cefotaxime and Kidney-Failure--Chronic

Tunneled-cuffed catheters (TCC) are often used among the elderly to commence and carry out haemodialysis (HD). Complications like infection and thrombosis frequently reduce the lifespan of TCC. The role of an antibiotic heparin 'lock' in the prevention of thrombotic and infectious complications and enhancement of TCC survival in the elderly has not been investigated previously.. In this prospective, double-blind clinical trial, TCC (n = 119, placed among 113 elderly patients requiring HD during March 2002 - February 2003) were randomised to either group I having TCC (n = 59, placed in 58 elderly patients) locked with cefotaxime (10 mg/mL) and heparin (5000 U/mL), or group II with TCC (n = 60, placed in 55 elderly patients) having catheter-restricted filling of heparin (5000 U/mL) alone. Symptomatic catheter-related blood stream infections (CRBSI) and catheter thrombosis were the primary end points in this study. Thrombosis was defined as an inability to use the catheter at a blood flow of 200 mL/min that did not respond to catheter repositioning and/or intraluminal thrombolysis. The incidence of catheter thrombosis, CRBSI and percentage of catheter survival were estimated and statistically compared between the two groups.. Kaplan-Meier survival analysis using log rank test showed higher thrombosis-free TCC survival (84.7%vs 63.3%, P = 0.021), infection-free survival (68.7%vs 31.3%, P < 0.001) and infection and thrombosis-free survival (65.0%vs 35.0%, P = 0.006) at 365 days in group I compared with group II.. Cefotaxime and heparin locks safely and effectively enhance the lifespan of TCC by lowering the incidence of thrombotic and infectious complications among elderly end-stage renal failure (ESRD) patients.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticoagulants; Bacterial Infections; Catheterization; Cefotaxime; Double-Blind Method; Drug Therapy, Combination; Equipment Design; Female; Heparin; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Renal Dialysis; Thrombosis; Time Factors

The pharmacokinetics of cefodizime (HR 221) were studied in 6 healthy male individuals and 12 male patients with various degrees of chronic renal failure following intravenous bolus injection of 1 g of the drug. Serum pharmacokinetics were described by an open two-compartment kinetic model. The serum levels of cefodizime exceeded the MIC90 for Enterobacteriaceae, Haemophilus influenzae and Neisseria gonorrhoeae for more than 12 h in healthy individuals and 24 h in renal failure patients. The half-life of elimination was significantly prolonged (p less than 0.001) from 2.7 +/- 0.2 h in healthy volunteers to 7.7 +/- 1.5 h in renal failure patients. The total systemic clearance decreased significantly (p less than 0.001) from 43.3 +/- 5.8 ml/h/kg in healthy volunteers to 23.2 +/- 5.6 ml/h/kg in renal failure patients. A linear correlation (r = 0.9; p less than 0.001) was found between creatinine clearance and the total systemic clearance of cefodizime. The AUC0-infinity in patients with renal failure was more than double the value in healthy volunteers. An equation to calculate the 1-gram dose interval of cefodizime in patients with compromised renal function is provided.

Topics: Adult; Cefotaxime; Drug Administration Schedule; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Microbial Sensitivity Tests; Middle Aged; Time Factors

The pharmacokinetic disposition of cefotaxime, desacetyl cefotaxime, and mezlocillin after the administration of each drug singly and in combination was examined in eight healthy volunteers and in five anuric patients with end-stage renal disease (ESRD). In the presence of ESRD, the total body clearance of cefotaxime decreased from 256.7 +/- 41.5 to 65.4 +/- 42.0 ml/min, and its elimination half-life (t1/2) increased from 1.1 to 3.6 hours as compared with healthy volunteers. Concomitant administration of mezlocillin in healthy volunteers decreased the total body clearance of cefotaxime by 42% and increased its steady-state volume of distribution. This reduction in clearance was reflected by a decrease in both renal and nonrenal clearances. In the presence of ESRD, coadministration of mezlocillin increased the t1/2 of cefotaxime to 5.8 hours. Desacetyl cefotaxime accumulated in ESRD with a prolongation of its elimination t1/2 to 18.7 hours from 1.7 hours in healthy volunteers. Desacetyl cefotaxime peak plasma concentrations occurred later with the combination regimen in the presence of ESRD. The clearance of mezlocillin was reduced and t1/2 prolonged in ESRD from 194.6 +/- 31.9 to 76.4 +/- 38.8 ml/min and 1.4 to 2.3 hours, respectively. Concomitant administration of cefotaxime did not alter the pharmacokinetics of mezlocillin. These data suggest that in the presence of normal renal function, lower doses of cefotaxime may be adequate to maintain similar cefotaxime plasma concentrations when mezlocillin is coadministered compared to when cefotaxime is given alone. Additional pharmacodynamic and clinical studies with this combination are warranted to further elucidate the clinical impact of this pharmacokinetic interaction.

