Short, extended and continuous infusion of β-lactams: predicted impact on target attainment and risk for toxicity in an ICU patient cohort.

Objectives: This study aimed to predict the impact of different infusion strategies on pharmacokinetic/pharmacodynamic (PK/PD) target attainment and the potential risk for toxicity in an ICU cohort treated with β-lactams.

Method: Using collected patient data from 137 adult ICU patients, and applying population PK models, individual PK parameters were estimated and used to predict concentrations and target attainment following cefotaxime 2 g q8h, piperacillin/tazobactam 4.5 g q6h and meropenem 1 g q8h, applying 15 min short infusions (SI), 3 h extended infusions (EI) and 24 h continuous infusion (CI).

Prevalence, misclassification, and clinical consequences of the heteroresistant phenotype in Escherichia coli bloodstream infections in patients in Uppsala, Sweden: a retrospective cohort study.

Background: Antibiotic heteroresistance is a common bacterial phenotype characterised by the presence of small resistant subpopulations within a susceptible population. During antibiotic exposure, these resistant subpopulations can be enriched and potentially lead to treatment failure. In this study, we examined the prevalence, misclassification, and clinical effect of heteroresistance in Escherichia coli bloodstream infections for the clinically important antibiotics cefotaxime, gentamicin, and piperacillin-tazobactam.

Environmental drivers of monomethylmercury photodegradation along the land-to-ocean aquatic continuum.

In surface waters, photodegradation is a major abiotic removal pathway of the neurotoxin monomethylmercury (MMHg), acting as a key control on the amounts of MMHg available for biological uptake. Different environmental factors can alter the rate of MMHg photodegradation. However, our understanding of how MMHg photodegradation pathways in complex matrixes along the land-to-ocean aquatic continuum respond to changes in salinity, dissolved organic carbon (DOC) concentration and dissolved organic matter (DOM) composition is incomplete.

Combining mathematical modeling, data and clinical target expression to support bispecific antibody binding affinity selection: a case example with FAP-4-1BBL.

The majority of bispecific costimulatory antibodies in cancer immunotherapy are capable of exerting tumor-specific T-cell activation by simultaneously engaging both tumor-associated targets and costimulatory receptors expressed by T cells. The amount of trimeric complex formed when the bispecific antibody is bound simultaneously to the T cell receptor and the tumor-associated target follows a bell-shaped curve with increasing bispecific antibody exposure/dose. The shape of the curve is determined by the binding affinities of the bispecific antibody to its two targets and target expression.