ro13-9904 and Kidney-Diseases

Ceftriaxone is a third-generation cephalosporin that exhibits saturable plasma protein binding, which influences its pharmacokinetic parameters depending on the dose. Systemic clearance and volume of distribution of total drug show dependence on both concentration and time, whereas for unbound drug these parameters remain constant. The decrease in renal or non-renal clearance with age or in the presence of disease states is often compensated by the concurrent increase in free fraction, resulting in no apparent changes in half-life and no need for dose adjustment. Because of its unusually long plasma half-life, the availability of intramuscular administration and its high intrinsic activity against many organisms, ceftriaxone has become a popular agent in once-daily therapy of infections in paediatric patients, gonococcal infections and outpatient management of pneumonia and osteomyelitis.

Topics: Ceftriaxone; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Kidney Diseases; Liver Diseases; Lyme Disease; Meningitis; Sexually Transmitted Diseases, Bacterial; 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

Acute pyelonephritis often leaves children with permanent renal scarring.. To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days.. In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars.. Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups.. In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring.

Topics: Acute Disease; Adolescent; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cicatrix; Drug Administration Schedule; Female; Humans; Infant; Kidney Diseases; Male; Pyelonephritis; Radionuclide Imaging; Regression Analysis; Statistics, Nonparametric; Treatment Outcome

Continuous hemofiltration is used widely in the management of patients with acute renal failure, but administration guidelines for many drugs have yet to be established. In this study, the pharmacokinetics of ceftriaxone were compared in patients with normal renal function (n = 9), mild renal insufficiency (n = 5), and acute renal failure receiving continuous veno-venous hemofiltration (n = 6). Pharmacokinetic parameters were determined under steady state conditions. Patients with mild renal insufficiency had a significantly lower renal clearance and longer half-life of ceftriaxone; however, drug recovery in the ultrafiltrate with continuous veno-venous hemofiltration was similar to that in the urine of patients with normal renal function. Pharmacokinetic parameters for renal, nonrenal, and systemic clearance and for volume of distribution and half-life were also similar between patients receiving continuous veno-venous hemofiltration and those with normal renal function. The sieving coefficient (S) of ceftriaxone (0.69) significantly exceeded the expected free fraction in plasma, confirming previous reports that protein binding does not limit the sieving of this compound. The results suggest that a reduction in the usual daily dose of ceftriaxone is not required in patients with acute renal failure receiving continuous veno-venous hemofiltration.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Area Under Curve; Ceftriaxone; Cephalosporins; Chromatography, High Pressure Liquid; Female; Hemofiltration; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged

To compare the efficacy and toxicity of single daily dosing of amikacin and ceftriaxone with that of multiple daily dosing of amikacin and ceftazidime for febrile episodes in patients with cancer and granulocytopenia.. A prospective, randomized, unblinded, multicenter trial.. Twenty-one tertiary care or university medical centers.. Six hundred seventy-seven patients with cancer and granulocytopenia (858 febrile episodes).. Random assignment to empiric therapy with a single daily dose of amikacin (20 mg/kg) and ceftriaxone (adults, 30 mg/kg; children, 80 mg/kg) (24-hour group) or with multiple daily doses of amikacin (6.5 mg/kg every 8 hours) and ceftazidime (33 mg/kg every 8 hours) (8-hour group).. Percentage response to each regimen and occurrence of nephrotoxicity and ototoxicity.. Single daily dosing of amikacin and ceftriaxone was as effective as multiple daily dosing of amikacin and ceftazidime (71% compared with 74%; difference, -3%; 95% Cl, -10% to 3%; P > 0.2). Equivalent responses also were noted for each category of infection. Median peak (30 minutes after a 60-minute infusion) serum concentrations of amikacin were higher in the 24-hour group than in the 8-hour group (45.6 compared with 21 micrograms/mL, P < 0.001), whereas trough (preinfusion) levels were lower (0.9 compared with 2 micrograms/mL, P < 0.001). Nephrotoxicity was 3% in the 24-hour group and 2% in the 8-hour group (difference, 1%; Cl, -1% to 4%). Increases in serum creatinine, however, were delayed (P = 0.048) and smaller (P = 0.06) in the 24-hour group than in the 8-hour group and occurred almost exclusively after other nephrotoxic drugs were added. Audiometry was only done in 144 patients (21%). Ototoxicity was 9% in the 24-hour group and 7% in the 8-hour group (difference, 2%; Cl, -7% to 11%; P > 0.2). Further infections developed in 15% and 12% of patients, respectively (difference, 3%; Cl, -2% to 9%). The overall mortality rate was 11% in both treatment groups (difference, 0%; Cl, -5% to 5%).. Single daily dosing of amikacin and ceftriaxone was as effective and no more toxic than multiple daily dosing of amikacin and ceftazidime for the empiric therapy of infection in patients with cancer and granulocytopenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Amikacin; Bacterial Infections; Ceftazidime; Ceftriaxone; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Ear Diseases; Female; Humans; Infant, Newborn; Infections; Kidney Diseases; Male; Middle Aged; Neoplasms; Prospective Studies; Treatment Outcome

