Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: Effect of type of dialysis membrane on dosing requirements
Ulldemolins M.,Fundacio Privada Clinic per la Recerca Biomedica |
Ulldemolins M.,Autonomous University of Barcelona |
Ulldemolins M.,University of Barcelona |
Martin-Loeches I.,Autonomous University of Barcelona |
And 24 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2016
Objectives: Thismulticentre study aimed to describe the pharmacokinetics (PK) of piperacillin in critically ill patients with multiple organ dysfunction syndrome (MODS) receiving continuous venovenous haemodiafiltration (CVVHDF), to identify the sources of PK variability and evaluate different dosing regimens to develop recommendations based on clinical parameters. Patients and methods: Nineteen patients with MODS and CVVHDF receiving piperacillin/tazobactamwere enrolled from three tertiary hospitals (95 plasma samples). Population PK modelling and Monte Carlo simulations were performed using NONMEM v7.3w. Results: Patients'median agewas 70 years (range 39-82),medianweightwas 80 kg (45-129),median APACHE II score at admissionwas 21 (13-33) andmedian SOFA score on the day of studywas 11 (8-21). The final population PK model was characterized by CL (L/h)=6.11* [weight (kg)/80]1.39*CLMEMB. If membrane=1.5 m2 AN69ST, CLMEMB=1; if membrane=0.9 m2 AN69, CLMEMB=0.51. Monte Carlo simulations showed that: (i) to maintain unbound piperacillin concentrations above the MIC for the bacteria for 100% of dosing interval T (100%fuT>MIC), patients receiving CVVHDF with 1.5 m2 AN69ST membranes required doses of 4000 mg q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC=8-16 mg/L) (2000 mg q8h was sufficient for patients with CVVHDF using 0.9 m2 AN69membranes); and (ii) for the treatment of bacteriawith high susceptibility to piperacillin (MIC ,4 mg/L) or for the attainment of a more traditional pharmacodynamic target (50%fuT>MIC), 2000 mg q8h sufficed regardless of type of membrane and body weight. Conclusions: Our results suggest that type ofmembrane and bodyweight should be considered for piperacillin dose titration in critically ill patients with MODS and CVVHDF requirement. © The Author 2016.
Acevedo J.,Hospital of Calella |
Fernandez J.,University of Barcelona |
Fernandez J.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Fernandez J.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed
World Journal of Gastroenterology | Year: 2014
Despite major advances in the knowledge and management of liver diseases achieved in recent decades, decompensation of cirrhosis still carries a high burden of morbidity and mortality. Bacterial infections are one of the main causes of decompensation. It is very important for clinical management to be aware of the population with the highest risk of poor outcome. This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently. Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines. Moreover, it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and, in infected patients, with the degree of sepsis. It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection, severe sepsis, hepatorenal syndrome and death. We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis. © 2014 Baishideng Publishing Group Inc. All rights reserved.
Pereira G.,University of Barcelona |
Pereira G.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Pereira G.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Pereira G.,Instituto Reina Sofia Of Investigacion Nefrologia Irsin |
And 28 more authors.
Journal of Hepatology | Year: 2012
Background & Aims: Skin and soft tissue infection in cirrhosis is considered a non-severe infection, but specific information is lacking. This study aimed at assessing the characteristics, occurrence of renal failure, and outcome of cirrhotic patients with skin and soft tissue infection. Methods: Ninety-two patients with cirrhosis and skin and soft tissue infection admitted to hospital within a 6-year period were retrospectively analyzed. A control group matched by severity of liver disease, admitted for reasons other than infection, was also studied. Results: Resolution of the infection was achieved in 96% of patients. Twenty (21.7%) patients with skin and soft tissue infection developed renal failure, compared to only five patients (5.4%) of the control group (p = 0.001). Renal failure was persistent despite infection resolution in 10 of the 20 patients vs. none of the control group. Renal failure was associated with poor prognosis. Hyponatremia developed in 40% and 25% of the infection and control group, respectively (p = 0.028). Within a 3-month follow-up period, 25 patients (23%) with skin and soft tissue infection died or were transplanted compared to only four patients (4%) of the control group (p <0.001). Factors independently associated with mortality in the infection group were: site of acquisition of the infection and MELD-sodium score at diagnosis. Conclusions: Skin and soft tissue infection is a severe complication of cirrhosis with high frequency of renal failure and hyponatremia that may persist despite resolution of the infection. MELD-sodium score is useful to assess 3-month mortality in these patients. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Prado V.,University of Barcelona |
Prado V.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Prado V.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Acevedo J.,Hospital Sant Jaume of Calella |
And 3 more authors.
