Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series.

Introduction: Nirmatrelvir/ritonavir (NIM/r) inhibits tacrolimus metabolism resulting in a profound drug-drug interaction that is further complicated by the use of azole antifungals.

Case Presentations: We describe three strategies, in 4 patient cases, for the initiation of NIM/r in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients on tacrolimus at the time of diagnosis. Patients 1 and 2 (strategy 1) experienced prolonged, elevated tacrolimus concentrations after an empiric 33% reduction in tacrolimus dose and adjustment of azole antifungal at NIM/r initiation (strategy 1) and with complete discontinuation of tacrolimus and azole antifungal at NIM/r initiation (strategy 2).

Quality and Clinical Outcomes Associated with a Gentamicin Use System Change for Managing Chorioamnionitis.

Chorioamnionitis is an intra-amniotic infection with serious maternal and neonatal complications. Clinical studies suggest antibiotic administration before delivery reduces the risk of complications compared to after delivery. Our center implemented a standardized intrapartum gentamicin computerized provider order entry and dosage form dispensing system intended to improve treatment initiation efficiency in hospitalized obstetric patients.

Catalytic Soman Scavenging by the Y337A/F338A Acetylcholinesterase Mutant Assisted with Novel Site-Directed Aldoximes.

Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of the soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman.

Analysis and interpretation of microplate-based oxygen consumption and pH data.

Breakthrough technologies to measure cellular oxygen consumption and proton efflux are reigniting the study of cellular energetics by increasing the scope and pace with which discoveries are made. As we learn the variation in metabolism between cell types is large, it is helpful to continually provide additional perspectives and update our roadmap for data interpretation. In that spirit, this chapter provides the following for those conducting microplate-based oxygen consumption experiments: (i) a description of the standard parameters for measuring respiration in intact cells, (ii) a framework for data analysis and normalization, and (iii) examples of measuring respiration in permeabilized cells to follow up results observed with intact cells.