Pioneering Computational Culture Within Pharmacy Schools by Empowering Students With Data Science and Bioinformatics Skills.

As advancements in digital health lead to the generation of increasingly diverse and voluminous pharmaceutical data, it is increasingly critical that we teach trainee pharmaceutical scientists how to leverage this data to lead future innovations in health care and pharmaceutical research. To address this need, the University of Southern California Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences is incorporating data science and bioinformatics into the graduate and undergraduate curricula through introductory courses tailored for students without prior programming experience.

Comparative in vitro efficacy of antibiotics against the intracellular reservoir of Staphylococcus aureus.

Unlabelled: Staphylococcus aureus (SA) is a leading cause of bloodstream infection. The liver represents the sentinel immune organ for clearance of bloodstream pathogens and eradication of intracellular SA from liver-resident macrophages (Kupffer cells, KCs) eliminates the likely pathogenic reservoir that contributes to persistent bacteraemia.

Objectives: We assessed antimicrobial activity at phagolysosome-mimicking pH, intracellular penetration, and SA eradication within KCs in vitro for clinically prescribed antistaphylococcal agents alone or in combination: vancomycin, daptomycin, ceftaroline, ceftobiprole, oritavancin, oxacillin, cefazolin; rifampin and fosfomycin.

Comparative In Vitro Activity of Ceftazidime-Avibactam, Imipenem-Relebactam, and Meropenem-Vaborbactam against Carbapenem-Resistant Clinical Isolates of and .

Co-infection with carbapenem-resistant (CRKP) and (CRPA) is associated with poor outcomes and historically relied on combination therapy with toxic agents for management. However, several novel β-lactam/β-lactamase inhibitor combination agents have been developed, offering potential monotherapy options. Here, we compare the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IRL), and meropenem-vaborbactam (MVB) against both CRKP and CRPA clinical isolates.

Machine learning to identify risk factors associated with the development of ventilated hospital-acquired pneumonia and mortality: implications for antibiotic therapy selection.

Background: Among patients with nosocomial bacterial pneumonia, those who decompensated to requiring mechanical ventilation (vHABP) faced the highest mortality followed by ventilator-associated pneumonia (VABP) and non-ventilated hospital-acquired pneumonia (nvHABP). The objectives of this study were to identify risk factors associated with the development and mortality of vHABP and to evaluate antibiotic management.

Methods: A multicenter retrospective cohort study of adult inpatients with nosocomial pneumonia during 2014-2019 was performed.

Risk factors and outcome associated with coinfection with carbapenem-resistant and carbapenem-resistant or a descriptive analysis.

Background: Nearly 30% of patients infected with carbapenem-resistant (CRKP) were previously shown to be coinfected with carbapenem-resistant (CRPA) or (CRAB). Infections caused by multiple carbapenem-resistant pathogens present significant challenge to infection control and therapeutic management. The study objective was to identify risk factors for acquisition of multiple carbapenem-resistant pathogens and associated outcomes.

Machine Learning with Alpha Toxin Phenotype to Predict Clinical Outcome in Patients with Bloodstream Infection.

bloodstream (SAB) infection remains a leading cause of sepsis-related mortality. Yet, current treatment does not account for variable virulence traits that mediate host dysregulated immune response, such as SA α-toxin (Hla)-mediated thrombocytopenia. Here, we applied machine learning (ML) to bacterial growth images combined with platelet count data to predict patient outcomes.

Prognostic significance of early platelet dynamics in Staphylococcus aureus bacteremia.

Background: Platelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB).

Method: Electronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data.

Temporal Dynamics of Host Immune Response Associated With Disease Severity and Time to Recovery in Patients Hospitalized for COVID-19.

Objectives: The objective of this study was to compare the temporal dynamics of two viral-induced inflammatory proteins interferon gamma inducible protein-10 (IP-10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as C-reactive protein (CRP) among patients hospitalized for COVID-19 and examine their prognostic significance.

Design: Prospective observational cohort study.

Setting: Multicenter, inpatient.

Unvaccinated Non-Elderly Adult Population Hospitalized for COVID-19: Risk for Severe Disease and Poor Outcomes.

Introduction: Vaccination offers significant protection against hospitalization and death due to severe COVID-19. However, a significant portion of the nonelderly U.S.

In-Human Multiyear Evolution of Carbapenem-Resistant Klebsiella pneumoniae Causing Chronic Colonization and Intermittent Urinary Tract Infections: A Case Study.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a frequent pathogen of the urinary tract, but how CRKP adapts over time is unclear. We examined 10 CRKP strains from a patient who experienced chronic colonization and recurrent urinary tract infections over a period of 4.5 years.

Increased Risk of Thrombocytopenia and Death in Patients with Bacteremia Caused by High Alpha Toxin-Producing Methicillin-Resistant .

