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Evolution of bacterial sensitivity to fosfomycin in the Cindad Sanitaria 'Francisco Franco' in Barcelona.

A revision was done of the sensitivity of isolated germs in urine cultures and various other cultures to fosfomycin from 1972 to the present in the Ciudad Sanitaria 'Francisco Franco' in Barcelona. The results obtained were analyzed. The general observation was that of a fairly uniform behavior in the majority of germs that had shown an increase in resistance in 1973, and a clear tendency to a decrease in resistance in 1974 and 1975 with the exception of P. rettgeri (Lact.+) and P. morganii.

Anti-Bacterial Agents↗

New studies on placental transfer of fosfomycin.

Passage of fosfomycin across the placental barrier and the dynamics of maternal and fetal levels were determined in a group of ten mothers in active labor. To obtain a series of intrauterine fetal samples the Saling technique was used. There exists a clear relation between the levels reached in the mother and in the fetus and in function of time, as well as between the amount of antibiotic in the fetal blood 90 min after injection, and the weight of the placenta.

Anti-Bacterial Agents↗

Bacteriological evaluation of fosfomycin in clinical studies.

Since fosfomycin has behaved in vitro as a broad-spectrum antibiotic, an attempt has been made to evaluate this behaviour in controlled clinical study carried out at different Spanish hospitals. A total of 959 patients were treated for some of the following infectious clinical processes: gonococcal urethritis, typhoid fever, enterocolitis, acute and chronic urinary tract infections, osteomyelitis, chronic otorrhoea, septicaemia, meningitis, peritonitis, surgical and suppurative infections, bronchitis, pneumonia, pharyngoamygdalitis, burns, endometritis, ocular infection, whooping cough and nasal carriers of S. aureus. The results obtained as a function of the microorganism isolated in these clinical processes in percentage of clinical and bacteriological success have been 96% of the S. aureus infections, 95% of the Streptococcus sp. including S. pneumoniae, 90% of the N. gonorrhoeae infections, 94% of the E. coli infections including enteropathogenic E. coli, 90% of the S. marcescens infections, 76% of the Proteus sp. infections, 72% of the Klebsiella-Enterobacter infections, 66% of P. aeruginosa infections and 78% of the S. typhi infections.

Anti-Bacterial Agents↗

Fosfomycin in the bacteriuria of paraplegic patients.

A study was made of the activity of fosfomycin in vitro and in vivo against different bacterial strains localized in the urinary tract of paraplegic patients hospitalized for their rehabilitation in our Hospital. A total of 22 patients were studied and 24 treatments were carried out. A total of 33 organisms were isolated in the initial cultures. In all patients, the pattern of administration of the antibiotic was 4 g/day intramuscularly during 8 days. From the bacteriological standpoint, the results were excellent, although there was no question of clinical results due to the special circumstances of these patients. A sterilization of the urocultures was achieved in 20 of the 24 cases treated. No signs of intolerance or toxicity were observed in any of the patients upon administering the antibiotic.

Anti-Bacterial Agents↗

Fosfomycin in the treatment of gynecological infections.

Here we present the results obtained in the treatment with fosfomycin of 58 patients of diverse obstetric-gynecological infections manifested by clinical symptomology and by the initial isolation of 70 strains of different germs, all of them sensitive to this antibiotic. The types of infections were urinary, abdominal wall, perennial septicemias, and endometritis; 45 of them motivated by or resulting from pregnancy, and the remaining 13 from gynecological causes. The most frequent treatment was 1 g/6h during 10 days, using sodium salt intramuscularly in 33 cases, and calcium salt taken orally in 26. The clinical results were good in 50 cases (86.2%) with improvement in 3 (5.1%) and persistency of the infection in 5. The bacteriological evolution was good on 34 occasions (58.6%), partial in 4 (6.8%), and poor in 6 (10.3%). In 14 cases no control could be made since the wound healed. The tolerance to the antibiotic was good and no manifestations of toxicity were observed.

