cefotaxime and Kidney-Diseases

Topics: Anthrax; Biopsy; Cefotaxime; Combined Modality Therapy; Drainage; Escherichia coli Infections; Humans; Infant; Kidney Diseases; Male; Ultrasonography; Urography

The pharmacokinetics of cefodizime (CDZ) were determined after i.v. and i.m. administration of single doses of up to 2 g and after i.v. administration of 2 g b.i.d. for six days. Serum concentrations were adequately described by three exponential functions, with a terminal half-life of about 4 h. Serum and urine levels and amounts excreted were dose-proportional, and derived pharmacokinetic characteristics were dose-independent. Steady state was established after the second dose (b.i.d.). CDZ is 100% bioavailable after i.m. administration. Concomitant administration of lidocaine did not alter either bioavailability or pharmacokinetic characteristics. Following administration of 1 and 2 g i.m., Cmax was reached after 1.2 h and amounted to 60 and 140 mg/l, respectively. CDZ is 88% bound to plasma proteins. CDZ was predominantly eliminated by the kidneys (80% of dose), a further 20% being excreted in the bile. Metabolites were not detectable in serum or urine. Dose adjustment does not seem warranted in the elderly. For renally impaired patients with CLcr between 30 and 10 ml/min, the daily dose should not exceed 2 g. For patients with CLcr below 10 ml/min, individual adjustment is suggested. CDZ showed good penetration into tissues and biological fluids (lung, bronchial secretions, pleural fluid, kidney, prostate, urine, bone, muscle, skin, Fallopian tube) with long-lasting concentrations. In urine, therapeutic concentrations were present for more than 24 h after administration of 1 and 2 g. Thus, on the basis of its pharmacokinetic profile, cefodizime is appropriate for effective treatment with once-daily administration.

Topics: Age Factors; Aged; Cefotaxime; Humans; Kidney Diseases; Tissue Distribution

Ceftizoxime is a 'third generation' cephalosporin administered intravenously or intramuscularly. Like other third generation cephalosporins it has a wide spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, is particularly active against Enterobacteriaceae (including beta-lactamase-positive strains), and is resistant to hydrolysis by beta-lactamases. However, the third generation cephalosporins are less active than earlier cephalosporins against staphylococci and so could not be considered the drugs of choice. Like many currently available third generation cephalosporins, ceftizoxime has limited activity against Pseudomonas aeruginosa, and thus cannot be recommended as sole treatment of known or suspected non-urinary tract pseudomonal infections. Similarly, although favourable clinical results have been obtained in patients treated with ceftizoxime for infections caused by mixed aerobic/anaerobic organisms (such as intra-abdominal, and obstetric and gynaecological infections), the relatively low in vitro activity of ceftizoxime (in common with most other third generation cephalosporins) against Bacteroides fragilis and enterococci may restrict its usage in situations where these organisms are the suspected or proven pathogens. Ceftizoxime appears to be similar in efficacy to several other cephalosporins in lower respiratory tract infections in elderly and/or debilitated patients, and in chronic and/or complicated urinary tract infections, 2 clinical situations in which third generation cephalosporins may have a major role. Ceftizoxime is also effective clinically and bacteriologically in skin, soft tissue, bone and joint infections, septicaemia/bacteraemia, meningitis and neonatal infections. However, a few large, well designed clinical comparisons of efficacy with aminoglycosides are needed before ceftizoxime can be recommended as an alternative in patients in whom potential aminoglycoside toxicity is a concern. Single intramuscular doses of ceftizoxime appear similar in efficacy to aqueous procaine penicillin G in gonorrhoeae due to nonpenicillinase-producing Neisseria gonorrhoea, and ceftizoxime is also highly effective against penicillinase-producing strains. Although only a few infections have been treated to date, ceftizoxime may be useful in the treatment of gonorrhoea in places where penicillinase-producing strains are common. Thus, ceftizoxime appears to be an effective addition to the growing number of third generation

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biotransformation; Blood Coagulation; Cefotaxime; Ceftizoxime; Drug Synergism; Ethanol; Humans; Intestinal Absorption; Kidney Diseases; Kinetics; Probenecid; Tissue Distribution

This article describes the pharmacokinetics of ceftriaxone, a new "third generation" cephalosporin. This antibiotic displays two major characteristics: a very long serum half-life and a good tissue penetration. The properties of ceftriaxone should allow its easy clinical handling.

Topics: Bile; Cefotaxime; Ceftriaxone; Diffusion; Female; Humans; Kidney; Kidney Diseases; Kinetics; Liver; Liver Diseases; Male; Maternal-Fetal Exchange; Pregnancy; Protein Binding; Tissue Distribution

In human subjects, ceftriaxone exhibits an exceptionally long elimination half-life (5.8 to 8.7 hours) and a small degree of nonlinearity in its pharmacokinetics which can be ignored in its clinical applications. Thirty-three to 67 percent of a dose is excreted in the urine as unchanged drug, and the remainder is secreted in the bile and ultimately is found in the feces as microbiologically inactive compounds. Ceftriaxone is rapidly and completely absorbed following intramuscular administration. Multiple dosing of ceftriaxone with doses ranging from 0.5 to 2 g at 12- or 24-hour intervals by intravenous and intramuscular routes resulted in 15 to 36 percent accumulation of ceftriaxone in plasma and no change in its elimination half-life. The volume of distribution and the plasma clearance of ceftriaxone in pediatric patients were threefold greater than those in adults, and ceftriaxone penetrated the inflamed meninges of infants and children with bacterial meningitis. Small changes in the pharmacokinetics of ceftriaxone in elderly subjects or patients with renal or hepatic dysfunction are such that dose adjustments should not be necessary with a ceftriaxone dosage up to 2 g per day. Ceftriaxone was not removed to any significant extent from plasma by hemodialysis. In a small percentage of patients, on dialysis, the elimination rate of ceftriaxone was significantly reduced, suggesting that plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary.

Topics: Adolescent; Adult; Age Factors; Aged; Blister; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Injections, Intravenous; Kidney; Kidney Diseases; Kinetics; Middle Aged; Milk, Human; Neoplasms; Placenta; Pregnancy

In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients.. We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization.. The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36). Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002). Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03). Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values.. In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone.

Topics: Adult; Aged; Albumins; Bacterial Infections; Cefotaxime; Cephalosporins; Combined Modality Therapy; Female; Humans; Infusions, Intravenous; Kidney Diseases; Liver Cirrhosis; Male; Middle Aged; Peritonitis; Plasma Volume; Renin

The epidemiology of aminoglycoside-induced nephrotoxicity is not fully understood. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure during therapy ranges from 8 to 10 and that the attributable risk is 70% to 80%. Further analysis of these data suggests that the duration of therapy, plasma aminoglycoside levels, liver disease, advanced age, high initial estimated creatinine clearance and, possibly, female gender all increase the risk for nephrotoxicity. Other causes of acute renal failure, such as shock, appear to have an additive effect. Predictive models have been developed from these analyses that should be useful for identifying patients at high risk. These models may also be useful in developing insights into the pathophysiology of aminoglycoside-induced nephrotoxicity.