Topics: Adult; Cefotaxime; Chromatography, High Pressure Liquid; Drug Interactions; Drug Therapy, Combination; Female; Half-Life; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Mezlocillin; Middle Aged; Random Allocation

Topics: Aged; beta-Lactamases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Renal Dialysis; Republic of Korea

We herein report a case of spontaneous bacterial peritonitis (SBP) caused by Staphylococcus epidermidis in an adult patient on regular hemodialysis (due to terminal renal failure caused by hypertension) and not on immunosuppressive therapy.

Topics: Adult; Anti-Bacterial Agents; Ascites; Cefotaxime; Drug Therapy, Combination; Humans; Imipenem; Kidney Failure, Chronic; Male; Peritonitis; Renal Dialysis; Staphylococcal Infections; Staphylococcus epidermidis; Vancomycin

Third-generation cephalosporins in general have few adverse effects and cefotaxime (Claforan) particularly is considered to be a good choice because of the favourable side effect profile. In patients with severe renal failure there have been reports of confusion and psychosis. The manufacturer therefore recommends that half the ordinary dose should be given to patients with severe renal failure. Half the ordinary dose can still be too much. We describe a patient in hemodialysis who reacted with a reversible encephalopathy with psychosis in spite of reduced doses of cefotaxime. The plasma concentration of cefotaxime was high and the reaction was diagnosed as a dose dependent side effect.

Topics: Aged; Anti-Bacterial Agents; Cefotaxime; Confusion; Half-Life; Humans; Kidney Failure, Chronic; Psychoses, Substance-Induced

Cefodizime has previously been shown to possess a number of immunomodulating properties in vivo and in vitro using several different test systems. Since most in vitro studies have been performed with cells from normal individuals, we first investigated whether cells from chronic renal failure patients would respond in vitro to cefodizime in the same way as healthy subjects. Subsequently, we investigated the effect of cefodizime (10 g over 10 days in 2-g doses) on phagocyte function ex vivo in an open study of 26 chronic renal failure patients and 16 healthy subjects. Polymorphonuclear leukocytes were tested for their ability to polarize in response to cefodizime and/or f-met-leu-phe peptide. Polymorphonuclear leukocytes and monocytes were tested for their ability to produce chemiluminescence on stimulation with either phagocytic (zymosan) or soluble phorbol myristate acetate stimuli. Phagocyte and lymphocyte membrane receptor expression was compared after exposure to cefodizime. Exposure to cefodizime in vitro causes a significant increase in polarization of polymorphonuclear leukocytes from both normal individuals and renal failure patients (both P < 0.001). It also caused increased chemotaxis and chemokinesis in a modified Boyden chamber assay. Cefodizime did not affect lucigenin-enhanced chemiluminescence and there were only minor effects on cell membrane antigen levels. In the ex vivo study there was a significant increase in polymorphonuclear leukocyte polarization (P < 0.001) attributable to cefodizime, but other investigations showed no significant differences. The results suggest that cefodizime may act as a mild priming agent for some functions, particularly chemotaxis.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Cefotaxime; Cell Polarity; Cephalosporins; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Kidney Failure, Chronic; Luminescent Measurements; Male; Middle Aged; Phagocytes; Receptors, Cell Surface

An assessment was made of the serum protein binding of representative oral cephems (cefdinir, cefixime and ceftibuten) for sera from healthy subjects (HS) and patients with chronic renal failure (CRF) using an application of equilibrium dialysis under a same set of conditions in vitro. The protein binding capacity of oral cephems in CRF patients being treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) was significantly less than that in HS, and a marked increase in free drug concentration was observed. While examining the protein binding of oral cephems with heparin in patients on HD, binding capacity decreased significantly immediately following the completion of dialysis compared to that prior to dialysis. On the other hand, the protein binding of oral cephems did not change when used nafamostat mesilate as an anticoagulant. The addition of palmitic acid (PA), a common non-esterified fatty acid (NEFA), to pooled sera from HS caused the binding capacity of oral cephems to decrease, accompanied by increase in PA concentration. It appears from these findings that changes in the binding capacity of oral cephems with HD have possibly been caused by increase in NEFA due to activation of lipase when heparin was used as an anticoagulant. In conclusion, changes in the protein binding capacity of oral cephems in CRF patients should be taken into consideration in attempts to avoid possible side effects.

