scholarly journals Pharmacokinetics of Amphotericin B Colloidal Dispersion in Critically Ill Patients with Cholestatic Liver Disease

2012 ◽  
Vol 56 (10) ◽  
pp. 5414-5418 ◽  
Author(s):  
Stefan Weiler ◽  
Elisabeth Überlacher ◽  
Julia Schöfmann ◽  
Eva Stienecke ◽  
Stefan Dunzendorfer ◽  
...  
Keyword(s):  
Steady State ◽  
Liver Disease ◽  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Liver ◽  
Colloidal Dispersion ◽  
Cholestatic Liver Disease ◽  
Normal Liver Function ◽  
Standard Dosage

ABSTRACTThe pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.

scholarly journals Pulmonary Epithelial Lining Fluid Concentrations after Use of Systemic Amphotericin B Lipid Formulations

2009 ◽  
Vol 53 (11) ◽  
pp. 4934-4937 ◽  
Author(s):  
Stefan Weiler ◽  
Gerda Falkensammer ◽  
Angelika Hammerer-Lercher ◽  
Markus Anliker ◽  
Helene Vogelsinger ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Colloidal Dispersion ◽  
Standard Errors ◽  
Epithelial Lining ◽  
Lipid Complex ◽  
Epithelial Lining Fluid ◽  
Lipid Formulations

ABSTRACT Amphotericin B (AMB) concentrations were determined in pulmonary epithelial lining fluid (ELF) of 44 critically ill patients, who were receiving treatment with liposomal AMB (LAMB) (n = 11), AMB colloidal dispersion (ABCD) (n = 28), or AMB lipid complex (ABLC) (n = 5). Mean AMB levels (± standard errors of the means) in ELF amounted to 1.60 ± 0.58, 0.38 ± 0.07, and 1.29 ± 0.71 μg/ml in LAMB-, ABCD-, and ABLC-treated patients, respectively (differences are not significant).

scholarly journals Penetration of Amphotericin B Lipid Formulations into Pleural Effusion

2007 ◽  
Vol 51 (11) ◽  
pp. 4211-4213 ◽  
Author(s):  
Stefan Weiler ◽  
Rosa Bellmann-Weiler ◽  
Michael Joannidis ◽  
Romuald Bellmann
Keyword(s):  
Pleural Effusion ◽  
Amphotericin B ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Colloidal Dispersion ◽  
Pleural Effusions ◽  
Lipid Complex ◽  
Penetration Ratio ◽  
Lipid Formulations

ABSTRACT The penetration of the amphotericin B (AMB) lipid formulations (liposomal AMB, AMB colloidal dispersion, and AMB lipid complex formulations) into pleural effusions in seven critically ill patients was assessed. AMB was detected in all pleural effusion samples at concentrations ranging from 0.02 to 0.43 μg/ml. The penetration ratio was 3 to 44%.

scholarly journals Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria

2009 ◽  
Vol 53 (8) ◽  
pp. 3430-3436 ◽  
Author(s):  
D. Plachouras ◽  
M. Karvanen ◽  
L. E. Friberg ◽  
E. Papadomichelakis ◽  
A. Antoniadou ◽  
...  
Keyword(s):  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Colistin Methanesulfonate

ABSTRACT Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

Continuous infusion versus intermittent administration of ceftazidime in critically ill patients with suspected gram-negative infections.

1996 ◽  
Vol 40 (3) ◽  
pp. 691-695 ◽  
Author(s):  
A S Benko ◽  
D M Cappelletty ◽  
J A Kruse ◽  
M J Rybak
Keyword(s):  
Steady State ◽  
Continuous Infusion ◽  
Clinical Isolate ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Apache Ii Score ◽  
Serum Drug Concentration ◽  
Gram Negative ◽  
Intermittent Bolus ◽  
Standard Deviations

The pharmacodynamics and pharmacokinetics of ceftazidime administered by continuous infusion and intermittent bolus over a 4-day period were compared. We conducted a prospective, randomized, crossover study of 12 critically ill patients with suspected gram-negative infections. The patients were randomized to receive ceftazidime either as a 2-g intravenous (i.v.) loading dose followed by a 3-g continuous infusion (CI) over 24 h or as 2 g i.v. every 8 h (q8h), each for 2 days. After 2 days, the patients were crossed over and received the opposite regimen. Each regimen also included tobramycin (4 to 7 mg/kg of body weight, given i.v. q24h). Eighteen blood samples were drawn on study days 2 and 4 to evaluate the pharmacokinetics of ceftazidime and its pharmacodynamics against a clinical isolate of Pseudomonas aeruginosa (R288). The patient demographics (means +/- standard deviations) were as follows: age, 57 +/- 12 years; sex, nine males and three females; APACHE II score, 15 +/- 3; diagnosis, 9 of 12 patients with pneumonia. The mean pharmacokinetic parameters for ceftazidime given as an intermittent bolus (IB) (means +/- standard deviations) were as follows: maximum concentration of drug in serum, 124.4 +/- 52.6 micrograms/ml; minimum concentration in serum, 25.0 +/- 17.5 micrograms/ml; elimination constant, 0.268 +/- 0.205 h-1; half-life, 3.48 +/- 1.61 h; and volume of distribution, 18.9 +/- 9.0 liters. The steady-state ceftazidime concentration for CI was 29.7 +/- 17.4 micrograms/ml, which was not significantly different from the targeted concentrations. The range of mean steady-state ceftazidime concentrations for the 12 patients was 10.6 to 62.4 micrograms/ml. Tobramycin peak concentrations ranged between 7 and 20 micrograms/ml. As expected, the area under the curve for the 2-g q8h regimen was larger than that for CI (P = 0.003). For IB and CI, the times that the serum drug concentration was greater than the MIC were 92 and 100%, respectively, for each regimen against the P. aeruginosa clinical isolate. The 24-h bactericidal titers in serum, at which the tobramycin concentrations were < 1.0 microgram/ml in all patients, were the same for CI and IB (1:4). In the presence of tobramycin, the area under the bactericidal titer-time curve (AUBC) was significantly greater for IB than CI (P = 0.001). After tobramycin was removed from the serum, no significant difference existed between the AUBCs for CI and IB. We conclude that CI of ceftazidime utilizing one-half the IB daily dose was equivalent to the IB treatment as judged by pharmacodynamic analysis of critically ill patients with suspected gram-negative infections. No evaluation comparing the clinical efficacies of these two dosage regimens was performed.

