ro13-9904 and Kidney-Failure--Chronic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might increase the risk of invasive pulmonary aspergillosis (IPA). Although several case reports and small series have been reported in the general population, scarce information is available regarding coronavirus disease 2019 (COVID-19)-associated IPA in the setting of solid organ transplantation. We describe a case of a kidney transplant recipient with severe COVID-19 that was subsequently diagnosed with probable IPA on the basis of the repeated isolation of Aspergillus fumigatus in sputum cultures, repeatedly increased serum (1 → 3)-β-d-glucan levels, and enlarging cavitary nodules in the CT scan. The evolution was favorable after initiation of isavuconazole and nebulized liposomal amphotericin B combination therapy and the withdrawal of immunosuppression.

Topics: Acute Kidney Injury; Administration, Inhalation; Amphotericin B; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antifungal Agents; Azithromycin; Ceftriaxone; COVID-19; Deprescriptions; Female; Glucocorticoids; Graft Rejection; Humans; Hydroxychloroquine; Hyperoxaluria, Primary; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Invasive Pulmonary Aspergillosis; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Nitriles; Oxygen Inhalation Therapy; Prednisone; Pyridines; Renal Dialysis; SARS-CoV-2; Sputum; Tacrolimus; Tomography, X-Ray Computed; Triazoles

A 73-year old man was brought to our hospital because of acute onset of fever and consciousness disturbance. He had been hemodialyzed three times a week because of chronic renal failure since 13 years ago. Neurological examination revealed deteriorated consciousness and neck stiffness. A lumbar puncture yielded clouded fluid with a WBC 7,912/mm³ (polymorphonuclear cells 88%, mononuclear cells 12%), 786 mg/dl of protein and 4 mg/dl of glucose (blood glucose 118 mg/dl). Brain CT and MRI were unremarkable. He was treated with ceftriaxone and ampicillin. Streptococcus salivarius was isolated from the blood sample, but not from cerebrospinal fluid. The patient responded promptly to antibiotics therapy (ampicillin 3g/day, ceftriaxone 1g/day), and within several days he became lucid and afebrile. Isolated S. salivarius was sensitive for ampicillin and ceftriaxone. We diagnosed this case as S. salivarius bacteremia/meningoencephalitis. A gastrointestinal diagnostic workup revealed an asymptomatic gastric adenocarcinoma. S. salivarius is a common inhabitant of the oral mucosa that has been associated with infection in different sites. Meningeal infection by S. salivarius generally related to neoplasia of colon or iatrogenia, has been described on few occasions. This is the first report of S. salivarius bacteremia/meningoencephalitis associated with gastric neoplasm. Neurologist should be aware of the association of S. salivarius bacteremia/meningoencephalitis and gastrointestinal disease.

Topics: Aged; Ampicillin; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Early Diagnosis; Gastroscopy; Humans; Kidney Failure, Chronic; Male; Meningoencephalitis; Renal Dialysis; Stomach Neoplasms; Streptococcal Infections; Sulbactam

Infection of permanent catheters (Permcath) in hemodialysis (HD) patients can lead to catheter removal. The successful use of an antibiotic-lock to treat infection has reported good results in the treatment of catheters' infections. This study was designed to evaluate the impact of the intraluminal vancomycin in comparison with intravenous antibiotic administration. We included 67 (37 males and 30 females) chronic HD patients requiring Permcath insertion at our tertiary care hospital from July 2004 to June 2007. We studied two subgroups: an intervention group, which received 500 mg vancomycin infusion via both lumens of the Permcath and antibiotic lock of 1.5 mL each 48 hours with 1 g i.v. ceftriaxone every 12 hours for 7 days, followed by oral antibiotics according to the culture for three weeks; and a control group, which received 500 mg intravenous vancomycin with daily 100-150 mg amikacin intravenously. Our endpoint was the rate of catheter removal. The patients characteristics including age, sex, time of insertion of the catheter and number of dialysis sessions per week did not differ between both subgroups. Of 28 patients in the intervention group, there was one catheter removal, and of 39 patients in the control group, there were 22 catheter removals, (P< 0.001). We conclude that administration of vancomycin as an antibiotic-lock in permcaths is more effective than its mere intravenous injection, and can increase the life span of catheters.