Ceftriaxone is a third-generation cephalosporin that exhibits saturable plasma protein binding, which influences its pharmacokinetic parameters depending on the dose. Systemic clearance and volume of distribution of total drug show dependence on both concentration and time, whereas for unbound drug these parameters remain constant. The decrease in renal or non-renal clearance with age or in the presence of disease states is often compensated by the concurrent increase in free fraction, resulting in no apparent changes in half-life and no need for dose adjustment. Because of its unusually long plasma half-life, the availability of intramuscular administration and its high intrinsic activity against many organisms, ceftriaxone has become a popular agent in once-daily therapy of infections in paediatric patients, gonococcal infections and outpatient management of pneumonia and osteomyelitis.

Topics: Ceftriaxone; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Kidney Diseases; Liver Diseases; Lyme Disease; Meningitis; Sexually Transmitted Diseases, Bacterial; Tissue Distribution

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

Antibiotic treatments are known to disturb gut microbiota, but their effects on the mucosal barrier and extraintestinal diseases are rarely discussed. The aim of this study was to evaluate and visualize the impact of antibiotics on colonic mucus and the microbial community, and to assess whether intestinal dysbacteriosis is involved in the pathogenesis and progression of extraintestinal diseases. Twenty-one SD rats were randomly assigned into three groups followed by different experimental treatments. The albumin-creatinine ratio, urinary protein and occult blood semi-quantified test were tested. Fecal samples were collected at different time points (0,4, and 12 weeks) for 16S rRNA gene sequencing. Colon and kidney specimens were examined using light microscopy and transmission electron microscopy (TEM) to identify morphological changes.. Ceftriaxone intervention for one week did not cause any symptoms of diarrhea or weight loss, but the alpha and beta diversities of gut microbiota decreased quickly and significantly, a lower Firmicutes/Bacteroidetes (F/B) ratio was observed. At week 12, although the alpha and beta diversities increased to a level similar to that of the control (CON) group, LEfSe analysis indicated that the microbial community composition still differed significantly in each group. In addition, KEGG metabolic prediction revealed different metabolic functions in each group. TEM examination of colon revealed that dramatic morphological changes were observed in the ceftriaxone (Cef) group, wherein microvilli were misaligned and shortened significantly and morphologically intact bacteria were seen on the epithelial cell surface. TEM examination of kidneys from the Cef group showed characteristic glomerular changes in the form of widely irregularly thickened glomerular basement membrane (GBM) and foot process fusion or effacement; mild thickening of the GBM and foot process fusion was detected when ceftriaxone and Resatorvid (TAK242, an inhibitor of TLR4 signaling) are used together in the ceftriaxone + TAK242 (TAK) group.. Short-term use of ceftriaxone induced dynamic changes of gut microbiota and lead to intestinal barrier disruption and ultrastructural changes of kidneys in the SD rats. Moreover, interference with the TLR4-dependent signaling pathway can alleviate the damage to the intestinal barrier and kidney.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Intestinal Mucosa; Kidney; Kidney Diseases; Rats; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Toll-Like Receptor 4

Topics: Actins; Animals; Biomarkers; Bromodeoxyuridine; Ceftriaxone; Cell Proliferation; Cisplatin; Creatinine; Cytoprotection; Disease Models, Animal; Fibrosis; Kidney; Kidney Diseases; Male; Protective Agents; Rats, Wistar; Transforming Growth Factor beta1; Urea; Uric Acid

