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At least 19 recordsLinked to original sources
PubMed1978

Synergism of fosfomycin-ampicillin and fosfomycin-chloramphenicol against Salmonella and Shigella.

Ninety strains of Salmonella and 50 strains of Shigella were tested for susceptibility to fosfomycin, chloramphenicol, and ampicillin by the agar dilution method. Drug interaction between fosfomycin-ampicillin and fosfomycin-chloramphenicol was studied by the agar dilution method. The fractional inhibitory concentration was calculated. The combination of fosfomycin-ampicillin was synergistic against Salmonella in 74 cases, additive in 7, indifferent in 7, antagonistic in none, and nonevaluable in 2; against Shigella it was synergistic in 27 cases, additive in 9, indifferent in 14, and antagonistic in none. The combination of fosfomycin-chloramphenicol was synergistic against Salmonella in 56 cases, additive in 9, indifferent in 13, nonevaluable in 12, and antagonistic in none; against Shigella it was synergistic in 29 cases, additive in 10, indifferent in 9, nonevaluable in 2, and antagonistic in none. Killing curves with combinations of each antimicrobial agent showed that the cultures that had proven to be indifferent by the agar dilution method showed a bactericidal effect until h 4, with posterior regrowth of the culture after this time period. For the strains in which synergism was demonstrated, total bactericidal activity was reached at 24 h.

Ampicillin↗
PubMed1975

Experimental studies on absorption, distribution and excretion of a new antibiotic, fosfomycin. II. Absorption of oral preparations of fosfomycin calcium salt in dogs (author's transl).

To establish the best usage and dosage of fosfomycin granule and capsules which had been prepared based on our fundamental experiences as described in the first report, absorption of calcium salt contained in both preparations was evaluated using dogs as test animals. (1) Granule containing the calcium salt equivalent to 200 mg of fosfomycin free acid per g showed almost the same absorption as the bulk (fosfomycin calcium), having no disadvantage due to processing. (2) Capsules containing the calcium salt equivalent to 250 mg and 500 mg of the free acid per capsule showed slightly more retarded absorption than the bulk, probably due to some inevitable factors such as disintegration rate of capsules and dispersion rate of the calcium salt. But, once dispersed, the calcium salt in capsules was well absorbed as well as the bulk material. (3) Gastrointestinal absorption of granule and the capsule contents was almost the same. (4) Simultaneous administration of capsules and water improved the absorption efficiency. Though administration after feeding caused somewhat retarded absorption of the drug, the serum levels were rather well sustained with a slight drop but sufficiency of absorption, suggesting better clinical advantages than in the fasted animals. (5) Fosfomycin calcium salt in both preparations was well absorbed in the test animals through gastrointestinal tract as well as the bulk calcium salt, without any possible disadvantage caused by processing. In addition, the absorption efficiency was improved by giving with water or meal to the animals.

Administration, Oral↗
PubMed1975

[Experimental studies on absorption, distribution and excretion of fosfomycin. I. Absorption distribution and excretion of fosfomycin calcium salt (author's transl)].

In order to develop some oral drug preparations containing calcium salt of fosfomycin ((minus)-cis-1,2-epoxypropylphosphonic acid) which is a new antibiotic, the absorption, distribution and excretion were studied when it was administered orally to fasted test animals such as rats, rabbits and dogs. The results are as follows: 1) In the case of rats, the more dose size was increased, the more ratio of excretion in urine as index of gastrointestinal absorption was reduced and ratio of excretion in stools was adversely increased, which suggested a decrease in absorption efficiency. But, as absolute amount of excretion in urine became larger with dose size, it was considered that increase in dose size would serve for elevation of serum levels. 2) When the calcium salt was given to rats and rabbits in form of solution and suspension, the former was more eminent than the latter regarding to absorption efficiency, as generally known. The solution, however, needed relatively large quantity of water to solubilize the calcium salt, and it was not considered that the absorption efficiency depends on only dissolution step or dissolution rate. 3) Difference of the particle size varying from 1.50 mu(bulk particle size) and 0.64 mu(mechanical limit size) measured by Kozeny-Carman method did not affect on the absorption in rats and dogs. So it was considered that the bulk could be use directly without micronizing in manufacturing process for the oral preparations. 4) There were some differences of absorption among the animal species. Good absorption was shown in turn in rats, dogs and rabbits. These differences might depend not only on physiological factors but also anatomical differences such as length of gastrointestinal tract. 5) In rabbits high concentration was observed successively in kidney, lung, heart and so on. In any organ its level decreased similarly to the serum level, not sustaining its initial high concentration. The calcium salt did not possess any affinity to certain organs. 6) In conclusion, though some differences of gastrointestinal absorption were observed among the animal species, fosfomycin calcium salt was well absorbed without problem of micronizing the bulk particles. Moreover, it was perceived that fosfomycin calcium salt, once distributed, would not remain in particular organs, being excreted out of body.