Topics: Administration, Oral; Amikacin; Anti-Bacterial Agents; Catheter-Related Infections; Catheterization, Central Venous; Catheters, Indwelling; Ceftriaxone; Device Removal; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Kidney Failure, Chronic; Male; Prospective Studies; Renal Dialysis; Treatment Outcome; Vancomycin

To determine the pharmacokinetic parameters of ceftriaxone following an infusion in haemodialysed outpatients and to use these parameters for an optimisation of dosing based on pharmacodynamic indices.. Fifty haemodialysed patients were enrolled in a single-centre, prospective, open-label study. They received short intravenous infusions of ceftriaxone 1 or 2 g every 48 hours for bronchopneumonia immediately after the dialysis session. Total plasma concentrations of ceftriaxone were analysed with a population pharmacokinetic approach using nonlinear mixed-effects modelling. Free drug concentrations were derived from published binding parameters in order to estimate the time when they exceed the minimum inhibitory concentration (MIC).. The pharmacokinetics were best described by a two-compartment model. None of the covariates tested (age, bodyweight, height, sex, body mass index, albumin) influenced the pharmacokinetic parameters. The estimated population pharmacokinetic parameters (interindividual variability [percentage of coefficient of variation]) were clearance 0.36 L/h (48%), volume of distribution of the central compartment 4.53 L (47%), intercompartmental clearance 10.8 L/h and volume of distribution of the peripheral compartment 9.54 L (63%). The terminal elimination half-life (t(1/2)beta) from plasma was 27.5 hours. The mean (range) times when the free drug concentration exceeded the MIC (T>MIC) following ceftriaxone 1 g infusion were 60.3 (53.0-67.7) hours and 2.5 (1.0-3.9) hours for the breakpoints 1 and 8 mg/L (based on free drug concentration), respectively. After administration of ceftriaxone 2 g, the T>MIC was 88.5 (78.8-98.3) hours and 17.7 (13.3-22.0) hours for the breakpoints 1 and 8 mg/L, respectively. The simulated free drug concentrations (median, first and third quartile) for 48 and 72 hours following the first dose of ceftriaxone 1g were 1.11, 0.63 and 1.89 mg/L, and 0.63, 0.28 and 1.18 mg/L, respectively. For ceftriaxone 2g infusion, the simulated free concentrations (median, first and third quartile) at 48 and 72 hours were 2.50, 1.40 and 4.52 mg/L, and 1.37, 0.60 and 2.70 mg/L, respectively.. On the basis of decreased clearance in haemodialysed patients, it can be argued that the dose of ceftriaxone should be decreased or the delay between doses should be increased. However, taking into account pharmacodynamic considerations, this study showed that following intravenous administration of ceftriaxone 1 g after each dialysis session, some patients were at risk of achieving a concentration below the MIC (1 mg/L), particularly if the second administration occurred 72 hours after the first dosing. Thus, a dose of ceftriaxone 2 g intravenously is recommended immediately following dialysis, particularly in patients with severe infections or when the dosing interval will be higher than 48 hours.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bronchopneumonia; Ceftriaxone; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Probenecid has been shown to decrease renal and biliary excretion of organic acids. In a randomized crossover study, the effect of coadministered probenecid on nonrenal excretion of ceftriaxone was studied in six functionally anephric patients in whom ceftriaxone is eliminated exclusively by nonrenal or presumably by biliary excretion. Each patient received 0.5 g IV ceftriaxone without and with probenecid (0.5 g at 10 and 2 hours prior to ceftriaxone and 0.5 g q12h X 3 doses post ceftriaxone). Serial blood samples were collected over 48 hours and plasma analyzed for ceftriaxone by high performance liquid chromatography (HPLC). Pharmacokinetic analysis was based on a model-independent approach. Probenecid did not significantly affect the disposition of ceftriaxone in this study, thus suggesting that nonrenal excretion of ceftriaxone is not inhibited by probenecid.

