Clinical Outcomes in Patients With Gram-Negative Infections Treated With Optimized Dosing Cefepime Over Various Minimum Inhibitory Concentrations.

Background: The Clinical and Laboratory Standards Institute (CLSI) revised cefepime interpretive criteria, introducing the susceptible dose-dependent category for Enterobacteriaceae with a minimum inhibitory concentration (MIC) of 4 to 8 μg/mL in 2014. Limited clinical data support these new categories. This study compares outcomes of patients treated with standard and high-dose cefepime across various MICs.

PI3K/mTOR Inhibitors in the Treatment of Luminal Breast Cancer. Why, When and to Whom?

Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in luminal breast cancer (BC). Despite the efficacy of endocrine agents, many patients with luminal BC do not respond to endocrine therapy and many others develop endocrine resistance over time, due to the activation of escape pathways such as the PI3K/AKT/mTOR signaling. Several clinical trials have demonstrated the efficacy of mTOR and PI3K inhibitors in overcoming endocrine resistance in hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic BC (MBC) patients.

Ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections.

Background: Ertapenem is a broad-spectrum antibiotic that is increasingly being utilized. Its dosing convenience renders it suitable for outpatient therapy, and its pharmacokinetic characteristics favour its use against complicated urinary tract infections (cUTIs). Despite this, sufficient clinical data are lacking for its use against cUTIs in the outpatient setting.

Blockade of AP-1 Potentiates Endocrine Therapy and Overcomes Resistance.

Unlabelled: The transcription factor AP-1 is downstream of growth factor (GF) receptors (GFRs) and stress-related kinases, both of which are implicated in breast cancer endocrine resistance. Previously, we have suggested that acquired endocrine resistance is associated with increased activity of AP-1 in an in vivo model. In this report, we provide direct evidence for the role of AP-1 in endocrine resistance.

Use of Statins and Risk of Dementia in Heart Failure: A Retrospective Cohort Study.

Objective: Heart failure (HF) is associated with an increased risk of dementia, and studies show that dyslipidemia may be involved in the pathogenesis of dementia. However, it is unclear whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are associated with a lower risk of dementia in HF patients. The present study examines the effectiveness of statins to prevent dementia in HF patients.

Significant publications on infectious diseases pharmacotherapy in 2014.

Purpose: The most important articles on infectious diseases (ID) pharmacotherapy published in the peer-reviewed literature in 2014, as nominated and selected by panels of pharmacists and others with ID expertise, are summarized.

Summary: Members of the Houston Infectious Diseases Network were asked to nominate articles published in 2014 from prominent peer-reviewed journals that were felt to have a major impact in the field of ID pharmacotherapy. A list of 19 nominated articles on general ID-related topics and 9 articles specifically related to human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) was compiled.

Modeling Heterogeneous Bacterial Populations Exposed to Antibiotics: The Logistic-Dynamics Case.

In typical in vitro tests for clinical use or development of antibiotics, samples from a bacterial population are exposed to an antibiotic at various concentrations. The resulting data can then be used to build a mathematical model suitable for dosing regimen design or for further development. For bacterial populations that include resistant subpopulations-an issue that has reached alarming proportions-building such a model is challenging.

Preferences and Outcomes for Chemotherapy Teaching in a Postgraduate Obstetrics and Gynecology Training Program.

Purpose: To determine whether chemotherapy teaching is a desired component of postgraduate training programs in obstetrics and gynecology and assess its effect on practicing clinicians.

Method: After obtaining institutional review board approval, 99 individuals who completed postgraduate training at a single academic medical center between 2005 and 2013 were invited to complete an online survey. Descriptive statistics were used to summarize responses.

Multiplex Real-Time PCR Method for Simultaneous Identification and Toxigenic Type Characterization of Clostridium difficile From Stool Samples.

Background: The aim of this study was to develop and validate a multiplex real-time PCR assay for simultaneous identification and toxigenic type characterization of Clostridium difficile.

Methods: The multiplex real-time PCR assay targeted and simultaneously detected triose phosphate isomerase (tpi) and binary toxin (cdtA) genes, and toxin A (tcdA) and B (tcdB) genes in the first and sec tubes, respectively. The results of multiplex real-time PCR were compared to those of the BD GeneOhm Cdiff assay, targeting the tcdB gene alone.

Assessment of minocycline and polymyxin B combination against Acinetobacter baumannii.

