Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV

Tetradecylthioacetic Acid Increases Hepatic Mitochondrial β-Oxidation and Alters Fatty Acid Composition in a Mouse Model of Chronic Inflammation

The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti-inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α-induced lipid modifications in human TNFα (hTNFα) transgenic mice. These mice are characterized by reduced β-oxidation and changed fatty acid composition in the liver. The effect of dietary treatment with TTA on persistent, low-grade hTNFα overexpression in mice showed a beneficial effect through decreasing TAG plasma concentrations and positively affecting saturated and monounsaturated fatty acid proportions in the liver, leading to an increased anti-inflammatory fatty acid index in this group. We also observed an increase of mitochondrial β-oxidation in the livers of TTA treated mice. Concomitantly, there were enhanced plasma levels of carnitine, acetyl carnitine, propionyl carnitine, and octanoyl carnitine, no changed levels in trimethyllysine and palmitoyl carnitine, and a decreased level of the precursor for carnitine, called γ-butyrobetaine. Nevertheless, TTA administration led to increased hepatic TAG levels that warrant further investigations to ascertain that TTA may be a promising candidate for use in the amelioration of inflammatory disorders characterized by changed lipid metabolism due to raised TNFα levels

Will the Conscious–Subconscious Pacing Quagmire Help Elucidate the Mechanisms of Self-Paced Exercise? New Opportunities in Dual Process Theory and Process Tracing Methods

The extent to which athletic pacing decisions are made consciously or subconsciously is a prevailing issue. In this article we discuss why the one-dimensional conscious–subconscious debate that has reigned in the pacing literature has suppressed our understanding of the multidimensional processes that occur in pacing decisions. How do we make our decisions in real-life competitive situations? What information do we use and how do we respond to opponents? These are questions that need to be explored and better understood, using smartly designed experiments. The paper provides clarity about key conscious, preconscious, subconscious and unconscious concepts, terms that have previously been used in conflicting and confusing ways. The potential of dual process theory in articulating multidimensional aspects of intuitive and deliberative decision-making processes is discussed in the context of athletic pacing along with associated process-tracing research methods. In attempting to refine pacing models and improve training strategies and psychological skills for athletes, the dual-process framework could be used to gain a clearer understanding of (1) the situational conditions for which either intuitive or deliberative decisions are optimal; (2) how intuitive and deliberative decisions are biased by things such as perception, emotion and experience; and (3) the underlying cognitive mechanisms such as memory, attention allocation, problem solving and hypothetical thought

Monotherapy with Vancomycin or Daptomycin versus Combination Therapy with β-Lactams in the Treatment of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections: A Retrospective Cohort Analysis

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with high morbidity and mortality. More in vitro, in vivo, and clinical data suggest that vancomycin (VAN) or daptomycin (DAP) combination therapy with β-lactams (BL) improves outcomes of MRSA infections. We hypothesize that BL combination with VAN or DAP would reduce the odds of clinical failure compared to VAN or DAP monotherapy. METHODS: A retrospective cohort study of adult patients ≥ 18 years treated with VAN or DAP for MRSA BSI from 2006 to 2019 at Detroit Medical Center. Combination therapy (CT) was defined as VAN or DAP plus any BL for ≥ 24 h within 72 h of index culture. Monotherapy (MT) was defined as ≥ 72 h VAN or DAP within 72 h of index culture and no BL for ≥ 24 h up to 7 days following VAN/DAP initiation. Primary outcome was composite endpoint of clinical failure defined as: (1) 30-day mortality, (2) 60-day recurrence, or (3) persistent bacteremia (PB). PB was defined as bacteremia \u3e 5 days. Multivariable logistic regression was used to evaluate the association between CT and the primary outcome. RESULTS: Overall, 597 patients were included in this analysis, 153 in the MT group and 444 in the CT group. CT was independently associated with reduced odds of clinical failure (adjusted odds ratio, 0.523; 95% confidence interval, 0.348-0.787). The composite endpoint was driven by 60-day recurrence and PB but not 30-day mortality. There were no difference in adverse events including nephrotoxicity between the two study arms. CONCLUSIONS: In hospitalized adults with MRSA BSI, CT with any BL was independently associated with improved clinical outcomes and may ultimately be selected as preferred therapy