Topics: Adult; Ceftriaxone; Chromatography, High Pressure Liquid; Humans; Kidney Failure, Chronic; Middle Aged; Probenecid; Random Allocation; Time Factors

The kinetics of ceftriaxone was investigated in 8 patients without infection, who were receiving continuous ambulatory peritoneal dialysis (CAPD). Ceftriaxone 1 g was injected i.v. and 1 g was given intraperitoneally in the CAPD fluid during a 4-h dwell time. Ceftriaxone was assayed by HPLC. After intravenous administration, the kinetic parameters of ceftriaxone were: plasma t1/2, 12.3 h, total plasma clearance, 14.0 ml/min, volume of distribution at steady state 0.18 l/kg, and peritoneal clearance 0.59 ml/min. Over 72 hours only 5.5% of the dose was eliminated by the peritoneal route. After intraperitoneal administration, ceftriaxone rapidly appeared in serum; the absorption t1/2 was 1.1 h and the mean peak concentration was 38.8 micrograms/ml. The absorption of ceftriaxone from the peritoneal space was 39%. A single 1.0 g IP dose led to serum and dialysate concentrations of ceftriaxone above the minimum inhibitory concentration for susceptible pathogens for 24 hours.

Topics: Adult; Aged; Ceftriaxone; Female; Half-Life; Humans; Injections, Intraperitoneal; Injections, Intravenous; Kidney Failure, Chronic; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Random Allocation

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.

Topics: Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Cytokines; Glomerulonephritis, IGA; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tacrolimus; Treatment Outcome

Topics: Ceftriaxone; Chorea; Diagnostic Tests, Routine; Humans; Kidney Failure, Chronic; Renal Dialysis

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country's transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.

Topics: Anti-Bacterial Agents; Azithromycin; Betacoronavirus; Ceftriaxone; Coronavirus Infections; COVID-19; Creatinine; Cryoglobulinemia; Cyclophosphamide; Enzyme Inhibitors; Glomerulonephritis, Membranoproliferative; Glucocorticoids; Greece; Humans; Hydroxychloroquine; Immunocompromised Host; Immunologic Factors; Kidney Failure, Chronic; Kidney Transplantation; Leukemia, Lymphocytic, Chronic, B-Cell; Lung; Male; Methylprednisolone; Middle Aged; Pandemics; Pneumonia, Viral; Renal Dialysis; Respiration, Artificial; Respiratory Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; Rituximab; SARS-CoV-2; Tomography, X-Ray Computed

Neisseria gonorrhoeae is one of the microbes that can causes male urethritis. This microbe is most likely to be transmitted via sexual intercourse. In men, the representative infection sites are the urethra, and oral mucosa but gonococcemia is rere. We present a case of gonococcemia in a 47-year-old male successful kidney recipient. He temporarily lost his graft function due to acute kidney injury followed by sepsis; however, short-course intermittent hemodialysis and long-term intensive ceftriaxone inoculation saved his life and his graft function.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Ceftriaxone; Gonorrhea; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neisseria gonorrhoeae; Renal Dialysis; Treatment Outcome

Topics: Administration, Intravenous; Anti-Bacterial Agents; Arthrobacter; Ceftriaxone; Gram-Positive Bacterial Infections; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritonitis; Ribotyping; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Treatment Outcome

We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Glomerular Basement Membrane Disease; Autoantibodies; Basement Membrane; Ceftriaxone; Drug Substitution; Escherichia coli Infections; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Nephritis, Hereditary; Plasmapheresis; Pulse Therapy, Drug; Pyelonephritis; Treatment Outcome