Antimicrobial resistance among Acinetobacter baumannii is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of A.

Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia.

Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state.

Risk factors for nephrotoxicity onset associated with polymyxin B therapy.

Objectives: Polymyxin B is an active agent against many MDR Gram-negative bacteria, but nephrotoxicity is a major hindrance to its widespread use. To guide its optimal use, we determined the risk factors for nephrotoxicity onset associated with polymyxin B.

Methods: In a multicentre, retrospective, cohort study, we evaluated adult patients with normal renal function who received ≥72 h of polymyxin B therapy.

Echinocandin use in hospitalized patients: a multi-institutional study.

Background: The echinocandin antifungals are recommended as initial therapy in hospitalized patients with candidemia. Contemporary usage rates and indication for use of echinocandins have not been studied in the United States. The purpose of this study was to evaluate echinocandin usage patterns in community and academic teaching hospitals over time and to evaluate dose, duration of therapy and indications for use.

Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus.

In the face of diminishing therapeutic options for the treatment of infections caused by multidrug-resistant, Gram-negative bacteria, clinicians are increasingly using colistin and polymyxin B. These antibiotics became available clinically in the 1950s, when understanding of antimicrobial pharmacology and regulatory requirements for approval of drugs was substantially less than today. At the 1st International Conference on Polymyxins in Prato, Italy, 2013, participants discussed a set of key objectives that were developed to explore the factors affecting the safe and effective use of polymyxins, identify the gaps in knowledge, and set priorities for future research.

Real-world performance of a microarray-based rapid diagnostic for Gram-positive bloodstream infections and potential utility for antimicrobial stewardship.

The Verigene Gram-positive blood culture assay (BC-GP) is a microarray-based rapid diagnostic test, which includes targets for 12 bacterial species and 3 resistance determinants. We prospectively compared the diagnostic accuracy of the BC-GP to routine microbiologic methods and evaluated the potential of the BC-GP for antimicrobial stewardship programs. A total of 143 consecutive patients with Gram-positive bacteremia were included in the analysis.

Assessment of Antimicrobial Stewardship Activities in a Large Metropolitan Area.

Purpose: To describe antimicrobial stewardship programs (ASPs) of acute and long-term acute care (LTAC) hospitals in Houston, Texas.

Methods: Two-part survey to clinical pharmacists and pharmacy directors. All acute care and LTAC facilities from the Harris County Medical Society database were invited to participate.

Validation of a model to predict the risk of nephrotoxicity in patients receiving colistin.

Despite concerns about its nephrotoxicity, colistin often remains the only effective agent for treating multidrug-resistant Gram-negative infections. Published studies have reported a wide range of nephrotoxicity risk factors. To assess the clinical utility of various models, we compared their performances for predicting the risk of nephrotoxicity.

Hepatopancreaticobiliary Values after Thoracoabdominal Aneurysm Repair.

Background: After thoracoabdominal aortic aneurysm (TAAA) repair, blood tests assessing hepatopancreaticobiliary (HPB) organs commonly have abnormal results. The clinical significance of such abnormalities is difficult to determine because the expected postoperative levels have not been characterized. Therefore, we sought to establish expected trends in HPB laboratory values after TAAA repair.

Mathematical model to quantify the effects of risk factors on carbapenem-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are increasing, and they are associated with an increased risk of mortality in hospitalized patients. Linear regression is commonly used to identify concurrent trends, but it cannot quantify the relationship between risk factors and resistance. We developed a model to quantify the impact of antibiotic consumption on the prevalence of CRAB over time.

Pharmacokinetics of ertapenem in outpatients with complicated urinary tract infections.

Objectives: Ertapenem is a broad-spectrum carbapenem antibiotic used to treat severe bacterial infections. In view of its dosing convenience, it is increasingly used as outpatient therapy. The objective of this study was to determine the pharmacokinetics and renal disposition of ertapenem in outpatients with complicated urinary tract infections.

Uptake of polymyxin B into renal cells.

Polymyxin B is increasingly used as a treatment of last resort against multidrug-resistant Gram-negative infections. Using a mammalian kidney cell line, we demonstrated that polymyxin B uptake into proximal tubular epithelial cells was saturable and occurred primarily through the apical membrane, suggesting the involvement of transporters in the renal uptake of polymyxin B. Megalin might play a role in the uptake and accumulation of polymyxin B into renal cells.