Current Hepatitis Reports | Year: 2014
Bacterial infection is a frequent complication in patients with advanced cirrhosis. Incidence ranges between 25 and 30 %. Most common infections are spontaneous bacterial peritonitis and urinary infections followed by pneumonia, skin/soft tissue infections and bacteremia. Cirrhosis increases the risk to develop sepsis, severe sepsis and death. Therefore, early diagnosis and adequate treatment of infection is essential in the management of these patients. Recent data show that currently recommended empirical antibiotic strategies (β-lactams) fail frequently in nosocomial and healthcare associated infections in cirrhosis, a feature that is related to the higher prevalence of multidrug resistant bacteria in infections acquired in the healthcare environment. Empirical antibiotic treatment should therefore be selected according not only to the type and severity of infection but also to the site of acquisition of infection. Antibiotic guidelines should be tailored according to the local epidemiological pattern of multiresistance. © 2014 Springer Science+Business Media.
Ariza X.,University of Barcelona |
Ariza X.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Ariza X.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Ariza X.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin |
And 50 more authors.
PLoS ONE | Year: 2015
Background: Biomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but information is very limited. Given the large number of biomarkers, adequate choice of which biomarker(s) to investigate first is important. Aim: Analysis of potential usefulness of a panel of urinary biomarkers in outcome assessment in cirrhosis. Patients and Methods: Fifty-five patients with acute decompensation of cirrhosis were studied: 39 had Acute Kidney Injury (AKI) (Prerenal 12, type-1 HRS (hepatorenal syndrome) 15 and Acute Tubular Necrosis (ATN) 12) and 16 acute decompensation without AKI. Thirty-four patients had Acute-on-chronic liver failure (ACLF). A panel of 12 urinary biomarkers was assessed, using a multiplex assay, for their relationship with ATN, ACLF and mortality. Results: Biomarker with best accuracy for ATN diagnosis was NGAL (neutrophil-gelatinase associated lipocalin): 36 [26-125], 104 [58-208] and 1807 [494-3,716] μg/g creatinine in Prerenal-AKI, type-1 HRS and ATN, respectively; p<0.0001 (AUROC 0.957). Other attractive biomarkers for ATN diagnosis were IL-18, albumin, trefoil-factor-3 (TFF-3) and glutathione-S-transferase-π (GST-π) Biomarkers with less accuracy for ATN AUCROC<0.8 were β2-microglobulin, calbindin, cystatin-C, clusterin and KIM-1 (kidney injury molecule-1). For ACLF, the biomarker with the best accuracy was NGAL (ACLF vs. No-ACLF: 165 [67-676] and 32 [19-40] μg/g creatinine; respectively; p<0.0001; AUROC 0.878). Interestingly, other biomarkers with high accuracy for ACLF were osteopontin, albumin, and TFF-3. Biomarkers with best accuracy for prognosis were those associated with ACLF. Conclusions: A number of biomarkers appear promising for differential diagnosis between ATN and other types of AKI. The most interesting biomarkers for ACLF and prognosis are NGAL, osteopontin, albumin, and TFF-3. These results support the role of major inflammatory reaction in the pathogenesis of ACLF. © 2015 Ariza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fernandez J.,University of Barcelona |
Fernandez J.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Fernandez J.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Tandon P.,University of Alberta |
And 3 more authors.
Hepatology | Year: 2016
Patients with cirrhosis, particularly those with decompensated cirrhosis, are at increased risk of bacterial infections that may further precipitate other liver decompensations including acute-on-chronic liver failure. Infections constitute the main cause of death in patients with advanced cirrhosis, and strategies to prevent them are essential. The main current strategy is the use of prophylactic antibiotics targeted at specific subpopulations at high risk of infection: prior episode of spontaneous bacterial peritonitis, upper gastrointestinal bleeding, and low-protein ascites with associated poor liver function. Antibiotic prophylaxis effectively prevents not only the development of bacterial infections in all these indications but also further decompensation (variceal bleeding, hepatorenal syndrome) and improves survival. However, antibiotic prophylaxis is also associated with a clinically relevant and increasing drawback, the development of infections due to multidrug-resistant organisms. Several strategies have been suggested to balance the risks and benefits of antibiotic prophylaxis. Conclusion: Antibiotic stewardship principles such as the restriction of antibiotic prophylaxis to subpopulations at a very high risk for infection, the avoidance of antibiotic overuse, and early deescalation policies are key to achieve this balance; nonantibiotic prophylactic measures such as probiotics, prokinetics, bile acids, statins, and hematopoietic growth factors could also contribute to ameliorate the development and spread of multidrug-resistant bacteria in cirrhosis. (Hepatology 2016;63:2019-2031). © 2015 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. government employees, and their contribution is in the public domain in the U.S.A.
