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PubMed1983

Viability and ultrastructure of S. aureus treated with fosfomycin.

Fosfomycin was administered to logarithmic growing cells of S. aureus ATCC 12600 when the number of viable cells (CFU) was about 5 X 10(7) cells/ml. Within 240 min the CFU i) increased for about 70% when 6 micrograms fosfomycin/ml were administered, ii) decreased for about 91% when 25 micrograms glucose-6-phosphate (G-6-P) were administered in addition to 6 micrograms fosfomycin/ml, and iii) decreased for about 98% when 60 micrograms fosfomycin/ml and 25 micrograms G-6-P/ml were added. By means of turbidity measurements mainly a retardation in cell reproduction could be recognized. Contrary to Gram-negative bacteria, the reduction of viable cells for about 90% was not accompanied by a loss of cell integrity in the same range. In addition to the ATCC strain this could be shown for eight further strains of S. aureus.

Anti-Bacterial Agents↗
PubMed1981

[Comparison of in vitro methods for the determination of the activity of fosfomycin with the efficacy determined in experimentally infected mice (author's transl)].

Effective doses of fosfomycin against 17 strains of bacteria were determined in therapeutic experiments using infected mice. The peak serum levels obtained after administration of these doses were compared with the minimum inhibitory concentrations determined in vitro. Reasonable minimum inhibitory concentrations were obtained only with Mueller-Hinton agar containing glucose-6-phosphate: 1. Correlation of in vivo and in vitro efficacy is much better in comparison with the use of media without glucose-6-phosphate. 2. Minimum inhibitory concentrations below the levels obtained after therapeutic doses were found only in Mueller-Hinton agar containing glucose-6-phosphate. 3. Minimum inhibitory concentrations are better reproducible when determined on solid media than in broth.

Animals↗
PubMed1978

[Effects of fosfomycin sodium upon renal functions (author's transl)].

Effects of fosfomycin-sodium (FOM-Na) upon renal functions were studied with male rats. 1) After fasting for 24 hours, 25 ml/kg body weight of physiological saline were orally administered and respectively 160 and 320 mg/kg of FOM-Na were intraperitoneally administered immediately thereafter. The subsequent urinations amounts at 4 hours' interval were determined to see no effect of FOM-Na upon the urination amount. 2) After suspending water supply for 2 days, 1,000 mg/kg of FOM-Na were intraperitoneally administered once a day for successive 2 days. On the 3rd day, 50 ml/kg of dextran were intraperitoneally administered, and one hour thereafter, 1,000 mg/kg of FOM-Na were intramuscularly administered to hind leg. Blood samples were collected the following day (suspension of water was continued until blood sample collection) to determine the BUN and UA in serum. FOM-Na was found exerting on reinforcing effect upon renal dysfunctions caused by dextran.

Animals↗
PubMed1982

[Transfer of fosfomycin into the cerebrospinal fluid].

After the fosfomycin (FOM) infusion, its levels in serum and cerebrospinal fluid (CSF) were repeatedly measured in 8 cases without meningitis. 1. The peak concentration of FOM in CSF was 15.5 micrograms/ml with the average of 10.3 micrograms/ml and was reached at 240 minutes with the average of 210 minutes after the infusion. The biological half life time of FOM in CSF was 2 to 6.5 hours. 2. The peak concentration in CSF was compared with it in serum. The average ratio was 4.3 per cent. Each area under the curve (AUC) of FOM concentration in CSF and serum was calculated and average of their ratio was 9.0 per cent. 3. In a case with middle cerebral artery aneurysm, FOM transferred into CSF with ease. The lowest diffusion into the CSF was shown in 2 cases of meningioma. In 3 cases of hypertensive intracerebral hemorrhage with intraventricular perforation, FOM moderately transferred into CSF.

Adolescent↗
PubMed1980

[Effect of fosfomycin-calcium on reproductive performance of rats. II. Fertility test (author's transl)].