Administration, Oral↗

Fosfomycin in treatment of respiratory bacterial infections.

A study was made of 40 patients suffering from clinically and bacteriologically demonstrated bacterial respiratory infections which were all treated with fosfomycin as the only antibiotic. Studies were made of the sensitivity of the isolated organisms and control of the eradicated and selected organisms. Analytical controls were performed on all patients before, during and after treatment. The average dose employed was 60 mg/kg/day, divided into four doses and administered parenterally. The duration of the treatment fluctuated between 6 and 11 days in 87% of the cases. A clinical and bacteriological evaluation was made of the results. The clinical response was satisfactory in 75% of the cases, partial in 7.5% and poor in 17.5%. The bacteriological evolution was satisfactory in 62.5%, partial in 12.5% and poor in 20%. It was not possible to control the evolution in 15% of the patients. The concentrations of the antibiotic were determined in the sputum of 6 patients and fluctuated between 0.6 and 12.9 mug/ml. In no case could any significant disorders be attributed to the antibiotic.

Adolescent↗

Neurosurgical infection treated with fosfomycin and 6-methylprednisolone.

A left parietal parasagittal meningioma was removed in a 67-year-old female patient. In the postoperative period she had a neurosurgical cerebral suppurating infection: subdural, epidural and epicranial, connected to the exterior by several fistulas. In the operative revision and after a culture, the germ causing the infection, E. coli, was isolated. Treatment was begun with 16 g of intravenous fosfomycin and 120 mg daily of 6-methylprednisolone intramuscularly, and this treatment cured the patient.

Aged↗

Diffusion of beta-lactam antibiotics and fosfomycin to interstitial tissue fluid in rabbits.

The ability of seven antibiotics (carbenicillin, cloxacillin, ampicillin, cephalothin, cephaloridine, cefoxitin and fosfomycin) to enter interstitial tissue fluid was evaluated. Using rabbits with implanted subcutaneous chambers, antibiotics were given intramuscularly as a single dose of 15 mg/kg, and antibiotic levels in serum and interstitial fluid of the chambers were determined at variously scheduled times after injection. The results indicated that antibiotic concentrations in the two compartments did not run parallel. The pharmacokinetic analysis showed that, in general, antibiotic diffusion from blood to interstitial fluid increased with the concentration gradient and the serum half-life, and there was an inverse relationship to pKa, protein binding and molecular weight of the antibiotic.

Animals↗

Susceptibility of 50 isolates of Clostridium perfringens to cefotaxime, fosfomycin, penicillin G and vancomycin; variable tolerance for vancomycin.

50 strains of Clostridium perfringens recovered from human fecal specimens were examined for susceptibility to cefotaxime (CTX), fosfomycin (Fosfo), penicillin G (Pen G) and vancomycin (Vanco) with the aid of a microtiter procedure. The geometric mean minimal inhibitory concentrations (MICs) of CTX, Fosfo, Pen G and Vanco were 0.81, 48.3, 0.15 and 0.33 micrograms/ml, respectively; the geometric mean bactericidal concentrations (MBCs) of the four drugs were 1.25, 109.8, 0.53 and 9.05 micrograms/ml, respectively. The geometric mean MBC:MIC ratios of CTX, Fosfo, Pen G and Vanco amounted to 1.56, 1.97, 3.64 and 27.0. It was concluded that the C. perfringens strains were not tolerant for CTX, Fosfo and Pen G; however, the strains displayed variable tolerance for Vanco.

Anti-Bacterial Agents↗

Fosfomycin-induced protoplasts and L-forms of Staphylococcus aureus.

The potency of fosfomycin (60 micrograms/ml) to induce bacterial L-forms and protoplasts was studied on two strains of Staphylococcus aureus. On osmotically appropriate agar, L-colonies could be grown and repeatedly transferred to fresh media. The L-forms were sensitive to tetracycline and resistant to penicillin. Protoplasts were produced by treatment of S. aureus in broth for more than 6 h.