Topics: Carrier Proteins; Cefdinir; Cefixime; Cefotaxime; Ceftibuten; Cephalosporins; Humans; Kidney Failure, Chronic; Palmitic Acid; Palmitic Acids; Renal Dialysis

The object of this study was to establish the most effective regimen of cefodizime (CDZM) for patients with chronic renal failure undergoing hemodialysis (HD). T 1/2 beta of CDZM upon 1 g intravenous administration was 3.50 +/- 0.72 hours in an on-HD group, and it was 11.26 +/- 3.89 hours in an off-HD group. When CDZM was administered consecutively at a dose of 1 g or 2 g only after HD, the serum concentration of CDZM was maintained at levels sufficient to exert antibacterial activity, and no tendency for accumulation was observed. The most effective regimen of CDZM to HD patients, therefore, has been that in which concluded to administration was done only after completion of HD, in a dose of 1 g for mild infections and that of 2 g for severe infections.

Topics: Cefotaxime; Dialysis Solutions; Humans; Injections, Intravenous; Kidney Failure, Chronic; Renal Dialysis

After a 200 mg intravenous or oral dose, the absolute bioavailability of cefixime, evaluated by comparison of areas under the serum concentration-time curve values, is 50 per cent. Because food has no effect on peak serum concentrations or on the extent of drug absorption, cefixime can be taken with or without meals. Protein binding is 70 per cent. Cefixime is cleared, mainly unchanged, partly by the liver (60 per cent) and partly by the kidneys (40 per cent). The elimination half-life varies between 3 and 4 hours. Plasma concentrations increase linearly but not proportionally to doses. No significant accumulation was observed after repeated administration in young and elderly subjects. The pharmacokinetic profile of cefixime is significantly altered in patients with marked renal impairment (creatinine clearance less than 20 ml/min), and in such cases dosage should be reduced from 400 to 200 mg/day. Haemodialysis or peritoneal dialysis do not remove significant amounts of the drug from the body. In cirrhotic patients, no dosage adjustment is needed, although the elimination half-life is increased twofold (congruent to 6.5 hours). The extravascular and tissue diffusion of cefixime is satisfactory in those areas where the organisms need to be eradicated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Biological Availability; Cefixime; Cefotaxime; Child; Child, Preschool; Chromatography, High Pressure Liquid; Creatinine; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Palatine Tonsil; Reference Values

In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments. Under conditions of CVHF, maximum doses were defined for cefotaxime, ceftazidime, digoxin, digitoxin, imipenem, metronidazole++, netilmicin, phenobarbital, phenytoin, theophylline, tobramycin, and vancomycin. For the estimation of sufficient doses without blood level measurements, sieving coefficients (S) were calculated by a new method. In addition, S was integrated as a CVHF-specific factor into a common equation for drug dose adjustment in patients with renal insufficiency. The regression of dosage received from kinetics on blood-level-independent equation adjustment was r = 0.9923. Since the volumes of distribution in ICU patients are variable, it is suggested that further drug monitoring is necessary for toxic drugs.

Topics: Adult; Aged; Cefotaxime; Ceftazidime; Digitoxin; Digoxin; Hemofiltration; Humans; Imipenem; Kidney Failure, Chronic; Metronidazole; Middle Aged; Netilmicin; Pharmaceutical Preparations; Phenobarbital; Phenytoin; Theophylline; Tobramycin; Vancomycin

Topics: Aged; Aged, 80 and over; Brain Diseases; Cefotaxime; Female; Humans; Kidney Failure, Chronic

In vitro experiments suggest that cefodizime, a new cephalosporin, causes an increase in phagocytic capacity. We therefore evaluated the effect of cefodizime on the phagocytic system in haemodialysis patients by an estimation of the 14CO2 production during glucose metabolisation by phagocytic cells, in the resting state, and after zymosan and latex. The production of 14CO2 after latex increased in five of six patients (mean +/- SD: from 17,932 +/- 11,859 before to 21,183 +/- 7849 d.p.m. at the end of treatment). The corresponding data after zymosan were 48,381 +/- 24,891 and 70,176 +/- 15,140 d.p.m. The improved 14CO2 production after stimulation persisted for 2 further weeks. These results suggest a stimulation in vivo of the depressed phagocytic system of the uraemic patient by cefodizime.