Topics: Acute Kidney Injury; Age Factors; Aminoglycosides; Cefotaxime; Clinical Trials as Topic; Double-Blind Method; Humans; Kidney Diseases; Nafcillin; Probability; Risk; Time Factors; Tobramycin

To determine if aminoglycoside use and liver disease interact to cause an increased risk for renal dysfunction, data from 179 hospitalized patients who had been enrolled in a prospective, randomized trial of nafcillin/tobramycin versus cefotaxime were analyzed. The cefotaxime-treated patients served as a control group not receiving an aminoglycoside. Renal dysfunction occurred in seven of 88 (8 percent) given cefotaxime and 37 of 91 (41 percent) given tobramycin (p less than 0.001), in 11 of 29 (38 percent) with liver disease and 33 of 150 (22 percent) without liver disease (p less than 0.08), and occurred in 11 of 15 (73 percent) with both liver disease and tobramycin use and in 0 of 14 (0 percent) with liver disease and cefotaxime use (p less than 0.001). By logistic regression analysis, the relative odds of renal dysfunction developing during tobramycin treatment in a patient were 6.0 (95 percent confidence interval: 3.8 to 9.5). The relative odds of renal dysfunction developing in a patient receiving tobramycin and having liver disease were 31.8 (95 percent confidence interval: 19.7 to 51.4). This analysis demonstrates an interaction between tobramycin use and liver disease for increasing the risk of renal dysfunction.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cefotaxime; Double-Blind Method; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Nafcillin; Tobramycin

In a prospective, randomized, double-blind study, we compared cefotaxime with nafcillin plus tobramycin in the treatment of serious bacterial infections. Of 195 patients with suspected or proven infections who were not neutropenic, definite bacterial infections were identified in 81; 34 of 38 patients given cefotaxime and 26 of 43 given nafcillin plus tobramycin (p less than 0.01) responded to treatment. The difference in response rates occurred primarily in patients with rapidly fatal underlying disease or with an infection outside the urinary tract. A logistic regression analysis showed that treatment with cefotaxime was still associated with a higher response rate after adjusting for several potential confounding factors. Among patients treated for 3 days or more, our criteria for nephrotoxicity were met in 2 of 68 (2.9%) given cefotaxime and 16 of 57 (28.1%) given nafcillin plus tobramycin (p less than 0.001). Prolongation of the prothrombin time and enterococcal colonization did not occur more frequently with cefotaxime. We conclude that cefotaxime may be more effective and less toxic than nafcillin plus tobramycin for patients with serious bacterial infections.

Topics: Adult; Aged; Bacterial Infections; Cefotaxime; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Humans; Infusions, Parenteral; Kidney Diseases; Male; Middle Aged; Nafcillin; Penicillin Resistance; Prognosis; Pseudomonas Infections; Random Allocation; Tobramycin; Urinary Tract Infections

During a 7 month trial for therapy of polymicrobial surgical sepsis, intravenous antibiotic treatment was randomized between gentamicin (1 mg/kg every 8 hours) plus clindamycin (8 mg/kg every 6 hours), and the cephalosporin, ceftriaxone (1 g every 12 hours) in 197 patients, of whom 99 were being treated for peritonitis, 93 for soft tissue sepsis, and 5 for other forms of infection. No significant differences were noted in patient demographics, type of sepsis, associated disease states, surgical procedure, or causative aerobic or anaerobic pathogens. Results demonstrated approximately equivalent efficacy, although cure rates obtained with ceftriaxone in patients with soft tissue sepsis or intraabdominal abscess were superior to those achieved with combination gentamicin and clindamycin. There were no significant side effects with ceftriaxone therapy, such as the renal failure noted in six of the patients treated with gentamicin and clindamycin. We conclude that single agent treatment with ceftriaxone is preferable because of the greater safety and the longer dosing intervals.

Topics: Abdomen; Abscess; Adolescent; Adult; Aged; Bacterial Infections; Cefotaxime; Ceftriaxone; Clindamycin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Gentamicins; Humans; Kidney Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Peritonitis; Postoperative Complications; Random Allocation; Recurrence

During 31 months of study, 808 patients with polymicrobial surgical infection were randomized for antibiotic therapy between a third-generation cephalosporin (moxalactam disodium [149], cefotaxime sodium [125], and cefoperazone sodium [141]) and the combination of gentamicin sulfate plus clindamycin (393). Results based on antibiotic therapy included the following: cure in 83% given cephalosporin, 73% with antibiotic combination; control but recurrent sepsis in 7% and 15%; and failure in 4% and 8%, respectively. Such data support the tenet that third-generation cephalosporins are at least equal, if not superior, to the combination of gentamicin plus clindamycin for treatment of polymicrobial surgical sepsis.

Topics: Abscess; Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Cefoperazone; Cefotaxime; Cephalosporins; Cephamycins; Child; Clindamycin; Clinical Trials as Topic; Female; Gentamicins; Humans; Kidney Diseases; Male; Middle Aged; Moxalactam; Peritoneal Diseases; Peritonitis; Postoperative Complications; Random Allocation; Surgical Wound Infection

We performed a survey of clinical experience of cefotiam (CTM: Pansporin) as postmarketing surveillance (PMS), and evaluated the efficacy and safety of CTM in 10,499 cases of data which were collected during the first 2 years after approval. The following results were obtained. The efficacy rate of CTM in the treatment of various infections was 83.2%, which was equal or superior to the clinical results obtained before approval. A total of 472 adverse drug reactions was reported by 10,499 patients (4.50%). The commonest adverse drug reactions was liver function abnormality (230 cases), followed by dermal symptoms (103 cases), gastrointestinal symptoms (53 cases) and renal function abnormality (20 cases) in the order mentioned. All of these adverse drug reactions had already been known for cephem antibiotics, and no remarkable adverse drug reactions specific to CTM was found. The above PMS results indicate the same efficacy of CTM that obtained from premarketing studies. As regards safety, there was no remarkable unexpected adverse drug reaction and their profile was also the same as that found in premarketing studies. Thus, the utility of CTM was confirmed.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cefotaxime; Cefotiam; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Clinical Trials as Topic; Drug Hypersensitivity; Evaluation Studies as Topic; Female; Hematologic Tests; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Middle Aged; Neurotic Disorders; Product Surveillance, Postmarketing; Skin; Skin Tests

Topics: Cefotaxime; Ceftizoxime; Creatinine; Humans; Infusions, Parenteral; Injections, Intravenous; Kidney Diseases; Kinetics; Models, Biological; Renal Dialysis

To describe the clinical presentation and medical management of a cat with perinephric abscessation and urosepsis following urethral obstruction and catheterization.. A 2-year-old intact male domestic shorthaired cat presented to an emergency and referral center for lethargy, vomiting, and hematuria. Severe azotemia and hyperkalemia were observed on a serum biochemistry panel. The patient was diagnosed with urethral obstruction and was treated with urethral catheterization, calcium gluconate, IV fluid therapy, buprenorphine, and prazosin. The patient's azotemia improved, and the hyperkalemia resolved. Urinary catheterization was discontinued. The patient developed pyrexia, worsening azotemia, hypoalbuminemia, hyperbilirubinemia, and dysuria. Urethral catheterization was repeated. Abdominal radiographs showed left renomegaly, and abdominal ultrasound revealed left perinephric fluid. Ultrasound-guided centesis of the perinephric fluid revealed septic inflammation, and the sample was consistent with urine based upon sample creatinine. Fluid from the perinephric abscess and urine from the bladder both grew Pasturella spp. The patient was treated with perinephric catheterization, saline lavage, and a continuous infusion of cefotaxime for 72 h. The patient's azotemia quickly resolved, and the patient was discharged after 6 days of hospitalization. The patient was reported to have made a full recovery.. This is the first described case of perinephric abscess and urosepsis following urethral obstruction in a cat and its successful medical management. Perinephric abscess not associated with intrarenal abscess has not previously been identified. Additionally, continuous antimicrobial infusion to treat overwhelming infection and the use of the RapidBac Vet immunoassay for point-of-care detection of urinary tract infection has not been described in cats.

