Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis.

The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID-19) pandemic. Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms, including fever, cough, fatigue, and loss of smell and taste. However, many individuals develop pneumonia, acute respiratory distress syndrome, septic shock, and multiorgan dysfunction.

In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4 T-cell activation/ exhaustion.

Background: In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation.

Hepatocytic transcriptional signatures predict comparative drug interaction potential of rifamycin antibiotics.

Current strategies to treat tuberculosis (TB) and co-morbidities involve multidrug combination therapies. Rifamycin antibiotics are a key component of TB therapy and a common source of drug-drug interactions (DDIs) due to induction of drug metabolizing enzymes (DMEs). Management of rifamycin DDIs are complex, particularly in patients with co-morbidities, and differences in DDI potential between rifamycin antibiotics are not well established.

Vancomycin-Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention.

Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed.

Implementation of an Extended-Infusion Piperacillin-Tazobactam Dosing Protocol: Unexpected Findings when Monitoring Safety and Compliance with Smart Pump Technology.

Compliance with recommended infusion rates was evaluated before, during, and after the implementation of extended-infusion (EI) piperacillin-tazobactam at an academic medical center. Software-controlled infusion-pump alert data were studied for piperacillin-tazobactam administrations before and after implementation of a four-hour EI protocol. Compliance was analyzed 16 weeks before (pre-EI), two weeks after (peri-EI), and an additional 16 weeks after (post-EI) protocol implementation.

Augmented renal clearance of aminoglycosides using population-based pharmacokinetic modelling with Bayesian estimation in the paediatric ICU.

Objective: To evaluate augmented renal clearance (ARC) using aminoglycoside clearance (CLAMINO24h) derived from pharmacokinetic (PK) modelling.

Methods: A retrospective study at two paediatric hospitals of patients who received tobramycin or gentamicin from 1999 to 2016 was conducted. Compartmental PK models were constructed using the Pmetrics package, and Bayesian posteriors were used to estimate CLAMINO24h.

Assessing the lymphoid tissue bioavailability of antiretrovirals in human primary lymphoid endothelial cells and in mice.

Background: The secondary lymphoid tissues (LTs), lymph nodes (LNs) and gut-associated lymphoid tissue (GALT) are considered reservoirs for HIV. Antiretrovirals (ARVs) have lower penetration into LT. In vitro models predictive of ARV LT penetration have not been established.