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PubMed1991

Selective medium containing fosfomycin, nalidixic acid, and culture supernatant of Rhodococcus equi for isolation of Corynebacterium pseudotuberculosis.

FNR medium containing fosfomycin, nalidixic acid, bovine blood and culture supernatant of Rhodococcus equi was prepared by the present authors, and the medium did not inhibit growth of Corynebacterium pseudotuberculosis but completely hampered the growth of Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The culture supernatant of R. equi facilitated detection of suspected colonies of C. pseudotuberculosis due to synergistic hemolysis. Rate of isolation of the organisms (from the trachea, larynx and nasal cavity of 16 slaughtered sheep with caseous abscess in the lung) was higher with FNR, the selective medium, than with nonselective medium. The selective medium was thus found to be useful for isolation of C. pseudotuberculosis from sheep.

Animals↗
PubMed1998

[Clinical efficacy of fosfomycin in combination with sulbactam/cefoperazone in the treatment of severe infections complicated to blood dyscrasia. Working Group of Kanto Combination Therapy for FOM + SBT/CPZ].

In the treatment of severe infections complicated to blood dyscrasia, the efficacy and usefulness of fosfomycin (FOM) in combination with sulbactam (SBT)/cefoperazone (CPZ) were compared between patients receiving FOM in the first followed by SBT/CPZ (Group A) and those receiving both drugs simultaneously (Group B). The following results were obtained. 1. The efficacy rate was 56.3% for Group A and 47.9% for Group B, with no significant difference. 2. The efficacy for patients suspected of the presence of septicemia, the efficacy rate was 57.9% for Group A and 54.3% for Group B, with no significant difference. 3. As for underlying disease, patients with acute myelogenous leukemia were most prevailing. In these patients, the efficacy rate was 57.1% for Group A and 27.3% for Group B, with no statistically significant difference. However, the efficacy rate tended to be higher in Group A. 4. The administration of antibiotics was effective to restore the neutrophil count to 501/microliters or higher in 77.8% and 45.5% of the cases for Groups A and B, respectively, with significantly higher efficacy for Group A. 5. In the safety evaluation a total of 115 cases were included. Side effects and laboratory abnormalities were seen in 3 cases each, but none of them were serious in degree. From these results, it was confirmed that the combination therapy consisting of administration of FOM followed by SBT/CPZ with some interval is effective for severe infections complicated to blood dyscrasia.

Anti-Bacterial Agents↗
PubMed1999

[Combination effect of fosfomycin otic solution and norfloxacin against chronic otitis media].

Studies on a combination therapy of fosfomycin (FOM) and norfloxacin (NFLX) against chronic otitis media were performed, and the following results were obtained. 1. The fractional inhibitory concentration index (FIC index) < or = 0.5 between FOM and NFLX showed 66.7% (4/6) against S. aureus isolated from chronic otitis media and 80.5% (4/5) against P. aeruginosa. 2. Clinical effects was excellent in 2 cases (18.2%), good in 6 cases (54.5%) and poor in 3 cases (27.3%). 3. Bacteriologically 9 strains out of 11 patients were eradicated after the combination treatment; 5/6 in S. aureus and 4/5 in P. aeruginosa. 4. No adverse effect and abnormal laboratory findings were observed in this study. It is suggested that the combination of FOM otic solution and NFLX is useful for the treatment of chronic otitis media.

Administration, Oral↗
PubMed1981

Fosfomycin kinetics after intravenous and oral administration to human volunteers.

The pharmacokinetics of fosfomycin, administered intravenously and orally at two different doses (20 and 40 mg/kg of body weight), was studied in seven volunteers. The elimination profile of this antibiotic, when administered intravenously, followed a two-compartment kinetic model, independent of dosage, giving an elimination half-life of 2.23 +/- 0.62 h and an average total volume of distribution at steady state of 0.34 liter/kg. Peak serum levels after rapid intravenous administration of 20 and 40 mg/kg were 132.1 +/- 31.8 and 259.3 +/- 32.5 micrograms/ml, respectively. Peak serum levels after oral administration were 7.1 +/- 1.6 and 9.4 +/- 3.6 micrograms/ml for the 20 and 40 mg/kg doses, respectively. During the first 24 h after administration, an average of 80% of the intravenous doses and less than 25% of the oral doses were recovered in the urine.

Administration, Oral↗
PubMed1986

Cloning and molecular epidemiology of plasmid-determined fosfomycin resistance.

