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PubMed1990

Antibacterial activity of teicoplanin and vancomycin in combination with rifampicin, fusidic acid or fosfomycin against staphylococci on vein catheters.

The bactericidal activities of teicoplanin and vancomycin, as single agents or combined with fosfomycin, fusidic acid or rifampicin, were investigated in an in vitro study involving 20 strains of Staphylococcus epidermidis isolated from infected vein catheters. Greater antibacterial effects were exhibited against certain bacterial strains by the combined antibiotics, rather than by teicoplanin or vancomycin alone. The vancomycin-fusidic acid combination showed less of a bactericidal effect than all other combinations. The strongest bactericidal effects on all strains were exhibited by the combinations of teicoplanin and vancomycin with rifampicin. These results may be important for the antibiotic treatment of staphylococcal infections of vein catheters, if immediate removal of an infected catheter is not possible.

Catheters, Indwelling↗
PubMed1990

[Evaluation of effectiveness of rokitamycin dry syrup in acute enteritis in pediatrics. A comparative study on rokitamycin and fosfomycin dry syrups].

Because Campylobacter jejuni is most frequently identified as a causative organism of bacterial enteritis in pediatrics, a study was done to evaluate the clinical efficacy against Campylobacter enteritis and the safety of a macrolide antibiotic, rokitamycin (RKM). In case of acute enteritis, RKM was used in a form of dry syrup at a dose level of approximately 30 mg (in potency)/kg body weight and its efficacy and safety were compared to those of fosfomycin (FOM) dry syrup which is currently in use at a dose level of 60 mg (in potency)/kg. Both drugs were administered, as a rule, in 3 divided daily dose (RKM before meal and FOM after meal) for 5 consecutive days. Comparisons of the drugs were made using a well-controlled method. Obtained results are summarized as follows. 1. No significant differences in background factors of the 2 drug groups were apparent, hence it was deemed that no obstacles existed in making comparative studies of the 2 groups with regard to their efficacies and safeties. 2. Overall efficacy rate against Campylobacter enteritis was 100% in the RKM group with a rate of excellent efficacy of 91.3% and the former was 94.4% in the FOM group with the latter of 72.2%. Though the RKM group apparently showed higher rates by 5.6% and 19.1%, respectively, for overall and excellent efficacies, they were not statistically significant as both drugs showed good efficacies. When acute cases of enteritis other than those caused by Campylobacter were included in the analysis, overall efficacy rates and rates of excellent efficacy were, respectively, 97.6% and 85.7% for the RKM group and 88.6% and 68.2% for the FOM group, thus RKM showed higher efficacy rates by 9.0% and 17.5%, respectively. These differences were deemed statistically significant using the U-test. 3. Numbers of days required for most of the major symptoms to subside were 3 days or less for the group for which RKM was used against Campylobacter enteritis. Similar results were observed for the FOM group also. In cases of acute enteritis due to other causes than Campylobacter, slower recoveries were observed for both the RKM and the FOM groups than in Campylobacter enteritis cases, with the latter group slower than the former. In cases of puruloid stool, the recovery in the RKM group was significantly faster by U-test than the FOM group, and a similar trend was observed overall. 4. Bacteriologically, the eradication rate of Campylobacter in the RKM group was very good at 91.3% with the FOM group showing a rate of 78.9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1990

[Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. I. Effect of sulbactam against beta-lactams resistant strains and in vitro combined effect of sulbactam/cefoperazone with each of piperacillin, latamoxef, ceftazidime, fosfomycin and doxycycline].

We evaluated relationships between production of beta-lactamase and their resistances to beta-lactams, effect of sulbactam (SBT), a beta-lactamase inhibitor, against beta-lactam resistant strains, and combined effect of sulbactam/cefoperazone (SBT/CPZ) with other antibiotics against multi-resistant strains. Through these studies, we obtained the following results. 1. Most of the strains resistant to beta-lactams were beta-lactamase producers. 2. Relationships between the production of beta-lactamase and their resistances to beta-lactams indicate that their resistances generally were the highest in producers of both penicillinase (PCase) and cephalosporinase (CEPase), moderate in producers of either PCase or CEPase, and the lowest in beta-lactamase non-producers. Most of highly-resistant strains of MRSA appeared to be beta-lactamase non-producers though some exceptions were observed among methicillin-resistant Staphylococcus aureus (MRSA), Serratia marcescens and Pseudomonas aeruginosa. 3. SBT showed good effect against PCase producers, moderate effect against producers of both PCase and CEPase, little effect against CEPase producers, and no effect against beta-lactamase non-producers. 4. Results of combined effect of SBT/CPZ with other antibiotics indicated that good synergism was obtained by combining SBT/CPZ with fosfomycin (FOM) or piperacillin against multi-resistant strains of Proteus spp., Enterobacter cloacae, and S. marcescens, by combining SBT/CPZ with ceftazidime (CAZ) or FOM in methicillin-sensitive S. aureus and by combining SBT/CPZ with CAZ in P. aeruginosa. 5. Better synergism was obtained with the higher concentrations of antibiotics.

