Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis.

Background: In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings.

Methods: Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control.

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.

Background: Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units.

Effects of procalcitonin testing on antibiotic use and clinical outcomes in patients with upper respiratory tract infections. An individual patient data meta-analysis.

Background: Several trials found procalcitonin (PCT) helpful for guiding antibiotic treatment in patients with lower respiratory tract infections and sepsis. We aimed to perform an individual patient data meta-analysis on the effects of PCT guided antibiotic therapy in upper respiratory tract infections (URTI).

Methods: A comprehensive search of the literature was conducted using PubMed (MEDLINE) and Cochrane Library to identify relevant studies published until September 2016.

Prognostic value of procalcitonin in respiratory tract infections across clinical settings.

Introduction: Whether the inflammatory biomarker procalcitonin provides prognostic information across clinical settings and different acute respiratory tract infections (ARIs) is poorly understood. In the present study, we investigated the prognostic value of admission procalcitonin levels to predict adverse clinical outcome in a large ARI population.

Methods: We analysed data from 14 trials and 4,211 ARI patients to study associations of admission procalcitonin levels and setting specific treatment failure and mortality alone at 30 days.

Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective.

Background: Whether or not antibiotic stewardship protocols based on procalcitonin levels results in cost savings remains unclear. Herein, our objective was to assess the economic impact of adopting procalcitonin testing among patients with suspected acute respiratory tract infection (ARI) from the perspective of a typical US integrated delivery network (IDN) with a 1,000,000 member catchment area or enrollment.

Methods: To conduct an economic evaluation of procalcitonin testing versus usual care we built a cost-impact model based on patient-level meta-analysis data of randomized trials.

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.

Background: Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs).

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.

Background: Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs).

Daptomycin for a complicated urinary tract infection with vancomycin-resistant Enterococcus faecium in a renal transplant recipient.

There is an increasing prevalence of urinary tract infection (UTI) caused by multiresistant gram-negative enteric bacilli such as extended-spectrum beta-lactamase as well as Gram-positive enterococci whose vancomycin-resistance can be as high as 25%. We report on a 68-year-old Caucasian female with a UTI caused by a vancomycin-resistant Enterococcus faecium, only tested to be susceptible to gentamycin, linezolid and daptomycin. Within a day after administration of the bactericidal daptomycin clinical and laboratory signs of infection regressed and graft function recovered.

Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis.

Background: Procalcitonin algorithms may reduce antibiotic use for acute respiratory tract infections (ARIs). We undertook an individual patient data meta-analysis to assess safety of this approach in different ARI diagnoses and different clinical settings.

Methods: We identified clinical trials in which patients with ARI were assigned to receive antibiotics based on a procalcitonin algorithm or usual care by searching the Cochrane Register, MEDLINE, and EMBASE.

Pharmacokinetics of ampicillin/sulbactam in critically ill patients with acute kidney injury undergoing extended dialysis.

Background And Objectives: The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2) of 2.

Quantitative analysis of the antifungal drug anidulafungin by LC-online SPE-MS/MS in human plasma.

The objective of this study was to develop a fast and robust method for the quantitation of the antifungal drug anidulafungin in human plasma samples by generic two-dimensional liquid chromatography (online-SPE/reversed phase LC) coupled to a tandem-quadrupole mass spectrometer (LC-online SPE-MS/MS). Online SPE was performed using an Oasis HLB cartridge column and for reversed-phase chromatography a Nucleodur Gravity C(18) column was used. A 100 μL aliquot of human plasma was extracted with 200 μL of 80:20 MeOH-0.

Rapid HPLC-MS/MS method for simultaneous quantitation of four routinely administered triazole antifungals in human plasma.

Background: Fluconazole, itraconazole, posaconazole and voriconazole are four triazole antifungal drugs administered for the prevention and in the treatment of invasive fungal infections. Therapeutic drug monitoring of these antifungals in human plasma is advised.

Methods: After protein precipitation by adding methanol/ZnSO(4) containing ketoconazole as internal standard (IS) the analytes were isolated from matrix and enriched by solid-phase extraction (SPE) and were separated on an Allure PFP HPLC column, maintained at 60°C.

Dosing of antibiotics in critically ill patients undergoing renal replacement therapy.

On September 11, 1945 Maria Schafstaat was the first patient who successfully underwent a dialysis treatment for acute kidney injury (AKI), formerly known as acute renal failure. Since then, the number of patients with AKI is increasing worldwide. Today AKI is generally one feature of a multiple organ dysfunction syndrome (MODS), which develops in response to major surgery, cardiogenic shock or sepsis.

Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock.

Purpose: To investigate the steady-state pharmacokinetics of moxifloxacin in critically ill patients after intravenous administration of the 400 mg fixed dose.

Methods: Fifteen adult patients with severe sepsis (n = 3) or septic shock (n = 12) were enrolled in this dual-centre, prospective, open-label study. Moxifloxacin was administered with the recommended dose of 400 mg once daily i.

Dosing of daptomycin in intensive care unit patients with acute kidney injury undergoing extended dialysis--a pharmacokinetic study.

Background: Daptomycin is a new intravenous cyclic lipopeptide antibiotic, licensed for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms including both susceptible and resistant strains of Staphylococcus aureus and for the treatment of various infections due to susceptible organisms, including serious and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis with associated bacteremia. Currently, no dosing recommendations exist for this drug for patients with acute kidney injury (AKI) undergoing renal replacement therapy. The aim of this study was to evaluate pharmacokinetics of daptomycin in critically ill patients with AKI undergoing extended dialysis (ED), a frequently used mean of renal replacement therapies in intensive care units (ICUs) around the world.

A simplified three-times weekly daptomycin dosing regimen for chronic hemodialysis patients.

Approximately 2.3 million patients worldwide are undergoing chronic renal replacement therapy. In that population, acute infections substantially contribute to the excessive morbidity and mortality.

Clinical pharmacokinetics and pharmacodynamics of tigecycline.

Rapid emergence of resistance against antibacterials emphasizes the need for the development of novel and/or more potent antibacterials. Tigecycline is the first representative of a new drug class, the glycylcyclines, and was approved in 2005 by the US FDA for the treatment of complicated skin and skin structure infections, as well as complicated intra-abdominal infections. Tigecycline distributes extensively into the intracellular space of tissue and accumulates in cells, which may qualify it for the treatment of intracellular infections.

10 years' experience with the pneumococcal quinolone moxifloxacin.

Moxifloxacin (MXF) is the latest broad-spectrum fluoroquinolone marketed worldwide. It has in vitro activity against a wide range of Gram-positive and Gram-negative pathogens including anaerobes and intracellular organisms, as well as strains resistant to beta-lactam or macrolide antibiotics. For relevant respiratory pathogens, MXF attains the threshold values of pharmacodynamic indices predictive of clinical efficacy and minimization of resistance development.

Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection.

Clostridium difficile infection (CDI) has become more refractory to standard therapy. We describe 4 patients with severe refractory CDI who were successfully treated with tigecycline. Symptoms improved within 1 week.