cefoxitin and Kidney-Diseases

The cephalosporin antibiotics have been employed with increasing frequency since their introduction into clinical practice in the early 1960s. With the exception of cephaloridine, cephalosporin compounds are not associated with the production of significant untoward effects. The availability of newer cephalosporins, both oral and parenteral, with enhanced antibacterial activity, has expanded the clinical indications for administration of these antibiotics.

Topics: Cefaclor; Cefamandole; Cefatrizine; Cefazolin; Cefoxitin; Cefuroxime; Cephacetrile; Cephalexin; Cephaloglycin; Cephaloridine; Cephalosporins; Cephalothin; Cephapirin; Drug Hypersensitivity; Humans; Kidney Diseases

Topics: Bacteria; Bile; Cefamandole; Cefoxitin; Cephalosporins; Humans; Kidney Diseases; Kinetics

Topics: Absorption; Animals; Biological Availability; Cefoxitin; Cephalosporins; Chemical Phenomena; Chemistry; Drug Interactions; Haplorhini; Humans; Kidney Diseases; Kinetics; Mice; Probenecid; Protein Binding; Rats

Topics: Cefoxitin; Cephalosporins; Clinical Trials as Topic; Humans; Kidney Diseases; Urinary Tract Infections

Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.

Topics: Animals; Biotin; Blood Urea Nitrogen; Captopril; Cefoxitin; Cephalexin; Cisplatin; Creatinine; Drug Interactions; Female; Glomerular Filtration Rate; Kidney; Kidney Diseases; Male; Mice; Mice, Inbred DBA; Organ Size; Penicillin G; Rats; Rats, Inbred Strains; Sulfathiazoles; Sulfur; Thiamine

The pharmacokinetics of cefoxitin was studied in 14 patients with a pleural effusion, 8 of which had normal renal function and the other 6 varying degrees of renal impairment. All patients received a single dose of 30 mg/kg i.v. bolus of the antibiotic. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The serum elimination half-life of the antibiotic in the group of patients with normal renal function had a mean value of 1.35 +/- 0.56 h while that of the second group ranged between 2.00 h and 40.79 h, according to the deterioration in renal function. The disappearance half-life of cefoxitin from pleural fluid increased parallel to the degree of renal impairment, reaching a value of 30.09 h for a creatinine clearance (Ccr) of 5.8 ml/min. From the data obtained, dosage regimens were programmed according to the degree of renal function with the aim of achieving safe and efficient cefoxitin levels in both biological fluids.

Topics: Adult; Aged; Aged, 80 and over; Cefoxitin; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Models, Biological; Pleural Effusion

Mice inoculated intravenously with Mycobacterium fortuitum 18367 were treated subcutaneously with cefoxitin or cefotetan once daily for 4 weeks, beginning 24 h after challenge. Both drugs suppressed spinning disease, and both reduced the severity of renal lesions and the number of organisms in the kidneys and liver but not in the lungs or spleen. These therapeutic effects were dose-dependent.

Topics: Animals; Cefotetan; Cefoxitin; Cephamycins; Female; Kidney Diseases; Mice; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous

The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml (16.7 to 25.1 mmol/liter) and glomerular filtration rates 25 to 35% of normal, and "severe," with blood urea concentrations greater than 150 mg/100 ml (greater than 25.1 mmol/liter) and glomerular filtration rates 10 to 20% of normal. Sham-operated animals were used as controls. Three dose schedules of cefoxitin were administered to these controls--500, 1,000, and 2,500 mg/kg per day administered as a divided dose for 5 days. Doses given to the moderately and severely uremic animals were adjusted so that serum levels of cefoxitin were similar to those attained in the sham-operated control animals. Concentrations of urea and creatinine in blood, glomerular filtration rates, and the urinary concentrating capacities of the experimental animals were monitored before and after cefoxitin treatment. There was no evidence of nephrotoxicity in even the most challenging experiment, in which blood serum levels of cefoxitin reached 2,000 microgram/ml in animals, with 15% renal function. These findings support available clinical data, suggesting that cefoxitin can be administered safely to patients with compromised renal function.