Anti-Bacterial Agents↗
PubMed1990

[Clinical evaluation of the combination of carumonam and fosfomycin in the treatment of complicated urinary tract infection].

Carumonam (CRMN), the first monobactam antibiotic in Japan, has excellent activity against gram-negative bacteria and is useful in the treatment of urinary tract infections. However, it may be insufficient in the treatment of complicated urinary tract infections because of the increase in isolation of gram-positive bacteria, and it may be necessary to co-administer antibiotics active against gram-positive organisms to achieve a broader spectrum of coverage in connection with severe infections. The combination of CRMN and fosfomycin (FOM) was evaluated for its effectiveness and safety at the Department of Urology, Yamagata University Hospital and 7 affiliated hospitals. Clinical efficacy was assessed on 64 patients with complicated urinary tract infection according to the Criteria for Clinical Evaluation of Antimicrobial Agents in UTI (3rd. ed.) recommended by the Japan UTI Committee. Clinical efficacy was evaluated as excellent in 16, moderate in 32, poor in 16, with an overall clinical effectiveness rate of 75.0%, which is superior compared with CRMN alone. Of the total of 92 bacterial strains isolated, 66 (71.7%) were eradicated. Subjective adverse reaction was seen in 1 patient (1.4%), as nausea and anorexia. Slight increases in serum GOT and GPT ware recorded in 5 patients (7.1%). These findings disappeared after the termination of administration without treatment. The combination of CRMN and FOM might therefore be useful in the treatment of complicated urinary tract infections.

Adult↗
PubMed1985

Chromosomal localization of resistance to fosfomycin and aminocyclitol antibiotics in hospital strains of Staphylococcus aureus.

The chromosomal localization of fosfomycin resistance genes in three hospital Staphylococcus aureus strains and in the standard strain NCTC 8507 was shown. Moreover, the chromosomal locus of the gene determining resistance to three aminocyclitol antibiotics: gentamycin, kanamycin and tobramycin in the one of hospital strains was determined. The possibility of transducing this resistance and the absence of plasmid DNA in the obtained transductants, suggest transposomal nature of the gene determining gentamycin, kanamycin and tobramycin resistance in the investigated strain.

Anti-Bacterial Agents↗
PubMed1989

[Use of fosfomycin tablets in the treatment of purulent skin diseases].

Fourteen patients with purulent skin diseases were treated orally with fosfomycin (FOM) 1.5-3 g in the tablet form for 1 week to determine its efficacy and safety. The results obtained are summarized as follows. 1. The clinical efficacy rate was 71.4%. A bacteriological eradication rate of 71.4% was obtained. 2. As adverse reactions 3 patients experienced diarrhea and abdominal pain. But in all of these patients, symptoms were relieved with a reduction in dosage. 3. Taking the efficacy and the safety into account, utility rate was assessed to be 71.4%. From these results it is considered that FOM tablets are useful equally to conventional FOM capsules.

Adolescent↗
PubMed1989

[Prophylactic effect of fosfomycin on CDDP nephrotoxicity].

