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PubMed1977

Sensitivity of Vibrio spp. to fosfomycin.

The behavior of 15 strains of Vibrio eltor, halophilic Vibrios and NAG vibrios with respect to 14 antibiotics was studied by means of the single disc method in Mueller-Hinton agar. In the case of fosfomycin, the MIC for all of them was determined as well by the technique of progressive dilutions in solid medium. No conclusions were made because of the small number of strains studied. Nevertheless, it can be asserted that there is a marked difference in the activity of fosfomycin, since it was minimal against V. eltor, moderate against the NAGs and maximal against the halophilic Vibrio.

Anti-Bacterial Agents↗
PubMed1977

Fosfomycin treatment of Haemophilus influenzae infection in mice.

Haemophilus influenzae is an important pathogen in respiratory infections in children and often is implicated in otitis media. It is sensitive in vitro to a number of antibiotics, some of which are used clinically for the treatment of such infections. We have checked the in vitro sensitivity of a type b strain of H. influenzae. When tested in Levinthal's broth prepared with laked rabbit blood, the culture was most sensitive to tetracycline, ampicillin and penicillin and was somewhat less sensitive to cephalothin, fosfomycin, cephaloridine, and chloramphenicol. However, when this same strain was used to infect mice, fosfomycin was more active than ampicillin, tetracycline, chloramphenicol, penicillin or the cephalosporins.

Ampicillin↗
PubMed1977

Pharmacokinetics of fosfomycin.

Fosfomycin, an antibiotic discovered in Spain, has a unique chemical structure and pharmacologic features that are promising for clinical therapy. It is only partially absorbed orally, with relatively low blood levels. Intramuscularly, however, absorption is complete with peak blood levels 3-5 times as high as orally, and rapid intravenous injections give serum concentrations almost twice as high as intramuscularly. Some accumulation occurs with all three routes, and concentrations in excess of 1,000 mug/ml are consistently obtained in the urine with parenteral doses every 6 h. The serum half-life is 1.5-2 h, urinary excretion is by glomerular filtration, the antibiotic is not bound to serum proteins, and the volume of distribution is large. Diffusion into tissues and body fluids is good. Thus, the pharmacologic characteristics of fosfomycin along with its low toxicity make it comparable in these respects to other well-established antibiotics.

Administration, Oral↗
PubMed1977

Fosfomycin: Absorption and excretion.

Summarized results of absorption and excretion of fosfomycin after oral and intravenous administration obtained from hospitals and institutions in Japan are reported. Fosfomycin was rapidly absorbed and excreted from the urine once it was distributed, the 6-hour urinary recovery reaching about 20% in the case of oral administration and 90% in the case of intravenous injection. These phenomena are almost the same as those previously published. Higher concentration was noticed in the kidney, which gradually decreased according to the fall of the blood level. The blood level reached its maximum of about 3 mug/ml after oral administration to adults at a dose of 500 mg.

Administration, Oral↗
PubMed1977

Blood and urinary concentrations of fosfomycin as a function of the renal function value.

The following parameters were considered in studying 43 subjects under treatment for urinary infections with different degrees of renal insufficiency: the maximum blood concentrations, the plasmatic half-life, and the urinary concentrations of fosfomycin as a function of the plasma creatinine of the subject treated. The curve of the average maximum blood concentrations show a parabola-like increase, the plasmatic half-life followed the same tendency, while the curve of the average urinary concentrations presented an exponential decrease. The urinary concentrations were, nevertheless, always higher than 100 mug/ml regardless of the degree of renal insufficiency and even in the subjects who had a very high plasma creatinine. Given its absence of renal and systemic toxicity, the daily dosage of fosfomycin could remain unchanged regardless of the degree of insufficiency.

Anti-Bacterial Agents↗
PubMed1977

Renal insufficiency and fosfomycin.

After the parenteral injection of 1 g sodium salt of fosfomycin the serum levels of the antibiotic are detected in a series of eight adult patients with different degrees of chronic renal insufficiencies four of them submitted to periodical dialysis. The results obtained reveal that the levels as well as the time of elimination of fosfomycin maintain an obvious relation to the degree of renal insufficiency in the patients.

Adolescent↗
PubMed1977

Pharmacokinetics of fosfomycin during hemodialysis.

A study was made of the elimination of fosfomycin by the membrane of the artificial kidney in 10 patients with hemodialysis and a creatinine clearance of less than 5 ml/min. To do so we determined the half-life, the dialysance, the percentage of total loss and the percentage of loss by the artificial kidney. We reached the conclusion that fosfomycin is heavily dialyzed (D = 64 ml/min), it is entirely eliminated by the kidneys and its half-life is therefore affected very little (an increase of only about 30 min is produced). All of this leads to a practical schema by which the entire initial dose should be replenished at the end of each dialysis.

