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Chris M Stainsby, Teodora M Perger, Vani Vannappagari, Karam C Mounzer, Ricky K Hsu, Cassidy E Henegar, James Oyee, Rimgaile Urbaityte, Charlotte E Lane, Lindsay M Carter, Gary E Pakes, Mark S Shaefer
INTRODUCTION: HLA-B*5701 screening identifies patients at increased risk for abacavir (ABC) hypersensitivity reaction (HSR). Screening was adopted in GlaxoSmithKline and ViiV Healthcare clinical trials in 2007 and HIV treatment guidelines in 2008. Company meta-analyses of trials pre-HLA-B*5701 screening reported HSR rates of 4% to 8%. We analyzed the effectiveness of HLA-B*5701 screening on reducing HSR rates using clinical trial, observational (OPERA) cohort, and spontaneous reporting data...
November 10, 2018: Pharmacotherapy
Christopher M Bland, Manjunath P Pai, Thomas P Lodise
Therapeutic drug management is regularly performed for aminoglycosides in an effort to maximize their effectiveness and safety. The ratio of maximum plasma drug concentration to minimum inhibitory concentration (Cmax /MIC) has long been regarded as the primary pharmacokinetic/pharmacodynamic (PK/PD) index of clinical efficacy for aminoglycosides due to their concentration-dependent killing. In this review, however, we discuss why the area under the plasma concentration-time curve (AUC)/MIC ratio may be a more reliable indicator of bacterial killing and clinical efficacy for these agents...
November 7, 2018: Pharmacotherapy
Nitipong Permpalung, Monica V Mahoney, Carolyn D Alonso
BACKGROUND: Infections with adenoviruses can result in considerable mortality and morbidity in solid organ transplant recipients. Standard therapy for adenovirus infections in transplant recipients is not established. At our institution, intravenous cidofovir and immunoglobulin have been used to treat disseminated or invasive adenovirus in solid organ and hematopoietic stem cell transplant recipients. METHODS: A retrospective case series of solid organ transplant recipients treated with cidofovir and intravenous immunoglobulin was performed...
November 7, 2018: Pharmacotherapy
Ryan J Fink, Andrew Young, N David Yanez, Marissa Hom, Jennifer Mai, Matthias Merkel
PURPOSE: A new postcardiac surgery fluid resuscitation strategy was implemented in our Cardiovascular Intensive Care Unit (CVICU) to implement evidence-based practice. We transitioned from a primarily albumin fluid-based strategy to a lactated Ringer's fluid-based strategy. We sought to determine whether a new postoperative fluid resuscitation strategy significantly altered the fluid composition for postcardiac surgery patients and what effect that would have on fluid resuscitation costs...
November 7, 2018: Pharmacotherapy
Kyle Troksa, Nikolas Kovacich, Michael Moro, Benjamin Chavez
Central nervous system stimulants are a commonly used, first-line treatment option for attention-deficit/hyperactivity disorder (ADHD). Generally, stimulants are well tolerated, with the most common adverse effects being anorexia and insomnia. However, there are some concerns with long-term use of stimulants, such as potential growth delay. Historically, data regarding this long-term adverse effect have been conflicting. In this article, we reviewed the newer data surrounding the effects of central nervous system stimulants on growth parameters in children with ADHD...
October 28, 2018: Pharmacotherapy
R Brigg Turner, Kyle Kojiro, Emily A Shephard, Regina Won, Eric Chang, Dominic Chan, Fawzy Elbarbry
BACKGROUND: Vancomycin area under the time-concentration curve (AUC) has been linked to efficacy and safety. An accurate method of calculating the AUC is needed. METHODS: Bayesian dose optimizing software programs available for clinician use and first-order pharmacokinetic equations were evaluated for their ability to estimate vancomycin AUC. A previously published rich pharmacokinetic dataset of 19 critically-ill patients was used for validation of the AUC estimation...
