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PubMed1984

Fosfomycin, piperacillin, azlocillin. Correlation between therapeutic response of mice infected with Pseudomonas aeruginosa and in vitro data.

Intramuscular infections of mice with eight different strains of Pseudomonas aeruginosa were treated with three doses each of fosfomycin, piperacillin and azlocillin. The therapeutic response (measured as decrease in colony-forming units in the homogenized infected tissue) was compared with the 'aggregate suprainhibitory time' (the time for which the serum concentration exceeds the minimal inhibitory concentration of the infecting bacteria during the whole treatment period). The therapeutic response improved with increasing aggregate suprainhibitory time. The correlation was better for fosfomycin than for piperacillin and, especially, azlocillin.

Animals↗
PubMedDate not supplied

Enhancement of the susceptibility of Staphylococcus aureus to phagocytosis after treatment with fosfomycin compared with other antimicrobial agents.

Phagocytosis and intracellular killing of invading pathogens by host cells play the major role in resistance to bacterial infections. In vitro, antibiotics improve the susceptibility of microorganisms to antimicrobial activity of leukocytes, suggesting that this effect may contribute to determine the antimicrobial therapy and safe dosing intervals. The susceptibility of Staphylococcus aureus to phagocytosis and killing by human polymorphonuclear leukocytes (PMNL) in the presence of normal human serum in the postantibiotic phase of fosfomycin were compared with ciprofloxacin, cefotaxime and pristinamycin. Pretreatment of S. aureus for 10 min with 4 x MIC of fosfomycin and ciprofloxacin clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v); cefotaxime and pristnamycin failed to enhance the phagocytic killing.

Anti-Bacterial Agents↗
PubMed1987

Effect of fosfomycin trometamol on bacterial adhesion in comparison with other chemotherapeutic agents.

The effect of fosfomycin trometamol in comparison with that of norfloxacin and co-trimoxazole on the hemagglutination, yeast cell aggregation and adhesive properties of both gram-positive and gram-negative microorganisms was studied. The strains were isolated from the urine of patients with urinary tract infections, or from vaginal swabs. At sublethal concentrations (1/4 and 1/8 of the minimal inhibitory concentration), the ability of the bacteria to adhere to human uroepithelial cells was reduced by any of the 3 drugs assayed. The reduction corresponded to a decrease in the agglutinating activity of the gram-negative bacteria tested, such providing further evidence for the efficacy of the different chemoantibiotics. In particular, fosfomycin trometamol and norfloxacin proved to be more effective than co-trimoxazole in affecting the adhesive properties of all the strains employed.

Bacterial Adhesion↗
PubMed1977

In vitro development of resistance to fosfomycin.

Resistant colonies develop with an apparent high frequency in zones of inhibition around fosfomycin filter discs on nutrient agar. The resistance is due, primarily, to loss of the fosfomycin transport system. The resistant colony type usually observed in the inhibition zones seldom arise directly by mutation from a cell sown in the area of the zone of inhibition. Instead, small translucent colonies develop first in the inhibition zone. Within these small translucent colonies, mutational events occur which give rise to the normal resistant type colonies.

Anti-Bacterial Agents↗
PubMed1978

Two kinds of mutants defective in multiple carbohydrate utilization isolated from in vitro fosfomycin-resistant strains of Escherichia coli K--12.

Two types of in vitro fosfomycin-resistant mutants defective in multiple carbohydrate utilization were selected from Escherichia coli strain K--12. One mutant, FR182, was defective in phosphoenolpyruvate: sugar phosphotransferase system and the ability to form adenosine 3',5'-cyclic monophosphate (cAMP) was lowered. Another mutant, FR190, was defective in cAMP formation. Restoration by cAMP of fosfomycin (FOM) sensitivity coupled with recovery of utilization of many carbohydrates including sn-glycerol-3-phosphate (G-3-P) was observed in both of the resistant mutants. FOM was not taken up by these resistant strains but, in the cells cultured in the presence of cAMP, accumulation of FOM was equivalent to that of the sensitive parent strain. Decreased uptake of G-3-P was also restored in both of the resistant strains cultured in the presence of cAMP. These results indicate that the resistance to FOM in these mutants is due to impairment of G-3-P transport system, one of the pathways for uptake of FOM. They were sensitized to FOM by D-glucose-6-phosphate because of the induction of hexose phosphate transport system, another uptake pathway.

Anti-Bacterial Agents↗
PubMed1978

[Antibacterial activity of fosfomycin in chronic kidney infections].

Authors have carried out a retrospective study in vitro on the bacteria isolated from renal parenchyma and stones in patients with CPN associated to kidney stones. Results show a different inhibitory action of the some antibiotics to Proteus, E. coli and P. aeruginosa. Fosfomycin inhibits the growth of bacteria in a wide range of concentration (50-1000 microgram/ml). A prospective study in vivo shows an excellent therapeutic action of fosfomycin in recurrent urinary infections, and a very good one in CPN and in some forms associated to kidney stones.

Adult↗
PubMed2005

Crystallization and preliminary X-ray crystallographic analysis of UDP-N-acetylglucosamine enolpyruvyl transferase from Haemophilus influenzae in complex with UDP-N-acetylglucosamine and fosfomycin.