Anti-Bacterial Agents↗
PubMed1977

Pharmacodynamic data on fosfomycin in underweight infants during the neonatal period.

A study was made of the blood levels, half-life and elimination of fosfomycin in two groups of underweight infants during the 1st to 3rd days of life and after 3-4 weeks. The test dose was 50 mg/kg i.v., administered in a single dose. The times at which the blood was controlled were 5 min, 1, 3, 6, 9 and 24 h; and 0-24 h for the urine. All samples were evaluated by the microbiological method of diffusion in plate. The results obtained indicate that the elimination of fosfomycin after 24 h is slower and occurs in smaller quantities in the group of infants 1-3 days old than in the group of 3- to 4-week-old infants, the half-life of the antibiotic being 7 and 4.9 h, respectively.

Age Factors↗
PubMed1977

Fosfomycin in chronic urinary infections.

Fosfomycin has been used on 40 patients with serious urinary infections of different clinical nature, and produced by repetitive infection (prostatisms, carcinomas, lithiasis, hydronephrosis, etc.) The following were isolated in the urocultures: E. coli (60%), Klebsiella (15%), P. aeruginosa (15.0%), Proteus sp. (15.0%), Staphylococcus (5%), S. faecalis (2.5%) and Paracolobactrum coliforme (2.5%). All the germs isolated before treatment were sensitive to fosfomycin. The results, as regards response to the bacteriuria, were 71.4% eradication of the infection, 17.2% reinfections and 11.4% failures. The results are considered very satisfactory in view of the etiopathogenic nature of the processes under treatment.

Adolescent↗
PubMed1977

Treatment of acute and subacute gonococcal urethritis with fosfomycin.

70 patients, 69 male and 1 female, 23 suffering from subacute gonococcal urethritis and the other 47 suffering from acute gonococcal urethritis, have been treated with fosfomycin with the intramuscular method. The treatment was planned as follows: (1) in 12 patients a total dose of 4 g (2g/4h) was tried with 11 bacteriological and clinical cures (92%) and 1 failure; (2) in another 43 patients a single dose of 4 g was tried (2 g in each buttock), with 37 cures (86%) and 6 failures; (3) finally, in another group of 15 patients with subacute gonococcal urethritis, fosfomycin was administered at the rate of 2g/8h for 2 days, clinical and bacteriological cures being achieved in all patients (100%). The failures, a total of 7, are patients with subacute gonococcal urethritis who were given a single dose of 4 g.

Acute Disease↗
PubMed1977

Enteropathogenic E. coli gastroenterocolitis in neonates treated with fosfomycin.

The effect of calcium salt of fosfomycin in the treatment of 43 neonates suffering from acute gastroenterocolitis produced by enteropathogenic E. coli is evaluated. The minimal inhibitory concentration of these E. coli was, generally, lower than 128 mug/ml. Dosages of 150-200 mg/kg body weight/day were administered orally every 8 h. This treatment lasted for 4 days only. Clinical evolution was favorable in 38 (88%) babies and bacteriological evolution in 30 (70%). In eight cases a different flora to the initial was selected during the treatment with fosfomycin. None of the cases treated showed any toxic alteration attributed to the antibiotic.

Acute Disease↗
PubMed1977

Fosfomycin in acute bronchopneumopathies.

Fosfomycin has been tested in 25 adult patients with bronchial or bronchopulmonary acute processes, of which 13 were simple acute processes of a greater or lesser severity, and 12 acutenesses of chronic bronchial processes. The germs found most frequently in the sputum cultures were Streptococcus pneumoniae and Klebsiella. Fosfomycin was used intramuscularly with doses of 4 g/day, for an average of 10 days. The results obtained were 16 cures, 7 improvements and 2 failures, which represents 92% success with 8% failures.

Acute Disease↗
PubMed1977

Treatment of respiratory infections with fosfomycin.

Results are presented for a series of 29 patients, 14 males and 15 females, with serious respiratory infections, in which fosfomycin proved effective. In all cases the study was completed by bacteriological, clinical, radiological and analytical controls. The average dose was 6 g/day (3 g orally and 3 g intramuscularly) for 1 or 2 weeks. The four isolated were P. aeruginosa, E. coli, Klebsiella-Enterobacter and D. pneumoniae. Overall sensitivity percentages were best for fosfomycin, gentamicin and colistin. Of the 29 germs isolated, only one strain of P. aeruginosa became resistant: this represents 3% resistance development. No side effects of intolerance or signs of hepatorenal insufficiency were observed during the treatment. Of the 29 patients treated, 22 were clinically cured, denoting 76% success.

Anti-Bacterial Agents↗
PubMed1977

Treatment of respiratory infections with fosfomycin.