October 26, 2018: Pharmacotherapy
Kennerly Sexton Patrick, Jennifer L Radke, John R Raymond, Lauren Koller, Linda V Nguyen, Wendy Rodriguez, Arthur B Straughn
In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). An immediate-release (IR) MPH pulse (22% of the dose) facilitates rapid onset of stimulant action, while the remaining MR portion of the dose provides for day-long duration of efficacy. A wide array of oral MR-MPH products has subsequently been approved that also allows for once daily dosing, though each product is characterized by distinctive exposure time courses...
October 23, 2018: Pharmacotherapy
Dalila Masic, Edith Liang, Christina Long, Ethan J Sterk, Brian Barbas, Megan A Rech
The purpose of this systematic review is to evaluate the safety and efficacy of intravenous (IV) lidocaine for the treatment of acute pain in adult patients. The PubMed database was searched for randomized controlled trials, retrospective cohort studies, case series, and case reports evaluating use of IV lidocaine for the treatment of acute pain in adult patients, published between January 1970 and January 2018. The primary outcome was pain reduction via Visual Analog Scale, Verbal Rating Scale, or Numeric Rating Scale among patients treated with IV lidocaine and placebo or active controls...
October 10, 2018: Pharmacotherapy
Jeffrey J Cies, Thomas Habib, Vidhy Bains, Megan Young, Ogechukwu R Menkiti
OBJECTIVE: Identify population pharmacokinetics and pharmacodynamic target attainment of gentamicin in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH). DESIGN: Prospective open-label pharmacokinetic study. Gentamicin concentrations were modeled and dosing regimens simulated for a 5000-patient neonatal population with HIE receiving CH using PMetrics, a nonparametric, pharmacometric modeling, and simulation package for R...
October 9, 2018: Pharmacotherapy
Amy L Carr, Mitchell J Daley, Kathryn Givens Merkel, Dusten T Rose
Significant clinical and financial consequences are associated with both inadequate and unnecessary exposure to broad-spectrum antibiotics. As such, antimicrobial stewardship programs seek objective, reliable, and cost-effective tests to identify patients at highest or lowest risk for drug-resistant organisms to guide empirical antimicrobial selection. Use of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA in lower respiratory tract infections has led to significant reductions in duration of vancomycin therapy...
October 9, 2018: Pharmacotherapy
Alexandra M Hanretty, Ishminder Kaur, Alan T Evangelista, Wayne S Moore, Adela Enache, Arun Chopra, Jeffrey J Cies
INTRODUCTION: Meropenem-vaborbactam is a new β-lactam/β-lactamase inhibitor combination designed to target Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae. Meropenem-vaborbactam was Food and Drug Administration FDA approved for complicated urinary tract infections (cUTI) in patients 18 years of age or older. An understanding of the pharmacokinetics of meropenem when given in combination with vaborbactam is important to understanding the dosing of meropenem-vaborbactam...
October 9, 2018: Pharmacotherapy
Katie E Barber, Alison M Bell, Mary Joyce B Wingler, Jamie L Wagner, Kayla R Stover
Omadacycline is a novel aminomethylcycline seeking approval for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. This article reviews existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics/pharmacodynamics, in vitro activity, and current progress with omadacycline in clinical trials. Omadacycline inhibits protein synthesis by binding to the 30S subunit of the bacterial ribosome at the tetracycline binding site with an affinity similar to glycylcyclines...
October 5, 2018: Pharmacotherapy
Monique R Bidell, Thomas P Lodise
A number of antibacterial agents have emerged into the United States market in the last two decades to address growing concerns of antimicrobial resistance. These agents have demonstrated noninferiority to comparators for treatment of a range of complicated infections in their respective clinical trials. However, with select agents, a trend of reduced therapeutic efficacy has been observed among study patients with baseline renal impairment. This phenomenon was seen in phase III studies involving ceftazidime-avibactam, ceftolozane-tazobactam, daptomycin, and telavancin...
October 5, 2018: Pharmacotherapy
Jie-Ying Wu, Ya-Ting Chang, Ying-Chin Lin, Chia-Hwa Lee, El-Wui Loh, Mei-Yi Wu, Yu-Sheng Chang, Ka-Wai Tam
OBJECTIVE: To evaluate the efficacy and safety of lesinurad for the treatment of hyperuricemia in patients with gout. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). PATIENTS OR PARTICIPANTS: Five RCTs, which included 1959 patients, compared the efficacy and safety of lesinurad in patients with hyperuricemia associated with gout. MEASUREMENTS AND RESULTS: Relevant studies were identified from PubMed, EMBASE, Cochrane Library databases, and the ClinicalTrials...