Topics: Cefotaxime; Female; Humans; Injections, Intravenous; Kidney Failure, Chronic; Macrophages; Male; Middle Aged; Phagocytosis

The pharmacokinetics of cefotiam (CTM) was investigated in 7 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). One gram of CTM was infused either intravenously (i.v. group) or intraperitoneally (i.p. group). In the i.v. group, the serum concentration of CTM at 6 hours after infusion was 25.9 mg/L and the half-life value was 5.09 hours, while the peak value of CTM in dialysate was 12.4 mg/L. In the i.p. group without peritonitis, the dialysate concentration of CTM at 6 hours after infusion was 108.6 mg/L. The serum concentration at 15 minutes after infusion was 3.0 mg/L, the corresponding peak value was 14.0 mg/L at 4 and 6 hours after infusion.

Topics: Adult; Cefotaxime; Cefotiam; Female; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Kidney Failure, Chronic; Male; Models, Biological; Peritoneal Dialysis, Continuous Ambulatory

A study was conducted of the effects of cefotaxime, a third generation cephalosporin antibiotic, on the function of the kidney, using several indices of renal function including urinary concentrations of the renal enzyme N-acetyl-beta-D-glucosaminidase (NAG). In 6 patients with respiratory infections and normal renal function (group I), the urinary concentrations of NAG before and after the administration of cefotaxime 2 to 4g daily were 5.7 +/- 0.6 U/L and 5.5 +/- 0.9 U/L, respectively (NS). Similarly, 9 patients with chronic renal failure who were not undergoing haemodialysis showed pre- and post-treatment urinary NAG concentrations of 8.7 +/- 4.0 U/L and 6.6 +/- 1.7 U/L, respectively (NS), while the corresponding values in 12 renally impaired patients undergoing haemodialysis (group III) were 8.1 +/- 3.5 U/L and 8.9 +/- 3.8 U/L, respectively (NS). With regard to other parameters of renal function (serum creatinine, BUN, beta 2M, and creatinine clearance), no statistically significant differences were found between the values obtained before and after therapy with cefotaxime. Therefore, it was concluded that the influence of cefotaxime on renal function is slight, and that this antibiotic can be safely used to treat patients with infections in the presence of renal dysfunction.

Topics: Acetylglucosaminidase; Bacterial Infections; Bronchitis; Cefotaxime; Humans; Kidney; Kidney Failure, Chronic; Pneumonia; Radioimmunoassay; Renal Dialysis

Topics: Adult; Aged; Bacterial Infections; Blood Coagulation; Blood Platelets; Cefotaxime; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prothrombin Time; Renal Dialysis

Topics: Acute Kidney Injury; Adult; Aged; Cefotaxime; Female; Hemofiltration; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged

The pharmacokinetics of cefotaxime and desacetylcefotaxime were evaluated in 11 female and 13 male subjects with end-stage renal disease. Subjects received single 1- or 2-g intravenous doses of cefotaxime sodium. Serum, urine, and dialysate concentrations of cefotaxime and desacetylcefotaxime were determined using high performance liquid chromatography. The results indicate that gender has no clinically significant influence on the disposition of cefotaxime or its active metabolite desacetylcefotaxime.

Topics: Cefotaxime; Female; Humans; Kidney Failure, Chronic; Male; Sex Factors

Twelve male patients with impaired renal function and six healthy male volunteers were given a single i.v. dose of cefotaxime (1000 mg). Serum concentrations of cefotaxime were determined by a microbiological assay. The pharmacokinetic parameters were obtained using an open two-compartment model. Results showed that the median elimination t1/2 of cefotaxime was prolonged in patients (3.25 h) compared to volunteers (1.4 h) (P less than 0.001). The median AUC0----infinity was increased in patients (211.99 micrograms/ml X h) compared with volunteers (78.21 micrograms/ml X h) (P less than 0.001). Also, the median clearance was decreased in patients (4.73 l/h) compared with volunteers (12.82 l/h) (P less than 0.001). This study shows prolonged half-life and decreased elimination of cefotaxime in patients with impaired renal function.