From 1985 to 1986, cisplatin (CDDP) therapy was performed 61 times in 24 patients with urological cancer. Thirty nine courses used fosfomycin (FOM) 4 g/day from the day before CDDP administration to the last dose of CDDP, and we statistically evaluated the prophylactic effect of FOM on CDDP nephrotoxicity using urinary NAG and FENa as parameters (t-test). In the 1-day CDDP group (CDDP 60-70 mg/m2 x 1 day) with FOM a peak NAG was seen on the 1st day but no significant NAG change, FENa has a peak on the 1st day, no significant increase between the previous and the 1st day, but a significant decrease was seen between the 3rd and the 5th day (p less than 0.05). In the 5-day CDDP group (CDDP 20 mg/m2 x 5 day) NAG reached a peak level on the 5th day with FOM, showed significant increase (p less than 0.05; between the previous and the 5th day) and decrease (p less than 0.01; between the 6th and the 14th), compared to those without FOM. FENa change tended to be similar, showing a significant increase, (p less than 0.05; between the 2nd and 4th) and decrease (p less than 0.05; between the 4th and 7th) with FOM but no significant change without FOM. NAG changes with FOM were classified by pre-CDDP dose creatinine clearance (Ccr, ml/min) into 3 groups (under 50, 50-100, over 100). In the 1-day CDDP group with any Ccr no significant NAG change obtained, but, in the 5-day CDDP group with 50-100 Ccr seen a NAG peak on the 6th day, significant increase (p less than 0.05; between the previous and the 6th) and decrease (p less than 0.05; between 6th and 12th). With over 100 Ccr NAG has 4th day peak, significant increase (p less than 0.05; between the previous and the 4th), and decrease (p less than 0.05; between 4th and 8th). A prophylactic effect of FOM on CDDP nephrotoxicity was found in the 5-day CDDP group not in the 1-day CDDP group, using urinary NAG and FENa. PVB and single CDDP regimen (5 day CDDP group) with FOM can be performed safely, if the pre-CDDP dose Ccr is over 50.

Acetylglucosaminidase↗
PubMed1989

[A successful treatment of an infective endocarditis caused by methicillin-resistant Staphylococcus aureus with a combination of cefmetazole with fosfomycin].

A case of infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) was successfully treated with a combination therapy with cefmetazole (CMZ) and fosfomycin (FOM). A 55 year old man was admitted to the Keio Hospital because of fever of unknown origin. Physical examination revealed blood pressure of 132/62 mmHg, heart rate of 118/min and body temperature of 39.8 degrees C. Diastolic regurgitant murmur (Levine II/VI) was heard at the left sternal border on the third intercostal space. Chest X-ray showed mild cardiomegaly. Two dimensional echocardiography and color flow mapping demonstrated mildly dilated and hyperkinetic left ventricle, redundant aortic valve, giant vegetation from the aortic valve and severe aortic regurgitation. MRSA was isolated from the blood of this patient. Bacteriostatic synergism between CMZ and FOM against S. aureus isolated from the blood of this patient was detected both by the Kirby-Bauer method and by the checker-board method. The combination therapy with CMZ and FOM cleared the clinical symptoms and normalized the inflammatory reactions. No relapse was observed for at least 10 months. We concluded that the combination therapy with CMZ and FOM was invaluable for the treatment of infections endocarditis by MRSA.

Cefmetazole↗
PubMed1986

[Urinary NAG and gamma-GTP activities as indicators of CDDP renal toxicity: effect of fosfomycin on CDDP renal toxicity].

Using urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities as the indicator of renal toxicity, the effect of fosfomycin (FOM) on cisdichlorodiamineplatinum (CDDP) renal toxicity was studied in 10 patients with urological malignant tumors. Regimen of chemotherapy was daily 20 mg of CDDP and 800 mg of administered by drip infusion for 5 days and 40 mg of adriamycin injected in one-push on day 1. FOM was not used at 1st cure. At 2nd cure, daily 2 g X 2 of FOM was administered for eleven days from the day before CDDP administration. Urinary NAG and gamma-GTP were measured for eleven days continuously in both 1st and 2nd cure. Effect of FOM on CDDP renal toxicity was discussed by comparison of the urinary NAG and gamma-GTP activities between 1st and 2nd cure. The results showed that urinary NAG and gamma-GTP activities following CDDP administration were deeply influenced by these activities before CDDP administration and the combined therapy of FOM had tendency to reduce CDDP renal toxicity when urinary NAG and gamma-GTP activities before CDDP administration were in the normal range.

Acetylglucosaminidase↗
PubMed1987

[Treatment with a cefotaxime-fosfomycin combination of staphylococcal or enterobacterial meningitis in adults].