Fosfomycin calcium (FOM-Ca) was orally administered to Wistar rats for 60 consecutive days in males and 14 consecutive days in females in varying doses of 140 mg/kg, 700 mg/kg and 1,400 mg/kg, and then the animals were subjected to mating. It was further administered to pregnant female rats for another week to investigate its effects upon the embryos and fetus. The following results were obtained. 1) In parent animals, soft stools were noted in both sexes of the groups with higher doses, but otherwise there was no remarkable abnormality noted. 2) No increase was seen in the rates of development of dead embryos or externally abnormal fetus. 3) Skeletal abnormality was seen only slightly in the animals of the group with 700 mg/kg, but otherwise all the other groups were similar to the control group, showing that there would be no adverse effects by the tested drug upon the fetal skeletal structure. 4) On the ground of the above-mentioned test results, it was claimed that FOM-Ca exerts adverse effects upon the fetus of rats even in the dose of 700 mg/kg and that the safe dose to fetus of rats would be 140 mg/kg. It was also judged that it has no teratogenicity through administration before or at the initial stage of gestation.

Animals↗
PubMed1980

[Effect of fosfomycin-calcium on reproductive performance of rats. III. Peri- and post-natal examination (author's transl)].

The peri- and post-natal examination of fosfomycin-Ca (FOM-Ca) was undertaken in Wistar strain rats. Rats were treated orally at dose levels of 140, 1,400 and 2,800 mg/kg/day from the 14th day of gestation to 21st day after delivery. One-third of pregnant rats in each group were sacrificed on 20th day of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. No effect of FOM-Ca treatment to rat mothers was found except soft stool was seen in 1,400 and 2,800 mg/kg groups. No effect of FOM-Ca on rat fetuses and newborns was found except fetal body weight and survival rate decreased and skeletal variation increased in maximum dose. Consequently, it can be concluded that FOM-Ca has no effect on rat mothers, fetuses, and newborns treated during peri- and post-natal period.

Abnormalities, Drug-Induced↗
PubMed1995

[Combination therapy with arbekacin and fosfomycin against postoperative severe mixed-pneumonia of MRSA in primary lung cancer patients].

We experienced successful treatment of postoperative severe pneumonia of Methicillin-resistant Staphylococcus aureus (MRSA) with combination therapy of Arbekacin (ABK) and Fosfomycin (FOM) in three lung cancer patients. Case 1 was a advanced age of seventy-nine man who had had right upper lobectomy. Case 2 was a 61-year-old man who had had left lower lobectomy and extended bilateral mediastinal lymph-node dissection through the median sternotomy. And case 3 was a 59-year-old man who had suffered from pulmonary embolism after right pneumonectomy and partial resection of left atrium and superior vena cava. All cases were immuno-compromised patients and super-infected with Gram-negative rods, and Pseudomonas aeruginosa in case 1 and case 3. Clinical symptoms were improved after the start of administration of ABK and FOM inspite of ineffectiveness of prior treatment with other antibiotics. We added staggered chemotherapy of Sulbactam/Cefoperazone (SBT/CPZ) and Ceftazidime (CAZ) for case 1 and case 3 respectively. Thus, the combination therapy of ABK and FOM might be useful for severe pneumonia of MRSA in the immunocompromised patients, and the combined staggered chemotherapy of beta-lactum agents and above would be the first choice in the treatment for the case involving Pseudomonas aeruginosa.

Aged↗
PubMed1995

[A combined consecutive therapy with fosfomycin and sulbactam/cefoperazone for bacterial infections associated with hematological diseases].

