Understanding vancomycin nephrotoxicity augmented by β-lactams: a synthesis of endosymbiosis, proximal renal tubule mitochondrial metabolism, and β-lactam chemistry.

The recent understanding that hydrophobic β-lactams have greater affinity for organic anion transporter-3 (OAT-3) of the proximal renal tubule could provide valuable insights for anticipating β-lactams that may exacerbate vancomycin-induced nephrotoxicity. Vancomycin alone provides oxidative stress on the highly metabolic proximal tubular cells. Hydrophobic β-lactams (eg, piperacillin and anti-staphylococcal β-lactams) could have greater OAT-3 mediated uptake into proximal tubular cells than hydrophilic β-lactams (eg, most cephalosporins and carbapenems), thereby causing greater mitochondrial stress on these susceptible cells.

Leveraging stewardship to promote ceftriaxone use in severe infections with low- and no-risk AmpC Enterobacterales.

AmpC β-lactamases are associated with development of ceftriaxone resistance despite initial susceptibility, but the risk of AmpC derepression is not equal among Enterobacterales. The purpose of this study was to evaluate the impact of an AmpC stewardship intervention on the definitive treatment of low- and no-risk Enterobacterales. This was an IRB-approved, single pre-test, post-test quasi-experiment at a 5-hospital system.

Ciprofloxacin in combination with bacteriophage cocktails against multi-drug resistant in simulated endocardial vegetation models.

-associated infective endocarditis represents difficult-to-treat, deep-seated infections. Phage-antibiotic combinations have shown to eradicate multi-drug resistant (MDR) , limit the development of phage resistance, and restore antibiotic sensitivity. The objective of this study was to evaluate the activity of phage-ciprofloxacin (CIP) combinations in 4-day simulated endocardial vegetation (SEV) models against drug-resistant isolates.

Phage-antibiotic combinations against multidrug-resistant in static and dynamic biofilm models.

Biofilm-producing infections pose a severe threat to public health and are responsible for high morbidity and mortality. Phage-antibiotic combinations (PACs) are a promising strategy for combatting multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat infections. Ten MDR/XDR strains and five .

PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.

Purinosomes serve as metabolons to enhance de novo purine synthesis (DNPS) efficiency through compartmentalizing DNPS enzymes during stressed conditions. However, the mechanism underpinning purinosome assembly and its pathophysiological functions remains elusive. Here, we show that K6-polyubiquitination of the DNPS enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) by cullin-5/ankyrin repeat and SOCS box containing 11 (Cul5/ASB11)-based ubiquitin ligase plays a driving role in purinosome assembly.

Targeting Dalbavancin Inoculum Effect: Adjunctive Single Dose of Daptomycin.

Introduction: Daptomycin (DAP) has proven to be a viable alternative amid vancomycin resistance; however, the use of DAP post vancomycin treatment has led to the development of DAP non-susceptible (DNS) strains. Dalbavancin (DAL), a novel single-dosed lipoglycopeptide, has shown enhanced activity against highly resistant Staphylococcus aureus strains. However, on the basis of previous reports and our observations, DAL does not demonstrate similar activity at high versus low inoculum levels.

Defective monocyte plasticity and altered cAMP pathway characterize USB1-mutated poikiloderma with neutropenia Clericuzio type.

Poikiloderma with neutropenia (PN) Clericuzio type (OMIM #604173) is a rare disease with areas of skin hyper- and hypopigmentation caused by biallelic USB1 variants. The current study was spurred by poor healing of a perianal tear wound in one affected child homozygous for c.266-1G>A (p.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including (MAB). This multicenter retrospective study across 16 U.

Anticoagulant drug-drug interactions with cannabinoids: A systematic review.

This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords.

Weighing the Odds: Novel β-Lactam/β-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pneumonia for Patients Who Are Morbidly Obese.

Background: is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index ≥35 kg/m) and non-morbidly obese (<35 kg/m) and receiving BL/BLI for HABP/VABP.

The design, synthesis, and inhibition of Clostridioides difficile spore germination by acyclic and bicyclic tertiary amide analogs of cholate.

Clostridioides difficile infection (CDI) is a major identifiable cause of antibiotic-associated diarrhea. In our previous study (J. Med.

Comparing Post-operative Opioid Consumption before and after a Patient-Controlled Analgesia Shortage: A Re-evaluation of Safety and Effectiveness.