Thirty-two patients were included in this trial: 22 with staphylococcal meningitis (including 5 methicillin-resistant) and 10 with enterobacterial meningitis. Mean duration of treatment was 14.5 and 15.9 days respectively. The combination was synergistic in vitro against 10 of the 12 strains of Staphylococcus and 5 of the 6 strains of Enterobacteriaceae studied. Bacteriological sterilization occurred in all cases which could be evaluated, and clinical recovery was obtained in 95.2% of patients with staphylococcal meningitis (4 unrelated deaths) and 100% of patients with enterobacterial meningitis (2 deaths). Bactericidal power of the cerebro-spinal fluid, often less than 1/8, was not correlated with effectiveness against Staphylococci. Mean CSF concentrations of cefotaxime, desacetylcefotaxime and fosfomycin on the 2nd and 15th days of treatment were 4, 3.5 and 39.8 mg/l and 2.2, 2.1 and 28.0 mg/l, respectively. Clinical and biological acceptability was satisfactory. There were three cases of superinfection or colonization, by Pseudomonas and Enterobacter.

Adolescent↗
PubMed1988

[A clinical evaluation of the protective effect of fosfomycin (FOM) against the cis-diamminedichloroplatinum (CDDP)-induced nephrotoxicity].

The protective effect of fosfomycin (FOM) against the cis-diamminedichloroplatinum (CDDP)-induced nephrotoxicity was evaluated clinically. Thirty-six cases suffering from urogenital cancers were subjected to CDDP therapy in which 50 mg of CDDP was administered on Day 0, with one week regarded as one course of treatment. The daily excretions of urinary N-acetyl-beta-D-glucosaminidase (NAG) and beta 2 microglobulin (beta 2 MG) levels were measured on Day 1, 3 and 5. Creatinine clearance (Ccr) was also determined on Day 1. CDDP was administered once a week for 6 weeks. Group A consisted of 18 patients who were treated with CDDP alone every alternate odd week. In the other even weeks, they received both FOM 4.0 g and CDDP on Day 0 and FOM 4.0 g on Day 1 and 2. The maximum values together with the total amounts of urinary NAG and urinary beta 2 MG were measured. Group B, also consisting of 18 cases, was divided into two sub-groups, one which was always administered with CDDP alone and another which received both FOM and CDDP. The maximum values of each course in urinary NAG and beta 2 MG were measured and Ccr level was also obtained. The changing pattern in the maximum values of two parameters and Ccr level between two subgroups was compared. Group A: The maximum values of urinary NAG excretions obtained in 4th week, using the combined therapy of CDDP and FOM was significantly lower than that obtained in the 3rd week.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1988

[Effect of fosfomycin on cellular immune reactions as affected by cyclophosphamide or corticosteroids].

The effect of fosfomycin (FM) has been examined on the "footpad swelling reaction" (FPSR) as a model for cellular immunity and on the course of experimental infection with FM resistant E. coli using normal and immunocompromised mice. FM given the day of immunization improved FPSR response progressively up to a dose of 30 mg/kg, higher doses had no effect. If FM was injected 1 or 3 days after immunization doses of 30 mg/kg induced a considerable stimulation, whereas higher doses were inhibitory. In contrast to the high dose of 50 mg of FM per kg, 30 mg/kg increased the stimulatory effect induced by small doses of CY and reduced the inhibitory effect of high CY doses. The depressing effect of hydrocortisone (HC) was also reduced by 30 mg/kg of FM, but not by the higher one. In experimental infection with E. coli, FM in doses of 30 mg/kg was more effective than the higher ones in reducing mortality rate. Comparable results were obtained with CY pretreated animals.

Animals↗
PubMed1988

[Effects of cefotaxime single administration and of cefotaxime + fosfomycin administration against respiratory tract infections].

Subjects in a cefotaxime (CTX) single administration group and in a CTX + fosfomycin (FOM) administration group were randomly selected for a comparative study on the utility of each product against respiratory tract infections. Overall improvement rates were 81.3% in 32 cases of the CTX single administration group, and 75.6% in 41 cases of the CTX + FOM concomitant administration group. No statistical difference was observed. As for adverse reactions and abnormal laboratory test results, pyrexia, thrombocytopenia, increases in GOT and GPT, and increase in GPT were observed in 4 cases of the CTX single administration group, while angialgia, increases in GOT and GPT (3 cases), and increases in BUN, (totalling 5), were observed in the CTX + FOM group. However, all the symptoms were transient, and none was serious in nature.

