fosfomycin and Body-Weight

Two trials were made to assess the efficacy of including calcium fosfomycin in the drinking water or in the feed for four days to control the adverse effects of experimentally induced colibacillosis in broiler chickens. Trial 1 had five groups of 15 chicks each: one group of negative controls; an untreated infected control group and three groups treated with 50, 100 or 200 ppm of calcium fosfomycin in drinking water. Trial 2 had the same groups but the antibiotic was incorporated into the feed. The chickens were infected via their air sacs with 1.7 x 10(8) - 3.6 x 10(8) CFU/chick of Escherichia coli O78:K80. The morbidity and mortality, a score for the gross lesions, the relative weight of the liver and spleen, performance and re-isolation of the challenge bacteria were recorded. Calcium fosfomycin in the drinking water controlled the colibacillosis, particularly in the group treated with 200 ppm. However, no effect of the antibiotic was seen when calcium fosfomycin was incorporated into the feed, the mortality, score of lesions and re-isolation of E. coli from the organs in the three treated groups being similar to those for the infected unmedicated group. The amount of antibiotic ingested in trial I was three times more than in trial 2. These results suggest that calcium fosfomycin is best used in the drinking water for the treatment of colibacillosis.

Topics: Administration, Oral; Animal Feed; Animals; Anti-Bacterial Agents; Body Weight; Chickens; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Liver; Male; Myocardium; Poultry Diseases; Survival Rate; Water

One hundred and twenty 1-day-old broiler chickens were divided into four groups: group I unmedicated and orally challenged with 1.5 x 10(8) cfu of Salmonella enteritidis phage type 4; group F infected and treated with 300 ppm of fosfomycin in their drinking water; group CF uninfected and treated, and group C maintained as a control group. Their performance, clinical signs, S. enteritidis PT4 reisolation and biochemistry variables were compared. Group F showed fewer symptoms and gross lesions than those from group 1. Fosfomycin treatment at 300 ppm improved body weight at 7 days of age by 42.3%. S. enteritidis PT4 reisolation in group I was higher than in the treated group, but total decontamination of challenged birds was not achieved. There was an increase in the levels of total protein and globulins in group I but not in the treated group. Fosfomycin caused no adverse effects on chickens from group CF, assessed by performance and biochemical variables. The results indicate that fosfomycin could be used in the treatment of S. enteritidis PT4 experimental infection.

Topics: Animals; Anti-Bacterial Agents; Bacteriophage Typing; Body Weight; Cecum; Chickens; Colony Count, Microbial; Fosfomycin; Liver; Poultry Diseases; Salmonella enteritidis; Salmonella Infections, Animal; Salmonella Phages; Spleen; Time Factors

The nephrotoxicity of vancomycin and cisplatin and the protective effects of fosfomycin and imipenem-cilastatin on renal function have been studied in rats. The renal clearance of vancomycin after the induction of renal dysfunction was also evaluated by calculating the glomerular filtration rate (GFR) and its secretory clearance. Plasma concentrations of creatinine and urea nitrogen increased dose-dependently after vancomycin injection. No such increases were observed after co-treatment with fosfomycin or imipenem-cilastatin. Changes of N-acetyl-beta-D-glucosaminidase activity in the urine of vancomycin-treated rats were not remarkable compared with those in cisplatin-treated animals. The reduced renal clearance of vancomycin in rats with acute renal failure induced by vancomycin was because of a decrease in both GFR and secretory clearance. However, the changes in GFR and secretory clearance were not proportional-the change in GFR was more pronounced than that of secretory clearance in the experimental groups. In addition, the renal clearance of vancomycin was maintained at the control level after co-administration of fosfomycin or imipenem-cilastatin with vancomycin. These results suggest that vancomycin impairs glomerular filtration more markedly than renal tubular function as compared with cisplatin. Co-administration with fosfomycin or imipenem-cilastatin confers significant protection against the nephrotoxic effects of vancomycin.

Topics: Acetylglucosaminidase; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Body Weight; Cilastatin; Cilastatin, Imipenem Drug Combination; Cisplatin; Creatinine; Dose-Response Relationship, Drug; Drug Combinations; Fosfomycin; Glomerular Filtration Rate; Imipenem; Kidney; Male; Nitrogen; Rats; Rats, Wistar; Vancomycin; Weight Gain

The protective effects of elastase (Ela) and fosfomycin against renal toxicity of cis-diamminedichloroplatinum (II) (CDDP) were evaluated in an experimental study using rats. When Ela was used concomitantly with CDDP, the elevation of urinary N-acetyl-beta-D-glucosaminidase levels in the early phase and the sharp fall in these levels in the latter phase were prevented. It was also found that the blood urea nitrogen levels and serum creatinine levels were significantly lowered. Histologically, atrophic and necrotic changes in the tubular epithelium were prevented. The total serum platinum levels showed no change with the addition of Ela; however, the platinum levels in the renal tissues were significantly reduced. These results suggested that Ela is effective against platinum deposits in the renal tissues, particularly in the tubular epithelium, thus protecting the kidneys. On the other hand, fosfomycin demonstrated no such positive results suggestive of a protective effect on the renal function parameters or during histological observation.

Topics: Acetylglucosaminidase; Animals; Blood Urea Nitrogen; Body Weight; Cisplatin; Creatinine; Female; Fosfomycin; Kidney Diseases; Pancreatic Elastase; Rats; Rats, Inbred F344

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.