Administration, Oral↗
PubMed1992

[Experimental study on intramaxillary injection of fosfomycin. Effects of fosfomycin on experimental acute sinusitis in rabbits].

We studied effects of intramaxillary injection of fosfomycin (FOM) on experimental sinusitis in rabbits. The experimental sinusitis was induced by intramaxillary injection of Staphylococcus aureus to rabbits for 3 successive days. 1. 0.5, 1, 3 or 5% FOM with saline as a control was instilled into the maxillary sinus and the maxillary sinus mucosa were examined macroscopically and light and electron microscopically. 3% and 5% FOM suppressed the damage of mucosa macroscopically and scanning electron microscopically. 2. After administration of 3% FOM and saline twice a week, the maxillary sinus mucosa was examined macroscopically and light and electron microscopically. The maxillary sinus injected with 3% FOM showed almost normal mucosa after 2 weeks while that injected with saline showed severe mucosal damage. S. aureus were decreased by 3% FOM injection and not found in the maxillary sinus in a week. The results indicate that intramaxillary injection of FOM is very effective in the treatment of sinusitis.

Acute Disease↗
PubMed1990

[Antibacterial activities and electron microscopic studies of imipenem in combination with fosfomycin against methicillin and fosfomycin resistant strains of Staphylococcus aureus].

UNLABELLED: Imipenem (IPM) and fosfomycin (FOM) have been reported to possess a synergistic relationship in their activities against both methicillin (DMPPC)-susceptible and -resistant strains of Staphylococcus aureus. However it was not concluded whether these antibacterial activities were bacteriostatic or bactericidal. The purpose of this report is to elucidate this point clearly. Activities of the 2 antibiotics against 15 strains S. aureus resistant to both DMPPC and FOM were investigated by means of the killing-curve method and electron microscopic studies. MICs of DMPPC and FOM against these strains determined using the agar dilution method were greater than or equal to 50 micrograms/ml and MICs of IPM by the broth dilution method ranged from 12.5 to 50 micrograms/ml. The killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth: 1. FOM 25 micrograms/ml, 2. FOM 25 micrograms/ml + IMP 1/2 MIC, 3. IPM 1MIC, 4. FOM 25 micrograms/ml + IPM 1 MIC and 5. FOM 25 micrograms/ml + IPM 2MIC. Morphological changes produced in 1 strain by 2 of the combinations, 2. FOM 25 micrograms/ml + IPM 1/2 MIC and 4. FOM 25 micrograms/ml + IPM 1MIC, were observed using scanning and transmission electron microscopy. The following results were obtained; (1) The synergistic effects were found in 6/15 strains (40%) and no antagonistic effect was found. (2) Electron microscopic observation showed that IPM in combination with FOM caused lysis of the cells. CONCLUSIONS: IPM in combination with FOM produced bactericidal and bacteriolytic effects on DMPPC-resistant S. aureus (MRSA). This combination therapy should be evaluated for FOM resistant MRSA infections.

Bacteriolysis↗
PubMed1990

Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives.