The bacterial enzyme UDP-N-acetylglucosamine enolpyruvyl transferase catalyzes the first committed step of peptidoglycan biosynthesis, i.e., transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetyl-glucosamine. We have overexpressed the enzyme from Haemophilus influenzae in Escherichia coli and crystallized it in the apo-form, as well as in a complex with UDP-N-acetylglucosamine and fosfomycin using ammonium sulfate as the precipitant. X-ray diffraction data from a crystal of the apo-form were collected to 2.8 A resolution at 293 K. The crystal quality was improved by co-crystallization with UDP-N-acetylglucosamine and fosfomycin. X-ray data to 2.2 A have been collected at 100 K from a flash-frozen crystal of the complex. The complex crystals belong to the orthorhombic space group I222 (or I212121) with unit-cell parameters of a = 63.7, b = 124.5, and c = 126.3 A. Assuming a monomer of the recombinant enzyme in the crystallographic asymmetric unit, the calculated Matthews parameter (VM) is 2.71 A3 Da-1 and solvent content is 54.6%.

Alkyl and Aryl Transferases↗
PubMed1990

Prophylactic single-dose fosfomycin and metronidazole compared with neomycin, bacitracin, metronidazole and ampicillin in elective colorectal operations.

Two antibiotic regimens for the prophylaxis of infection after colorectal operations were compared in a prospective, double blind, randomised controlled trial in 244 patients. Ninety-five patients (39%) were either excluded before randomisation or withdrawn, leaving 149 for analysis. Group 1 (n = 72) received a single infusion of 8 g fosfomycin and 1 g metronidazole at the induction of anaesthesia. Group 2 (n = 77) received bacitracin 250 mg plus neomycin 250 mg (as four tablets on three occasions over two days), metronidazole 500 mg tablets three times a day for one day, and ampicillin 1 g intravenously at induction of anaesthesia. Nine patients in group 1 (13%), 95% confidence interval (CI) 6.9 to 22.4, developed infective complications, compared with 8 in group 2 (10%), 95% CI 4.6 to 19.4. The overall infection rate was 17 of 149 evaluable patients (11%), 95% CI 6.8 to 17.7. Seven patients died (five in group 1 and 2 in group 2), two of whom (one in each group) died as a direct result of infective complications. Long operations and obesity were the most important risk factors, and may indicate a need for longer prophylaxis. Fosfomycin, which is mainly active against aerobic bacteria, was both safe and useful when combined with metronidazole.

Adult↗
PubMed1990

Host defence and bacterial growth in fosfomycin-treated peritonitis. Experimental observations in pigs.

An approximately steady state of bacterial density intraperitoneally has been observed in bacterial peritonitis. This state, which follows an initial (0-4 h) phase of rapid elimination of bacteria, was now studied in a model of porcine peritonitis. Twelve pigs were intra-abdominally infected with 10(10) CFU each of Escherichia coli and Bacteroides fragilis. Six of the pigs received no antibiotic and six were given two doses of fosfomycin (anti-aerobic), 1 g i.v., with the aim of disturbing possible equilibrium between rapid proliferation and destruction of the sensitive E. coli. Levels of fosfomycin up to 90 times the minimum inhibitory concentration (1 mg/l) were detected in the peritoneal exudate, but the antibiotic had no discernible effect on E. coli density or elimination pattern compared with B. fragilis in the same pig or with observations in controls. The results favoured the concept of slow-replicating E. coli and hence declining activity of the defence mechanisms a few hours after the induction of peritonitis.

Animals↗
PubMed1989

[A fosfomycin-gentamicin combination in the treatment of experimental endocarditis caused by Klebsiella pneumoniae producing type TEM-3 beta-lactamase].

The authors studied the activity of fosfomycin (FOS) and/or gentamicin (GEN) against a Klebsiella pneumoniae strain resistant to all beta-lactams--except cephamycins and imipenem--by production of a plasmid mediated extended broad-spectrum beta-lactamase-TEM-3, to all aminoglycosides--except gentamicin--by production of a plasmid mediated 6' aminoglycoside acetyltransferase IV, to sulfonamides and to tetracyclines. In vitro, the combination FOS (MIC = MBC = 32 mg/l) + GEN (MIC = MBC = 2) appeared indifferent (FIC = 0.75; FBC = 1). In vivo, on experimental endocarditis in rabbits, FOS alone was ineffective, GEN alone was active but only at high dose regimen, FOS - GEN combination was active as compared with controls. Fosfomycin - gentamicin combination may be an alternative in the therapy of severe infections due to multiresistant Enterobacteriacae.

Animals↗
PubMed1985

[Fosfomycin-cefotaxime combination in severe staphylococcal infections in newborn infants].

Clinical and bacteriological effectiveness of the fosfomycin-cefotaxime combination is reported in four cases of serious staphylococcal infections in neonates (1 meningitis, 2 osteomyelitis, 1 superinfection of congenital varicella). Owing to the strong synergistic effect of this combination on methicillin-resistant staphylococcal strains, the authors suggest that the fosfomycin-cefotaxime combination should be considered for anti-staphylococcal therapy in neonates with deep tissue and/or methicillin-resistant infections.