Evaluation was made of the clinical-bacteriological results of treatment with fosfomycin on a group of 27 patients with infectious respiratory pathology. The group is made up of patients with respiratory infections diagnosed as pneumonias, bronchopneumonias, acute bronchitis and chronic bronchopneumopathies. The doses of fosfomycin used varied between 4 and 12 g/day, administered during a period of 1 or 2 weeks. The results of the treatment expressed in clinical and bacteriological parameters have been successful in 15 and 21 cases for their bacteriological response and their clinical response respectively.

Administration, Oral↗
PubMed1977

Activity of fosfomycin in the treatment of bacterial infections.

30 patients with different infections were treated with fosfomycin: 13 had urinary infections, 14 had pneumonial infections, 2 had staphylococcus osteomyelitis and 1 had staphylococcus septicemia. The antibiotic was administered in doses ranging from 100 to 230 mg/kg/day, with periods of treatment that lasted from 5 to 58 days. The doses were administered every 6 h by the oral or intramuscular route. A total of 35 organisms were isolated: 7 E. coli, 7beta-hemolitic Streptococcus, 6 Proteus sp., 6 S. aureus, 6 S. viridans, 2 Klebsiella sp. and 1 negative coagulase S. aureus. All were sensitive to fosfomycin in vitro, as was revealed by the diffusion in discs method. The therapeutic results were good in 29 of the 30 cases (96.7%). There were no important side effects. A patient complained of a local pain in the area of the injection. The transaminases increased temporarily in 2 patients. One patient had a moderate eosinophilia while under treatment.

Administration, Oral↗
PubMed1977

Fosfomycin in a traumatological department.

Fosfomycin has been used in the treatment of 99 patients suffering from varying kinds of osseous processes and divided into 2 groups, one of 60 patients who were not operated on, and another of 39 who were operated. A treatment only with fosfomycin was tried initially by intravenous infusion (8-16 g/day during 2-4 days), then by the intramuscular route (2-8 g/day during 2-6 days) and finishing with treatment by the oral route (2-4 g/day during 2-6 days). The results have been excellent, all cases progressing with no septic complications. As for secondary effects, we have had only one case in which a rash appeared at the end of treatment. Intravenous infusion has been well tolerated with no sign of phlebitis in any patient.

Administration, Oral↗
PubMed1981

Variable tolerance of a clinical isolate of Staphylococcus epidermidis from an infected hydrocephalus shunt for several beta-lactam antibiotics, vancomycin and fosfomycin.

A strain of Staphylococcus epidermidis isolated from an infected hydrocephalus shunt with associated ventriculitis in a 3-month-old infant proved variably tolerant for the beta-lactam antibiotics ampicillin, cephalothin, cefotaxime, cefoxitin, oxacillin, penicillin G, as well as vancomycin and fosfomycin. In contrast, Staphylococcus aureus control strain ATCC 25923 was regularly tolerant to the above stated beta-lactam antibiotics; however, this latter strain displayed variable tolerance for vancomycin and fosfomycin. The beta-lactam tolerance of both strains proved inoculum sizes. Penicillin G-tolerant variants were detected more readily among cells of the S. epidermidis strain in the stationary than in the logarithmic growth phase; in contrast, the yield of penicillin G-tolerant variants from S. aureus ATCC 25923 was independent of the growth phase. Tolerant variants of both staphylococcal strains failed to survive more than three successive passages in Mueller-Hinton broth with added beta-lactam antibiotics at concentrations identical to those which had originally served to select these tolerant variants. Gentamicin combined with vancomycin displayed additive bactericidal activity against both staphylococcal strains; conversely, the combination of rifampin plus vancomycin showed inadequate bactericidal activity against both strains.

Anti-Bacterial Agents↗
PubMed1983

Interactions of antimicrobial drugs and combined phagocytic/serum bactericidal activity of defibrinated human blood against Serratia marcescens. III. beta-Lactam antibiotics and fosfomycin.

Neither cefoperazone, cefotaxime, mezlocillin nor piperacillin significantly killed intraphagocytic bacteria of representative assay strains of Serratia marcescens, as determined with 55 vol% of fresh defibrinated human blood treated with 2 mg/ml of phenylbutazone, which permitted phagocytic ingestion of bacteria, but selectively inhibited the microbicidal activity of peripheral blood leukocytes. Extraphagocytic bacteria were killed with group A (phage tail) bacteriocins of S. marcescens. However, minimal bactericidal concentrations of fosfomycin displayed intraphagolysosomal bactericidal activity which approximated that of rifampin. Inhibitory and subinhibitory concentrations of cefoperazone, cefotaxime, fosfomycin, mezlocillin, and piperacillin combined with 55 vol% of defibrinated human blood, respectively, yielded additive effects against all test strains of S. marcescens utilized and Escherichia coli control strain ATCC 25922.

Anti-Bacterial Agents↗