Deltamethrin (DLM) is a synthetic class II pyrethroid acaricide and insecticide widely used for veterinary and agricultural purposes. However, its animal and human exposure leads to nephrotoxicity. Our experimental objective was to evaluate protective effects of ceftriaxone and/or ascorbic acid against DLM-induced renal injury in male Wistar albino rats. DLM-treated animals revealed significant alterations in serum biochemical parameters related to renal injury; urea, uric acid and creatinine. There was a significant increase in renal lipid peroxidation and a significant inhibition in antioxidant biomarkers. Moreover, DLM significantly reduced serum acetylcholinesterase (AChE) activity. In addition, It induced serum and kidney tumor necrosis factor-α (TNF-α). Both ceftriaxone and ascorbic acid protect against DLM-induced biochemical alterations in serum and renal tissue when used alone or in combination along with DLM-intoxication. Furthermore, both ceftriaxone and ascorbic acid produced synergetic nephroprotective and antioxidant effects. Therefore, it could be concluded that ceftriaxone and/or ascorbic acid administration able to minimize the toxic effects of DLM through their free radical-scavenging and potent antioxidant activity.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Ceftriaxone; Creatinine; Disease Models, Animal; Insecticides; Kidney Diseases; Lipid Peroxidation; Male; Nitriles; Oxidative Stress; Protective Agents; Pyrethrins; Rats; Rats, Wistar; Treatment Outcome; Tumor Necrosis Factor-alpha; Uric Acid

We wanted to compare the first line intravenous administration of ceftriaxone to a subcutaneous administration in patients more than 75 years of age.. We performed a retrospective monocentric study on all patients more than 75 years of age admitted to the Ales hospital between January 1 and December 31, 2011, having received at least two doses of ceftriaxone intravenously (IV) or subcutaneously (SC).. One hundred and forty-eight patients (70 females/78 males patients) were included, 110 received ceftriaxone IV and 38 SC. They were a mean age of 84.7 years, older in the SC group (86.9 years) than in the IV group (83.9 years) (P = 0.0052). The SC group patients presented more frequently with dementia (57% vs. 25% P = 0.001), were more often bedridden (22% vs. 7% P = 0.023), had a higher mean World Health Organization status (3.13 vs. 2.76, P = 0.0181), and higher ADL score (7.79 vs. 5.76, P = 0.0056). There was no statistical difference for isolated bacteria, site of infection, death rate, and patients cured.. Subcutaneous ceftriaxone administration seems to be preferred for fragile elderly patients independently of disease severity. This administration is not associated to an impaired effectiveness or to an increased death rate.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Blood Coagulation Disorders; Ceftriaxone; Comorbidity; Dementia; Female; Frail Elderly; Hospital Mortality; Hospital Units; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Diseases; Male; Mental Disorders; Retrospective Studies

Uropathogenic E. coli (UPEC) strains are described as extraintestinal pathogenic E. coli with preference for the urinary tract. Bottone et al2 recently described the first documentation of a hypermucoviscous phenotype of a UPEC strain that displays a "stringing" phenomenon analogous to those produced by Klebsiella pneumonia strains known to invade the liver. The occurrence of this hypermucoviscous phenotype of UPEC strains causing urinary tract infection has not been well established. Following, we present a case report of two separate renal isolates from a patient with recurrent renal abscesses yielding the aforementioned hypermucoviscous phenotype of UPEC strains.

Topics: Abscess; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Drainage; Escherichia coli Infections; Female; Humans; Kidney Diseases; Middle Aged; Phenotype; Tomography, X-Ray Computed; Urinary Tract; Urinary Tract Infections; Uropathogenic Escherichia coli

Days of therapy (DOTs) are an important measure to quantify antimicrobial use but may not reflect patients' true antimicrobial exposure. Three methods of calculating DOTs were compared to determine whether including "exposure days," when antimicrobials are given less frequently than daily due to renal dysfunction, makes a difference.

Topics: Adult; Anti-Infective Agents; Ceftriaxone; Drug Dosage Calculations; Humans; Kidney Diseases; Ofloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Time Factors; Tobramycin; Vancomycin

Topics: Anti-Bacterial Agents; Ceftriaxone; Humans; Hypokalemia; Kidney Diseases; Leptospirosis; Male; Middle Aged; Paralysis; Penicillins; Treatment Outcome