Fibrin Monomer Polymerization in Liver Disease

1975 ◽  
Author(s):  
G. Green ◽  
I. W. Dymock ◽  
Jean M. Thomson ◽  
L. Poller
Keyword(s):  
Liver Disease ◽  
Normal Liver ◽  
Acute Liver Damage ◽  
Normal Liver Function ◽  
Primary Hepatoma ◽  
True Incidence ◽  
Coagulation Defect ◽  
Fibrin Monomer ◽  
Hepatocellular Disease ◽  
Normal Controls

Despite a few reports of abnormal fibrin monomer polymerization in liver disease, particularly primary hepatoma, the true incidence of this phenomenon remains to be determined. The unexplained frequency of prolongation of the thrombin-fibrinogen and reptilase times in such patients suggest it is more common than previously suspected.Over a hundred patients with hepatocellular dysfunction or jaundice have been screened for evidence of abnormal fibrinogen polymerization by a calorimetric method utilizing reptilase. The results have been compared with normal controls and patients with diverse diseases but normal liver function.Of the patients with primary hepatocellular disease such as cirrhosis and acute liver damage over a quarter exhibited abnormal fibrinogen polymerization. In addition these same patients had prolonged thrombin-fibrinogen and reptilase times, this latter test being the most reliable single index of the presence of abnormal polymerization.In patients with jaundice due to extra-hepatic biliary obstruction abnormal fibrin monomer polymerization was not observed.These findings may have important implications in the aetiology of the coagulation defect of liver disease.

scholarly journals 2113. Evaluation of Empiric Antifungal Therapy in Critically Ill Patients with Liver Disease, Sepsis, and No Evidence of Active Fungal Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S715-S715
Author(s):  
Rachel S Britt ◽  
Monica V Mahoney ◽  
Howard Gold ◽  
Christopher McCoy
Keyword(s):  
Liver Disease ◽  
Fungal Infection ◽  
Clinical Outcomes ◽  
Critically Ill ◽  
Antifungal Therapy ◽  
Critically Ill Patients ◽  
Univariate Analysis ◽  
Organ Transplant ◽  
Unknown Origin ◽  
Inpatient Mortality

Abstract Background While candidemia is uncommon in the immunocompetent, critically ill population, it is associated with longer lengths of stay (LOS), higher cost, and higher mortality. In critically ill patients with liver disease and sepsis of unknown origin, antifungals (AF) are commonly used empirically. Recent studies suggest that this practice may not improve clinical outcomes but had little representation of patients with liver disease. This study aims to evaluate clinical outcomes of critically ill patients with liver disease, sepsis, and no evidence of active fungal infection who received empiric AF vs. those who did not. Methods This was a single-center, retrospective review of adults with liver disease and sepsis, identified by ICD-10 codes, who were discharged from the intensive care unit (ICU) between October 1, 2015 and December 31, 2018. Patients with neutropenia, marrow or organ transplant, HIV infection, systemic immunosuppressants, or fungal infection at sepsis onset were excluded. The primary outcome was inpatient mortality. Secondary outcomes included ICU LOS, total LOS, and development of fungal bloodstream infection (BSI) > 48 hours after sepsis onset. Fisher’s exact and Wilcoxon rank-sum tests were used to compare baseline characteristics. Multivariable logistic regression models were used to compare outcomes. Model covariates were variables with P-values < 0.2 in univariate analysis. Results A total of 119 patients were included with 92 receiving empiric AF (micafungin or fluconazole) and 27 receiving no AF. Patients receiving empiric AF were more likely to have hepatic disease upon admission and less likely to have a bacterial infection. Both groups were similar in intubation and vasopressor requirements, febrile episodes, and Candida score. Unadjusted inpatient mortality for empiric vs. no AF was 70.4% vs. 70.7%. Unadjusted ICU LOS, total LOS, and development of a fungal BSI were 10 vs. 11 days, 19 vs. 19 days, and 63.0% vs. 2.2% (P < 0.001). In multivariable models, there was no difference in inpatient mortality between groups (OR 1.20, 95% CI 0.77–1.63). Conclusion In critically ill patients with liver disease, sepsis, and no evidence of active fungal infection, receipt of empiric antifungal therapy did not improve inpatient mortality, ICU LOS, or total LOS but did reduce fungal BSI. Disclosures All authors: No reported disclosures.

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