Neurologic manifestations, such as myoclonus, asterixis, seizures and altered level of consciousness, may be induced in patients with impaired renal function receiving β-lactam antibiotics, which stem in part from drug accumulation because of altered pharmacokinetics. Because of its long half-life and easy penetration into the cerebrospinal fluid, the third generation cephalosporin, ceftriaxone (CTRX), is often chosen to treat patients with end-stage renal disease (ESRD). Here, the authors describe 4 patients with ESRD complicated with bacterial infection and choreoathetosis after the administration of CTRX. Choreoathetosis disappeared without leaving sequelae after CTRX therapy was withdrawn, although the severity and symptom duration varied. To our knowledge, there are few reports on choreoathetosis associated with β-lactam antibiotic administration in patients with kidney diseases. To prevent delayed diagnosis, one should bear in mind that choreoathetosis might occur in patients with ESRD treated with CTRX, when it is given in high or even regular doses.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Athetosis; Ceftriaxone; Chorea; Female; Humans; Kidney Failure, Chronic; Male

Topics: Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Cystitis; Emphysema; Female; Humans; Incidental Findings; Kidney Failure, Chronic; Klebsiella pneumoniae; Middle Aged; Renal Dialysis; Tomography, X-Ray Computed; Treatment Outcome; Urinary Bladder; Urine

Patients with End-stage Renal Disease being immunocompromised; are prone to a variety of infections, sometimes, rare ones, more than the general population. This fact should alert the physicians to be more vigilant and have a broader scope when considering the etiology of infections in such patients. We report the case of a 65-year-old man who had a very stormy hospital stay secondary to cerebral nocardiosis with multiple brain abscesses, prolonged unconsciousness and neurological deficits. However, the patient was treated successfully, surgically and chemotherapeutically. He was discharged home in a good condition.

Topics: Aged; Amikacin; Brain Abscess; Brain Diseases; Brain Edema; Ceftriaxone; Humans; Kidney Failure, Chronic; Male; Nocardia Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Unconsciousness; Vancomycin

Though the pathogenic significance and the reservoir of Ewingella americana have not been clarified, this organism has caused several pathogenic infections, especially in immunocompromised patients. We report a pneumonia in a patient with chronic renal failure, who had chronic rejection of transplanted kidney. E. americana was identified to be the pathogen of pneumonia with clinical symptoms and signs and radiological examination. As soon as he was treated with ceftriaxone and isepamicin, clinical improvement was followed with no further growth of E. americana or other pathogenic isolates from sputum culture. This suggests to be the case of pneumonia caused by E. americana for the first time in the Korean literature.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Pneumonia; Sputum; Time Factors

Topics: Adult; Ceftriaxone; Epilepsies, Myoclonic; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Infusions, Intravenous; Kidney Failure, Chronic; Kidney Transplantation; Lupus Nephritis; Postoperative Complications; Risk Assessment; Tacrolimus; Tomography, X-Ray Computed; Transplantation Immunology; Treatment Outcome

A 34-year-old female with end-stage renal disease was admitted for severe metabolic acidosis, uremic encephalopathy, pericarditis and severe anemia following a bout of acute gastroenteritis. She improved on aggressive medical management including intensive hemodialysis and was initiated onto maintenance heparin-free hemodialysis (twelve hours per week) and discharged. After a week, she presented with fever with chills and rigors for three days, was toxic, severely orthopenic and had a pulsus paradoxus of 36 mmHg. Echocardiography suggested cardiac tamponade. Aspiration revealed frank pus with polymorphonuclear predominance and Staphylococcus aureus on culture. CT of the thorax revealed pericardial effusion. In the absence of any obvious septic foci, concomitant pleuro-pulmonary sepsis, mediastinal or intra-abdominal pathology; a diagnosis of "acute primary purulent pericarditis" was made. Patient was put on parenteral antibiotics-ceftriaxone and metrogyl. Vancomycin was added after sensitivity results. Pericardial drainage was required initially. After toxemia improved, paradox decreased and fever subsided, the pericardial catheter was removed and antibiotics continued for a period of four weeks. Maintenance hemodialysis was continued during hospital stay and after discharge.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Echocardiography; Female; Humans; Kidney Failure, Chronic; Metronidazole; Pericarditis; Renal Dialysis; Staphylococcal Infections; Staphylococcus aureus; Tomography, X-Ray Computed; Vancomycin

Renal abscesses in patients with end stage renal disease are quite rare, and misdiagnosis or delaying in diagnosis is frequent. This report examines a case of renal abscess in a patient with end stage renal disease on maintenance hemodialysis and diabetes mellitus, which presented with a prolonged fever. An infected diabetic foot was impressed initially. Purulent urine, pyuria, bacteriuria, and bacteremia were noted after admission. Renal abscess was diagnosed by percutaneous needle aspiration under computerized tomography guidance. The patient was treated with parenteral antibiotics and percutaneous aspiration of the abscess. Follow-up ultrasonography showed renal abscess resolution. This case demonstrated that nephrectomy was not required in selected uremic patients with renal abscess.