September 23, 2018: Pharmacotherapy
Kathryn E Smith, Caitlin S Brown, Bridget M Manning, Teresa May, Richard R Riker, Patricia A Lerwick, Timothy L Hayes, Gilles L Fraser
STUDY OBJECTIVE: High-dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point-of-care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results. DESIGN: Prospective observational pilot study. SETTING: Intensive care unit in a large academic tertiary care medical center. PATIENTS: Five consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy...
September 19, 2018: Pharmacotherapy
Amy D Robertson, Chenghui Li, Drayton A Hammond, Tiffany A Dickey
INTRODUCTION: Vancomycin (VAN) is associated with an increased risk of acute kidney injury (AKI). Evidence is conflicting regarding the risk of AKI when VAN is combined with an antipseudomonal β-lactam. OBJECTIVES: To determine the comparative incidence of AKI when VAN is combined with piperacillin-tazobactam (PTZ) or meropenem (MER). METHODS: This was a retrospective cohort study of acutely ill adults receiving the combination of VAN and PTZ or MER for at least 48 hours between November 1, 2014, and October 31, 2016, in a tertiary care hospital...
September 2, 2018: Pharmacotherapy
Ralph C Ward, David J Taber, Robert Neal Axon, Mulugeta Gebregziabher
STUDY OBJECTIVE: Summary measures of medication adherence, such as the proportion of days covered (PDC), are often used to analyze the association between medication adherence and various health outcomes. We hypothesized that PDC and similar measures may lead to biased results in some situations when used to estimate the association between adherence and the outcome event (e.g., mortality). Thus, the objective was to determine the conditions under which PDC and similar measures might produce biased estimates of the association between adherence and mortality and to review methods to avoid such bias...
August 24, 2018: Pharmacotherapy
James R Krenz, Yaman Kaakeh
Both calcium channel blockers (CCBs) and β blockers (BBs) are associated with fatal substance exposures within the United States. Cases of overdose with these agents have the potential to be both complex and difficult to manage. A variety of pharmacologic treatment options are available for clinicians to use to help mitigate harm from these poisonings. Hyperinsulinemic-euglycemic therapy (HIET) was once regarded as a last-ditch effort to treat patients in highly refractory cases. In recent years, this therapy has become a routine therapy in the treatment of CCB/BB overdose...
August 23, 2018: Pharmacotherapy
Raymond J Yost, Bradley J Haan, Kyle C Mangan
Dosing of enoxaparin for deep vein thrombosis (DVT) prophylaxis in acutely burned patients has been shown to result in anti-Xa levels below target range. We describe the first case report, to our knowledge, of a severely burned patient who, despite prophylactic dosing of enoxaparin 30 mg subcutaneously twice daily, developed an acute DVT that required high-dose enoxaparin (100 mg [1.5 mg/kg] subcutaneously every 8 hours) to maintain anti-Xa levels within the therapeutic range (0.6-1 IU/ml). Pharmacokinetic evaluations were performed using anti-Xa levels measured throughout the patient's hospital stay to validate the appropriateness of this high-dose regimen based on established therapeutic anti-Xa level ranges...
August 20, 2018: Pharmacotherapy
Jimin Lee, Sukhyang Lee
STUDY OBJECTIVE: Patients with coronary heart disease (CHD) frequently use the combination of a statin and renin-angiotensin-aldosterone system (RAAS) blocker, an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), to control lipid levels and blood pressure, respectively, and the use of ARBs is increasing in Korean patients. Few studies are available, however, that have compared combination therapy with statin-ACEIs versus statin-ARBs. The objective of this study was to evaluate whether ARBs are associated with a reduced risk of major adverse cardiovascular and cerebrovascular events (MACCEs) compared with ACEIs when used in combination with statins in patients with established CHD...
November 2018: Pharmacotherapy
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