Bacterial and crystal adherence to the surfaces of indwelling urethral catheters was investigated by scanning electron microscopy and immunofluorescence method in relation to microbiological examination. Gram-negative bacteria were isolated more frequently than gram-positive bacteria in urine and catheter cultures. Microorganisms and crystals frequently were associated with fibrillar material, some of which was considered to be fibrin. On the surfaces of catheters indwelling for more than 1 week bacteria often were embedded in an amorphous matrix. It was believed that the thick coherent matrix adherent to the catheter served as a protected reservoir of microorganisms that persisted despite antimicrobial chemotherapy. Additionally, urease-producing bacteria attached to the catheter could have an important role in the development of calculous incrustation.
The pharmacokinetics of cefimetazole, a new cephamycin antibiotic, were examined after a 1-h intravenous drip infusion of 1 g to 5 healthy volunteers with normal renal function and 16 Group 1 was composed of five healthy volunteers with creatinine clearances of 95.6 to 155.6 ml/min. Group 2 was composed of four patients with creatinine clearances of 65.5 to 86.8 ml/min. In group 3 were four patients with creatinine clearances of 35.2 to 52.7 ml/ min. Group 4 had four patients with creatinine clearances of 10.2 to 24.8 ml/min. Group 5 was composed of four patients with creatinine clearances of 0 to 9.7 ml/min. Two patients in this group were being treated by hemodialysis twice weekly over 6 to 8 h.All of the subjects were given 1 g of cefmetazole dissolved in 200 ml of 5% dextrose-water. The drug was administered intravenously by drip infusion over a 1-h period. Blood samples were obtained just before infusion and 1, 2, 4, and 6 h after beginning the infusion. Urine specimens were collected from 0 to 2, 2 to 4, and 4 to 6 h. Because only two patients in group 5 were treated by periodic hemodialysis, they were studied between two dialysis sessions.Serum and urine samples were stored at -20°C until assayed. The concentrations of cefinetazole in serum and urine were determined by the thin cupplate method, with Micrococcus luteus ATCC 9341 as the test organism and heart infusion agar as the medium. For the measurement of serum concentrations, a standard solution series was prepared in pooled normal human serum. The assay range was from 200 to 7.8 itg/ml. For the measurement of urinary concentrations, the standard solution series of 20 to 1.25 ,ug/ ml was prepared with 1% phosphate buffer (pH 6.0). Urine was diluted with 1% phosphate buffer (pH 6.0) to give approximately a 5-,ug/ml sample solution. Table 1. The results demonstrated significant negative correlation between the serum concentration and the creatinine clearance (P < 0.05 at 1 h and P < 0.001 at 2, 4, and 6 h). As renal function declined, peak serum concentrations increased, i.e., the mean peak concentration in group 5 (severely impaired renal function) was 1.5 times that of normal subjects.
Cefaclor is an oral cephalosporin antibiotic which has a broad antibacterial spectrum. The purpose of this study was to investigate the effect of food on the absorption of cefaclor and to analyze kinetically the absorption process of this drug. Cefaclor was given to eight volunteers at five test times: after overnight fasting, after two rice meals (350 and 700 cal [1 cal = 4.184 JI), and after two bread meals (500 and 1,000 cal). Urinary recoveries of cefaclor and concentrations of the drug in plasma were determined for each administration. Areas under the concentration-time curves and urinary recoveries were not affected by food intake, but the maximum concentration of drug in serum was reduced and the time to maximum concentration of drug in serum was prolonged depending on the type and the quantity of the meal. The larger the quantity of the meal, the more the maximum concentration of drug in serum and the time to maximum concentration of drug in serum were affected. The rice meals affected the absorption process of cefaclor more than the bread meals. The concentrations of cefaclor in plasma following administration after overnight fasting were well fitted to a conventional one-compartment model with a first-order absorption process, but those after the other administrations were not fitted to the model. For the pharmacokinetic analysis of those data, it was necessary to introduce a transfer process from administration site to absorption site to the conventional model. The concentrations in plasma after rice and bread meals were best fitted to the model with a zero-order transfer process than to that with a first-order process. The velocity of the transfer process depended on the type and volume of the meal.
The pharmacokinetics of cefotaxime, a new semi-synthetic cephalosporin for injection, was studied in 30 subjects with various degrees of renal function after a single 1-gram intramuscular injection. Serum and urinary concentrations of cefotaxime and desacetyl cefotaxime were determined by high pressure liquid chromatography. The pharmacokinetic parameters of cefotaxime were obtained using a one-compartment open model. The mean serum half-life of the parent compound (cefotaxime), 0.87 h in normal subjects, was prolonged to 2.35 h in hemodialysis patients. There was a significant lineal correlation between the elimination rate constant of cefotaxime and creatinine clearance. The mean cumulative urinary recovery of the administered dose in the 24-hour urine was 51.7% as cefotaxime and 25 6% as desacetyl cefotaxime in normal subjects.
The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both bioassay and high-pressure liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated on the basis of a two-compartment open model. Serum concentrations of cefotetan immediately after administration were approximately 180 ,ug/ml in all subjects regardless offunction; however, serum concentrations during the P-phase increased directly with the degree of renal impairment. The mean serum half-life during the p-phase was 3.0 h in normal subjects as compared with 13.1 h in hemodialysis patients. There was a linear correlation (P < 0.0001) between the elimination rate constant of cefotetan and creatinine clearance. The mean cumulative urinary recovery of cefotetan in the 24-h urine was 83.3% of the administered dose in normal subjects and decreased with reduced renal function.
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