibilities and further should be tested clinically.

Administration, Oral↗
PubMed1981

[The effects of fosfomycin on antigenicity (author's transl)].

The antigenicity of fosfomycin (FOM), a new antibiotic agent, was studied. The binding of 3H-FOM with human serum protein was measured by the short term dialysis method. The binding was very weak only by 2.16% and reversible. The rabbits were immunized subcutaneously by fosfomycin as sodium salt (FOM-Na) with FREUND'S complete adjuvant. Antigenicity of IgG was examined by means of agar gel precipitation, passive cutaneous anaphylaxis and passive hemagglutination. To study the antigenicity of IgE, the BALB/cA mice were immunized intraperitoneally by FOM-Na with aluminum hydroxide gel and, passive cutaneous IgG and IgE. Consequently, it can be concluded that FOM does not conjugate with human serum protein to form its hapten and has not antigenicity.

Animals↗
PubMedDate not supplied

[Synergic action of the combination of fosfomycin and kanendomycin against gram-positive and gram-negative bacteria].

Association between kanendomycin, an aminoglycoside antibiotic with a high antibacterial activity, non susceptible to inactivating action of acetylating enzymes and fosfomycin, an antimicrobial drug active only on bacterial cells, and without toxicity in man, was studied by Authors. An evidence synergism of two examined drugs was found particularly against Proteus spp. and Pseudomonas aeruginosa. A discussion about mechanisms of action of fosfomycin and kanendomycin is referred by Authors to explain this synergism.

Anti-Bacterial Agents↗
PubMed1994

Combined therapy with arbekacin and fosfomycin for methicillin-resistant Staphylococcus aureus infections.

We examined the clinical efficacy of a combination of arbekacin and fosfomycin in the treatment of various methicillin-resistant Staphylococcus aureus (MRSA) infections. The combination of arbekacin plus fosfomycin displayed 65.4% (17/26) clinical efficacy and 65.4% (17/26) bacteriological efficacy. This combination thus appeared to be an effective regimen for the treatment of MRSA infections. However, its bacteriological efficacy against concomitant Pseudomonas aeruginosa strains was only 16.7% (1/6). In addition, in 4 episodes of superinfection involving P. aeruginosa strains developed during the combination therapy.

Aminoglycosides↗
PubMedDate not supplied

Combination chemotherapy for infections due to methicillin-resistant Staphylococcus aureus with combination therapy by cefuzonam and fosfomycin or minocycline in the urologic field.

To determine the bacterial and clinical effects of methicillin-resistant Staphylococcus aureus (MRSA) on urinary tract infection (UTI), postoperative wound infection, and bacteremia, 22 strains of MRSA from infected patients were examined; minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) index, coagulase typing, and change in MIC in the combination of cefuzonam (CZON) and fosfomycin (FOM) or minocycline (MINO), and the clinical effects of the combination therapy of CZON+FOM or CZON+MINO were investigated in 23 patients. MIC distribution was assessed for 11 drugs: methicillin (DMPPC), cefazolin (CEZ), cefotiam (CTM), cefuzonam (CZON), minocycline (MINO), vancomycin (VCM), arbekacin (ABK), imipenem (IPM), fosfomycin (FOM), ofloxacin (OFLX), and clarithromycin (CAM). For VCM and ABK, MICs ranged from 0.2 to 12.5 micrograms/ml. MINO showed a wide range of MIC, from 0.05 to 25 micrograms/ml. All strains were less sensitive to other antimicrobials. This MIC distribution was assessed in categories by coagulase typing. For CAM, type II strains revealed > or = 100 micrograms/ml of MIC50 and MIC90 compared with 0.2 and 3.13 micrograms/ml in type VII strains. For mixed combinations of CZON and MINO at ratios of 10 to 1 and 40 to 1, the rates of blood concentration for drugs 10 and 120 min after the intravenous injection, MIC distribution was observed between MINO and CZON. For mixed combinations of CZON and FOM at ratios of 1 to 1 and 1 to 4, MIC distribution was more sensitive than for FOM or CZON alone. With respect to the clinical effects of combination therapy by CZON+MINO and CZON+FOM, of seven cases of UTI with CZON+MINO, MRSA was eliminated completely in 4 patients (57.1%). In all patients who received CZON+FOM, MRSA was completely eliminated by this treatment regimen. In 4 of 7 (57.1%) patients with would infection and bacteremia, MRSA was eliminated by the combination of CZON+FOM or CZON+MINO. These results suggest that CZON+FOM is an effective combination in treating UTI and other MRSA infections in urology.

Adult↗
PubMed1997

Antimicrobial potentiality of a new beta-lactum antibiotic fosfomycin.

