cefotaxime and Liver-Diseases

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

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

A full-term neonate with a history of umbilical venous catheterization followed by coagulase-negative staphylococcal sepsis is presented. The infant developed a solitary hepatic abscess with saprophytic organisms. Her liver abscess resulted in acute glomerulonephritis characterized by hypertension, proteinuria, oliguria, and azotemia. Surgical drainage and antibiotic treatment of the abscess was associated with resolution of the glomerulonephritis. Glomerulonephritis due to solitary liver abscess in a neonate has not been reported previously. Acute onset of glomerulonephritis should prompt a search for occult sources of infection.

Topics: Abscess; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Cephalosporins; Drainage; Drug Therapy, Combination; Female; Glomerulonephritis; Humans; Infant, Newborn; Liver Diseases; Magnetic Resonance Imaging; Micrococcus; Staphylococcal Infections; Vancomycin

Topics: Adult; Angiography, Digital Subtraction; Catheterization, Peripheral; Cefotaxime; Cephalosporins; Child; Embolization, Therapeutic; Gelatin Sponge, Absorbable; Hemorrhage; Hemostatics; Hepatic Artery; Humans; Liver Diseases; Male; Radiography, Interventional

The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241 micrograms.h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 micrograms.h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required.

Topics: Adult; Cefotaxime; Chromatography, High Pressure Liquid; Chronic Disease; Half-Life; Humans; Liver Diseases; 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 disposition profile of ceftriaxone was studied in eight normal subjects and in 15 subjects with various degrees of chronic liver damage (alcoholic fatty liver [FL] and cirrhosis without [C] and with [CA] ascites) who received bolus injections of ceftriaxone, 1 gm iv. Plasma protein binding fell in all. As a result, mean free fraction in plasma rose between 140% (FL) and 320% (CA). An exceptionally large rise (1270%) occurred in one subject with CA when the condition was aggravated by renal impairment. Fourteen of 15 subjects had renal clearance of unbound drug of the same order as that in healthy adults. In chronic liver disease, mean nonrenal clearance of unbound drug fell with severity of liver damage. Kinetic parameters with reference to total drug differed in normal subjects and subjects with CA. Kinetic changes in the latter were such that elimination t 1/2 beta did not differ (9.7 and 8.4 hr). Because of the wide therapeutic range of ceftriaxone, subjects with chronic liver disease would require no dose adjustments, whereas dose reductions are envisaged for subjects with cirrhosis (C,CA) on the basis of increased unbound drug concentrations.

Topics: Adult; Cefotaxime; Ceftriaxone; Chromatography, High Pressure Liquid; Female; Humans; Injections, Intravenous; Kidney; Kinetics; Liver Diseases; Liver Function Tests; Male; Middle Aged; Protein Binding; Serum Albumin

Ceftizoxime (CZX), a parenteral cephalosporin derivative belonging to the so-called third generation cephalosporin is reported to have a broad antibacterial activity, particularly against Gram-negative aerobic bacilli and some anaerobes, such as Bacteroides fragilis and a good stability to beta-lactamases. Clinical study was performed on a total of 20 cases, 9 females (1 case had urinary tract infection 3 times) and 11 males, aged from 27 to 82 years. All patients had the underlying diseases. They were bronchial asthma in 3 cases, influenza in 1, chronic pulmonary emphysema in 1, pulmonary fibrosis in 1, chronic bronchitis with strongyloidiasis in 1, lung cancer in 3, esophagus cancer in 2, stomach cancer in 1, hepatoma with urolithiasis in 1, liver cirrhosis with diabetes mellitus in 1, alcoholism with strongyloidiasis in 1, cholelithiasis in 1 and congestive heart failure in 1, respectively. Clinical diagnoses for infections were 2-acute bronchitis, 2-exacerbation of chronic bronchitis, 2-broncho-pneumonia, 2-pneumonia including one suspected case, 1-obstructive pneumonia, 2-secondary pulmonary infection, 1-pulmonary infection, 3-urinary tract infection (UTI), 1-UTI with sepsis, 1-sepsis, 1-sepsis with purulent meningitis, 1-biliary tract infection and 1-infected bronchoesophageal fistula. CZX was given by intravenous drip infusion, at a dose of 1 to 2 g, twice daily for 3 to 15 days. Because of severity in infections and underlying diseases, some cases were treated either steroid, gamma-globulin preparations or other antibiotics in combination with CZX. Twelve out of 15 cases assessed clinically responded satisfactorily to the treatment and efficacy rate was 80.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Bacterial Infections; Cefotaxime; Ceftizoxime; Drug Evaluation; Female; Gram-Negative Bacteria; Humans; Liver Diseases; Lung Diseases; Male; Middle Aged

In an eighteen-year-old boy with a high fever, an intra-hepatic infectious hematoma following blunt hepatic trauma was treated twice with intrahepatic arterial injection chemotherapy in an attempt to prevent conversion of the hematoma to an abscess. A decrease in body temperature occurred after the arterial injections, and the hematoma was gradually diminished in size. In selected patients with blunt hepatic trauma, intrahepatic arterial injection chemotherapy seems to be an effective treatment for prevention of liver abscess formation.

Topics: Adolescent; Cefmetazole; Cefoperazone; Cefotaxime; Cefotiam; Cephalothin; Cephamycins; Dibekacin; Hematoma; Humans; Injections, Intra-Arterial; Liver; Liver Abscess; Liver Diseases; Male; Wounds, Nonpenetrating

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

Serum levels of cefotaxime and desacetyl-cefotaxime were studied in 18 patients with hepatic cirrhosis after an intravenous bolus injection of 2 g of cefotaxime. Blood levels were independent of the degree of hepatic dysfunction and did not differ from those reported in normal individuals.

Topics: Adult; Aged; Cefotaxime; Female; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

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

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