Topics: Abdominal Abscess; Animals; Anti-Bacterial Agents; Cat Diseases; Cats; Cefotaxime; Fluid Therapy; Hyperkalemia; Kidney Diseases; Male; Sepsis; Ultrasonography; Urethral Obstruction; Urinary Bladder; Urinary Catheterization; Urinary Tract Infections

Topics: Abdominal Pain; Abscess; Anti-Bacterial Agents; Cefazolin; Cefotaxime; Child, Preschool; Drainage; Fever; Humans; Kidney; Kidney Diseases; Male; Pyelonephritis; Staphylococcus aureus; Tomography, X-Ray Computed; Vancomycin

The treatment of complicated urinary tract infection in children is still a matter of debate. In our hospital, antimicrobial treatment is initiated intravenously, and the duration of this treatment is adapted according to the results of a Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy.. This study was conducted to evaluate retrospectively the frequency and the importance of late renal sequelae when treating intravenously for 7 days those patients with an abnormal acute DMSA.. A review was conducted of the medical charts of all patients consecutively admitted between 2005 and 2008 with positive urine culture and clinical and biological evidence of complicated urinary tract infection (UTI).. There were 144 patients (59 %) with abnormal early DMSA scintigraphy and 98 (41 %) with normal scintigraphy. The median duration of intravenous treatment was 7.0 days in the children with DMSA lesions and 5.0 days in those without lesions. Obvious renal sequelae were observed on late DMSA scintigraphy in 4 (6 %) out of the 65 patients with an abnormal early DMSA who came back for control scintigraphy.. Sequelae of acute DMSA lesions observed during complicated UTI treated 7 days intravenously were infrequent. Whether the mode and duration of antimicrobial treatment might explain the low rate of sequelae remains to be demonstrated.

Topics: Acute Disease; Administration, Intravenous; Adolescent; Ampicillin; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Penicillins; Pyelonephritis; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Technetium Tc 99m Dimercaptosuccinic Acid; Treatment Outcome; Urinary Tract Infections

Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection as a complication of end stage liver disease. The outcome is related to the severity of hepatorenal function, gastrointestinal bleeding, and many others; however it is not well known whether the infection acquisition sites have an effect on the prognosis of SBP. In order to identify the prognostic significance of the acquisition sites, we studied 106 patients who were diagnosed as culture positive SBP between October 1998 and August 2003. Thirty-two episodes were nosocomial and 74 were community acquired. Gram-negative bacilli such as Escherichia coli were dominant in both of the nosocomial and community-acquired SBPs. Despite significantly higher resistance to cefotaxime in nosocomial isolates compared to community-acquired isolates (77.8% vs. 13.6%, p=0.001), no difference was found regarding short or long term prognosis. Infection acquisition sites were not related to short or long term prognosis either. Shock, gastrointestinal bleeding and renal dysfunction were related to short term prognosis. Only Child-Pugh class C was identified as an independent prognostic factor of long-term survival.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Ciprofloxacin; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Female; Gastrointestinal Hemorrhage; Humans; Kidney Diseases; Klebsiella pneumoniae; Male; Middle Aged; Multivariate Analysis; Peritonitis; Prognosis; Shock; Survival Rate; Time Factors

Topics: Bacterial Infections; Cefotaxime; Cephalosporins; Drug Therapy, Combination; Humans; Kidney Diseases; Peritonitis; Randomized Controlled Trials as Topic; Serum Albumin

Topics: Albumins; Bacterial Infections; Cefotaxime; Cephalosporins; Combined Modality Therapy; Humans; Infusions, Intravenous; Kidney Diseases; Liver Cirrhosis; Paracentesis; Peritonitis; Plasma Volume

Topics: Albumins; Bacterial Infections; Cefotaxime; Central Venous Pressure; Cephalosporins; Fluid Therapy; Humans; Infusions, Intravenous; Kidney Diseases; Liver Cirrhosis; Paracentesis; Peritonitis

The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis.. Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon.. Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney.. The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics.. Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.

Topics: Acute Disease; Administration, Oral; Amphotericin B; Animals; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Cecal Diseases; Cefotaxime; Colistin; Disease Models, Animal; Drug Therapy, Combination; Imipenem; Injections, Intravenous; Kidney Diseases; Male; Necrosis; Pancreas; Pancreatic Diseases; Pancreatitis; Rats; Rats, Sprague-Dawley; Survival Rate; Tobramycin

The pharmacokinetics of single, 1- or 2-g intravenous doses of cefodizime were studied in subjects with normal, impaired renal function or requiring chronic hemodialysis. Drug concentrations were measured using high-performance liquid chromatography. Forty-five subjects (20 with creatinine clearance of > or = 90 mL/min, 15 with creatine clearances between 5 and 89 mL/min, and 10 requiring chronic hemodialysis) were studied. The concentration-time curve of cefodizime was best represented by an open two-compartment model. The elimination half-lives in subjects with normal (Group 1) and impaired renal function (Group 2) or requiring chronic hemodialysis (Group 3) were 4.14 +/- 1.55, 5.10 +/- 2.24, and 10.1 +/- 6.01 hours, respectively (Group 3 versus 1 or 2, P < .05; Group 1 versus 2, P > .05). The total body (serum) clearances in the same groups were 3 +/- 0.52, 2.22 +/- 0.61, and 0.99 +/- 0.33 L/hour, respectively (Group 1 versus 2 or 3, P < .05; Group 2 versus 3, P < .05). Although renal function has an effect on the pharmacokinetics of cefodizime, its effect on the elimination half life is marginal in subjects with creatinine clearance of more than 25 mL/min. In individuals with more severe renal impairment or those requiring chronic hemodialysis, dosage adjustment would be required.

Topics: Adult; Aged; Cefotaxime; Female; Half-Life; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Renal Dialysis

It is generally assumed that the renal clearance of drugs in patients with renal impairment are affected to a similar extent regardless of the type of renal disease (intact nephron hypothesis). We have studied the effect of underlying renal disease on the pharmacokinetics of cefotaxime and desacetylcefotaxime in two groups of children (ages 7 to 16 y) with varying degrees of renal dysfunction. Patients in group 1 (n = 5) had intrinsic renal disease and those in group 2 (n = 5) had extrinsic renal disease, as identified by the primary renal lesion. After a single intravenous dose of cefotaxime timed blood and urine samples were collected for 24 h; cefotaxime and desacetylcefotaxime were measured by HPLC. There were no significant differences between the groups in age, body surface area, urine output, creatinine clearance, total body clearance, nonrenal clearance, renal clearance, and volume of distribution at steady state of cefotaxime, and renal clearance of desacetylcefotaxime. However, the renal clearance: creatinine clearance (CLR:CLCR) ratios for both cefotaxime [1.34 in group 1 vs. 0.51 in group 2] and desacetylcefotaxime [1.58 in group 1 vs. 0.75 in group 2] were statistically significant between the two groups. Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR = 24 ml.min-1.73 m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Cefotaxime; Child; Creatinine; Humans; Kidney Diseases; Pharmaceutical Preparations; Regression Analysis; Urodynamics

The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulate in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 micrograms.ml-1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL.f-1) was 154 ml.min-1, the mean renal clearance (CLR) was 39.1 ml.min-1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12-14 h in patients with an endogenous creatinine clearance below 20 ml.min-1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.