Topics: Alanine Transaminase; Animals; Anti-Bacterial Agents; Aspartate Aminotransferases; Blood Cell Count; Body Weight; Cisplatin; Fosfomycin; Kidney; Kidney Tubules; Male; Rats; Rats, Inbred F344; Specific Pathogen-Free Organisms

The protective effect of fosfomycin against cisplatin-induced ototoxicity was studied in rats. Sixty-four Fischer rats were injected intravenously with daily doses of 1, 2, 5, and 10 mg/kg of cisplatin with or without 300 mg/kg of fosfomycin for a varying period from 1 to 10 days. The total dose of 10 mg/kg of cisplatin was given equally in all animals. Inner ear damage appeared to be more reduced histopathologically in animals given both cisplatin and fosfomycin than in animals given cisplatin alone. Similarly, renal damage appeared to be reduced histopathologically and functionally by the combined administration of cisplatin and fosfomycin.

Topics: Animals; Body Weight; Cisplatin; Cochlea; Fosfomycin; Hair Cells, Auditory; Kidney Diseases; Labyrinth Diseases; Male; Rats

The protective effect of fosfomycin against cisplatin-induced toxicities was studied in rats. A total of 64 Fischer rats were injected intravenously with daily doses of 1, 2, 5 and 10 mg/kg of cisplatin with or without 300 mg/kg of fosfomycin for a period varying from 1 to 10 days. The same total dose of 10 mg/kg of cisplatin was given to all animals. Cisplatin-induced toxic side-effects of body weight loss, nephrotoxicity and ototoxicity were significantly reduced functionally or histopathologically by the combined administration of cisplatin and fosfomycin. A comparison of different dosage schedules with a total dose of 10 mg/kg of cisplatin showed that a higher daily dose for a shorter time period produced more marked toxicities.

Topics: Alanine Transaminase; Animals; Anti-Bacterial Agents; Aspartate Aminotransferases; Blood Proteins; Blood Urea Nitrogen; Body Weight; Cisplatin; Creatinine; Dose-Response Relationship, Drug; Ear, Middle; Fosfomycin; Kidney; Male; Rats; Rats, Inbred F344

FOM-Na solution in distilled water for injection, J.P., with its pH adjusted to 7.0 +/- 0.2 with diluted hydrochloric acid, was administered to rats and rabbits for subacute toxicity test. The results revealed the following: 1. It was intraperitoneally administered to Wistar rats each weighing 100 +/- 10 g at their age of 5 weeks, and intravenously into auricular veins of male albino rabbits each weighing about 3 kg, for 35 successive days except Sundays through one administration per day. There was no death in rats of both sexes with the doses less than 1,000 mg/kg, while 3/10 males and 5/10 females died with the dose of 2,000 mg/kg. In terms of general conditions, both stretched physical position and vocalization were noted, which were presumed to be attributable to the stimuli of the administration. In the postmortem examination mutual adhesion of organs in the peritoneum was noted, while in the lightmicroscopic examinations histological proliferation and adhesion were found out in the hepatic capsules or serous membrane of the intestine etc., but no abnormalities were detected in the other organs. In the mean body weights, there were no significant differences between the control group and the groups of males with doses less than 500 mg/kg and females with doses less than 1,000 mg/kg whereas in the groups of males with doses more than 1,000 mg/kg and the females with a dose of 2,000 mg/kg, a trend of reduced weight gain was noted in comparison with the control group. The feed intake also was reduced as the dose was elevated. In terms of the male group hematology, the In. P increased with doses higher than 250 mg/kg, while BUN was reduced in the groups with a dose of 250 mg/kg and doses higher than 1,000 mg/kg, and Na was reduced in the groups with doses from 125 up to 500 mg/kg. In the female groups, the loss of Hgb and rise in the Cl were noted in the doses higher than 500 mg/kg while the loss of WBC was noted in almost all the treated groups. However, none of these changes was suggestive of specific abnormalities when compared with the photomicroscopic findings and our hematological background data. 2. There were no significant changes in the general conditions of any group of rabbits. Their mean body weights and their mean feed intakes proceeded almost similarly with those of the control group. In the hematological and histopathological tests also, no specific abnormal finding was experienced, which were deemed to be attributable to the administrat

Topics: Animals; Anti-Bacterial Agents; Body Weight; Eating; Female; Fosfomycin; Intestines; Liver; Male; Organ Size; Rabbits; Rats; Sodium; Urine

Topics: Animals; Anti-Bacterial Agents; Body Weight; Dogs; Drinking; Eating; Female; Fosfomycin; Kidney; Liver; Male; Organ Size; Rats; Sodium; Urine

The teratogenicity study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats and New Zealand white rabbits. Rats were treated intraperitoneally at dose levels of 125, 250, 750 and 1,500 mg/kg/day from day 7 to day 17 of gestation, and rabbits were treated intravenously at dose levels of 80, 100, 200, 400 and 800 mg/kg/day from day 6 to day 18 of gestation. In the case of rats, two-thirds of pregnant mothers in each group was sacrificed on day 20 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. In the case of rabbits, all pregnant mothers were sacrificed on day 29 of gestation and their fetuses were examined. Body weight of rat mothers during gestation were decreased and 4 mothers were dead until day 20 of gestation in the maximum dose. In this dose, foetal toxicity was recognized too. However, external, visceral and skeletal anomalies related with FOM-Na treatment were not observed in all groups. No effect on development of offsprings was observed. No effect of treatment of FOM-Na to rabbits was found except foetal body weight was slightly decreased in the maximum dose.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Body Weight; Female; Fetus; Fosfomycin; Pregnancy; Rabbits; Rats; Teratogens

Topics: Animals; Anti-Bacterial Agents; Body Weight; Calcium; Dogs; Ear, Inner; Electroretinography; Eye; Female; Fosfomycin; Fundus Oculi; Guinea Pigs; Male; Organ of Corti; Rabbits; Reflex; Retina; Sodium; Succinate Dehydrogenase