Topics: Adult; Cefotaxime; Half-Life; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Kinetics; Male; Middle Aged

In a study in which i.v. bolus injections of cefotiam were administered at a dose of 1000 mg directly before the start of hemofiltration sessions, the purification capacity of the drug was seen to be similar to that of other cephalosporins. Hemofiltration did not completely restore normal renal function, though it was only slightly less efficient with mean values and standard deviations for the extraction coefficient (E.C.) and hemofiltration clearance (Clh) of 0.25 +/- 0.06 and 74.02 +/- 17.05 ml/min, respectively.

Topics: Adult; Blood; Cefotaxime; Cefotiam; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Ultrafiltration

The pharmacokinetics of cefmenoxime were studied after a single intravenous 1.0-g dose to 24 subjects grouped according to their renal functions. Creatinine clearance was above 85, 50 to 85, 10 to 50, and below 10 ml/min per 1.73 m2 in groups 1, 2, 3, and 4, respectively. Cefmenoxime obeyed two-compartment-model kinetics in all four groups. The volume of distribution based on the area under the serum concentration-time curve was renal function independent, the average value being 0.270 +/- 0.075 liters/kg. The elimination-phase half-life (t1/2 beta) was 0.82 +/- 0.30 h in group 1, 1.38 +/- 0.36 h in group 2, 3.32 +/- 1.82 h in group 3, and 7.60 +/- 1.28 h in group 4. Cumulative 24-h urinary excretion accounted for 65.5 +/- 7.6% of the dose in group 1 and for 7.50 +/- 3.72% in group 4. Recommendations for dosage adjustment in patients with renal insufficiency are proposed based on the data obtained in this study. The effect of hemodialysis on cefmenoxime pharmacokinetics was studied in six patients in group 4; hemodialysis shortened the average t1/2 beta from 7.60 +/- 1.28 to 4.19 +/- 1.66 h. It was estimated that in a hypothetical anephric subject with a body weight of 60 kg, 5-h hemodialysis would remove 28.2% of the drug present in the body at the start of hemodialysis.

Topics: Adult; Cefmenoxime; Cefotaxime; Female; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of the extended-half-life, broad-spectrum oral cephalosporin cefixime (CL 284,635; FK 027) were studied in 7 healthy volunteers and 35 patients with various degrees of renal insufficiency, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis. Apparent total body, renal, and apparent nondialysis-nonrenal clearances and protein binding declined and elimination half-life increased with decreasing creatinine clearance. All of these alterations became statistically significant as the creatinine clearance fell below 20 ml/min per 1.73 m2. Cefixime concentrations in urine exceeded the MICs for most urinary tract pathogens for up to 24 h postdose, even in patients with severe renal insufficiency. CAPD removed an insignificant fraction of cefixime body burden over the 72-h study period (1.57 +/- 0.60% [mean +/- the standard error of the mean]). Area under the curve data suggested that hemodialysis similarly removed an insignificant fraction of the cefixime body burden. Volume of distribution at steady state was not altered significantly by renal insufficiency. It is recommended that standard doses of cefixime be administered at extended intervals, especially in patients with creatinine clearances less than 20 ml/min per 1.73 m2. In addition, supplemental doses are not necessary during CAPD and at the end of hemodialysis.

Topics: Adult; Aged; Cefixime; Cefotaxime; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Protein Binding

Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 gm intravenous dose were evaluated in five groups of subjects: group I, normal creatinine clearance (CLCR greater than 90 ml/min); group II, mild renal insufficiency (CLCR 30 to 89 ml/min); group III, moderate renal insufficiency (CLCR 16 to 29 ml/min); group IV, severe renal insufficiency (CLCR 4 to 15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR less than 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR. The terminal t1/2 values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 hours in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.

