Neutrophils in the Spotlight-An Analysis of Neutrophil Function and Phenotype in ARDS.

Acute respiratory distress syndrome (ARDS) is a complex disease pattern in which pathogenesis polymorphonuclear neutrophil granulocytes (PMN) play a key role. In previous experiments, we could show that interaction with collagen III (an important component of pulmonary tissue) is a possible trigger of neutrophil reactive oxygen species (ROS) production. To investigate possible correlations, further elucidate ARDS pathophysiology, and maybe find pharmacological targets, we evaluated PMNs from blood (circulating PMNs: cPMNs) and tracheal secretion (tPMNs) from patients with and without ARDS with regard to function and phenotype.

Free serum concentrations of antibiotics determined by ultrafiltration: extensive evaluation of experimental variables.

To assess the impact of experimental conditions on free serum concentrations as determined by ultrafiltration and HPLC-DAD analysis in a wide range of antibiotics. Relative centrifugation force (RCF), temperature, pH and buffer were varied and the results compared with the standard protocol (phosphate buffer pH 7.4, 37°C, 1000 × g).

Perioperative administration of cefazolin and metronidazole in obese and non-obese patients: a pharmacokinetic study in plasma and interstitial fluid.

Objectives: To assess plasma and tissue pharmacokinetics of cefazolin and metronidazole in obese patients undergoing bariatric surgery and non-obese patients undergoing intra-abdominal surgery.

Patients And Methods: Fifteen obese and 15 non-obese patients received an IV short infusion of 2 g cefazolin and 0.5 g metronidazole for perioperative prophylaxis.

Measurement of Free Plasma Concentrations of Beta-Lactam Antibiotics: An Applicability Study in Intensive Care Unit Patients.

Background: The antibacterial effect of antibiotics is linked to the free drug concentration. This study investigated the applicability of an ultrafiltration method to determine free plasma concentrations of beta-lactam antibiotics in ICU patients.

Methods: Eligible patients included adult ICU patients treated with ceftazidime (CAZ), meropenem (MEM), piperacillin (PIP)/tazobactam (TAZ), or flucloxacillin (FXN) by continuous infusion.

The association of the anesthesiologist's academic and educational status with self-confidence, self-rated knowledge and objective knowledge in rational antibiotic application.

Objective: This study aimed to investigate the association of anesthetists' academic and educational status with self-confidence, self-rated knowledge and objective knowledge about rational antibiotic application. Therefore, anesthetists in Germany were asked about their self-confidence, self-rated knowledge and objective knowledge on antibiotic therapy via the Multiinstitutional Reconnaissance of practice with Multiresistant bacteria (MR2) survey. Other analysis from the survey have been published elsewhere, before.

Determination of free clindamycin, flucloxacillin or tedizolid in plasma: Pay attention to physiological conditions when using ultrafiltration.

Pharmacokinetic/pharmacodynamic indices of anti-infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC-UV. The drugs were separated isocratically within 3-6 min on a C column using mixtures of phosphate buffer-acetonitrile of pH 7.

Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial.

Objectives: To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients.

Methods: Fifteen obese patients undergoing bariatric surgery and 15 non-obese patients undergoing major intra-abdominal surgery received an intravenous single short infusion of 8 g of fosfomycin. Fosfomycin concentrations were determined by LC-MS/MS in plasma and microdialysate from subcutaneous tissue up to 8 h after dosing.

Impact of Experimental Variables on the Protein Binding of Tigecycline in Human Plasma as Determined by Ultrafiltration.

Tigecycline, a tetracycline derivative, shows atypical plasma protein binding behavior. The unbound fraction decreases with increasing concentration at therapeutic concentrations. Moreover, uncertainty exists about the magnitude of tigecyline's protein binding in man.

Variable Linezolid Exposure in Intensive Care Unit Patients-Possible Role of Drug-Drug Interactions.

Background: Standard doses of linezolid may not be suitable for all patient groups. Intensive care unit (ICU) patients in particular may be at risk of inadequate concentrations. This study investigated variability of drug exposure and its potential sources in this population.

Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance.

Spectrum adequacy of antibiotic regimens for secondary peritonitis: a retrospective analysis in intermediate and intensive care unit patients.

Background: Secondary peritonitis requires surgical source control and adequate antimicrobial treatment. Antimicrobial regimens are usually selected according to local susceptibility data of individual pathogens against single agents, but this neglects both the polymicrobial nature of the infection and the use of combination therapy. We analysed the probability of common regimens to cover all relevant pathogens isolated in one patient ("spectrum adequacy rate", SAR) in a real-life data set.

Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients.

Continuous infusion of meropenem is a candidate strategy for optimization of its pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are difficult to predict in critically ill patients. Steady-state concentrations of meropenem were determined prospectively during continuous infusion in 32 surgical ICU patients (aged 21-85 years, body weight 55-125 kg, APACHE II 5-29, measured creatinine clearance 22.

Estimation of creatinine clearance using plasma creatinine or cystatin C: a secondary analysis of two pharmacokinetic studies in surgical ICU patients.

Background: In ICU patients, glomerular filtration is often impaired, but also supraphysiological values are observed ("augmented renal clearance", >130 mL/min/1.73 m(2)). Renally eliminated drugs (e.

Protein binding characteristics and pharmacokinetics of ceftriaxone in intensive care unit patients.

Aims: The aim of the present study was to assess the pharmacokinetics of total and unbound ceftriaxone in intensive care unit (ICU) patients and its protein binding characteristics.

Methods: Twenty patients (m/f 15/5, age 25-86 years, body weight 60-121 kg, APACHE II 7-40, estimated glomerular filtration rate 19-157 ml min(-1) , albumin 11.7-30.

Pharmacodynamic and response surface analysis of linezolid or vancomycin combined with meropenem against Staphylococcus aureus.

Purpose: To systematically assess the impact of pharmacodynamic interactions when adding either linezolid or vancomycin to meropenem on the antibacterial activity against methicillin-susceptible Staphylococcus aureus (MSSA). These regimens are frequently used in empiric therapy when risk factors for MRSA are present, but MSSA will often turn out as pathogen.

Methods: Checkerboard and time-kill curve studies were performed against three strains of MSSA covering clinically relevant concentrations of all antibiotics.

Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections.

The objective of this study was to provide a pharmacokinetic/pharmacodynamic (PK/PD) analysis of moxifloxacin in patients with diabetic foot infections (DFI). The plasma concentration-time courses were determined in 50 DFI patients on day 1 and 3 after intravenous moxifloxacin 400 mg once-daily. A two-compartment population pharmacokinetic model was developed, identifying as covariates total body weight on central and peripheral volume of distribution (V1, V2) and ideal body weight on clearance (CL), respectively.

Unbound fraction of ertapenem in intensive care unit patients.

Objectives: To determine unbound ertapenem concentrations in plasma and to describe the pharmacokinetics of unbound ertapenem in intensive care unit (ICU) patients.

Patients And Methods: For assessing the influence of experimental conditions and for development of the ultrafiltration protocol, plasma from healthy volunteers was used. Concentrations of total and unbound ertapenem were determined by HPLC in 29 plasma samples from six ICU patients treated with 1 g of ertapenem once daily.