Topics: Administration, Oral; Adult; Anti-Infective Agents, Urinary; Biological Assay; Cefixime; Cefotaxime; Chromatography, High Pressure Liquid; Humans; Kidney Diseases; Male; Metabolic Clearance Rate; Time Factors; Uremia

Sisomicin (SMN) and cefotaxime (CTX) antimicrobial effect (AME) kinetics were studied under in vitro stimulation the drug monoexponential pharmacokinetic profiles mimicking normal and impaired elimination of SMN or CTX administered in various doses to humans. Similar general shape of the AME intensity or duration vs the SMN and CTX AUC curves, i.e. the appearance of the "bacteriostatic" and "bactericidal" phases, was established irrespective of the antibiotic elimination rate. At the same time the AME vs AUC curves simulated normal and delayed drug elimination did not match. Thus, AME is defined not only the AUC value but also the peculiarities of the pharmacokinetic profile and, subsequently, the term of "antibiotic efficient concentration" is unseparable of the pharmacokinetic profile.

Topics: Anti-Bacterial Agents; Cefotaxime; Escherichia coli; Half-Life; Humans; Infusions, Intravenous; Kidney Diseases; Models, Biological; Sisomicin

We studied cefotaxime (CTX) and desacetylcefotaxime (dCTX) pharmacokinetics in 19 children (ages, 7 to 16 years) with various degrees of renal function. The patients were stratified into three groups according to 24-h urinary creatinine clearance (CLCR) values: group I, CLCR greater than 80 ml/min/1.73 m2 (n = 7); group II, CLCR from 30 to 80 ml/min/1.73 m2 (n = 6); and group III, CLCR less than 30 ml/min/1.73 m2 (n = 6). A single 50-mg/kg dose of CTX was given intravenously to each patient after which blood and urine samples were collected and analyzed for CTX and dCTX by high-performance liquid chromatography. Safety was assessed by pre- and poststudy blood chemistries and urinalysis. The mean values for total body clearance of CTX for groups I, II, and III were 158.1 +/- 38.8, 118.3 +/- 50.8, and 84.8 +/- 11.7 ml/min/1.73 m2, respectively (P less than 0.01). Renal clearance also decreased across groups, I, II, and III, with values of 77.5 +/- 20.2, 41.3 +/- 18.5, and 11.4 +/- 7.7 ml/min/1.73 m2 respectively (P less than 0.0001). Both the CTX fraction nonrenally cleared and elimination half-life increased with decreasing renal function. The CTX volume of distribution at steady state was not affected by renal disease. The renal clearance values of dCTX were 146.4 +/- 71.4, 64.5 +/- 32.1, and 14.4 +/- 8.7 ml/min/1.73 m2 for groups I, II, and III, respectively (P less than 0.0004). Elimination half-life values were 2.04 +/- 0.39, 3.87 +/- 1.93, and 6.19 +/- 3.22 h for the respective groups (P less than 0.006). Both the maximum concentration of dCTX in plasma and time to reach the maximum concentration of dCTX in plasma were increased with decreased CLCR. The results of this study indicate that dosage adjustment may be necessary for CTX in children with renal dysfunction. On the basis of the pharmacokinetics and antimicrobial activities of the parent drug and its metabolite, dosage reductions of 25 to 50% in children with moderate renal impairment (CLCR from 30 to 80 ml/min/1.73 m2) and 50 to 75% in children with severe renal impairment (CLCR < 30 ml/min/1.73 m2) are recommended.

Topics: Adolescent; Cefotaxime; Child; Half-Life; Humans; Infusions, Intravenous; Kidney Diseases

In young adults, the elimination half-life of cefodizime is 3.5-4 h. A pharmacokinetic study was performed in eight patients, aged 63 to 85 years, divided into two groups with the following creatinine clearances (group I: greater than or equal to 50 ml/min and group II: less than 30 ml/min). Cefodizime was administered as a 1.0-g iv bolus. In group I, pharmacokinetic parameters did not differ from those observed in young healthy volunteers in a previous study. In group II, the half-life was increased (3.42-7.41 h). There is a linear correlation between the creatinine clearance and total clearance. The daily dose given needs to be based not on the age of the patient but on the degree of renal impairment. In elderly patients with severe renal impairment, the daily dose should be reduced if the creatinine clearance falls below 30 ml/min.

Topics: Adult; Aged; Aged, 80 and over; Aging; Cefotaxime; Creatinine; Half-Life; Humans; Kidney Diseases; Middle Aged

Effects of cefpirome (CFP, HR 810; CAS 84957-29-9) and other cephalosporins such as cefotaxime (CFX), cephaloridine (CPH) and ceftazidime (CFZ) on the renal biochemical processes such as peroxidation of lipids, organic cation transport or gluconeogenesis were investigated in vitro or after i.v.-administration of cephalosporins to 200 g male Wistar rats. In a series of in vitro experiments renal cortical slices were incubated for 60 min in a cephalosporin free medium or in a cephalosporin containing medium (1.25, 2.5, 5.0 and 10 mg/ml) at 37 degrees C under a 100% O2 atmosphere. Subsequently, peroxidation of lipids (LPO), measured as malondialdehyde (MDA) production, tissue accumulation of the organic cation tetraethylammonium (TEA) and gluconeogenesis were determined. In one series of in vivo experiments, 2 h after i.p.-administration of saline, CFP, CFX, CPH and CFZ (0, 500, 1000 and 2000 mg/kg), rats were killed and the amount of the reduced glutathione (GSH) in the renal cortex was measured. In another series of experiments, CFP, CFX, CPH and CFZ were administered (1200 mg/kg/d, i.v.) for 5 days. Subsequently, the effects of these cephalosporins on MDA production, cytosolic lactate dehydrogenase (LDH) activity, TEA accumulation and gluconeogenesis in the renal cortex were investigated. Results of the in vitro experiments show a significant concentration-dependent increase in MDA production only after incubation of renal cortical slices with CPH. CFZ and CPH caused a dose-dependent decrease in gluconeogenesis and except CFX, all other investigated cephalosporins induced a dose-dependent decrease in TEA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cefotaxime; Cefpirome; Cephalosporins; Cytosol; Gluconeogenesis; Glutathione; In Vitro Techniques; Kidney Cortex; Kidney Diseases; L-Lactate Dehydrogenase; Male; Malondialdehyde; Oxidation-Reduction; Rats; Rats, Inbred Strains; Tetraethylammonium; Tetraethylammonium Compounds

The effect of meropenem on animal kidneys has been assessed in rats (5 of each sex/group), rabbits (3 of each sex/group) and monkeys (3 of each sex/group) in comparative iv studies with ceftazidime, cefotaxime, cephaloridine and imipenem (without cilastatin). Diarrhoea occurred in rabbits and monkeys dosed with imipenem or meropenem. Emesis occurred only after the administration of imipenem to monkeys. After 14 days administration to rats evidence of nephrotoxicity was seen only in males dosed with cephaloridine (850 mg/kg); no changes were seen with ceftazidime, cefotaxime or meropenem (all at 1000 mg/kg). Four days after a single dose to rabbits renal tubular necrosis was seen in all animals receiving imipenem (150 mg/kg) and cephaloridine (250 mg/kg). Minimal histopathological changes to the kidneys were seen with cefotaxime, ceftazidime and meropenem (all at 400 mg/kg). After seven days' administration to cynomolgus monkeys imipenem (180 mg/kg) caused moderate to severe tubular necrosis. No tubular damage was seen with meropenem at 180 mg/kg or with cefotaxime or ceftazidime (both at 500 mg/kg). At 500 mg/kg meropenem caused mild tubular regeneration and/or fat accumulation in 3/6 animals, with mild tubular necrosis in one of these. The data from these three species indicate that meropenem has a low nephrotoxic potential in these animal models.