The pharmacokinetic comparison of phosphonic acid derivatives is based upon a survey of available literature on the whole group of compounds and on our own studies on fosfomycin. All three clinically used compounds, fosfomycin, fosmidomycin, and alafosfalin, are available for both oral and parenteral administration. The highest bioavailability is observed for the trometamol derivative of fosfomycin (37-44%); the calcium salt of fosfomycin is 2-2.5 times less absorbed and fosmidomycin has a bioavailability of 20-30%. The peak serum concentration of fosfomycin when given as the trometamol salt is about 2 times higher than the one reached with fosfomycin calcium or fosmidomycin. Urine recovery of unchanged drug is comparable after intravenous doses of fosfomycin and fosmidomycin, 80-95%, whereas the figure is only 10-20% for alafosfalin because it is extensively metabolized. After oral administration, urine recovery is highest for fosfomycin trometamol, 35-60%, compared to approximately 25% (range 18-29%) for fosfomycin calcium, 26% for fosmidomycin, and 6-17% for alafosfalin. The serum half-life of fosfomycin is 2-4 h (higher, up to 5.5 h, for some formulations of the calcium salt), 1.5-2.0 h for fosmidomycin, and about 1 h for alafosfalin. Thus, among available phosphonic acid derivatives and formulations, the trometamol derivative of fosfomycin has the most favourable characteristics. This applies to both bioavailability and urinary recovery, while at the same time the medium long half-life renders moderate fluctuation of concentrations whereby longer dosage intervals are possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1977

Treatment of typhoid fever with fosfomycin alone and associated to chloramphenicol or ampicillin.

Treatment with fosfomycin alone and associated to subtherapeutic doses of chloramphenicol or of ampicillin, has been tried on 50 patients with typhoid fever and on four carriers of S. typhi in the Hospital del Rey. 15 patients were treated with fosfomycin alone, 22 with fosfomycin plus chloramphenicol and 13 with fosfomycin plus ampicillin. The treatment lasted 15-20 days. The results have been evaluated clinically and bacteriologically, haemo- and coprocultures being carried out. The sensitivity of the isolated germs has been studied, including MIC and the synergism in vitro between fosfomycin-chloramphenicol and fosfomycin-ampicillin. Fosfomycin, chloramphenicol and ampicillin determinations have been carried out on the blood. The cures obtained were 67, 82 and 92% respectively with fosfomycin, fosfomycin-chloramphenicol and fosfomycin-ampicillin. We believe that this antibiotic can be useful in the treatment of typhoid fever, associating it to chloramphenicol or ampicillin, due to the synergism existing between them and given the results we have obtained.

Administration, Oral↗
PubMed1977

Fosfomycin in the treatment of bacterial infections: summary of clinical trials in Japan.

The Japan Research Committee of Fosfomycin was organized in the fall of 1972 to promote the basic and clinical studies on fosfomycin. First of all, a subcommittee of fosfomycin consisting of a limited number of members was organized to establish the methods of determination on its antibacterial activity and its concentration in the biological fluid, and the most applicable methods were devised. The clinical trials on its oral form in a small scale were commenced from spring in 1973, and then gradually expanded to almost all of Japan. The clinical trials on its parenteral intravenous form were also undertaken from the latter half of 1973. The basic and clinical results obtained from hospitals and institutes almost all over Japan, to which members of the above Committee belong, were presented by speakers under a hot discussion in two symposia which were held by the Japan Society of Chemotherapy; one on its oral form in June 1974, and another on its parenteral form in December 1974. I served as chairman in both of the symposia. The clinical results of fosfomycin in Japan which were mainly collected in both symposia are described below. Its antibacterial activity, and absorption and exretion will be presented elsewhere in this volume. Clinical results of its oral form: Dosage forms of fosfomycin-Ca salt, capsule and granules, were prepared for its clinical trials. It resulted effective in about 76% of 1,200 patients with infection due to gram-positive or gram-negative (Pseudomonas, Salmonella, Escherichia coli, etc.) bacteria in several fields. As far as rates of efficacy were concerned, it was more effective in surgical, urological, ophthalmic and some other fields than in internal and pediatric ones. Fosfomycin was given in a dose of 2-3 g/day for adults or 100-130 mg/kg for infants and children in most cases. Furthermore, it can be favorably mentioned that fosfomycin was proved to be effective in salmonellosis and resistant shigellosis by a certain research group specialized in the therapy of infectious enteritis. Clinical results of its parenteral form: Sterlized bulk material of fosfomycin-Na salt was prepared in a vial for clinical use. Similarly as in the case of oral form, it was applied to about 500 patients with several infections. It resulted effective in about 68% of them. This percentage was not as high because of the higher frequency of application to severe patients or patients with underlying disease. Fosfomycin was intravenously administered by one shot or drip infusion in a dose of 2-4 g/day for adults, or 100-250 mg/kg for infants and children in most cases. Adverse reactions: In oral form, the incidence of adverse reactions was about 10% but most of them were slight gastrointestinal disorders. In an extremely small number of patients a rise of SGOT and/or SGPT was observed. In parenteral form, the incidence of adverse reactions was a little higher, being about 17% including a rise of SGOT and/or SGPT, vascular pain, nausea, and vomiting, etc...