The plasmid determinant of resistance to fosfomycin (For) was cloned into pBR322 and located in a 0.7-kilobase segment of DNA by transposon mutagenesis and in vitro deletion analysis. It encodes an 18-kilodalton protein located in the cytoplasm of resistant cells. Its synthesis is constitutive. The For genetic determinant is common to all plasmids isolated since 1975 in an hospital environment as determined by DNA-DNA hybridization. However, plasmids which carry For can be divided into two groups on the basis of size, pattern of antibiotic resistances, incompatibility specificity, and restriction and hybridization properties.

Cloning, Molecular↗
PubMed1993

Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro.

Recent investigations have shown that some antibiotics also work as immunomodulators. We have recently reported that fosfomycin (FOM) has an immunomodulatory effect on human B-cell activation. FOM is a unique antibiotic which is chemically unrelated to any other known antibacterial agent. In the present study, we examined the effect of FOM on human T-cell function. FOM inhibited the proliferation of human lymphocytes induced by polyclonal T-cell mitogens in a dose-dependent manner. FOM also strongly suppressed mixed lymphocyte reaction and interleukin-2 (IL-2) production by T cells. Moreover, FOM inhibited the expressions of IL-2 receptor (CD25) and transferrin receptor (CD71) on the activated T-cell surfaces. These data suggest that FOM may block the T-cell division during the transition from G1 to S phase of the cell cycle. Combined treatment with FOM and low-dose cyclosporin A or FK506 caused additive or synergistic suppression of T-cell proliferation, but not on IL-2 receptor expression. It seems that the mode of action of FOM on T-cell function involves a specific suppression of IL-2 production.

Animals↗
PubMed1993

Immunomodulatory effect of fosfomycin on human B-lymphocyte function.

Fosfomycin (FOM) is an unique antibiotic which is chemically unrelated to any other known antimicrobial agent. Recent investigations have demonstrated that FOM inhibits histamine release from basophils. In this study, we examined the effect of FOM on human B-cell functions. FOM inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan 1 in a dose-dependent manner. FOM interfered with the transition from the G0 to the G1 phase of the cell cycle, leading to cell arrest. The proliferative response of in vivo-activated B cells and lymphokine-induced B-cell proliferation were also affected by FOM. In addition, FOM suppressed immunoglobulin secretion by antibody-producing B cells. Interestingly, FOM did not affect the expression of activation antigens such as the CD25 (interleukin-2 receptor) and CD71 (transferrin receptor) antigens. Moreover, FOM sustained the increased Ia expression on B-cell membranes induced by S. aureus Cowan 1 stimulation, which suggests that FOM may not block the role of B cells in antigen presentation in T-cell-B-cell interaction.

Adjuvants, Immunologic↗
PubMed1999

Fosfomycin alters lipopolysaccharide-induced inflammatory cytokine production in mice.

To determine the mechanisms of immunomodulating action of fosfomycin (FOF), we examined its effect on the production of inflammatory cytokines in mice injected with lipopolysaccharide (LPS). Treatment with FOF significantly lowered the peak serum levels of tumor necrosis factor alpha and interleukin-1 beta, indicating that FOF alters inflammatory cytokine production after LPS stimulation.

Animals↗
PubMed1999

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin.

Penicillium decumbens is able to epoxidize cis-propenylphosphonic acid (cPA) to produce the antibiotic fosfomycin [FOM; also referred to as phosphonomycin and (-)-cis-1,2-epoxypropylphosphonic acid], a bioconversion of considerable commercial significance. We sought to improve the efficiency of the process by overexpression of the genes involved. A conventional approach of isolating the presumed epoxidase and its corresponding gene was not possible since cPA epoxidation could not be achieved with protein extracts. As an alternative approach, proteins induced by cPA were detected by two-dimensional gel electrophoresis. The observation that a 31-kDa protein (EpoA) was both cPA induced and overaccumulated in a strain which more efficiently converted cPA suggested that it might take part in the bioconversion. EpoA was purified, its amino acid sequence was partially determined, and the corresponding gene was isolated from cosmid and cDNA libraries with oligonucleotide probes. The DNA sequence for this gene (epoA) contained two introns and an open reading frame encoding a peptide of 277 amino acids having some similarity to oxygenases. When the gene was subcloned into P. decumbens, a fourfold increase in epoxidation activity was achieved. epoA-disruption mutants which were obtained by homologous recombination could not convert cPA to FOM. To investigate the regulation of the epoA promoter, the bialaphos resistance gene (bar, encoding phosphinothricin acetyltransferase) was used to replace the epoA-coding region. In P. decumbens, expression of the bar reporter gene was induced by cPA, FOM, and phosphorous acid but not by phosphoric acid.

Amino Acid Sequence↗
PubMed1976

Fosfomycin resistance: selection method for internal and extended deletions of the phosphoenolpyruvate:sugar phosphotransferase genes of Salmonella typhimurium.