A combination antibacterial therapy with fosfomycin (FOM) and sulbactam/cefoperazone (SBT/CPZ) was applied to 78 patients with severe infections associated with hematological diseases. In this protocol, FOM was followed by SBT/CPZ and each drug was administered for 1 hour intravenously and consecutively. Among 72 evaluable patients, 43 patients had acute leukemia, myeloblastic or lymphoblastic, 22 had malignant lymphoma, 3 had multiple myeloma, and 4 had other hematological diseases as underlying diseases. Bacterial infections diagnosed were sepsis in 21 patients, suspected sepsis in 47, and other infections in 4. The overall efficacy rate of this treatment was 72.2%, and those for individual infections were 66.7% for sepsis, 74.5% for suspected sepsis, and 75.0% for other infectious diseases. Among 22 bacteria separated from patients with sepsis, 78.6% (11/14 strains) were eradicated by this treatment. This protocol was also effective in 57.1% (8/14) of patients whose granulocyte count was less than 100/mm3 during the course of treatment as well as in 83.3% (15/18) of patients with granulocyte count over 500/mm3. There was no difference in effectiveness between those patients to whom G-CSF was administered and those to whom it was not (17/24, 70.8% vs 35/48, 72.9%). As an adverse reaction, a transient increase of GOT and/or GPT was observed in 2 patients (2.8%). The consecutive administration treatment of FOM and SBT/CPZ is thus an effective and safe regimen for the treatment of patients with hematological diseases complicated by severe infections.

Adult↗
PubMed1995

[In vitro studies on the combined effects of arbekacin and fosfomycin on methicillin-resistant Staphylococcus aureus].

We investigated the bactericidal activity and post-antibiotic effect (PAE) of arbekacin (ABK) and fosfomycin (FOM) on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) strain 1936, and the morphological changes of the bacterium. Both antibiotics were used in combination at concentrations lower than their respective MICs. The following results were obtained. 1. When the bacterium was simultaneously exposed to ABK and FOM, growth inhibition and a PAE longer than that effected by ABK alone were observed. 2. When exposed to ABK after treatment with and removal of FOM, bactericidal activity was stronger than that obtained when exposed to ABK alone. However, no increase in bactericidal activity was obtained when exposed to FOM after pretreatment with ABK. 3. Transmission electron microscopy revealed that, when the bacterium was exposed to ABK after treatment with and removal of FOM, large bacterial cells with cross walls at irregular sites and lysed cells showing destruction of the cell wall at the site of bacterial segmentation caused by ABK and FOM. These results demonstrated that ABK in combination with FOM shows stronger bactericidal activity against MRSA in vitro than ABK alone.

Aminoglycosides↗
PubMed1995

[Antibacterial activities of fosfomycin against recent clinical isolates from patients of otitis media and otitis externa].

Clinical isolates from patients with otitis media and/or otitis externa were collected at otorhinology clinics nationwide and sent to us during 1989, 1991 and 1993. Minimum inhibitory concentrations (MICs) of fosfomycin (FOM) and of reference drugs against these strains were determined to investigate year-to-year antibacterial activity of FOM. A comparative analysis of the results revealed trends described below. 1. The MIC90 of FOM against Staphylococcus aureus subsp. aureus increased 4 times by 1993 as compared to those measured for strains isolated in 1984 and 1985, when FOM for otic use was under development. This was thought to be due to the recent increase in the detection frequency of methicillin-resistant S. aureus (MRSA) which is also resistant to FOM. 2. No annual changes were seen for MIC distribution of FOM against Proteus group and Pseudomonas aeruginosa. 3. Since there was no large annual change in the antibacterial activity of FOM against recent clinical isolates obtained from patients with otitis media and/or otitis externa, FOM may be considered as one of the useful drugs even now, in the mid-1990's.

Drug Resistance, Microbial↗
PubMed1994

[Clinical usefulness of the combined empirical therapy with flomoxef and fosfomycin for intractable respiratory tract infections. With a background of increasing MRSA incidence].

We conducted a multicenter trial to determine the clinical usefulness of the combined therapy with flomoxef (FMOX) and fosfomycin (FOM) (FF therapy) as an empirical therapy in the treatment of intractable respiratory tract infections, because FF therapy has clinically been proved to be very useful for the treatment of severe infections including MRSA infections. The overall efficacy rate of FF therapy was 69.2%. The efficacy rate for "pneumonia/lung abscess," which occupy the largest portions of respiratory tract infections, was 70.0%, showing a statistically significant difference from the efficacy rate for FMOX alone (56.7%) found in a previous study (P = 0.09 by chi-squared test). Although MRSA was eradicated in only 3 cases (37.5%) including superinfection cases, of 8 patients, from whom MRSA had been isolated as causative organisms, none of our patients were superinfected with MRSA. Thus it has been concluded that FF therapy is clinically very useful when used as an empirical therapy in the treatment of respiratory tract infections.