Topics: Abscess; Aged; Anti-Bacterial Agents; Biopsy, Fine-Needle; Ceftriaxone; Diabetes Mellitus, Type 2; Drainage; Female; Gentamicins; Humans; Kidney; Kidney Failure, Chronic; Renal Dialysis; Staphylococcal Infections; Tomography, X-Ray Computed

Topics: Adult; Ceftriaxone; Cephalosporins; Cholelithiasis; Female; Humans; Kidney Failure, Chronic

Patients with chronic renal failure were admitted to the Neurological Department and symptoms of cholelithiasis were observed. Ceftriaxone therapy in one case was clinically effective.

Topics: Ceftriaxone; Cephalosporins; Cholelithiasis; Female; Humans; Kidney Failure, Chronic; Middle Aged

Increased susceptibility to infection is observed in patients with chronic renal failure (CRF). Therefore, when antibiotic therapy is indicated, it is reasonable to use a drug which is usually reserved as a second-choice antibiotic in other patients. Antibiotic prevention before surgical procedures with a high risk of infection, especially before renal transplantation is also often necessary. Evaluation of Biotrakson (ceftriakson) (produced in Poland) efficacy in patients with CRF was the aim of this study. The antibiotic was administered in a single, complete prophylactic dose or once daily when given therapeutically in 25 patients: 13 with end-stage renal disease treated with hemodialysis, 5 with end-stage renal disease treated with peritoneal dialysis, 4 with chronic renal failure, 1 with acute renal failure treated with peritoneal dialysis, 2 after renal transplantation. The antibiotic was given for local and generalised bacterial infections in 10 patients; in 15 the drug was administered prophylactically before serious surgical procedures (including 10 patients before renal transplantation). Resolution of infection was observed in 9 out of 10 treated patients (90%). When the antibiotic was given prophylactically, its efficacy was assessed as good in 8 of 10 patients (80%) after renal transplantation and in 4 of 5 patients (80%) after other surgical procedures. There were no significant adverse side effects in any patient. Biotrakson is, therefore, an effective drug for therapeutic and preventive use in patients with renal failure.

Topics: Adolescent; Adult; Bacterial Infections; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Humans; Infant; Kidney Failure, Chronic; Kidney Transplantation; Peritoneal Dialysis; Premedication; Renal Dialysis

Clinical efficacy of ceftriaxone (CTRX) against complicated urinary tract infections in 20 patients was examined, and the serum CTRX level was also measured in the patients with chronic renal failure (CRF). CTRX was administered at a dose of 1.0 g once a day for 5 to 10 days. The overall clinical efficacy was rated excellent in 4 cases (20%), moderate in 13 cases (65%) and poor in 3 cases (15%) with a total efficacy of 85%. Seventeen out of 27 strains (62.8%) isolated were eradicated after CTRX administration. In the patients with CRF, serum levels were very high and showed a plateau 4 hours after the injection. Furthermore, CTRX may not be removed by usual hemodialysis treatment. There were no severe side effects due to CTRX in these patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; Bacteria; Ceftriaxone; Drug Evaluation; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Urinary Tract Infections

In patients on peritoneal dialysis drug movement across the peritoneum depends on the physiology of the peritoneal membrane, the physiochemical properties of the drug, the dialysis regimen and the basic pharmacokinetic properties of the particular pharmacon. Besides the low dialysate flow rate in continuous ambulatory peritoneal dialysis (CAPD), the latter point-drug kinetics-is thought to be of major importance for the influence of CAPD on drug kinetics. The eliminative potency of CAPD for drugs is limited due to the low dialysate outflow rate, an unfavorable ratio of the dialysate to the body volumes of distribution, the usually low ratio of the peritoneal to body clearance and the effect of drug protein binding. With intraperitoneal application, the drug appears rapidly in the circulation. This again results from the large differences in the volumes of the body to the peritoneal compartments, leading to a high concentration gradient across the peritoneal membrane. Thus a rapid disappearance of a pharmacon from the peritoneal cavity following intraperitoneal application combined with an insufficient drug elimination by CAPD may be explained by basic pharmacokinetic considerations. Unidirectional peritoneal transport of a particular drug has so far not been demonstrated.