Selection for resistance to the antibiotic fosfomycin (FOS; L-cis 1,2-epoxypropylphosphonic acid, a structural analogue of phosphoenolpyruvate) was used to isolate mutants carrying internal and extended deletions of varying lengths within the ptsHI operon of Salmonella typhimurium. Strains carrying "tight" ptsI point mutations and all mutants in which some or all of the ptsI gene was deleted were FOS resistant. In contrast, strains carrying ptsH point mutations were sensitive to FOS. Resistance to FOS appeared to result indirectly from catabolite repression of an FOS transport system, probably the sn-glycerol-3-phosphate transport system. Resistant ptsI mutants became sensitive to FOS when grown on D-glucose-6-phosphate, which induces an alternate transport system for FOS, or when grown in the presence of cyclic adenosine 3',5'-monophosphate. A detailed fine-structure map of the pts gene region is presented.

Anti-Bacterial Agents↗
PubMed1985

Structural and functional analyses of the fosfomycin resistance transposon Tn2921.

The fosfomycin resistance transposon Tn2921 is flanked by directly repeated sequences homologous to the Tn10-related insertion sequence IS10. The nonrepeated DNA sequences of Tn2921 can be deleted without affecting the transposition ability of the element, showing that at least one of the direct repeats is an active insertion sequence. Transposition of Tn2921 seems to occur through direct transposition, since cointegrates have not been observed. The evolutionary relatedness of Tn2921 and IS10 is discussed.

Anti-Bacterial Agents↗
PubMed1986

In vitro evaluation of combined usage of fosfomycin and 5-fluorouracil for selective isolation of Leptospira species.

The combined usage of fosfomycin (FOM) and 5-fluorouracil (5-FU) as selective agents for the isolation of leptospires from contaminated materials was investigated. Additive or synergistic antibacterial activity was apparent with the combination compared with each agent used separately. Of 54 bacterial strains tested, 52 were inhibited, while all 5 Leptospira strains tested were unaffected by the combined addition of FOM (400 micrograms/ml) and 5-FU (100 micrograms/ml) to Korthof medium. Furthermore, this combination successfully supported the selective growth of Leptospira interrogans serovar copenhageni in experimentally contaminated specimens. This FOM-5-FU combination is surmised to be useful for the selective isolation of leptospires from contaminated clinical, pathological, or environmental materials.

Bacteriological Techniques↗
PubMed1984

The activity of rosoxacin, fosfomycin, cefotiam, and spectinomycin on beta-lactamase producing Neisseria gonorrhoeae.

We measured the activity of rosoxacin, fosfomycin, cefotiam, and spectinomycin against 51 isolates of beta-lactamase producing Neisseria gonorrhoeae, all of which were susceptible to each drug at sufficient concentrations. The development of strains of penicillinase producing N gonorrhoeae (PPNG) which are resistant to spectinomycin can therefore be avoided, as there are alternative drugs.

4-Quinolones↗
PubMed2003

Intracellular activity of fosfomycin against two distinct enteropathogenic bacteria, Salmonella enterica and Listeria monocytogenes, alive inside host cells.

We studied the effect of fosfomycin (FOM) on the intracellular growth of two different facultative intracellular bacteria, Salmonella enterica serovar Typhimurium and Listeria monocytogenes, in an enterocyte-like cell line, Caco-(2). These bacteria replicate in different compartments within the host cells; Salmonella serovar Typhimurium grow inside phagosomes, whereas L. monocytogenes escape the phagosomal environment and multiply in the cytosol of the host cells. At concentrations equal to 0.25 of the MIC and 4 times the MIC, respectively, FOM effectively decreased the number of intracellular Salmonella serovar Typhimurium. Although FOM was ineffective at inhibiting the extracellular growth of L. monocytogenes in vitro, this antibiotic induced a marked reduction in intracellular L. monocytogenes, indicating that, comparatively, FOM may be more effectively taken up by L. monocytogenes in the intracellular environment.

Anti-Bacterial Agents↗
PubMed1977

Evolution of sensitivity to fosfomycin at Jimenez Diaz Foundation.

The sensitivity to fosfomycin of more than 8,000 strains of bacteria isolated from products recevied by the laboratory between 1972 and 1974 has been studied. Some were studied by the dilution technique in a solid medium and the remainder was studied by diffusion. A single 50-mug disc was used and the strains inhibited by concentrations of less than 64 mug/ml or with inhibition halos of 15 mm diameter or more were considered sensitive. It is clear from this study that there are no significant changes in the sensitivity of the bacteria studied during the above-mentioned time, with the exception of a decrease in that of indole-positive Proteus, Providentia and Klebsiella.

Anti-Bacterial Agents↗