Antimicrobial action of penicillin and some of its derivatives including fosfomycin was studied with respect to 225 strains of Gram-positive and Gram negative bacteria. Fosfomycin was found to possess somewhat less activity against Staphylococcus aureus compared with other penicillins; however, it showed powerful activity towards Escherichia coli, Klebsiella spp. and Proteus mirabilis.

Anti-Bacterial Agents↗
PubMed1998

Appearance of fosfomycin resistant Rahnella aquatilis clinically isolated in Japan.

Among recent clinical isolates in Japan, strain CU264 was discovered which formed unusual colonies. This strain was identified as Rahnella aquatilis which is usually found in water. The antibiotic susceptibilities against tetracycline, carbenicillin, chloramphenicol, streptomycin, kanamycin, gentamicin, sulphonamide, neomycin, fosfomycin, rifampicin, norfloxacin and nalidixic acid, were investigated. The result demonstrated that the strain was highly resistant to fosfomycin only. It was further shown that this resistance was transmissible with low frequency to Serratia marcescens whereas it was not transmissible to Escherichia coli.

Anti-Bacterial Agents↗
PubMed1988

Transtympanic iontophoresis of dexamethasone and fosfomycin.

The effects of transtympanic iontophoresis of corticosteroids and antibiotics on otitis media with effusion (OME) were investigated. An experimental study using guinea pigs revealed that transtympanic passage of dexamethasone sodium phosphate and fosfomycin sodium by iontophoresis had sufficient anti-inflammatory and antimicrobial effects. Twenty children with OME (33 ears) who were treated by iontophoresis were compared with 28 untreated children with OME (35 ears) with respect to improvement assessed by tympanoaudiometry. After one month, tympanoaudiometry revealed improvement in 21 (63.6%) of the treated ears but in only 13 (37.1%) of the untreated ears, indicating the efficacy of this treatment for OME.

Acoustic Impedance Tests↗
PubMed1987

Self-consistent field-molecular orbital (SCF-MO) calculations and nuclear magnetic resonance measurements for fosfomycin and related compounds.

In the present work, the mechanism of action of fosfomycin [(-)-(1R,2S)-(1,2-epoxypropyl)phosphonic acid] as an antibiotic agent is studied by "ab initio" quantum mechanical calculations and by 1H, 13C, and 31P NMR measurements. Attention is focused on the relative charge density and chemical shift of the C(2) atom of the epoxy ring, which seems to be closely related with the activity of this antibiotic. The theoretical results suggest that the sulfhydryl addition should be preceded by a necessary anchoring of the phosphonate moiety on a positive group of the receptor.

Anti-Bacterial Agents↗
PubMed2002

Flow injection spectrophotometric determination of the antibiotic fosfomycin in pharmaceutical products and urine samples after on-line thermal-induced digestion.

A new flow injection (FI) method for the precise and rapid spectrophotometric determination of the antibiotic fosfomycin (FMC) in urine and pharmaceutical samples is described. The method is based on the on-line quantitative thermal-induced digestion of the analyte prior to injection into the FI system. Ammonium persulfate was used as the oxidation reagent. The resulting orthophosphate ions were determined spectrophotometrically (lambda(max) = 690 nm) using the molybdenum blue approach. Chemical and FI variables that affected on-line oxidation were studied and optimized. The proposed method is very precise (s(r) = 1.2% at 1.0 x 10(-4) mol L(-1) FMC, n = 12), offers a high sampling rate of 60 h(-1), and allows for the determination of the analyte in the range 3.0 x 10(-6) to 3.0 x 10(-4) mol L(-1) with a satisfactory 3sigma detection limit of 1.0 x 10(-6) mol L(-1). Application of the proposed method to urine and pharmaceutical samples yielded accurate results with percentage recoveries in the range 96.4-102.5%.

Ammonium Sulfate↗
PubMed1992

Optimum culture conditions for the epoxidation of cis-propenylphosphonate to fosfomycin by Cellvibrio gilvus.

Approximately 470 strains of various microorganisms were tested for their ability to epoxidize cis-propenylphosphonate (PPOH) to (-)-cis-1,2-epoxypropylphosphonate (fosfomycin, FOM). Cellvibrio gilvus KY 3412 was selected as the best strain. To obtain higher activity, FOM-resistant strains were derived by N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. Mutant KY 3413, showing ten times higher FOM resistance, was selected. The conditions for the conversion of PPOH to FOM during the cultivation of the mutant were optimized. The addition of both cobalt and vanadium ions to the culture medium greatly stimulated the conversion. Furthermore, when the pH was maintained at pH 8.0 during cultivation, the highest conversion was attained. The molar conversion yield of FOM was inversely dependent on the initial concentration of PPOH, that is, conversions of 100% at less than 0.05% PPOH and of 40% at 0.5% PPOH were attained after 5 days cultivation.

Cobalt↗