Aged↗
PubMed1994

Susceptibility of multiresistant serotype 012 Pseudomonas aeruginosa to fosfomycin in combination with other antibiotics.

Serotype 012 represented 15% of 244 isolates of Pseudomonas aeruginosa isolated in the hospital over a 2 year-period and most isolates of this serotype were resistant to multiple antibiotics. Combination experiments showed that fosfomycin and amikacin together were active against 92% of 012 isolates. It is recommended that serotyping be used systematically to identify 012 strains rapidly and fosfomycin/amikacin be considered as a presumptive antipseudomonal therapy in 012 infections.

4-Quinolones↗
PubMed1994

[Laboratory and clinical studies on combined effects of fosfomycin plus sulbactam/cefoperazone for mixed infections of MRSA and Pseudomonas aeruginosa].

The time-lag/sequential/step by step chemotherapy by fosfomycin plus sulbactam/cefoperazone including a short time small dose of steroid was done for 27 severely infected patients suffered from various cancer or other severe basal diseases. And the staggered "intensive" chemotherapy with added arbekacin or vancomycin to the previous staggered chemotherapy was done against 13 severely infected patients having MRSAs among their infecting pathogens. 1. Bacteriological effects Pseudomonas aeruginosa 6/8, Staphylococcus epidermidis 5/5, Enterococcus faecalis 3/6, Acinetobacter calcoaceticus 2/2, Klebsiella pneumoniae 2/2, MRSA 2/2, Xanthomonas maltophilia 2/3 and other 10/10 were eradicated (84.2%) by the staggered chemotherapy and MRSA 7/13, P. aeruginosa 3/4, E. faecalis 3/5, A. calcoaceticus 2/2, X. maltophilia 1/1 and others 2/2 were eradicated (53.8% in MRSA, 78.6% in others and 66.7% in total) and 3 of MRSAs were colonized. 2. Clinical effects 1) Staggered chemotherapy: Excellent 18/27, good 8/27, fair 1/27, poor 0/27 (96.3%). 2) Staggered "intensive" chemotherapy: Excellent 6/13, good 4/13, fair 2/13, poor 1/13 (76.9%) in total: excellent 60.0%, efficacy rate 90.0%.

Adult↗
PubMed1994

[Antimicrobial activities of fosfomycin against Streptococcus pneumoniae and Haemophilus influenzae recently observed in sinusitis patient].

In order to examine antimicrobial activities of fosfomycin (FOM), the minimum inhibitory concentrations (MICs) of FOM and those of control drugs were determined against Streptococcus pneumoniae and Haemophilus influenzae isolated from sinusitis patients from September to November, 1993, and the following results were obtained. 1. Among 50 S. pneumoniae strains tested, there were 10 strains (20.0%) of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and 2 strains (4.0%) of PCG-resistant S. pneumoniae (PRSP); but the MIC distributions of FOM among the PISPs and the PRSPs were almost identical to those among the PCG-susceptible S. pneumoniae (PSSP). 2. There were 12 strains (24.0%) of beta-lactamase producing strains among 50 strains of H. influenzae tested, but the FOM's MIC distribution among these strains was almost identical to that among beta-lactamase non-producing strains. 3. The results obtained on the MIC90s of FOM against S. pneumoniae and H. influenzae suggest that the nebulization treatment with FOM nasal preparation satisfies the condition "above the MIC".

Drug Resistance, Microbial↗
PubMed1994

[Clinical effects of a combination treatment with fosfomycin and clavulanic acid/ticarcillin for infections in patients complicated with hematological disorders].