Topics: Animals; Anti-Bacterial Agents; Blood Chemical Analysis; Carbapenems; Cefotaxime; Ceftazidime; Cephaloridine; Female; Kidney Diseases; Macaca fascicularis; Male; Meropenem; Rabbits; Rats; Rats, Inbred Strains; Species Specificity; Thienamycins

Renal effects of cefodizime sodium (THR-221) administered by the intravenous route singly and for 7 consecutive days to male rabbits, were compared with those of cefazolin sodium (CEZ) and cephalothin sodium (CET). Four animals were used in each group including control groups. In the single-dose study, THR-221 (600 and 1800 mg/kg) and CET (1800 mg/kg) caused no nephrotoxic effects. In the CEZ groups (600 and 1800 mg/kg), findings indicative of the decreased renal function were obtained: serum urea nitrogen and creatinine levels increased over the control values, and phenolsulfonphthalein (PSP) retention test showed a delay in PSP excretion from the blood. In addition, the white surface of the kidney was macroscopically observed, and microscopic examination revealed renal proximal tubular changes such as necrosis, hyaline cast and calcification, suggesting renal disorders. The repeated-dose study also showed similar results to those described above. Administration of THR-221 (200 and 600 mg/kg/day) and CET (600 mg/kg/day) caused no effects on the kidney. In the CEZ groups (200 and 600 mg/kg/day), serum chemical and PSP test results suggested the decreased renal function, and macroscopic and microscopic findings included organic changes in the kidney. These results suggest that under the conditions tested THR-221 dose not elicit signs of nephrotoxicity in contrast to CEZ, and behaves almost equally to CET.

Topics: Animals; Calcinosis; Cefazolin; Cefotaxime; Cephalothin; Drug Administration Schedule; Injections, Intravenous; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Tubules; Male; Necrosis; Rabbits

Ten patients (two with normal, eight with impaired renal function) on their usual diet were treated with cefodizime (HR 221) for seven days. The dosage was 4 g/day, adapted to renal function as appropriate. Platelet function, plasma coagulation and vitamin K metabolism were investigated before and on day 7 of therapy. Platelet function and plasma coagulation remained unchanged, regardless of the size of the serum antibiotic trough levels, in both normal and impaired renal function. Vitamin K1 metabolism remained unaffected, since no increase in vitamin K1 2,3 epoxide in the circulation was observed during the therapy. Cefodizime (HR 221), a parenteral aminothiazole cephalosporin, does not affect hemostasis.

Topics: Adult; Aged; Bacterial Infections; Bleeding Time; Blood Coagulation; Cefotaxime; Chemical Phenomena; Chemistry; Female; Hemostasis; Humans; Kidney Diseases; Male; Middle Aged; Platelet Aggregation; Platelet Count; Vitamin K

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

Cefixime (CFIX) was given orally in a single dose of 100 mg to 7 patients with varying degrees of impaired renal function (Ccr 12.0-56.7 ml/min) and serum concentrations and urinary excretion rates were measured with time for the first 24 hours by the bioassay method to investigate in vivo pharmacokinetics of the drug. The results obtained are summarized as follows. The mean peak serum concentration of CFIX in 3 patients with moderately impaired renal function (group I: Ccr greater than or equal to 30-less than 60 ml/min) was 2.04 micrograms/ml at 6 hours after dosing and gradually declined to 0.10 microgram/ml at 24 hours after dosing. The half-life was 4.15 hours. The mean peak serum concentration of CFIX achieved was 2.27 micrograms/ml at 8 hours after dosing in 4 patients with severely impaired renal function (group II: Ccr greater than or equal to 10-less than 30 ml/min) and the concentration of CFIX was 0.99 microgram/ml even after 24 hours. The half-life was prolonged to 11.05 hours. There was no great difference between groups I and II in the first 24-hour urinary excretion rates. However, the first 4-hour urinary excretion accounted for 2.14% of the administered dose of CFIX in group I but only 0.47% in group II. Urinary concentrations of CFIX peaked at 4-6 hours after dosing in both groups, and thereafter gradually decreased in group I. Whereas, they did not decline much in group II until 24 hours after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Cefixime; Cefotaxime; Drug Administration Schedule; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Middle Aged

Serum and renal tissue concentrations of ceftizoxime (CZX) after intravenous dosing with 1 g were determined in 15 patients with renal disease. The highest serum concentration of CZX was 105 micrograms/ml 6 minutes after dosing and the lowest concentration was 10.5 micrograms/ml at 170 minutes. The highest renal tissue concentration was 155 micrograms/g and the lowest concentration was 7.46 micrograms/g. There were no correlation between the tissue concentrations and sampling time. Tissue to serum concentration ratios ranged from 0.28 to 5.73. These patients were divided into 3 groups; hydronephrosis, normal kidneys and renal atrophy according to pyelographic findings. Their renal tissue concentrations were compared with serum concentrations in each group. The tissue concentrations were lower than the serum concentrations in the first group, and were almost the same or higher in the other groups. CZX concentrations in the medulla and the cortex were determined in 5 patients; and were higher in the medulla in 4 of these patients. Urinary tract infection due to E. coli, K. pneumoniae, P. mirabilis, S. pyogenes or S. epidermidis was present in 5 of the 25 patients. Intravenous injection of 1 g of CZX provided therapeutically effective concentrations against these urinary tract infections.

Topics: Adult; Aged; Cefotaxime; Ceftizoxime; Child; Female; Humans; Injections, Intravenous; Kidney; Kidney Diseases; Male; Middle Aged

The pharmacokinetics of cefotaxime, its desacetyl metabolite and ceftriaxone were studied in 72 patients with various degrees of renal and hepatic failure. Patients with severe renal failure (creatinine clearance 3 to 10 ml/min) had a cefotaxime serum half-life of 2.6 h, a desacetyl cefotaxime serum half-life of 10 h and ceftriaxone serum half-life of 17 h. In the case of ceftriaxone, this serum half-life could be very variable--increasing to over 50 h, possibly due to co-existing hepatic dysfunction. Increases in serum half-life were found for cefotaxime in the presence of liver disease.

