cefamandole 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

A combination of tobramycin sulfate and cefamandole nafate was used as initial empiric therapy for the treatment of 71 evaluable febrile (temperature greater than 38.5 degrees C) episodes in 64 (neutrophils, less than 1,000/microL) adult patients with cancer and granulocytopenia. Carbenicillin sodium or ticarcillin disodium was substituted for cefamandole in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Twenty-nine episodes were randomized to receive tobramycin by continuous infusion, while 42 were randomized to receive tobramycin by interrupted infusion. Twenty-seven (79%) of the 34 documented infections responded to the initial empiric antibiotic combination, ten (83%) of 12 being given continuous infusion and 17 (77%) of 22 being given interrupted infusion of tobramycin. Nephrotoxic reaction occurred in 7% of patients treated with continuous infusion and 15% treated with interrupted infusion, mostly patients older than 60 years. Tobramycin, by either continuous or interrupted infusion, plus cefamandole is safe and efficacious empiric therapy for infections in patients with cancer and granulocytopenia.

Topics: Adult; Aged; Agranulocytosis; Bacterial Infections; Blood Urea Nitrogen; Cefamandole; Clostridium Infections; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Ear Diseases; Female; Humans; Infusions, Parenteral; Kidney Diseases; Male; Middle Aged; Neoplasms; Pseudomonas Infections; Tobramycin

Cefonicid (15 mg/kg) was administered intravenously at a constant rate of infusion over 15 min to 10 geriatric patients (mean age, 77 years) and to 4 young subjects (mean age, 35 years). Model-dependent and noncompartmental pharmacokinetic parameters were calculated and found to be congruous; noncompartmental data are reported. Significant differences in the values for area under the curve, mean residence time, total body clearance, and renal clearance were observed between the geriatric and young groups. Mean elimination half-life values were 9.59 and 4.88 h for the geriatric and young groups, respectively. Total body and renal clearances were inversely correlated to age and directly correlated to creatinine clearance. Free fraction was not correlated to albumin concentration but was correlated exponentially to total cefonicid concentration. Despite the prolonged half-life values observed in our geriatric patients, the difference in mean trough concentrations was slight. Daily administration of a 15-mg/kg dose should provide adequate concentrations in serum and should not produce appreciable accumulation in geriatric patients.

Topics: Adult; Aged; Aged, 80 and over; Aging; Cefamandole; Cefonicid; Creatinine; Humans; Kidney Diseases; Male

We gave 2-g intravenous doses of either cefamandole or moxalactam to 22 patients before vitrectomy. At 1 1/2 to 2 1/2 hours after administration, cefamandole vitreous concentrations varied from 0.36 to 2.05 micrograms/ml (mean, 0.94 micrograms/ml). Individual levels above the minimum inhibitory concentration of cefamandole for 90% (MIC90) of Staphylococcus aureus were found in five of 11 patients. Levels above the MIC90 for S. epidermidis were found in only two of 11 samples. Vitreous concentrations above the MIC90 of cefamandole for common gram-negative pathogens were found in only two patients. Moxalactam concentrations in the vitreous varied from 1.1 to 4 micrograms/ml 30 minutes to six hours after administration. These levels were not above moxalactam's MIC90 for S. aureus or S. epidermidis but were many times higher than the MIC90 of moxalactam for Enterobacteriaceae excluding Pseudomonas.

Topics: Cefamandole; Diabetic Retinopathy; Humans; Iris Diseases; Kidney Diseases; Microbial Sensitivity Tests; Moxalactam; Vitrectomy; Vitreous Body

The pharmacokinetics of multiple-dose administration of cefonicid to patients with normal and impaired renal function were studied by using high-performance liquid chromatography to measure serial serum and urine concentrations. Eighteen patients received an initial dose of 15 mg/kg intravenously over 12 min plus two or three subsequent modified doses at intervals of 24 to 72 h, depending upon the degree of renal impairment. Six patients chronically requiring hemodialysis and 12 nondialysis subjects (creatinine clearance, 10 to 80 ml/min per 1.73 m2) were studied. The concentrations of cefonicid in serum after the initial dose were best described by an open two-compartment model. The elimination half-life of cefonicid ranged between 5.5 and 84.9 h. Mean peak and trough concentrations in serum for all patients were 178.2 +/- 29.3 micrograms/ml (plus or minus standard deviation) and 39.0 +/- 17.5 micrograms/ml, respectively. Trough concentrations were higher in patients requiring hemodialysis than in nondialysis subjects, but the difference was clinically insignificant. The renal clearance/plasma clearance ratio of cefonicid was linearly related to creatinine clearance and decreased with impaired renal function. Therefore, nonrenal mechanisms of elimination become more important as renal function declines. Since cefonicid concentrations were within the therapeutic range for nearly all dosing intervals, we conclude that the guidelines used for dosage reduction and interval prolongation in this study result in therapeutically adequate concentrations in serum and, at the same time, result in no significant drug accumulation.