Topics: Animals; Cefoxitin; Female; Glomerular Filtration Rate; Kidney; Kidney Diseases; Male; Nephrectomy; Rats; Uremia

The pharmacokinetics of cefoxitin were examined in 4 healthy volunteers, 6 patients with normal renal function (inulin clearance, greater than 80 ml/min per 1.73 m2), and 35 patients with various degrees of renal insufficiency (inulin clearance, 80 to less than 5 ml/min per 1.73 m2). A single dose of 30 mg of cefoxitin per kg of body weight was injected intravenously over 3 min. Antibiotic concentrations in plasma were determined by the agar diffusion technique. The cefoxitin half-life increased progressively from 39 min in subjects with normal renal function to 23.5 h in oligoanuric patients. Correspondingly, total body clearance decreased from 340 to 13 ml/min per 1.73 m2. In addition to the study of cefoxitin kinetics, in 29 of the 41 patients, three different renal clearance tests were performed (inulin, p-aminohippurate, and creatinine clearances). Of these, p-aminohippurate clearance showed the best correlation with the elimination rate constant beta as well as total body clearance of cefoxitin; but with respect to beta, the differences between the p-aminohippurate and creatinine clearances were quantitatively negligible. Therefore, even in substances which are eliminated predominantly by active tubular secretion, creatinine clearance could be recommended for dosage adjustments.

Topics: Adolescent; Adult; Aged; Cefoxitin; Female; Humans; Injections, Intravenous; Kidney Diseases; Kinetics; Male; Middle Aged

Topics: Adult; Aged; Bacterial Infections; Cefoxitin; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Urinary Tract Infections

A case of renal infection with Mycobacterium chelonei is described. The infection probably occurred via haematogenous spread from an infected arteriovenous shunt in a uraemic woman. Prolonged treatment with intravenous cefoxitin combined with oral erythromycin and rifampicin eradicated the organism from the urine. Although renal function stabilised for one year, gradual deterioration to end-stage renal failure occurred.

Topics: Adult; Cefoxitin; Drug Therapy, Combination; Erythromycin; Female; Humans; Kidney Diseases; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Rifampin

Topics: Aged; Cefoxitin; Female; Humans; Kidney Diseases; Male; Middle Aged

The pharmacokinetics of cefoxitin have been determined after a single i.v. injection of 15 mg/kg body weight in 10 patients with normal renal function and 20 patients with varying degrees of renal impairment. The kinetics of the antibiotic followed an open two-compartment model. In patients with normal renal function the following pharmacokinetic parameters were found: alpha = 8.66 h-1 beta = 1.21 h-1 K12 = 3.47 h-1 K21 = 3.17 h-1 K13 = 3.15 h-1 Vc = 4.24 l. Vp = 4.87 l. Vdss = 9.11 l. In the patients with renal impairment there was a significant decrease in alpha, beta, K12, K21 and K13, and an increase in the apparent volume of distribution. The degree of plasma protein binding in patients with normal renal function was 73.6% and this was diminished in patients with renal impairment. A linear relationship between K13 of cefoxitin and creatinine clearance was demonstrated. The dosage regimen for patients with renal impairment should be adjusted by modifying the dosage interval whilst maintaining the amount administered.

Topics: Adolescent; Adult; Aged; Blood Proteins; Cefoxitin; Creatinine; Female; Humans; Injections, Intravenous; Kidney Diseases; Kinetics; Male; Middle Aged; Protein Binding; Urea

Cefoxitin, a new semi-synthetic cephamycin, has been studied in the treatment of patients with a variety of infections. Included have been a number of patients who have impaired renal function. The drug proved to be effective in treating gram-positive, gram-negative and anaerobic infections, and can be given by the intravenous or intramuscular route. Adverse effects occurred in six of 34 patients. These were not usually serious. The presence of renal failure did not interfere significantly with the efficacy of cefoxitin in treating urinary tract infection and it is considered, in contrast to the aminoglycosides, that this preparation can be used successfully without the necessity for measuring blood or urine levels in patients with reduced or unknown renal function.

Topics: Adult; Aged; Bacterial Infections; Cefoxitin; Cephalosporins; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Kidney Diseases; Male; Middle Aged