Topics: Adult; Aged; Cefotaxime; Ceftriaxone; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Liver Diseases; Male; Middle Aged

The pharmacokinetics of cefotiam were investigated after intravenous administration of 1 g to 2 healthy volunteers with normal renal function and to 16 patients whose creatinine clearance ranged from 4.7 to 0.1 l/h (78 to 1.66 ml/min). The elimination half-life varied from 1.1 h in normal subjects to 13 h in patients and the total plasma clearance from 21 to 0.6 l/h (350 to 10 ml/min). The urinary recovery decreased from 62% of the dose in normal subjects to 1.1% in patients, and the renal clearance from 15 to 0.01 l/h (250 to 0.5 ml/min). Plasma and renal clearances of cefotiam correlated well with the creatinine clearance. The dosage schedule for cefotiam in patients with normal renal function can be used in the presence of renal failure when the creatinine clearance is equal to or greater than 1 l/h (16.6 ml/min). For patients whose creatinine clearance is less than 1 l/h, the dose must be decreased to 75% of that for a patient with normal renal function only when it is given every 6 or 8 h.

Topics: Adult; Cefotaxime; Cefotiam; Creatinine; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Time Factors

Ceftriaxone (CTRX) was examined in the blood level and urinary excretion between a healthy group of 2 persons receiving 1 g CTRX for 1 day and the other of 3 patients with renal failure receiving 1 g for 3 days, both by intravenous injection or intravenous drip infusion. In the healthy group, the blood half-life time of CTRX was 6.0 hours in 1 person and 8.2 hours in the other, being 7.1 hours on average. The mean blood level in the healthy group was 199 micrograms/ml at peak and was 13 micrograms/ml at 24 hours after administration. In patients with renal failure, the peak blood level ranged from 136.8 to 161.1 micrograms/ml on the 1st day, from 163.1 to 217.0 micrograms/ml on the 2nd day and from 156.4 to 189.7 micrograms/ml on the 3rd day, showing no tendency of getting higher, while the bottom level did from 15.2 to 47.4 micrograms/ml on the 1st day, from 23.3 to 67.9 micrograms/ml on the 2nd day and from 10.9 to 72.6 micrograms/ml on the 3rd day. The urinary excretion rate was 54.6 +/- 3.7% on average in the healthy group while it ranged from 13.7 +/- 1.8 to 27.9 +/- 7.9% in the patient group. CTRX was effective especially against E. coli among the strains clinically isolated from the patients with renal failure. No side effects were observed in any case.

Topics: Adult; Aged; Cefotaxime; Ceftriaxone; Escherichia coli; Female; Humans; Infusions, Parenteral; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Pseudomonas

In patients with normal hepatic and renal function, between 30 and 60 percent of administered ceftriaxone is eliminated by nonrenal (biliary) mechanisms. Substantial nonrenal elimination reduces the need for dose adjustments in mild and moderate renal impairment. Minor increases in the biologic half-life (12 hours versus normal of 8 hours) of ceftriaxone have been seen in (functionally) anephric patients with normal extrarenal clearance mechanisms. Anephric patients with decreased nonrenal elimination (additional liver damage) showed a greater increase in biologic half-lives (greater than 15 hours). In patients with various degrees of liver insufficiency (alcoholic fatty liver and cirrhosis with and without ascites), only those with ascites showed significant changes in total drug clearance and volume of distribution. However, these changes in patients with ascites were such that they did not demonstrate significantly different biologic half-lives (9.7 hours versus normal of 8 hours). Simulations of observed concentration versus time data support a physiologic disposition model whereby ceftriaxone, like other cephalosporins, distributes only in plasma and in the extravascular-extracellular (interstitial) fluid and ceftriaxone is saturably bound to albumin in both spaces. All observations in normal subjects and patients were in good agreement with the physiologic disposition model predictions. The consequences of the nonlinear binding behavior of ceftriaxone are such that they favor the administration of ceftriaxone in a large single dose rather than in divided doses. No major drug accumulation is expected in patients with renal or hepatic insufficiency, but anephric patients with a decrease of more than 80 percent in nonrenal elimination will require dose adjustments.

Topics: Blister; Blood Proteins; Cefotaxime; Ceftriaxone; Humans; Kidney Diseases; Kinetics; Liver Diseases; Models, Biological; Protein Binding

The pharmacokinetic behavior of ceftriaxone was studied in 60 patients with severe community- or hospital-acquired infections. Serum concentrations one to three hours after a 30-minute intravenous infusion appeared to be dose related. The mean two-hour levels were 110, 138, and 146 mg/liter, and trough values averaged 54.9, 28.5, and 16.1 mg/liter after doses of 1.0, 2.0, and 3.0 g, respectively. At 24 hours, values were at least 10 mg/liter in all but seven patients. The serum half-life of ceftriaxone in all patients and for all dosage regimens varied from 3.5 to 59.4 hours. In patients with normal renal function (serum creatinine 1.30 mg/dl or less) the mean half-life was 8.2 hours. In patients with moderate (creatinine 1.34 to 1.83 mg/dl) and severe (creatinine 2.40 mg/dl or greater) renal insufficiency, the mean serum half-lives were 12.8 and 12.4 hours, respectively. In six patients who had severe renal failure and concomitant hepatic dysfunction, half-lives ranged from 23.7 to 59.4 hours. Single daily doses of 2.0 g of ceftriaxone produced adequate serum concentrations. Dose reductions are recommended in patients with both renal and hepatic dysfunction.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Half-Life; Humans; Kidney Diseases; Kinetics; Liver Diseases; Middle Aged

The pharmacokinetics of cefmenoxime were determined after a 30-min intravenous infusion of 15 mg/kg of total body weight to 33 adult subjects with normal renal function (CLCR, greater than 80 ml/min per 1.73 m2, group I), mild renal insufficiency (CLCR, 40 to 79 ml/min per 1.73 m2, group II), moderate renal insufficiency (CLCR, 10 to 39 ml/min per 1.73 m2, group III), or severe renal impairment, (CLCR, less than 10 ml/min per 1.73 m2, group IV) or to patients between hemodialysis (CLCR, less than 10 ml/min per 1.73 m2, group V). Concentrations of cefmenoxime in serum and urine were determined by high-pressure liquid chromatography, and serum concentrations were fit to a two-compartment model. There was no significant relationship between creatinine clearance and either peak serum concentrations or volume of distribution at steady state. Patients in group I excreted 81% of the dose into the urine within 24 h; recovery decreased with worsening renal function. The mean terminal half-lives in groups I to V were 1.06, 1.50, 3.55, 4.60, and 11.4 h, respectively. There were good linear relationships between creatinine clearance, and the elimination rate and total body clearance of cefmenoxime. Dosage recommendations for subjects with renal insufficiency are proposed.

Topics: Cefmenoxime; Cefotaxime; Creatinine; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Metabolic Clearance Rate

The possible influence of the concomitant administration of cefotiam and cefsulodin on their respective pharmacokinetics was studied in 15 patients with renal insufficiency and 10 anuric patients. Linear relations were found between the clearance of creatinine and the total clearance, as well as the renal clearance, of each drug. These relations for each cephalosporin were not significantly different from previous results obtained after separate administration. In hemodialyzed patients, the two cephalosporins were readily eliminated from the blood after simultaneous administration: ca. 35% of the dose of cefotiam and 30% of the dose of cefsulodin was recovered in the dialysate over 5 h. These results suggest that the pharmacokinetics of the two drugs are not modified by their simultaneous administration and that the dosing schedule previously proposed for administration of the two cephalosporins alone in the presence of renal insufficiency can be applied without modification when they are given together. Patients on hemodialysis should receive a loading dose after each dialysis period, and then reduced doses according to recommendations for anuric patients.