Topics: Adult; Aged; Cefamandole; Cefonicid; Creatinine; Female; Half-Life; Humans; Kidney Diseases; Kidney Function Tests; Kinetics; Male; Middle Aged

We describe a "high-performance" liquid-chromatographic assay for quantifying cefamandole in biological fluids from patients with renal impairment. Serum samples are deproteinized with acetonitrile, then extracted with dichloromethane; dialysis-fluid samples are injected directly; urine samples are diluted appropriately before injection onto the reversed-phase column. The mobile phase is a methanol/aqueous solution (31/69 by vol) containing 500 microL of phosphoric acid, 20 mmol of sodium sulfate, and 200 microL of triethylamine per liter, the mixture being adjusted to pH 6.0 with NaOH. Retention time for cefamandole is 12 min. Its peak is well resolved in highly contaminated samples from renally impaired subjects. The assay's selectivity, reproducibility (within-day and between-day CVs less than 8% in all three sample fluids), and sensitivity--0.5 mg/L in serum, 1.0 mg/L in dialysis fluid, and 5.0 mg/L in urine--make it applicable to pharmacokinetic studies.

Topics: Cefamandole; Chromatography, High Pressure Liquid; Humans; Infusions, Parenteral; Kidney Diseases; Peritoneal Dialysis, Continuous Ambulatory

Topics: Biological Transport; Cefamandole; Cefonicid; Drug Stability; Drug Therapy; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Kidney Diseases; Kinetics; Respiratory Tract Infections; Tissue Distribution; Urinary Tract Infections

Cefonicid is a cephalosporin with a longer t1/2 than currently available cephalosporins. Cefonicid kinetics after an intravenous dose of 7.5 mg/kg were followed in four groups of subjects: group 1, four subjects with normal creatinine clearance (Clcr greater than 80 ml/min); group II, seven subjects with mild renal insufficiency (Clcr 50 to 80 ml/min); group III, five subjects with moderate to severe renal impairment (Clcr 8 to 49 ml/min); and group IV, five subjects with end-stage renal disease who were receiving maintenance hemodialysis (Clcr less than 8 ml/ml). Cefonicid volume of distribution ranged from 6.9% to 17.6% body weight but was not related to Clcr. Elimination t1/2 was 4.6 +/- 0.7 hr in group 1,6.0 +/- 2.7 hr in group II, 25.6 +/- 14.0 hr in group III, and 65.3 +/- 43.6 hr in group IV. There was a strong correlation between plasma cefonicid clearance and Clcr. Nonrenal clearance did not change with decreasing Clcr. Hemodialysis clearance calculated from plasma concentrations and recovery in dialysate was 2.5 +/- 0.9 ml/min. These kinetic parameters were used to formulate dosage regimens for patients with renal impairment.

Topics: Cefamandole; Cefonicid; Creatinine; Humans; Kidney Diseases; Kinetics; Metabolic Clearance Rate; Renal Dialysis

Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creatinine clearance decreased; i.e., with normal renal function the half-life was 1.49 +&- 0.10 h, and in anephrics the half-life was 11.48 +/- 1.9 h. The greatest increase in half-life occurred when the creatinine clearance was less than 20 ml/min. At these levels of renal impairment, there was significant variance in calculated half-life among patients. The maximum urine concentration and rate of cefamandole urinary excretion decreased as renal function declined. Evidence suggesting renal and nonrenal methods of drug elimination is presented. Hemodialysis resulted in increased cefamandole elimination.

Topics: Adult; Cefamandole; Cephalosporins; Half-Life; Humans; Kidney; Kidney Diseases; Kinetics; Male

The cephalosporins cefamandole, EMD 29 645, and EMD 29 946 were tested for their nephrotoxicity in female albino Wistar rats (n = 120). The antibiotics were administered i.m. over a course of 5 days; dosage interval 12 h, dosages 1000, 2000, 3000, and 5000 mg/kg per day, respectively. For comparative evaluation of nephrotoxicity, the urinary excretion of tubular cells and enzymes (MDH, GOT, LDH) were taken. Additionally serum urea and urine protein (qualitatively) were determined. Furthermore the kidneys were investigated histologically. These experiments revealed the following tubulotoxic threshold doses: cefamandole: 3000 mg/kg per day, EMD 29 645: 2000 mg/kg per day, and EMD 29 946: 5000 mg/kg per day. EMD 29 645 was also found to be glomerulotoxic at higher doses.