A growing body of evidence now suggested that cyclosporine A (CycA)-induced nephrotoxicity is a crucial clinical problem and oxidative stress is importantly responsible for its toxicity. Ceftriaxone induced antioxidant effect in brain and neuronal tissues against oxidative damage although its antioxidant potential effect on kidney has not been clarified. The aim of this study was to evaluate whether ceftriaxone protects CycA-induced oxidative stress kidney injury in rats. Twenty-four rats were equally divided into four groups. First group was used as control. Ceftriaxone (200 mg/kg) and CycA (15 mg/kg) were administrated to second and third groups for 10 days, respectively. The ceftriaxone and CycA combination was given to rats constituting the fourth group for 10 days. Lipid peroxidation (LP), urea nitrogen and lactate dehydrogenase (LDH) levels were higher in CycA group than in control and ceftriaxone groups although LP, urea nitrogen and LDH levels were lower in ceftriaxone + CycA group than in control and ceftriaxone groups. Glutathione peroxidase and catalase activities were lower in CycA group than in control whereas their activities were increased in control and ceftriaxone groups. Superoxide dismutase activity did not change by the treatments. Ceftriaxone administration recovered also CycA-induced atrophy, vacuolization and exfoliations of tubular epithelium and glomerular collapse in histopathological evaluation of kidney. In conclusion, we observed that ceftriaxone is beneficial on CycA-induced oxidative stress in kidney of rats by modulating oxidative and antioxidant system.

Topics: Animals; Antioxidants; Ceftriaxone; Cyclosporine; Disease Models, Animal; Female; Humans; Kidney; Kidney Diseases; Oxidative Stress; Rats; Rats, Wistar

To study the clinical characteristics of ceftriaxone-associated biliary pseudolithiasis in children with renal diseases.. Three children with renal diseases developed biliary pseudolithiasis when they were treated with ceftriaxone. Their clinical and laboratory data were retrospectively analyzed.. Case one was an 11-year-old boy. The initial diagnosis was primary nephrotic syndrome. Ceftriaxone was administered intravenously at a dose of 2 g/d [50 mg/(kg * d)] for gastroenteritis. After that the boy complained of nausea and loss of appetite. Abdominal sonogram obtained on day 3 of ceftriaxone therapy revealed gallbladder sludge. After cessation of ceftriaxone treatment, symptoms and ultrasound abnormalities gradually disappeared, with complete sonographic resolution after 16 days. Case two was a 10-year-old boy. The primary diagnosis was post-streptococcal glomerulonephritis with acute renal failure. The child was treated with 1.5 g/d [30 mg/(kg * d)] intravenous ceftriaxone for gastroenteritis. After that, the boy complained of nausea and abdominal pain with positive Murphy's sign. Gallstone was detected by ultrasonographic examination on day 6 of ceftriaxone therapy. After cessation of ceftriaxone treatment, symptoms and sonographic abnormalities gradually disappeared, with complete sonographic resolution after 18 days. Case three was a 12-year-old boy. The primary diagnosis was nephrotic syndrome. He was treated with 2 g/d [40 mg/(kg.d)] ceftriaxone for gastroenteritis. Gallbladder lithiasis was detected 17 days after the initiation of ceftriaxone therapy (3 days after cessation of ceftriaxone treatment). Gallbladder sonogram was found to be normal two months after the discontinuation of the therapy.. Biliary pseudolithiasis occurred in 3 cases with renal diseases receiving low doses of ceftriaxone. The risk of developing ceftriaxone-associated biliary pseudolithiasis might increase in patients with renal diseases who are treated with ceftriaxone.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Cholecystolithiasis; Humans; Kidney Diseases; Male; Retrospective Studies

The pharmacokinetic profile of ceftriaxone was studied in female healthy goats, induced hepatopathic and nephropathic goats after a single intravenous dose at 50 mg kg(-1). Ceftriaxone persisted for 2 h in plasma of hepatopathic goats compared to 1 h of healthy goats, but the kinetic behaviour followed 'one-compartment open model' in both healthy and hepatopathic goats. Mean value of t((1/2))beta (0.32 +/- 0.008 h) was significantly higher in hepatopathic goats compared to healthy goats (0.19 +/- 0.002 h). Ceftriaxone was recovered at 24 h in urine of hepatopathic goats but it could not be detected in urine of healthy goats. However, its metabolite ceftizoxime was present in urine of healthy goats but not in urine of hepatopathic goats. On the other hand ceftriaxone persisted for 2 h in plasma of kidney damaged goats with significant higher concentration compared to healthy goats but kinetic behaviour followed 'one Compartment open model'. Ceftizoxime was identified with an adequate plasma concentration from 8 h to 12 h post dosing in nephropathic goats. Elimination halflife (t(1/2)beta) of Elimination ceftriaxone (0.38 +/- 0.01 h) in nephropathic goats increased significantly compared to healthy goats (0.19 +/- 0.002 h). Ceftriaxone, not the metabolite ceftizoxime was recovered at 24 h and 48 h post dosing in urine of nephropathic goats, while only ceftizoxime not ceftriaxone was detected in urine of healthy goats.