Topics: Adult; Aged; Cefotaxime; Cefotiam; Cefsulodin; Drug Combinations; Female; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of cefotaxime and probenecid, given by intravenous injection, were determined in six Merino ewes which had been subjected to a 75% reduction in renal mass. These results were compared with results previously determined in sheep with normal renal function. In the sheep with reduced renal mass, the following significant changes in parameter values for cefotaxime were observed. The elimination rate constant (kel) decreased by 47%, the apparent volume of the central compartment (Vc) decreased by 59%, the steady state volume (Vss) decreased by 50%, and the total body clearance (ClB) decreased by 78%. The rate constant for distribution of drug into tissues (k12) increased 6.9 times, the rate constant for distribution out of tissues (k21) increased 3.7 times, and the area under the plasma concentration-time curve (AUC) increased by a factor of 4.9. The parameter values, determined in sheep with reduced renal mass, for probenecid plasma half-life, Vss and the rate constants k12, k21, and kel were not significantly different from the values obtained previously in sheep with normal renal mass. However, the rate constant for renal excretion of probenecid (ke), renal clearance (ClR), ClB and Vc decreased by 79, 90, 54 and 36%, respectively. The results indicate that reduced renal mass increased the plasma half-life for cefotaxime as well as increasing its diffusion into tissue. In the case of probenecid the overall distribution and elimination kinetics were not altered by reduced renal mass; however, the rate of urinary excretion of the drug was reduced.

Topics: Animals; Cefotaxime; Female; Glomerular Filtration Rate; Hydrogen-Ion Concentration; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Kinetics; Probenecid; Renal Circulation; Sheep; Sheep Diseases

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 pharmacokinetics of cefmenoxime were characterized in five healthy volunteers and in 15 subjects with various degrees of renal insufficiency after a single 10-mg/kg, 5-min intravenous infusion. Five of these subjects were studied both on hemodialysis and during an interdialytic period. Plasma, urine and dialysate were assayed for cefmenoxime by a specific high-pressure liquid chromatographic assay. Peak plasma concentrations of cefmenoxime were ca. 94 micrograms/ml after completion of the infusion. The mean plasma and renal clearances in the healthy volunteers were 281 +/- 66 and 228 +/- 52 ml/min, respectively. Plasma clearance declined in patients with renal insufficiency and correlated significantly with creatine clearance. The mean apparent volume of distribution at steady state in the healthy volunteers was 0.23 liters/kg and was not found to be significantly different in subjects with renal insufficiency. The mean cumulative 24-h urinary recovery of cefmenoxime in healthy volunteers was 81% of the administered dose and decreased with reduced renal function. Cefmenoxine dosage should be reduced in proportion to the decline in creatinine clearance. A simple nomogram for dose selection is provided.

Topics: Adult; Aged; Cefmenoxime; Cefotaxime; Chromatography, High Pressure Liquid; Creatinine; Female; Humans; Kidney Diseases; Kidney Function Tests; Kinetics; Male; Middle Aged; Renal Dialysis

Cefotaxime (CTX) kinetics, alone and in combination with azlocillin (AZ), were determined in 18 subjects with either normal or impaired renal function. After the single dose and with increasing renal insufficiency, total CTX clearance fell from 266 to 71 ml/min/1.73 m2. At the same time the terminal t1/2 rose from 1.1 to 2.8 hr. Regardless of the degree of renal function, CTX clearance in combination with AZ in all patients was only 50% to 60% of that with CTX alone. This reduction in total body clearance was due to a parallel decrease in renal and nonrenal clearance. In advanced renal failure, particularly after AZ, the terminal t1/2 of the CTX metabolites increased up to 1000% to 1500% of normal. On the basis of these findings, CTX dosage adjustment is recommended only in patients with a glomerular filtration rate (GFR) below 20 ml/min. After AZ, however, dosage reduction of CTX seems to be advisable at an earlier stage of renal impairment (GFR 40 ml/min).

Topics: Adult; Azlocillin; Cefotaxime; Drug Interactions; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Penicillins

The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, urine and dialysate samples were collected at predetermined times and analyzed for ceftriaxone by high-pressure liquid chromatography. The elimination half-life (group mean ranged from 11.7 to 17.3 h) and plasma clearance (group mean ranged from 529 to 705 ml/h) did not correlate linearly with creatinine clearance. The renal clearance and fraction of dose excreted unchanged in urine were related linearly, however weakly, with creatinine clearance. Ceftriaxone was not removed from plasma to a significant extent during hemodialysis. The half-life was prolonged twofold, the plasma clearance was lowered less than 50%, and the volume of distribution was relatively unchanged in renally impaired patients compared with young or elderly healthy subjects with normal renal function at an equivalent dose. Since these changes are moderate, adjustment in the dosage regimen of ceftriaxone for patients with impaired renal function should not be necessary when ceftriaxone dosage is 2 g or less per day (2 g every 24 h or 1 g every 12 h). It was reported that the elimination half-life of ceftriaxone is substantially prolonged in a small percentage of patients with end-stage renal disease maintained on hemodialysis. Therefore, plasma concentrations of ceftriaxone should be monitored in dialysis patients to determine whether dosage adjustments are necessary.

Topics: Adult; Aged; Aging; Cefotaxime; Ceftriaxone; Female; Half-Life; Humans; Infusions, Parenteral; Kidney Diseases; Kinetics; Male; Middle Aged; Renal Dialysis; Time Factors

7 beta-[2-(2-Aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido]-3-[(1- methyl-1H-tetrazol-5-yl)thiomethyl]-ceph-3-em-4-carboxylic acid hemihydrochloride (Cefmenoxime), a new cephalosporin with a broad spectrum of activity against gram-positive and gram-negative bacteria, was investigated pharmacokinetically. 10 healthy volunteers and 20 patients with renal disease each received 2 g of the substance i.v. The plasma levels were monitored for 6 h in healthy volunteers and for 24 h in the patients with renal disease. The analysis of the data showed that the majority of the curves could be properly evaluated only with the aid of a two-compartment model. Therefore a simple half-life cannot be given. Cefmenoxime is eliminated more rapidly than cefoperazone, but more slowly than cefotaxime. The area under the serum level curves (AUC) increases when renal function is impaired. There is a mathematical correlation between the AUC and the renal function parameters, plasma creatinine and glomerular filtration rate. This gives the dose reduction factors, allowing the calculation of the doses with the same AUC on restricted renal function as that observed in healthy persons after normal doses. Dosage recommendations are given in the form of tables regarding the questions 1. to what extent the dose may be reduced in impaired renal function without lowering the AUC and 2. what is the highest safe dose.

Topics: Cefmenoxime; Cefotaxime; Creatinine; Female; Glomerular Filtration Rate; Half-Life; Humans; Injections, Intravenous; Kidney Diseases; Kinetics; Male

We developed a protocol to study interference by cefotaxime and one of its major metabolites with 24 common chemical tests. Serum pools simulating specimens from healthy adults of both sexes, pregnant women, patients with liver disease, cardiac disease, or renal disease, and patients receiving gentamicin and tobramycin were supplemented with high and low concentrations of cefotaxime and desacetylcefotaxime. Using a discrete analyzer (the American Monitor Parallel), we tested 12 replicate samples from each condition for 24 analytes. Although statistically significant changes were found in many tests, 85% of the differences were less than 15% of the control value and more than half were less than 5%. The apparent concentration of creatinine was not significantly changed. Test results for phosphorus were increased in patients who were receiving gentamicin and tobramycin. No other changes were considered clinically significant.