Topics: Acute Kidney Injury; Adult; Analysis of Variance; Cefotaxime; Chromatography, High Pressure Liquid; Creatinine; Female; Half-Life; Humans; Infusions, Parenteral; Kidney Failure, Chronic; Kinetics; Male; Middle Aged

We investigated the kinetics of cefotaxime in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 1 gm iv dose was injected and a 1 gm dose was given intraperitoneally in the CAPD fluid during a 4-hour dwell time. Cefotaxime and desacetylcefotaxime were assayed by HPLC. After intravenous injection the cefotaxime serum kinetic parameters were as follows: plasma t 1/2, 2.31 +/- 0.20 hours; volume of distribution, 0.35 +/- 0.04 L/kg; total plasma clearance, 118.7 +/- 12.3 ml/min; and peritoneal clearance, 6.7 +/- 1.3 ml/min. Dialysate cefotaxime concentrations rose rapidly, but only 5% of the dose was eliminated by the peritoneal route. After intraperitoneal instillation, cefotaxime appeared in the serum rapidly and the peak serum concentrations ranged from 9 to 20 micrograms/ml between 1 and 3 hours. The absorption of cefotaxime from peritoneal space was 58.7% +/- 5.4%. Data suggest that cefotaxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of cefotaxime in CAPD fluid may permit rapid absorption to achieve therapeutic serum concentrations.

Topics: Absorption; Adult; Aged; Biotransformation; Cefotaxime; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Infusions, Parenteral; Injections, Intravenous; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory

Eleven patients with terminal renal insufficiency requiring dialysis were treated with 3 X 2 g cefotaxime in an open study lasting five days when the clinical findings strongly indicated a serious bacterial infection. The effect of the administration of the high-dose antibiotic on the coagulation system (Quick test, partial thromboplastin time, thrombin time, antithrombin III and platelets) and on brain function (EEG) was investigated. The serum levels showed that the serum concentrations were not abnormally high in cases of terminal renal insufficiency requiring dialysis. In contrast to previous investigations in other beta-lactam antibiotics, no changes in the coagulation system or EEG occurred. On the basis of these findings, no reduction in the dose appears necessary for cefotaxime, if therapy does not exceed five days.

Topics: Adult; Blood Coagulation; Cefotaxime; Drug Tolerance; Electroencephalography; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged

The pharmacokinetics of cefotiam were studied after a single intravenous 1.0-g dose to 18 subjects grouped according to their creatinine clearances (CLCR); CLCR was above 75, 75 to 20, and below 20 ml/min per 1.73 m2 in groups 1, 2, and 3, respectively. Cefotiam obeyed two-compartment model kinetics in all three groups. The volume of distribution based on the area under serum concentration-time curve (Varea) was renal function independent, the average value being 0.350 +/- 0.159 liters/kg. The elimination-phase half-life (t1/2 beta) was 0.916 +/- 0.090 h in group 1, 2.03 +/- 1.62 h in group 2, and 7.09 +/- 3.06 h in group 3. Cumulative 24-h urinary excretion accounted for 65 to 93% of the dose in four subjects with CLCRS above 80 ml/min per 1.73 m2 and 19 to 41% in three subjects with CLCRS below 20 ml/min per 1.73 m2. We give recommendations for dosage adjustment in patients with renal insufficiency. The effect of hemodialysis on cefotiam pharmacokinetics was studied in six patients in end-stage renal failure; hemodialysis shortened the average t1/2 beta from 8.02 +/- 4.04 h to 2.74 +/- 2.15 h. We estimated that in a hypothetical anephric patient with a body weight of 60 kg, 6-h hemodialysis would remove 49.7% of the drug present in the body at the start of dialysis.

Topics: Adult; Cefotaxime; Cefotiam; Creatinine; Female; Humans; Injections, Intravenous; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Male; Renal Dialysis