Cefotaxime↗
PubMed1988

[In vitro effect of combinations of netilmicin and amikacin with fosfomycin and pefloxacin on 31 strains of heterogeneous methicillin- resistant Staphylococcus aureus].

The Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) of 31 strains of Staphylococcus aureus resistant to methicillin and gentamicin were determined towards aminoglycosides: netilmicin (N) and amikacin (A). The results of the study showed a large discordance between the technic using dilution in Mueller-Hinton broth and the technic using agar diffusion with antibiotic discs. The level of sensitivity appears to decrease by dilution. The problem of using these aminoglycosides in combination with other antibiotics as fosfomycin (F) and pefloxacin (P) was faced. In vitro, antibacterial activity of combinations [N-F], [N-P] and [A-F], [A-P], was studied by microtiter checkerboard method. The antibacterial effects of these combinations were evaluated by determination of Fractional Bactericidal Indices (FBC-indices). The combination netilmicin or amikacin with pefloxacin has an additive bactericidal effect in most cases, without discrimination between the different aminoglycosides (FBC #0.82). Netilmicin or amikacin in combination with fosfomycin are found to be additive or moderately synergistic (FBC #0.53). No occurrence of antagonism was observed.

Amikacin↗
PubMed1987

Single-dose treatment of lower urinary tract infections with fosfomycin trometamol: preliminary experiences.

In recent years many clinical trials were carried out in order to evaluate the efficacy of single dose therapy in lower urinary tract infections (UTIs). In this trial we treated 26 patients (5 M and 21 F) suffering from lower UTI with an single oral dose of 3 g of fosfomycin trometamol, a new phosphonic acid derivative. The overall cure rate four weeks after treatment was 77% (20 out of 26 patients). A cure rate of 89% (16 out of 18 patients) was observed in adult females with uncomplicated UTI. No patients complained of side effects due to fosfomycin trometamol.

Adolescent↗
PubMed1987

[Comparative pharmacokinetics of fosfomycin in the neonate: 2 modes of administration].

In newborn, fosfomycin-cefotaxime in combination is more and more commonly used for the treatment of nosocomial infections. A pharmacokinetic study was conducted in ten newborns in the aim of suggesting a therapeutic schedule of the fosfomycin. Each newborn received 200 mg/kg, intravenously twice a day. Two groups have been formed according to the time of perfusion: 2 h or 30 min. The study of pharmacokinetic parameters do not demonstrated significant difference between the two populations. In addition, residual serum concentrations, twelve hours after the administration, are greater than the minimal inhibitory concentrations of most common pathogens causing nosocomial infections in neonates.

Age Factors↗
PubMed1987

[Determination of fosfomycin in biological fluids by gas chromatography].

A method in gas chromatography is proposed to determine fosfomycin in biological and bacterial or cellular culture medium. This technique is carried out on capillary column OV 17-01 after "Flash Methylation" with a thermionic detector. The detection limit is about 1 microgram per millilitre of serum for a trial assay of 100 microliters. His characteristics have been furthered. The treatment by antibiotics generally associated with fosfomycin don't cause any chromatographic interference for plasmatic assays.

Chromatography, Gas↗
PubMed1987

[Fosfomycin levels in the cerebrospinal fluid of patients with and without meningitis].

18 neurosurgical patients were given 15 g fosfomycin at 8-hour intervals. Simultaneously serum and cerebrospinal fluid (CSF) concentrations were determined periodically over 8 hrs. In patients with noninflamed meninges the CSF-concentrations ranged between 6.48 and 8.98 micrograms/ml. In patients with meningitis the CSF-levels amounted to 20.28 and 39.80 micrograms/ml. For perioperative short-time prophylaxis and postoperative infections in neurosurgical patients therapeutically relevant fosfomycin levels against Staph. aureus und Staph. epidermidis can be achieved.

Adolescent↗
PubMed1979

Fosfomycin therapy of experimental infections in mice.

Fosfomycin inhibits the development of severe pyogenic infection by Staphylococcus aureus in kidneys if administered during establishment of infection. It inhibits the development of lethal infection by Escherichia coli. It has a positive therapeutic effect on listeria infection in mice even with a fosfomycin resistant mutant.

Animals↗
PubMed1979

[Conditions influencing the activity of fosfomycin in vitro (author's transl)].

The determination of the antibacterial activity of fosfomycin in vitro is most suitably carried out in serial dilution tests on Mueller-Hinton agar. In this, the reproducibility of the minimal inhibitory concentrations (MIC) is the best and is the least dependent on the size of the inoculum. In addition, there is no "skip-tube" effect with this method of determination. The reproducibility of the MIC values increases for several bacterial species on addition of glucose-6-phosphate and at the same time the inhibitory values are lower. If human urine is used as the nutrient medium, the inhibitory values of fosfomycin increase for many species. The action of the antibiotic is not reduced on addition of human blood to the Mueller-Hinton agar.

Anti-Bacterial Agents↗