Pharmacokinetics of Piperacillin-Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation.

Background: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin-tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment.

Methods: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CL) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid.

Targeting of under-75 years for the optimization of medication reconciliation with an approach based on medication risks: An observational study.

Purpose: To date, how medication reconciliation (MR) could be prioritized in younger patients remains poorly evaluated. This study aimed at assessing whether a MR prioritization strategy based on the identification of high-risk medication at patients' admission treatment could be of interest in non-elderly patients.

Method: This prospective study was conducted between July and September 2017 in an internal medicine unit at Bordeaux teaching hospital.

Subcutaneous Antibiotic Therapy: The Why, How, Which Drugs and When.

Objectives: To describe the rationale for subcutaneous (SC) administration of antibiotics from available published data and to make propositions to help clinicians in daily practice.

Design: Narrative review.

Setting And Participants: Hospitalized patients, persons in long-term care facilities and ambulatory care.

Pharmacokinetics and Pharmacodynamics of Anti-infective Agents during Continuous Veno-venous Hemofiltration in Critically Ill Patients: Lessons Learned from an Ancillary Study of the IVOIRE Trial.

Background: Hemofiltration rate, changes in blood and ultrafiltration flow, and discrepancies between the prescribed and administered doses strongly influence pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents during continuous veno-venous hemofiltration (CVVH) in critically ill patients.

Methods: Ancillary data were from the prospective multicenter IVOIRE (hIgh VOlume in Intensive caRE) study. High volume (HV, 70 mL/kg/h) was at random compared with standard volume (SV, 35 mL/kg/h) CVVH in septic shock patients with acute kidney injury (AKI).

Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy.

The aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the effect of 10 covariates (age, sex, total body weight [TBW], adapted body weight [ABW], body surface area [BSA], modified sepsis-related organ failure assessment [SOFA] score, vasopressor use, creatinine clearance [CL], fluid balance, and amount of fluids collected by the NPT over the sampling day) in patients who underwent continuous renal replacement therapy (CRRT) or did not receive CRRT.

Implementation of infliximab standardized doses after pharmacokinetic modelization in a cohort of patients with Crohn's disease.

Background: According to infliximab (IFX) license in Crohn's disease (CD), infusion doses are based on patient's body-weight. Dose banding providing standardized doses (SD) has been implemented in parenteral chemotherapy in order to optimize aseptic unit capacity and reduce drug expenditure, duration of hospital stay and costs without decreasing efficacy.

Material And Method: The first part was a single-center retrospective analysis of consecutive CD patients receiving IFX maintenance therapy to determine standardized doses covering more than 50% of infusions.

Is the subcutaneous route an alternative for administering ertapenem to older patients? PHACINERTA study.

Background: Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria.

Objectives: To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons.

Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CL) measurements and therapeutic drug monitoring of unbound ceftriaxone.

Higher than standard dosing regimen are needed to achieve optimal antibiotic exposure in critically ill patients with augmented renal clearance receiving piperacillin-tazobactam administered by continuous infusion.

Purpose: To determine whether augmented renal clearance (ARC) impacts negatively on piperacillin-tazobactam unbound concentrations in critically ill patients receiving 16 g/2 g/day administered continuously.

Material And Methods: Fifty nine critically ill patients without renal impairment underwent 24-h creatinine clearance (Cr) measurement and therapeutic drug monitoring during the first three days of antimicrobial therapy by piperacillin-tazobactam. The main outcome was the rate of piperacillin underexposure, defined by at least one of three samples under 16 mg/L.

Breakthrough invasive aspergillosis and diagnostic accuracy of serum galactomannan enzyme immune assay during acute myeloid leukemia induction chemotherapy with posaconazole prophylaxis.

Posaconazole prophylaxis has demonstrated efficacy in the prevention of invasive aspergillosis during prolonged neutropenia following acute myeloid leukemia induction chemotherapy. Antifungal treatment decreases serum galactomannan enzyme immunoassay diagnostic accuracy that could delay the diagnosis and treatment. We retrospectively studied patients with acute myeloid leukemia who underwent intensive chemotherapy and antifungal prophylaxis by posaconazole oral suspension.

Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study.

This study assessed whether augmented renal clearance (ARC) impacts negatively on antibiotic concentrations and clinical outcomes in patients treated by high-dose β-lactams administered continuously. Over a 9-month period, all critically ill patients without renal impairment treated by one of the monitored β-lactams for a documented infection were eligible. During the first 3 days of antibiotic therapy, every patient underwent 24-h CL measurements and therapeutic drug monitoring.

A new reliable, transposable and cost-effective assay for absolute quantification of total plasmatic bevacizumab by LC-MS/MS in human plasma comparing two internal standard calibration approaches.

The quantification of monoclonal antibodies (mAbs) such as bevacizumab, a recombinant humanized immunoglobulin G1 (hIgG1), in biological fluids, is an essential prerequisite to any pharmacokinetic preclinical and clinical study. To date, reference techniques used to quantify mAbs rely on enzyme-linked immunosorbent assay (ELISA) lacking specificity. Furthermore, the commercially available ELISA kit to quantify bevacizumab in human plasma only assesses the free fraction of the drug.

Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under- and Overdosing.

Objective: Obesity and critical illness modify pharmacokinetics of antibiotics, but piperacillin-tazobactam continuous IV infusion pharmacokinetics has been poorly studied in obese critically ill patients. We aimed to compare pharmacokinetics of piperacillin in severely obese and nonobese patients with severe sepsis or septic shock. We hypothesized that plasma concentration variability would expose the critically ill to both piperacillin under and overdosing.

Pre-dose plasma concentration monitoring of mycophenolate mofetil in patients with autoimmune diseases.

Aim: To date, neither the benefit of mycophenolic acid (MPA) therapeutic drug monitoring (TDM), the prodrug of mycophenolate mofetil (MMF), nor the optimal monitoring technique have been established in autoimmune diseases. This study was undertaken to confirm, in a cohort of new patients, the plasma MPA thresholds previously published in patients with systemic lupus erythematosus (SLE) or vasculitis.

Methods: MPA areas under the concentration-time curves between 0 and 12 h, 12 h trough concentrations and pre-dose concentrations (C0 ) were determined for 23 patients with SLE and 21 with systemic vasculitis.

In vivo interactions of continuous flucloxacillin infusion and high-dose oral rifampicin in the serum of 15 patients with bone and soft tissue infections due to Staphylococcus aureus - a methodological and pilot study.

Background: Increased antibiotic resistance against Staphylococcus aureus and low penetration into bone requires regimen optimization of available drugs.

Methods: We evaluate pharmoacokinetic and pharmacodynamic parameters (PK/PD) as well as in vivo interactions of continuous flucloxacillin 12 g/d administration combined with high dose oral rifampicin 600 mg bid in the serum of 15 adult patients with bone and soft tissue infections. We use the patient's own serum directed against his own isolated S.

Chemical stability of azacitidine suspensions for injection after cold-chain reconstitution of powder and storage.

Purpose: The 72-hour chemical stability of refrigerated syringes of azacitidine suspension prepared via a cold-chain method is investigated.

Methods: Three 25-mg/mL azacitidine suspensions were prepared from different lots of powdered drug. The suspensions were stored in 2-mL polypropylene syringes at 2-8 °C and protected from light.

Carbapenems.

Objective: To assess the relative strengths and weaknesses of carbapenems by considering their microbiological, clinical, pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) properties and defining optimal conditions of uses of the new generation of carbapenems.

Methods: Literature review.

Results: Except for ertapenem, the spectrum of activity is similar for all carbapenems, with little differences in activities of individual agents.

Alveolar diffusion and pharmacokinetics of linezolid administered in continuous infusion to critically ill patients with ventilator-associated pneumonia.

Objectives: This study aimed to determine the steady-state serum and alveolar concentrations of linezolid administered by continuous infusion to critically ill patients with ventilator-associated pneumonia (VAP).

Patients And Methods: This was a prospective, open-label study performed in an intensive care unit and research ward in a university hospital. Twelve critically ill adult patients with VAP received 600 mg of linezolid as a loading dose followed by 1200 mg/day by continuous infusion.

A sensitive liquid chromatography coupled with mass spectrometry method for the intracellular and plasma quantification of raltegravir after solid-phase extraction.

Introduction: Liquid chromatography coupled with mass spectrometry for the quantification of raltegravir in human plasma and peripheral blood mononuclear cells has been developed.

Methods: Sample preparations were based on a fully automated solid-phase extraction process. Mass spectrometric data were acquired in a single-ion monitoring method.

Chemotherapy and targeted agents for colorectal cancer in a real-life setting anticipate guidelines: the COLCHIC cohort study.

Introduction of new agents for the treatment for colorectal cancer (CRC) has been accompanied by the publication of guidelines. The COLCHIC cohort was set up to evaluate CRC treatment practices and the use of these innovative and expensive agents. Patients initiating CRC treatment at the Bordeaux teaching hospital between 1 March 2005 and 1 March 2006 were identified, and treatment courses from 1 March 2005 to 31 December 2006 were studied; 192 patients were included, 188 with analysable data: 43 patients initiated 51 courses for non-metastatic cancer, 153 initiated 366 courses for metastatic cancer, eight patients initiated courses for both non-metastatic and metastatic cancer.

Quantitative analysis of erythropoietin in human plasma by tandem mass spectrometry.

The extended use of protein drugs in therapeutics has created the need for their quantification in human plasma. A methodology using the therapeutic protein itself as internal standard for quantitative analysis by multiple reaction monitoring (MRM) has been designed and applied to epoetin beta, a recombinant human erythropoietin (rhEPO). After depletion of major proteins, plasma samples were desalted and enriched in rhEPO by reversed phase liquid chromatography prior to tryptic cleavage.

Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study.

Introduction: The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares.

Methods: At inclusion, steady-state PK parameters of the MMF active form, mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) were determined for 25 stable SLE patients without renal manifestations. Disease activity was assessed during 6 months of follow-up.