Topics: Blood Chemical Analysis; Cefotaxime; False Positive Reactions; Female; Gentamicins; Heart Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Pregnancy; Probability; Tobramycin

We investigated the kinetics of ceftizoxime, a beta-lactamase stable cephalosporin, in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 500-mg or 1-gm dose was injected IV, or a 500-mg dose was given intraperitoneally in the CAPD fluid during a 6-hr dwell time. The ceftizoxime (500 mg) serum kinetic parameters were as follows: peak concentrations, 21 to 46 mg/l; volume of distribution, 0.27 l/kg; elimination rate constant, 0.0784 hr-1; plasma clearance, 1.66 l/kg hr-1; and t1/2, 10.2 hr. The t1/2 after 1 gm was 12 hr. Dialysate ceftizoxime concentrations rose rapidly between 0.25 and 2 hr and slowly over the next 4 hr, but only 4.04 +/- 1.8 and 7.4 +/- 2.9 mg ceftizoxime/hr was eliminated by the peritoneal route over a 6-hr dwell time after 500 mg or 1 gm IV. This represents only 4% to 5% of the dose. After intraperitoneal instillation, the antibiotic appeared in the serum within 15 min in all four subjects, and the peak serum concentrations ranged from 12 to 19.8 mg/l (mean +/- SD = 16.4 +/- 3.3) between 5 and 6 hr. Approximately 78% of ceftizoxime was absorbed from the peritoneal dialysis fluid during a single 6-hr dwell time. Rate constant for absorption, ka, was 0.3959 hr-1 and absorption t1/2 was 1.75 hr (as calculated by the residual equation). These data suggest that ceftizoxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of ceftizoxime in CAPD fluid alone may permit rapid absorption to reach therapeutic serum concentrations.

Topics: Absorption; Adult; Aged; Cefotaxime; Ceftizoxime; Female; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory

The pharmacokinetics of ceftizoxime (FK-749) were studied in 20 volunteers with various degrees of renal function. Creatinine clearances ranged from zero to 157 ml/min per 1.73 m2. One gram of ceftizoxime was administered by a 30-min drip infusion, and blood and urine samples were collected for up to 48 h after drug administration. For volunteers with a creatinine clearance of greater than or equal to 80 ml/min per 1.73 m2 (group I), the mean half-life was 1.65 h, whereas for volunteers with a creatinine clearance of less than 10 ml/min per 1.73 m2 (group IV), the half-life was 34.7 h. The volume of distribution at steady state (Vdss) and the volume of distribution area (Vdarea) were calculated for each group and ranged from 0.377 to 0.263 and 0.421 to 0.264 liters/kg for groups I and IV, respectively. Total body clearance of ceftizoxime correlated with creatinine clearance (r = 0.953), and the mean urinary recovery of unchanged drug in normal volunteers was 72.4%. A 4-h hemodialysis procedure reduced serum ceftizoxime concentrations by approximately 52%; however, serum concentrations at 48 h after drug administration were still greater than 10 micrograms/ml in dialysis subjects. By using the relationship between total body clearance of ceftizoxime and creatinine clearance, a nomogram was developed to assist in the administration of ceftizoxime to patients with renal dysfunction.

Topics: Adult; Cefotaxime; Ceftizoxime; Creatinine; Female; Humans; Kidney Diseases; Kinetics; Male; Metabolic Clearance Rate; Middle Aged

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Biotransformation; Cefotaxime; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Kidney; Kidney Diseases; Kinetics; Male; Metabolic Clearance Rate; Middle Aged

Plasma concentrations of cefotaxime and desacetyl cefotaxime were determined by HPLC in geriatric patients with multiple diseases. Comparison with a younger control group of healthy volunteers showed a prolongation of half-life of CTX and dCTX in the older patients. A significant correlation between pharmacokinetic parameters of dCTX and other clinical and chemical parameters was found. Half-life of dCTX was positively correlated with age of the geriatric patients (P less than 0.05). There was also a significant relationship between CHE in serum and plasma peak concentrations of dCTX. Time until reaching plasma peak concentrations correlated closely with total bilirubin (P less than 0.01), CHE (P less than 0.001), cholesterol (P less than 0.01), and urea (P less than 0.01). Accumulation of the pharmacologically active metabolite dCTX could not be excluded in one patient with kidney disease. In accordance with other investigators it is recommended to reduce the dose of cefotaxime in geriatric patients with kidney diseases.

Topics: Aged; Arteriosclerosis; Cefotaxime; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Female; Half-Life; Heart Failure; Humans; Hypertension; Kidney Diseases; Kinetics; Male; Pneumonia; Urinary Tract Infections

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

Cefotiam (CGP 14221/E; SCE 963), a semisynthetic cephalosporin, was administered as a single dose by i.v. injection to rats l(up to 1.8 g/kg body-weight) and rabbits (up to 1.7 g/kg body-weight). Cephaloridine served as positive control (1.0 and 0.75 g/kg in rats; 0.3 and 0.28 g/kg in rabbits). The animals were sacrificed 24 h after injection and the kidneys preserved for routine histology and enzyme histochemistry (alkaline phosphatase, aminopeptidase, succinate dehydrogenase, esterase). Serum samples (Na+, K+, Cl-, urea, creatinine, LDH, alkaline phosphatase) and 24-h urine (Na+, K+, Cl-, urea, creatinine, protein, LDH, aminopeptidase) were analysed before and 24 h after injection. Minimal, irregularly scattered, degenerative changes in the proximal tubules which were not dose-dependent in degree were observed in rat kidneys following cefotiam injection. A slight dose-dependent degeneration in up to 50% of proximal tubular cells with loss of brush-border membrane enzyme activity was observed in rabbit kidneys. In both animal species the ability to concentrate urine was retained and urea and creatinine serum levels hardly affected. Following cefotiam injection a dose-dependent 4-fold excretion of urinary protein but not of LDH was observed in rabbits only. By contrast, cephaloridine caused extensive degeneration and necrosis in up to 90% of proximal tubular cells in both rats and rabbits, which was accompanied with formation of enzymically active hyaline casts, loss of urine-concentrating capacity of the kidney, elevated serum levels of urea and creatinine and an increased urinary excretion of LDH (60-fold in rats, 20-fold in rabbits) and protein (3-fold in rats, 10-fold in rabbits). Histochemistry and electron microscopy of rabbit kidneys suggested a loss of microvilli from proximal tubule cells by endocytosis and thus degeneration following injection of large doses of cefotiam, whereas cell disruption and necrosis prevailed after cephaloridine. The action of cefotiam on the proximal tubule cells is, therefore, not only quantitatively but possibly also qualitatively different from that of cephaloridine. Semiquantitative evaluation of tubular injuries in alkaline phosphatase-stained kidney sections and measurements of LDH and protein content in 24-h urine samples were advantageous in determining the quantity and the quality of nephrotoxic effects.

Topics: Animals; Cefotaxime; Cefotiam; Cephaloridine; Enzymes; Female; Histocytochemistry; Kidney Diseases; Male; Proteinuria; Rabbits; Rats

Topics: Animals; Cefotaxime; Cephalosporins; Dogs; Drug Interactions; Female; Furosemide; Kidney Diseases; Lethal Dose 50; Male; Mice; Mutagens; Pregnancy; Rats; Reproduction