Administration, Oral↗
PubMed1990

Fosfomycin trometamol versus ofloxacin/co-trimoxazole as single dose therapy of acute uncomplicated urinary tract infection in females: a multicentre study.

20 urologists took part in a single blind, randomized study. Female patients with acute uncomplicated UTI were recruited. The patients received either a single dose of 3 g fosfomycin trometamol versus 200 mg ofloxacin or 1.92 g co-trimoxazole. Follow-up examinations were carried out after one and four weeks. Of 562 patients 446 could be evaluated for efficacy and 496 for tolerance. Patients were analysed according to the amount of bacteriuria: "significant" (greater than or equal to 10(5)/ml), "low count" (10(2) - 10(4) ml) and "no bacteriuria" (less than or equal to 10(1)/ml), as well as according to the sensitivity of the infecting organisms: sensitive (resistant): fosfomycin trometamol less than or equal to 16 mg/l (greater than or equal to 128 mg/l), ofloxacin less than or equal to 1 mg/l (greater than or equal to 8 mg/l), co-trimoxazole less than or equal to 2/38 mg/l (greater than or equal to 16/304 mg/l). Up to one week the following results could be achieved: clinical improvement was attained in patients with "significant" bacteriuria (fosfomycin trometamol-150, ofloxacin-89, co-trimoxazole-69) in 94.7% for fosfomycin trometamol, in 95.4% for ofloxacin, and in 94% for co-trimoxazole; in patients with "low count" bacteriuria (fosfomycin trometamol-44, ofloxacin-18, co-trimoxazole-30) in 95.2% for fosfomycin trometamol, in 93.7% for ofloxacin, and in 96.4% for co-trimoxazole; and in patients with no bacteriuria (fosfomycin trometamol-11, ofloxacin-6, co-trimoxazole-4) in 81.8% for fosfomycin trometamol, in 100% for ofloxacin and in 100% for co-trimoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Spectrum and susceptibility of pathogens causing acute uncomplicated lower UTI in females and its correlation to bacteriologic outcome after single dose therapy with fosfomycin trometamol versus ofloxacin/co-trimoxazole.