Acevedo J.,University of Barcelona |
Acevedo J.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Acevedo J.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Fernandez J.,University of Barcelona |
And 26 more authors.
Hepatology | Year: 2013
The prevalence of relative adrenal insufficiency (RAI) in critically ill cirrhosis patients with severe sepsis is over 60% and associated features include poor liver function, renal failure, refractory shock, and high mortality. RAI may also develop in noncritically ill cirrhosis patients but its relationship to the clinical course has not yet been assessed. The current study was performed in 143 noncritically ill cirrhosis patients admitted for acute decompensation. Within 24 hours after hospitalization adrenal function, plasma renin activity, plasma noradrenaline and vasopressin concentration, and serum levels of nitric oxide, interleukin-6 and tumor necrosis factor alpha were determined. RAI was defined as a serum total cortisol increase <9 μg/dL after 250 μg of intravenous corticotropin from basal values <35 μg/dL. Patients were followed for 3 months. RAI was detected in 26% of patients (n = 37). At baseline, patients with RAI presented with lower mean arterial pressure (76 ± 12 versus 83 ± 14 mmHg, P = 0.009) and serum sodium (131 ± 7 versus 135 ± 5 mEq/L, P = 0.007) and higher blood urea nitrogen (32 ± 24 versus 24 ± 15 mg/dl, P = 0.06), plasma renin activity (7.1 ± 9.9 versus 3.4 ± 5.6 ng/mL*h, P = 0.03), and noradrenaline concentration (544 ± 334 versus 402 ± 316 pg/mL, P = 0.02). During follow-up, patients with RAI exhibited a higher probability of infection (41% versus 21%, P = 0.008), severe sepsis (27% versus 9%, P = 0.003), type-1 hepatorenal syndrome (HRS) (16% versus 3%, P = 0.002), and death (22% versus 7%, P = 0.01). Conclusion: RAI is frequent in noncritically ill patients with acute decompensation of cirrhosis. As compared with those with normal adrenal function, patients with RAI have greater impairment of circulatory and renal function, higher probability of severe sepsis and type-1 HRS, and higher short-term mortality. © 2013 by the American Association for the Study of Liver Diseases.
Barreto R.,University of Barcelona |
Barreto R.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS |
Barreto R.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Barreto R.,Instituto Reina Sofia Of Investigacion Nefrologica |
And 4 more authors.
Gastroenterologia y Hepatologia | Year: 2013
Acute kidney injury (AKI) is an ominous event in the natural history of cirrhosis. The differential diagnosis of this entity is hampered by the absence of specific biomarkers of tubular damage in cirrhosis. The clinical usefulness of such biomarkers is determined by their effectiveness in the diagnosis of AKI and their ability to provide critical information to ameliorate clinical outcomes and survival. The lack of biomarkers has hindered the development of interventions aimed to improve the prognosis of kidney impairment in cirrhosis. Currently, biomarkers are an area of intense research in nephrology. Emerging genomic and proteomic technologies have revealed novel plasma and urinary biomarkers of AKI. The present article discusses the most promising candidate biomarkers with potential application in cirrhosis, such as NGAL, KIM-1, cystatin-C, IL-18, L-FABP, N-acetyl glucosaminidase and netrin-1, are discussed below. © 2013 Elsevier España, S.L. and AEEH y AEG.
Elia C.,University of Barcelona |
Elia C.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS |
Elia C.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed |
Elia C.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin |
And 52 more authors.
Journal of Hepatology | Year: 2015
Background & Aims Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. The aim of the study was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs. Methods Prospective cohort study in a tertiary referral center of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients. Results Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4 ± 3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953 ± 1,198 vs. 83 ± 79 μg/g of creatinine, respectively, p = 0.008). Moreover, seven of the 11 patients with persistent AKI (64%) died within three months compared with only one of the 19 (5%) patients with transient AKI (p = 0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of three-month mortality was persistent AKI. Conclusions Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome. © 2015 European Association for the Study of the Liver.