Anti-Bacterial Agents↗

Chemotherapeutic efficacy of cefotaxime and failure of fosfomycin in murine Salmonella typhimurium infection.

Six clinical isolates and 1 reference strain of Salmonella typhimurium were sensitive to conventional antibiotics (ampicillin, chloramphenicol, cotrimoxazole), cefotaxime (CTX), and fosfomycin ( FOSFO ). All 7 strains carried a 55 megadalton plasmid ( Birnboim - Doly agarose gel electrophoresis technique) and were of comparable virulence for outbred NMRI mice (LD50 values = range of 1.7 X 10(5)-1.0 X 10(6) CFU; intraperitoneal route). CTX (5 mg/25 g mouse/day, divided into 2 doses; duration = 7 days) proved efficacious against 3 selected strains (No. H 8800, 14, and 20) of S. typhimurium (p less than 0.01). FOSFO (same therapeutic regimen) failed in this regard; following transitory improvement of diseased animals (days 2-4), the mortality of treated animals eventually approached that of untreated control animals. Administration of 15 mg FOSFO /mouse/day likewise failed to enhance murine survival. Reisolated S. typhimurium bacteria of these 3 assay strains still were susceptible to FOSFO . In vitro, CTX likewise surpassed FOSFO in bactericidal activity against the same 3 S. typhimurium strains on a weight-for-weight basis in various biological fluids (human midstream urine; human defibrinated blood; murine thioglycolate-induced macrophage-rich peritoneal exudate).

Animals↗

Influence of beta-lactam antibiotics, fosfomycin and vancomycin on the adherence (hemagglutination) of Escherichia coli-containing different adhesins.

The adherence of Escherichia coli of certain adhesin types can be influenced by subinhibitory concentrations of beta-lactam antibiotics. Subinhibitory concentrations (1/4MIC) of those penicillin and cephalosporin compounds which lead to filament formation increase mannose-sensitive adhesion (MS+). Antibiotics with ovoid cell formation did not change or only slightly reduced MS+ adherence. Strains with mannose-resistant (MR+) adhesins were not affected by these antibiotics. Only azthreonam increased the adherence of both MS+ and MR+ strains. Vancomycin and fosfomycin reduced the adherence of all strains tested. The degree of change was strain and antibiotic specific. No relation could be detected between the changes of adherence and the changes of hydrophobicity under the influence of antibiotics. Electron microscopic investigation has not yet yielded an explanation of the observed phenomenon.

Adhesiveness↗

Unstable L-form of Proteus mirabilis induced by fosfomycin.

An unstable L-form of Proteus mirabilis was induced on solid medium by sensitivity test discs (200 micrograms of fosfomycin + 20 micrograms of glucose-6-phosphate). The L-colonies were subcultured on agar containing the antibiotic at a concentration of 60 micrograms/ml. On antibiotic-free medium, all the cells reverted to the bacterial phase. On antibiotic-containing agar, the reversion took place as well although at a much lower frequency. Parents and revertants differed in glucose metabolism while they reacted identically in H2S, indole, and urea tests.

Anti-Bacterial Agents↗

A comparative double-blind randomised study of single dose fosfomycin trometamol with trimethoprim in the treatment of urinary tract infections in general practice.

A double-blind, double-dummy trial comparing a single dose treatment with fosfomycin trometamol (FT, 3 g) versus trimethoprim (TMP, 200 mg) was carried out in women with uncomplicated urinary tract infections. From 51 clinically evaluable patients, 44 were bacteriologically assessable at the 6-week follow-up. The results were as follows in the FT group (n = 22): eradication in 17 (77.3%); recurrence in 2 (9%); reinfection in 2 (9%), and persistence in 1 (4.5%). For the TMP group (n = 22) the results were: eradication in 12 (54.5%); recurrence in 1 (4.5%); reinfection in 1 (4.5%), and persistence in 8 (33.3%). There were no significant adverse events reported with either agent.