Alpha toxin (Hla) is a major virulence factor of that targets platelets but clinical data on Hla pathogenesis in bacteremia (SAB) is limited. We examined the link between in vitro Hla activity and outcome. Study isolates obtained from 100 patients with SAB (50 survivors; 50 non-survivors) were assessed for in vitro Hla production by Western immunoblotting in a subset of isolates and Hla activity by hemolysis assay in all isolates.

Factors associated with prompt recovery among hospitalised patients with coronavirus disease 2019.

Background: Patients who survived hospitalisation for COVID-19 experienced varying durations of illness but the factors associated with prompt recovery are unknown. This study identifies factors differentiating hospitalised patients who recovered promptly versus survived a prolonged course of illness because of COVID-19.

Methods: This was a retrospective study from March-August 2020 of hospitalised adults with COVID-19 which were grouped based on time to recovery: short (≤3 days), intermediate (4-10 days) and prolonged (>10 days).

Risk factors and outcome associated with infection or colonization due to carbapenem-heteroresistant .

Background: Up to 32% of ESBL-producing Enterobacterales strains display a carbapenem-heteroresistant (cHR) phenotype but its clinical relevance is unknown.

Objectives: To determine risk factors and clinical outcome associated with infection due to cHR ESBL-producing (ESBL-EC).

Methods: A retrospective, case-control study was conducted on patients from whom a pair of clonally related strains were isolated during separate healthcare encounters with (case) or without (control) development of cHR phenotype in the latter strain.

Cytokine measurements add value to clinical variables in predicting outcomes for Staphylococcus aureus bacteremia.

Background: We demonstrated that an early dysregulated cytokine response [high interleukin-10 to tissue necrosis factor (IL-10/TNF) ratio] predicted poor outcomes in patients with Staphylococcus aureus bacteremia (SAB). However, high interpatient variability in cytokine levels were observed. We grouped cytokine measurements in quartiles and assessed their additive value to clinical variables for predicting bacterial persistence and 30-day mortality in patients with SAB.

Distance Between Home and the Admitting Hospital and Its Effect on Survival of Low Socioeconomic Status Population With Bacteremia.

Objective: Bacteremia is the presence of bacteria in the bloodstream. The objective of this study was to determine the relationship between low socioeconomic status (SES) and the epidemiology, process of care, and outcomes of patients with bacteremia (SAB).

Methods: We conducted a multicenter, retrospective, cohort study that evaluated adult patients with SAB in 3 Los Angeles County hospitals from July 15, 2012, through May 31, 2018.

Variable Release of Lipoteichoic Acid From Bloodstream Isolates Relates to Distinct Clinical Phenotypes, Strain Background, and Antibiotic Exposure.

Background: is a leading cause of bacterial bloodstream infections. The heterogeneity in patient outcomes in bacteremia (SAB) can be attributed in part to strain characteristics, which may influence host response to infection. We specifically examined the relationship between lipoteichoic acid (LTA) release from and disease phenotype, strain background, and antibiotic exposure.

Impact of Socioeconomic Status and Race on Sepsis Epidemiology and Outcomes.

Background: Socioeconomic status (SES) is a complex variable that is derived primarily from an individual's education, income, and occupation and has been found to be inversely related to outcomes of health conditions. Sepsis is the sixth most common admitting diagnosis and one of the most costly conditions for in-hospital spending in the United States. The objective of this review is to report on the relationship between SES and sepsis incidence and associated outcomes.

Differential effects of antibiotics on neutrophils exposed to lipoteichoic acid derived from Staphylococcus aureus.

Background: Persistent bacteremia occurs in at least 30% of patients with Staphylococcus aureus bloodstream infection (SAB) and may be attributable to a dysregulated host immune response. Neutrophils interact with a variety of S. aureus microbial factors, including lipoteichoic acid (LTA), to activate phagocytic function in a concentration-dependent manner.

Antibiotics Differentially Modulate Lipoteichoic Acid-Mediated Host Immune Response.

In bacteremia, our group has shown that a dysregulated balance of pro- and anti-inflammatory cytokine response biased towards an immunoparalysis phenotype is predictive of persistence and mortality, despite receipt of antibiotics. Certain antibiotics, as well as lipoteichoic acid (LTA) released from , can modulate immune response ex vivo. Here, we evaluated the effects of three anti-staphylococcal antibiotics (vancomycin, tedizolid, and daptomycin) on the expression of cytokines and cell surface markers of immune activation (TNFα, HLA-DR) and immunoparalysis (IL-10, PD-L1) in human peripheral blood mononuclear cells (PBMC) exposed to high (10 μg) and low (1 μg) doses of LTA.

Therapeutic Monitoring of Vancomycin for Serious Methicillin-resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-system Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity.

Executive Summary: Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.

Background: Recent vancomycin PK/PD and toxicodynamic studies enable a reassessment of the current dosing and monitoring guideline in an attempt to further optimize the efficacy and safety of vancomycin therapy. The area-under-the-curve to minimum inhibitory concentration (AUC/MIC) has been identified as the most appropriate pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin. The 2009 vancomycin consenus guidelines recommended specific trough concentrations as a surrogate marker for AUC/MIC.