Topics: Animals; Anti-Bacterial Agents; Carbon Tetrachloride; Ceftriaxone; Female; Goats; Half-Life; Injections, Intravenous; Kidney Diseases; Liver Diseases; Models, Animal; Time Factors; Uranyl Nitrate

To determine the effects of melatonin combined with antibiotic administration on the suppression of renal scarring in an experimental pyelonephritis model.. The control group underwent a sham operation without infection. In the other groups, treatment began 72 hours after direct bacterial inoculation. In the no-treatment group, rats received daily intraperitoneal injections of saline. In the antibiotic-only group, the rats were treated only with ceftriaxone intramuscularly at a dose of 50 mg/kg once daily for 5 days. In the melatonin-only group, only 20 mg/kg of melatonin once daily was given by intraperitoneal injection for 5 days. In the antibiotic plus melatonin group, melatonin and ceftriaxone were administered at the same dosages and duration as for the single-modality treatment groups. After 6 weeks, the kidneys were removed for malondialdehyde measurements and histopathologic examination (inflammatory response and cicatrization).. Melatonin only (134.25 +/- 13.42) and antibiotic plus melatonin treatment (122.62 +/- 8.91) caused a marked reduction in the mean malondialdehyde values compared with no treatment (214.12 +/- 17.77) and antibiotic-only treatment (161.37 +/- 16.03), with no significant difference compared with that of the control group (120.75 +/- 9.83). Histopathologically, in the no-treatment group, the severity of scarring correlated directly with the severity of inflammation (r = 0.93). No significant differences were found in the renal scarring scores in rats receiving no treatment and those treated only with antibiotic or melatonin. In the antibiotic plus melatonin treatment group, the cicatrization score was not statistically different from that of the control group.. When combined with antibiotics, melatonin causes a significant inhibition of malondialdehyde production and neutrophil infiltration caused by acute pyelonephritis in an experimental rat model, and these are responsible for the protective effect of melatonin against renal damage, preventing renal scarring formation.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cicatrix; Disease Models, Animal; Drug Therapy, Combination; Kidney Diseases; Male; Melatonin; Pyelonephritis; Rats; Rats, Sprague-Dawley

Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.

Topics: Acyclovir; Adolescent; Antiviral Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Creatinine; Drug Combinations; Female; Humans; Infant; Kidney; Kidney Diseases; Kidney Function Tests; Male; Retrospective Studies

Renal absceeses in childhood are rare and require hospitalization, antibiotic therapy and drainage.. Two cases of renal abscess in childhood are described. In both cases there was no history of either antecedent skin infection or urinary tract infection or reflux. Flank pain and fever had a sudden onset.. The diagnosis was made in the first case by ultrasound and gadolinium-enhnaced magnetic resonance, in the second case ultrasound and computerized axial tomography were used. The patients were successfully treated at home with antibiotic therapy but without drainage.. Renal abscesses must be suspected in children with loin pain, fever and leukocytosis. They may heal even without hospitalization and drainage.

Topics: Abscess; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Drainage; Female; Hospitalization; Humans; Kidney; Kidney Diseases; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Radiography; Staphylococcal Infections; Ultrasonography

Topics: Adult; Ceftriaxone; Cephalosporins; Humans; Kidney Diseases; Lithiasis; Male

The protective effect of ceftriaxone on isepamicin-induced nephrotoxicity was investigated. For 14 d, Wistar rats were administered either ceftriaxone 100 mg/kg intraperitoneally, isepamicin 300 mg/kg subcutaneously, or ceftriaxone isepamicin in combination. The animals given 300 mg/kg of isepamicin showed a significant increase in urine NAG (N-acetyl-beta-D-glucosaminidase) levels as compared with the control animals which received saline (p<0.01). However, the increase in NAG level was markedly less when isepamicin was administered in combination with ceftriaxone (p<0.01). Ceftriaxone alone had no effect on urine NAG activity. Serum creatinine levels were significantly higher in animals treated with isepamicin alone than in control animals (p<0.01) or animals receiving the isepamicin ceftriaxone combination (p<0.01). After 14 d of treatment, ceftriaxone had not accumulated in renal tissue, but it did reduce the renal intracortical accumulation of isepamicin (p<0.01). Histopathologically, ceftriaxone induced very few cellular alterations and considerably reduced the manifestation of typical signs of isepamicin nephrotoxicity. This investigation demonstrates that ceftriaxone protects animals against isepamicin-induced nephrotoxicity.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Creatinine; Gentamicins; Hexosaminidases; Kidney Cortex; Kidney Diseases; Male; Rats; Rats, Wistar