Double-Blind Method↗

Single-dose fosfomycin trometamol versus multiple-dose cotrimoxazole in the treatment of lower urinary tract infections in general practice. Multicenter Group of General Practitioners.

A randomized trial, comparing a single dose treatment of fosfomycin trometamol (FT, 3 g) versus a 3-times daily regimen of cotrimoxazole (CTX, 960 mg) was carried out in women with uncomplicated urinary tract infections. Of 36 evaluable patients, 19 were treated with FT and 17 with TMP. The bacteriological results after 4 weeks of follow-up were in the FT group (n = 19): cure in 17 (89%), and failure in 2 (11%). For the CTX group (n = 17) the results were cure in 13 (76%), and failure in 4 (24%). Adverse events were reported in 3 patients on FT (2 diarrhoea, 1 epigastralgia) and in 2 on CTX (1 stain rash, 1 asthenia).

Bacteriuria↗

Fosfomycin trometamol versus netilmicin in children's lower urinary tract infections.

Fosfomycin trometamol (FT), an antibiotic active against the common urinary pathogens, may be demonstrated in adequate urine concentrations up to 36-48 h after a single oral dose of 1-2 g. This pharmacokinetic peculiarity seems to indicate that this antibiotic may be used in single doses in the therapy of lower urinary tract infections (UTIs) in infants and children. The efficacy and safety of FT in single oral doses was compared with those of netilmicin (NM), an aminoglycoside antibiotic with a demonstrated efficacy in bolus doses against UTIs, shown in a multicentric study. One hundred and thirty-five children with lower UTI, diagnosed on the basis of fever (less than 38 degrees C), erythrocyte sedimentation rate (less than 25 mm/l h) and C-reactive protein (less than 20 micrograms/ml), were included in the study: 71 received 2 g of FT, 64 5 mg/kg of NM. Cure, defined as persistence of sterile urine up to 30 days after therapy, was reached in 80.2% of children in the FT group and in 81.2% of children in the NM group. Persistence of infection was demonstrated in 7 and in 3 children, respectively. Recurrence of infection was noticed in 7 patients in the FT group and in 9 in the NM group. No differences between FT- and NM-treated children are demonstrable even if the patient population is analyzed according to the higher risk of UTI because of the presence of an anatomical and/or functional abnormality of the urinary tract or due to a previous tendency to recurrent UTIs. FT is as effective as NM in the treatment of lower UTIs in infants and children.

Adolescent↗

Activity of Monuril in lower urinary tract infections due to fosfomycin-resistant bacteria.

Oral single-dose therapy with fosfomycin-trometamol (F-T) was used in 18 patients with lower urinary tract infections. The isolated bacterial strains presented a minimum inhibitory concentration of greater than 128 micrograms/ml in vitro. In spite of this 'resistance' in vitro, a clinical and bacteriological cure was obtained in 12 cases (66%). There were relapses in 2 cases, and clinical and bacteriological failure in only 2 cases. These results are due to the high urinary levels and prolonged bactericidal activity of urine after single-dose therapy with 3-5 g F-T. The clinical and biological tolerance was very good.

Administration, Oral↗

Prophylactic chemotherapy with fosfomycin trometamol salt during transurethral prostatic surgery: a controlled multicenter clinical trial.

A prospective, randomized controlled study was carried out in 24 Italian urology wards in 675 patients undergoing transurethral prostatic resection, utilizing three different chemoprophylactic treatments with either amoxycillin (AMX), co-trimoxazole (CTX) or fosfomycin trometamol salt (FT) in order to prevent postoperative urinary tract infections. FT significantly lowered the incidence of both postoperative bacteriuria and symptomatic infections in comparison to AMX and CTX. Transient side effects, mild or moderate, were observed in 6.6% of cases. Similar safety and protective results were obtained in 233 patients undergoing different transurethral instrumentations who were chemoprophylactically treated with FT.

Aminoglycosides↗