The kinetic disposition of a single intravenous dose of ceftriaxone (250 to 665 mg) was studied in six normal subjects and nine patients with renal insufficiency and normal hepatic function. In normal subjects, ceftriaxone was eliminated with a t1/2 beta of 5.2 h (range, 4.1 to 5.8). The total body clearance (Qb) was 13.5 ml/kg per h (range, 8.4 to 23.3), and renal clearance was 8.3 ml/kg per h (range, 5.8 to 13.3). In patients with severe renal insufficiency requiring peritoneal or hemodialysis, the mean t1/2 beta was prolonged to 13.4 h (range, 7.7 to 15.8) and the mean Qb was reduced to 6.9 ml/kg per h (range, 3.4 to 12.8). The apparent volumes of distribution (Vc and Vss) were not different from those determined in normal subjects. Peritoneal dialysis did not remove ceftriaxone. The dialysate of three patients on continuous peritoneal dialysis did not contain any measureable ceftriaxone, and the kinetic disposition in these patients was similar to the hemodialysis patients between their dialysis treatment. During a 4-h hemodialysis session, the total body clearance of ceftriaxone was reduced, perhaps secondary to a decrease in hepatic blood flow induced by the hemodialysis procedure. After a 12- or 24-h dose regimen, predicted trough concentrations of ceftriaxone in plasma at steady state derived from kinetic data generated from the study and assuming linear pharmacokinetic behavior were well above the minimum inhibitory concentrations of most sensitive bacteria, suggesting the feasibility of a once-a-day dosage regimen especially for patients with severe renal insufficiency.

Topics: Adult; Aged; Cefotaxime; Ceftriaxone; Female; Half-Life; Humans; Injections, Intravenous; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis

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 linear 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.

Topics: Adult; Aged; Cefotaxime; Humans; Injections, Intramuscular; Kidney Failure, Chronic; Kinetics; Middle Aged; Renal Dialysis

The pharmacokinetics of ceftizoxime were studied in 12 patients on continuous ambulatory peritoneal dialysis. After a 3-g intravenous dose, the steady-state volume of distribution was 0.23 +/- 0.05 liter kg-1, with an elimination half-life of 9.7 +/- 5.1 h. The peritoneal clearance of ceftizoxime (2.8 +/- 0.7 ml min-1) contributed modestly to the overall serum clearance of the drug (17.1 +/- 7.4 ml min-1) and was greater than the renal clearance (0.8 +/- 0.8 ml min-1). The peritoneal concentration rose to 91 +/- 29 micrograms ml-1 at 6 h, which was 0.61 +/- 0.17 of the serum concentration. A 3-g intravenous dose of ceftizoxime given every 48 h would result in adequate activity against most susceptible organisms, but more frequent dosing may be necessary for less susceptible organisms.

Topics: Bacteria; Cefotaxime; Ceftizoxime; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Metabolic Clearance Rate; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory

The pharmacokinetic parameters of ceftriaxone in eight patients with end-stage renal disease were determined during dialysis and during the interdialysis period. The mean half-life, clearance, and apparent volume of distribution during dialysis were 16 h, 722 ml/h, and 16.7 liters, respectively. During the interdialysis period, the half-life was 14 h, clearance was 739 ml/h, and volume of distributions was 14 liters. Individual variability in plasma concentrations occurred even in patients with apparently normal hepatic function. Based on these parameters, a dose of 1 g every 24 h would yield concentrations in excess of the concentrations needed to inhibit most gram-positive and gram-negative aerobic species.

Topics: Adult; Cefotaxime; Ceftriaxone; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of a single 500-mg intramuscular dose of ceftizoxime were studied in 11 healthy adult volunteers and in 22 patients with various degrees of renal dysfunction. The mean serum half-life of ceftizoxime was 1.44 h in normal subjects and 30.2 h in hemodialysis patients. A significant correlation (P less than 0.001) between the elimination rate constant of ceftizoxime and creatinine clearance was demonstrated. The mean urinary recovery in normal subjects was 75.6% within 6 h of dosage; recovery decreased progressively with reduced renal function.

Topics: Adult; Aged; Cefotaxime; Ceftizoxime; Creatinine; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged

The study was done after a single dose in 6 normal subjects and 24 patients with varying degrees of renal insufficiency. In normal subjects, the results are similar whatever the assays are used. In uremic patients, the half-life for the terminal phase increased with renal failure with the microbioassay, but it is demonstrated that deacetyl cefotaxime has only a prolonged half - life with a more specific assay = HPLC method. After repetitive doses, the tendency for accumulation was only noted in patients with very severe renal failure (creatinine clearance less than 5 ml.min-1).