Topics: Animals; Blood Urea Nitrogen; Cefamandole; Cephalosporins; Enzymes; Female; Kidney Diseases; Kidney Tubules; Proteinuria; Rats; Time Factors

The pharmacokinetics of cefamandole have been studied in rabbits with normal renal function and varying degrees of renal impairment caused experimentally, by uranyl nitrate, after i.v. administration of a single dose of 30 mg/kg of the antibiotic. The plasma concentrations of cefamandole 80 minutes after administration were 3 micrograms/ml in normal rabbits reaching 90 micrograms/ml at 9 hours in the case of terminal renal impairment. With respect to the pharmacokinetic parameters established in rabbits with normal renal function, the following modifications may be observed in the case of rabbits with renal impairment: alpha, beta, K12, K21, K13, Vc and Vp are decreased, while there is an increase in t 1/2 alpha, t 1/2 beta and (AUC)infinity 0. Linear relationships have been established between log alpha and log beta, respectively, and serum creatinine. Biliary excretion of cefamandole is increased parallel to the increase in the degree of renal impairment, there being a linear relationship between the percentage excreted of the antibiotic and serum creatinine. The values of KB fall from 0.57 h-1 in rabbits with normal renal function, to 0.26 h-1 in rabbits with severe renal impairment.

Topics: Animals; Bile; Cefamandole; Cephalosporins; Kidney Diseases; Kinetics; Male; Rabbits

Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creatinine clearance decreased; i.e., with normal renal function the half-life was 1.49 +/- 0.10 h, and in anephrics the half-life was 11.48 +/- 1.91 h. The greatest increase in half-life occurred when the creatinine clearance was less than 20 ml/min. At these levels of renal impairment, there was significant variance in calculated half-life among patients. The maximum urine concentration and rate of cefamandole urinary excretion decreased as renal function declined. Evidence suggesting renal and nonrenal methods of drug elimination is presented. Hemodialysis resulted in increased cefamandole elimination.

Topics: Cefamandole; Cephalosporins; Half-Life; Humans; Kidney Diseases; Kinetics; Middle Aged; Renal Dialysis; Time Factors

Cefamandole, a new cephalosporin derivative, has been used in treatment of six patients who had diminished renal function and respiratory infections, and of 14 patients with urinary tract infections (UTI). Infection was eliminated in all patients with respiratory infections, and in seven of the patients with UTI. No serious side effects were encountered and, even in patients with pre-existing renal dysfunction, no reduction in renal function occurred.

Topics: Adolescent; Adult; Aged; Cefamandole; Cephalosporins; Child; Drug Evaluation; Humans; Kidney Diseases; Middle Aged; Respiratory Tract Infections; Urinary Tract Infections

The pharmacokinetic characteristics of cefamandole were determined after intravenous administration of a 1-Gm dose to 10 subjects with normal renal function, 10 patients with stabilized renal failure, and five chronic nephritic patients included in a intermittent hemodialysis program. In normal subjects, biological half-life (t1/2) averaged 0.94 hour, the overall elimination rate constant (Ke) was 0.7378 (hr-1), total clearance (Ct) was 223 ml/min/1.73 m2, renal clearance (Cr) was 164 ml/min/1.73 m2, and urine recovery of cefamandole over the 6 hours following a dose amounted to 74 per cent of the administered dose. In patients with stabilized renal failure and in patients on hemodialysis, biological half-life was markedly increased, with a theoretical value of 10.4 hours in case of a creatinine clearance of zero. The amount of antibiotic extracted over a 6-hour dialysis period accounted for 29 per cent of the cefamandole present in the vascular compartment at the beginning of the dialysis procedure. A significant correlation was established between the values of Ke and creatinine clearances, Ccr: Ke = 0.0289 + 0.0063Ccr (r = 0.937). This relationship was used to calculate the loading dose (LD), maintenance doses (D), and dosage intervals (tau) with regard to renal function. From these data recommendations regarding the adjustment of cefamandole dosage to the renal status can be made.

Topics: Cefamandole; Cephalosporins; Half-Life; Humans; Kidney Diseases; Kinetics; Renal Dialysis