In a multicentric study comparing oral single-dose therapy of fosfomycin trometamol (3 g as fosfomycin) versus co-trimoxazole (1.92 g) or ofloxacin (200 mg) as many as possible of the pathogens were sent to and analysed in a central laboratory. The pathogens were identified and minimal inhibitory concentrations (MIC) of fosfomycin, trimethoprim alone and in combination with sulfamethoxazole, ofloxacin, ampicillin, amoxicillin combined with clavulanic acid, and cephadroxil were determined. The eradication of pathogens (cfu < 10(3)/ml at one week after single-dose therapy) was analysed according to species and MIC of the antibiotic used. Urine cultures of 349 patients were analysed. Escherichia coli was the predominating species followed by staphylococci and Proteus mirabilis. Enterococci were mostly found in mixed culture. Baseline pathogens of monoinfections were eradicated in 87.1%, in 88.9% and in 86.4% of 284 patients treated with fosfomycin trometamol, co-trimoxazole and ofloxacin, respectively. The MICs of the five antibacterial agents and the two antibiotic combinations for 253 baseline pathogens showed that of the E. coli strains none was resistant to ofloxacin, three (MIC = 128 mg/l) were resistant to fosfomycin, 3.6% to co-trimoxazole, 6.2% to trimethoprim, 8.8% to ampicillin, and 5.7% to amoxicillin/clavulanic acid. The eradication rates according to the MICs of the corresponding drugs showed equally good eradication rates for fosfomycin up to an MIC of 64 mg/l. Above this level two out of three strains were also eradicated by fosfomycin trometamol. For co-trimoxazole and ofloxacin no intermediately sensitive or resistant strains were found. Within the range of MICs found there were equally good eradication rates for both antibacterial agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1977

Combined action of fosfomycin with beta-lactam and aminoglycoside antibiotics.

The combined action of fosfomycin with penicillin G, ampicillin and streptomycin was investigated. A total of 11 S. aureus and 10 E. coli were included in these studies. It has been shown that a combination of fosfomycin with penicillin G and streptomycin resulted in a synergistic effect. When S. aureus strains were tested, the combination of fosfomycin with penicillin G was more frequently effective than the combination of fosfomycin with streptomycin. The combinations of fosfomycin with ampicillin and streptomycin showed a similar synergistic effect on 7 of 10 E. coli strains. The antagonistic effect never resulted when the above-mentioned combination of antibiotics were used. The authors postulate that a combination of fosfomycin with beta-lactam or aminoglycoside antibiotics may be used in clinical practice and such a procedure should prevent an emergence of fosfomycin-resistant strains.

Ampicillin↗
PubMed1977

Fosfomycin and plasmidic resistance.

60 fosfomycin-resistant strains of gram-negative bacilli are submitted to conjugation experiments using as recipient cell E. coli K12 which is nalidixic acid resistant. After mating, the number of fosfomycin-resistant E. coli K2 colonies growing on selection plates containing nalidixic acid and fosfomycin never surpassed the normal rate of mutation for fosfomycin-resistance of the recipient strain. In 65% of the experiments, plasmidic resistance to other antimicrobials was transferred to E. coli K12, but was never accompanied by demonstrable fosfomycin resistance. High rate of normal mutation of recipient strain is signaled as the main problem for detecting the plasmidic nature of fosfomycin resistance. With our criteria regarding this fact we have been unable to confirm the plasmidic nature of fosfomycin resistance.

Acinetobacter↗
PubMed1977

Fosfomycin in patients subjected to periodic hemodialysis.

The sensitivity to fosfomycin which is found in organisms that are frequently found in urinary infections and the lack of toxicity of this antibiotic were the reasons for which we tested fosfomycin on patients who were subjected to periodic hemodialysis. We were interested in studying (1) if fosfomycin was dialyzable, and (2) its therapeutic pattern in these patients. We selected a group of 27 patients from our programme of periodic hemodialysis who spend 18 h each week in three sessions with an RSP Travenol artificial kidney, using Ultra Flo II as the dialytic unit. They were all free of infection and had not received any antibiotics for 40 days before the test was carried out. They were administered 1 or 2 g of fosfomycin by the intravenous route at the time of beginning the dialysis. Blood samples and samples from the dialytic bath were taken before administering the fosfomycin, and 1/2, 3 and 6 hours after administering it. Our results show that fosfomycin is 70-80% dialyzed by the membranes of the artificial kidney and that during the hemodialysis, given the clearance which the dialyzing membrane makes of the antibiotic, the usual doses of fosfomycin should not be altered. No side effects were observed in any of the patients.

Anti-Bacterial Agents↗