We evaluated clinical effects and toxicities of a combination of fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) for treatment of infections complicated with hematological disorders in 61 patients. Fifty-eight patients were evaluable, including 40 with acute leukemia, 13 with malignant lymphoma and 5 with other hematological disorders. Clinical efficacies were excellent in 21 cases, good in 13 cases, fair in 2 cases and poor in 22 cases. The efficacy rate was 58.6% (34 cases/58 cases). This treatment was also effective in 12 of 20 cases in which granulocyte counts were less than 500/microliters through the course of administration. No subjective side effects were observed. Abnormal values in laboratory tests were noted in 1 case. Mild elevations of GOT and GPT were observed. Thus, the combination of FOM and CVA/TIPC is an effective and safe regimen for the treatment of infections in patients complicated with hematological disorders.

Adolescent↗
PubMed1994

[Staggered intensive chemotherapy using arbekacin, fosfomycin and ceftazidime on polymicrobial infections involving MRSA].

Bacteriological and clinical studies were carried out on staggered intensive chemotherapy regimen for methicillin-resistant Staphylococcus aureus (MRSA) infections combined with Gram-negative opportunistic pathogens as polymicrobial infections. The regimen consisted of administering ceftazidime (CAZ) 30 minutes after infusion of arbekacin (ABK) and a bolus injection of fosfomycin (FOM). The combination of these drugs strongly inhibited the growth of MRSA and Pseudomonas aeruginosa. By this combination treatment, both of MRSA and P. aeruginosa in mixed culture became more susceptible to killing by macrophages. We evaluated the clinical efficacy and safety of combination of ABK, FOM and CAZ in the treatment of 15 patients with MRSA infections. The total efficacy rate was 80.0% and the bacterial eradication rate of MRSA was 60.0%. It is considered that staggered intensive chemotherapy with ABK, FOM and CAZ is useful for such polymicrobial infections involving MRSA.

Aged↗
PubMed1975

[Bacteriological studies on fosfomycin. Antibacterial activity in vitro and in vivo (author's transl)].

We have examined the antibacterial activity of the new antibiotic, fosfomycin (FOM) in vitro and in vivo. The following results were obtained. 1. FOM showed a broad antibacterial spectrum. 2. The antibacterial activity of FOM was enhanced in the medium at pH 6 and pH 7, and was also influenced by the addition of rabbit serum, calf serum, glucose-6-phosphate or defibrilated sheep blood to the growth medium, and by the size of inoculum. 3 FOM showed especially strong bactericidal action upon the bacteria at the logarithmic phase. 4. FOM showed remarkable therapeutic effect against most strains of gram-positive and gram-negative bacteria tested in experimental infections of mice. 5. The therapeutic effect of FOM was especially remarkable for infection with Salmonella. 6. The therapeutic effect of FOM was more potent than the other drugs tested against infection of Pseudomonas aeruginosa. 7. It seems that FOM is more active in vivo than in vitro with respect to antibacterial activity.

Animals↗
PubMed1994

[Studies on the combined effect of fosfomycin with sulbactam/cefoperazone on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa].

We studied the combined effect of fosfomycin (FOM) with sulbactam/cefoperazone (SBT/CPZ) on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA, 246 strains) and Pseudomonas aeruginosa (190 strains) in vitro. In ratio of mixed serum concentration of antibiotics at three hours after intravenous administration, the combination of FOM with SBT/CPZ and alone of arbekacin showed over 90% in cumulative percentage of MIC against MRSA and P. aeruginosa. The effect of the combination of FOM and SBT/CPZ was observed in MRSA strains of > 16 micrograms/ml of SBT/CPZ MIC and > 256 micrograms/ml FOM MIC. As well as in P. aeruginosa strains, the effect of the combination of FOM and SBT/CPZ was observed in strains of > 16 micrograms/ml of SBT/CPZ MIC and < 256 micrograms/ml FOM MIC, but it was not remarkable in strains of > 256 micrograms/ml FOM MIC. These results suggests that the combination treatment of FOM and SBT/CPZ may be effective for mixed infection of MRSA and P. aeruginosa.

Cefoperazone↗