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Drug Therapy, Combination; Female; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Kidney Diseases; Liver Abscess; Lung Diseases; Metronidazole; Nafcillin; Penicillins; Sepsis; Syndrome

The effect of ceftriaxone on tobramycin-induced nephrotoxicity was investigated. Female Sprague-Dawley rats were treated during 4 and 10 days with saline (NaCl, 0.9%), ceftriaxone at a dose of 100 mg/kg of body weight/12 h subcutaneously, tobramycin at doses of 40 and 60 mg/kg/12 h intraperitoneally, or the combination ceftriaxone-tobramycin. Creatinine levels in serum were significantly higher in animals treated with tobramycin alone given at 60 mg/kg/12 h during 10 days, compared with control animals (P < 0.01) or animals receiving the combination tobramycin-ceftriaxone (P < 0.01). After 10 days of treatment, ceftriaxone did not accumulate in renal tissue but did reduce the renal intracortical accumulation of tobramycin (P < 0.05). Tobramycin given alone at either 40 or 60 mg/kg/12 h induced a significant inhibition of sphingomyelinase activity compared with control animals (P < 0.05). However, this enzyme activity was significantly less inhibited when tobramycin was injected in combination with ceftriaxone (P < 0.05). Ceftriaxone alone had no effect on the activity of this enzyme. The [3H]thymidine incorporation into the DNA of renal cortex was also significantly lower in animals treated with tobramycin-ceftriaxone compared with animals receiving tobramycin alone (P < 0.05). The 24-h urinary excretion of beta-galactosidase was significantly reduced in animals treated with the combination tobramycin-ceftriaxone compared with the administration of tobramycin alone at 40 and 60 mg/kg/12 h after 5 and 10 days (P < 0.05). Histologically, ceftriazone induced very few cellular alterations and reduced considerably the presence of typical signs of tobramycin nephrotoxicity. This investigation demonstrated that ceftriaxone protects animals against tobramycin-induced nephrotoxicity.

Topics: Animals; beta-Galactosidase; Ceftriaxone; Creatinine; Drug Interactions; Enzymes; Female; Kidney Cortex; Kidney Diseases; Microscopy, Electron; Rats; Rats, Sprague-Dawley; Sphingomyelin Phosphodiesterase; Thymidine; Tobramycin

Ceftriaxone is a third-generation cephalosporin exhibiting a long half-life and a concentration-dependent protein binding. This study compared three techniques of protein binding determination (equilibrium dialysis chamber, ultrafiltration cones (Centriflo), and ultrafiltration (Centrifree micro-partition system) on human plasma and serum at ceftriaxone concentrations achieved clinically. A second objective was to determine the effect of 2-hydroxybenzoylglycine (HBG) on the protein binding of ceftriaxone. High performance liquid chromatography (HPLC) and liquid scintillation counting assays were used. Equilibrium dialysis was rotated for 12 h. The supplier's recommendations were followed for ultrafiltration techniques. The plasma protein binding of ceftriaxone, as determined by equilibrium dialysis and assayed by HPLC, decreased from 98.6 to 73.5% for drug concentrations varying from 25 to 400 micrograms/ml. Somewhat lower values were obtained with Centrifree, the binding fell from 92.1 to 73.5% for the same concentration range. Serum protein binding was similar to results obtained with plasma samples. Centriflo cones yielded more inconsistent results. A significant difference was seen between the three techniques (p less than 0.0001, three-way analysis of variance). The addition of HBG, a compound that inhibits drug binding in uremia, resulted in ceftriaxone binding defects similar to those seen in uremic serum. Although equilibrium dialysis remains a classic method of protein binding determination, Centrifree appears to be a better system.

Topics: Adolescent; Adsorption; Adult; Ceftriaxone; Chromatography, High Pressure Liquid; Dialysis; Female; Hippurates; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Male; Protein Binding; Ultrafiltration; Uremia

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

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 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