Adult↗
PubMed1986

[A clinical bacteriological efficacy study on a fosfomycin otic solution].

Fosfomycin (FOM) otic solution was administered to 587 patients with suppurative otitis media infections including 190 patients in the dose-establishment test, 126 patients in the open clinical trial and 271 patients in the double blind test. Various bacteria were detected in the 549 cases in which bacteriological investigation was possible. Main bacteria detected from the above cases were S. aureus (261 strains, 47.5%), P. aeruginosa (93 strains, 16.9%), coagulase negative Staphylococci (CNS) (89 strains, 16.2%), Providencia spp. (35 strains, 6.4%) and Proteus spp. (28 strains, 5.1%). Twenty-seven strains of anaerobic bacteria (4.9%) were also detected. The MIC of FOM, and the reference drug, chloramphenicol (CP), fradiomycin (FRM), cefmenoxime (CMX) and cephalexin (CEX), were determined up to a concentration of 800 micrograms/ml with inoculum sizes of 10(6) and 10(8) CFU/ml. About 30% of S. aureus was multi-drug resistant, including methicillin and cephems, but FOM showed excellent antibacterial activity against it. The FOM had superior antibacterial activity against P. aeruginosa to CP, FRM and CMX, and was also active against other bacteria. The antibacterial activity of FOM was inferior to other drugs against CNS, Enterobacter spp., P. putida and P. cepacia. The detection rate of these bacteria, however, was low and since their role as causative organisms is not well defined, the inferior activity of FOM has no effect on the bacteriological evaluation of FOM. Since the concentration in the tympanic cavity about 1 hour after the administration of 3% FOM solution was estimated to be 2,000 to 3,000 micrograms/ml, it could be presumed that bacteria inhibited by 800 micrograms/ml of FOM at an inoculum size of 10(8) CFU/ml would be eradicable. The low ototoxicity of FOM is likely due to its characteristic as an inhibitor of bacterial cell wall synthesis. From these results, 3% FOM otic solution may be considered as a remarkably useful topical preparation for the treatment of suppurative otitis media.

Administration, Topical↗
PubMed1988

[Preliminary study of the antagonistic effects between fosfomycin and beta-lactams on Pseudomonas aeruginosa observed on the antibiogram].

Antagonism patterns between beta-lactams (BL) and fosfomycin (FOS) were observed in antibiotic assay by agar diffusion method against the most of Pseudomonas aeruginosa strains. This antagonism was confirmed by antibiotic assays made on Mueller-Hinton agar containing subinhibiting concentrations of FOS. FOS + BL combinations, studied on the strain of Pseudomonas aeruginosa ATCC 27853 by means of checker board method, exhibit antagonism of FOS concentrations below 1 mg/l on ceftriaxone, piperacillin, ticarcillin and, less strongly, on imipenem. These results suggest that in vivo combination FOS + BL dosages must avoid low concentrations of FOS at the site of infection.

Anti-Bacterial Agents↗
PubMed1985

[Preventive effect of fosfomycin on the renal toxicity of cisplatin].

Cisplatin caused toxic effects in adult male rats, such as renal disturbance, decrease of platelet and WBC, increase of RBC, elevation of GPT and GOT activity, decrease of plasma protein and albumin, loss of body weight gain and lethal effect when treated intravenously with 1 mg/kg/day of cisplatin for 12 days. Fosfomycin (FOM) exerted preventive effects on the renal disturbance, the changes in blood cells and plasma protein and the lethal effect induced by cisplatin when treated with a combination of FOM and cisplatin. However, FOM did not prevent the cisplatin-induced effects on GPT and GOT activity and body weight gain. These results suggest that FOM prevents the cisplatin-induced disturbance of renal and hematopoietic function but does not the cisplatin-induced hepatic disturbance.

Alanine Transaminase↗
PubMed1988

[A clinical experience of fosfomycin tablet on cystitis].

Twenty-five adult female patients with acute cystitis were treated with 500 mg fosfomycin tablets, at a dose of 6 tablets per day for 7 days. The clinical effects were evaluated on the 3rd day, and the treatment was found effective in all the 18 patients evaluated. The cystitis recurred in 1 patient, one week after the treatment. As for the side effects, three patients complained gastric discomfort and/or diarrhea.

Acute Disease↗