Topics: Administration, Oral; Ceftriaxone; Cimetidine; Digoxin; Humans; Injections, Intravenous; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Tobramycin

We report the pharmacokinetic parameters of ceftriaxone in 11 patients on hemodialysis with end-stage renal disease (ESRD; creatinine clearance less than 5 ml/min/1.73 m2). The patients were studied during the interdialysis period and during 4 h of hemodialysis. The mean age was 53.4 years. After the administration of 1 g of ceftriaxone during a constant intravenous infusion over a 30-min period, t 1/2 was 16.6 h, beta was 0.0418 +/- 0.0106 h-1, VD was 14.5 +/- 3.0 liters/1.73 m2 and Clp was 0.40 +/- 0.05 liters/h for the interdialysis period. Hemodialysis started 24 h after the infusion. The initial plasma ceftriaxone concentration was 68.6 +/- 10.8 micrograms/ml. This value dropped to 40.4 +/- 4.7 micrograms/ml at the end of the 4th hour, indicating a significant 41% decay in blood levels during hemodialysis (p less than 0.001). The t 1/2 decreased to 4.88 h, kel rose to 0.142 +/- 0.0250 h-1 and Clp increased to 1.73 +/- 0.44 liters/h. All values were highly significantly different (p less than 0.001) from those during the interdialysis period. The plasma ceftriaxone concentration of 40.4 +/- 4.7 micrograms/ml at the end of hemodialysis was well within the therapeutic range of the drug. We conclude that ceftriaxone has a moderated increase in t 1/2 in patients with ESRD. Ceftriaxone is significantly dialyzable, however, the plasma concentrations are in the therapeutic range by the end of a 4-hour hemodialysis, 28 h after the administration of the drug. We propose that 1 g given intravenously before each hemodialysis will be sufficient to keep the patient's plasma concentrations within the therapeutic range until the next hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Bacterial Infections; Blood Proteins; Ceftriaxone; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Kidney Failure, Chronic; Male; Middle Aged; Protein Binding; Renal Dialysis

The influence of hemodialysis on the pharmacokinetics of ceftriaxone was studied in 5 patients with chronic renal failure, with a glomerular filtration rate of less than 5 ml/min, and treated by regular hemodialysis. A single dose of 2 g ceftriaxone was administered IV at the end of a hemodialysis, and venous samples were drawn 12 and 24 h thereafter. Two hemodialysis were performed at the 44th (HD1) and the 92nd (HD2) hour, and blood samples were drawn simultaneously on arterial and venous sides of the dialyzer at the onset of HD1 and at the end of HD2. Plasma ceftriaxone concentrations were measured on each sample by both microbiological and chromatographic (HPLC) methods. In these patients, ceftriaxone kinetics are considerably longer than in normal subjects, with an elimination half-life of 16 h, an apparent distribution volume of 800 ml/kg, but without decrease of plasma clearance, except in one patient who had hepatic cytolysis at the time of injection. Plasma concentrations on both sides of dialyzers, or before and after hemodialysis, are not significantly different, and the mean hemodialysis clearance ranges between 26 and 30 ml/min/m2 dialyzer area. According to these data, the dose-interval between successive administrations of ceftriaxone 2 g IV should be 48 h in patients with chronic renal failure, and supplemental doses do not appear necessary after hemodialysis.

Topics: Adult; Aged; Bacteriological Techniques; Ceftriaxone; Chromatography, High Pressure Liquid; Humans; Kidney Failure, Chronic; Male; Middle Aged; 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 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