This retrospective cohort study aimed to compare post-surgical opioid consumption before and after a PCA (patient-controlled analgesia) shortage. The study evaluated patients who received PCA nurse-administered opioid analgesia (non-PCA). Two hundred and twenty-four patients ≥18 years who were initiated on analgesia within 24 h of surgery were included.

Protection against Severe Illness versus Immunity-Redefining Vaccine Effectiveness in the Aftermath of COVID-19.

Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get infected in high numbers, and viral loads in vaccinated individuals were as high as those in the unvaccinated. However, even with high viral loads, vaccinated individuals were significantly less likely to develop severe illness; this begs the question as to whether the main effect of anti-SARS-CoV-2 vaccines is to confer protection against severe illness or immunity against infection.

Evaluation of standard versus prolonged magnesium infusion rates in hospitalized patients: a retrospective cohort study.

Background: Hypomagnesemia is a common electrolyte abnormality in hospitalized patients. Prolonging the infusion rate of magnesium has been hypothesized to increase retention of magnesium, however, there is limited evidence to support prolonging the rate of infusion.

Aim: To compare the absolute change in serum magnesium levels from baseline to levels drawn within 24 hours after the end of infusion between two groups receiving standard or prolonged infusion.

A comprehensive review on the global efforts on vaccines and repurposed drugs for combating COVID-19.

The recently discovered coronavirus, known as SARS-CoV-2, is a highly contagious and potentially lethal viral infection that was declared a pandemic by the World Health Organization on March 11, 2020. Since the beginning of the pandemic, an unprecedented number of COVID-19 vaccine candidates have been investigated for their potential to manage the pandemic. Herein, we reviewed vaccine development and the associated research effort, both traditional and forward-looking, to demonstrate the advantages and disadvantages of their technology, in addition to their efficacy limitations against mutant SARS-CoV-2.

Community Pharmacists' Knowledge and Perceptions of Buprenorphine for Patients with Opioid Use Disorder.

Objectives: The aims of the study are to evaluate community pharmacists' knowledge and perceptions regarding buprenorphine for opioid use disorder and their willingness to dispense buprenorphine and to identify opportunities for education.

Methods: An electronic survey of Michigan pharmacists (n = 11,123) assessed demographics, training, buprenorphine knowledge, dispensing, perceptions of stigma, diversion, and confidence in patient/provider interactions. Composite scores for knowledge, stigma, diversion, and confidence were calculated.

Helping fourth year student pharmacists develop their professional brand.

Background And Purpose: Building a professional brand is an important skill for student pharmacists, as this could provide them with a competitive edge given the current market environment and employment opportunities. One way to do this is through developing a personal digital brand. A pilot program was created to introduce fourth year pharmacy students to the basics of personal branding and positive uses of social media for professional development and networking.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

Background: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) , XDR , and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections.

Methods: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial.

Incretin Analogs for Weight Management in Adults Without Diabetes.

Objective: This is a narrative review of incretin analogs and their effect on weight management in adult without diabetes.

Data Sources: Randomized controlled trials were identified by English language. PubMed/MEDLINE, Scopus, and Embase databases were searched from inception through June 2023 to identify all pertinent trials reporting outcomes on efficacy and safety search using the terms: tirzepatide, semaglutide, liraglutide, and obesity.

A Fluorescence-Based Assay for N -Carboxyaminoimidazole Ribonucleotide Mutase.

The enzyme N -carboxylaminoinidazole ribonucleotide (N -CAIR) mutase is found in microbial de novo purine biosynthesis but is absent in humans making it an attractive antimicrobial target. N -CAIR mutase catalyzes the synthesis of carboxyaminoimidazole ribonucleotide (CAIR) from N -CAIR which is itself prepared from aminoimidazole ribonucleotide (AIR) by the enzyme N -CAIR synthetase. During our research on identifying inhibitors of N -CAIR mutase, we developed an innovative, fluorescence-based assay to measure the activity of this enzyme.

A New Method to Detect Variants of SARS-CoV-2 Using Reverse Transcription Loop-Mediated Isothermal Amplification Combined with a Bioluminescent Assay in Real Time (RT-LAMP-BART).

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which there are several variants. The three major variants (Alpha, Delta, and Omicron) carry the N501Y, L452R, and Q493R/Q498R mutations, respectively, in the gene. Control of COVID-19 requires rapid and reliable detection of not only SARS-CoV-2 but also its variants.