Topics: Adult; Aged; Biological Assay; Cefotaxime; Chromatography, High Pressure Liquid; Creatinine; Escherichia coli; Half-Life; Humans; Kidney; Kidney Failure, Chronic; Middle Aged

Topics: Cefotaxime; Cephalosporins; Humans; Kidney; Kidney Failure, Chronic

The pharmacokinetics of cefotaxime were investigated in 6 healthy subjects and in 22 uraemic patients with various degrees of renal insufficiency. After i.v. bolus injection of a single 15 mg/kg dose, pharmacokinetic data were calculated using a two compartment model. Serum and urine concentrations were determined by microbiological (M.A.) and HPLC assays. With microbiological assay, the elimination serum half-life (T 1/2) increased in patients according to their degree of renal insufficiency and reached 10 hours when creatinine clearance fell below 10 ml.min-1. When concentrations of cefotaxime and its derivatives (desacetyl cefotaxime, M2 and M3) were determined by HPLC assay, the elimination serum half-life of cefotaxime (T 1/2) was not modified in severe uraemic patients; however the elimination half-life of the metabolites increased when creatinine clearance decreased. Cefotaxime can be administered at a dose of 1 g i.v., twice daily in patients with stable chronic renal insufficiency when creatinine clearance is above 5 ml min-1. In cases of more severe renal failure, the dose should be halved and given i.v. every 12 hours.

Topics: Adult; Aged; Biological Assay; Cefotaxime; Cephalosporins; Chromatography, High Pressure Liquid; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Middle Aged; Models, Biological

The pharmacokinetics of intravenously administered cefotaxime were studied in 11 patients with creatinine clearances of less than 7 ml/min who were undergoing chronic hemodialysis. Eight were studied during dialysis, and 3 were studied between dialyses. Pharmacokinetic parameters were determined using a two-compartment linear model. The serum half-life of cefotaxime off dialysis ranged from 1.48 to 3.78 hr. The half-life during dialysis was 2.52 +/- 0.34 hr. There was a 28% reduction in serum concentration per hour. A dosage schedule for the use of intravenously administered cefotaxime in patients undergoing hemodialysis is presented.

Topics: Adult; Cefotaxime; Cephalosporins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Kinetics; Renal Dialysis

The pharmacology of cefotaxime and the metabolite desacetyl cefotaxime was studied in 40 patients with various degrees of renal and hepatic failure who received 0.5 or 1 g of cefotaxime intravenously. Patients with severe renal impairment (creatinine clearance, 3 to 10 ml/min) had a cefotaxime serum half-life of 2.6 h and desacetyl cefotaxime serum half-life of 10.0 h. The equivalent figures were 1.0 and 1.5 h, respectively, in subjects with normal renal function. The presence of an acute coexisting illness together with severe renal impairment was associated with a further prolongation of the serum half-lives. Hepatic dysfunction was accompanied by a reduction in desacetyl metabolite formation. A reduction of cefotaxime dosing to 0.5 g twice a day would appear prudent when the creatinine clearance is 5 ml/min or less to avoid accumulation of the parent compound and the metabolite.

Topics: Cefotaxime; Cephalosporins; Female; Half-Life; Humans; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Liver Diseases; Male; Middle Aged

The pharmacokinetic properties of cefotaxime were studied in 30 subjects with various degrees of renal function after a single 1-gm intramuscular injection. Serum and urinary concentrations of cefotaxime and desacetyl cefotaxime were determined by high-pressure liquid chromatography. The pharmacokinetic parameters were obtained using a one-compartment open model. A significant (P less than 0.0001) linear correlation was demonstrated between the elimination rate constant of cefotaxime and creatinine clearance. The mean serum half-life of cefotaxime was 0.86 hour in normal subjects and was prolonged to 2.35 hours in hemodialysis patients. The mean 24-hour urinary recovery was 51.7% as cefotaxime and 25.6% as desacetyl cefotaxime in normal subjects. In the present study, modification of the dosage is probably unnecessary in patients with creatinine clearance of more than 30 ml/min; however, dose reduction or prolongation of dosage interval, or both, may be appropriate in patients with severe renal dysfunction.

Topics: Anti-Bacterial Agents; Cefotaxime; Creatinine; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

Topics: Adult; Aged; Cefotaxime; Cephalosporins; Humans; Kidney Failure, Chronic; Kinetics

Topics: Adult; Aged; Cefotaxime; Cephalosporins; Female; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Renal Dialysis

Topics: Adult; Bile; Biotransformation; Cefotaxime; Cephalosporins; Humans; Kidney Failure, Chronic; Kinetics; Male