Pharmacotherapy

Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes...

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output...

The HIV epidemic continues to pose a significant burden on the health care system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high-risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations...

Sickle cell anemia (SCA) is a life-threatening genetic condition contributing to high-risk pregnancies affecting both the mother and fetus. With improved management of children with SCA, this life-threatening hematological disorder has evolved into a chronic disease of adults, and consequently parenthood has now become a possible and important life goal for many patients. Providing continuous management with healthy red blood cell function and avoiding SCA-associated complications, such as pain crises, acute chest syndrome, and stroke, are crucial for a healthy pregnancy...

Sickle cell disease (SCD) is a common and life-threatening inherited blood disorder that affects more than 300,000 newborns per year. Because of the origins of the sickle gene mutation as a protective mechanism against malaria for those with sickle cell trait, more than 90% of annual SCD births are in sub-Saharan Africa (sSA). Over the past several decades, there have been many important advances in the care of individuals with SCD, including early diagnosis through newborn screening programs (NBS), prophylactic penicillin, the development of vaccines to prevent invasive bacterial infections, and the emergence of hydroxyurea as the primary disease-modifying pharmacologic therapy...

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent...

BACKGROUND: Little is known about antidepressant medication use patterns during pregnancy among periconception (before and immediately following conception) users. Additionally, the associations between these patterns and birth outcomes is unclear, after taking into account underlying depression severity. OBJECTIVE: This study describes patterns of antidepressant use among periconception users and examines associations between usage patterns and birth outcomes. STUDY DESIGN: This retrospective cohort study included pregnant Kaiser Permanente Northern California (KPNC) members with a live birth between 2014-2017 and an antidepressant medication fill that overlapped the 8th week of pregnancy...

INTRODUCTION: The accelerated approval pathway allows for drug approval based on surrogate outcome measures "reasonably likely" to predict clinical benefit. FDA guidance states that, when an indication is based on accelerated approval and hasn't yet received full approval, the drug label must describe the accelerated approval and should specify the specific surrogate marker(s) that supported it, as well as the clinical outcomes being evaluated in post-approval commitment trials. METHODS: We reviewed the labels of all drugs with indications receiving accelerated approval after January 1, 1992 that had not received full approval by December 31, 2020...

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is associated with significant improvement in lung function in people with Cysfic Fibrosis (pwCF); however, some patients experience adverse effects (AEs) including hepatotoxicity. One potential strategy is dose reduction of ETI with the goal of maintaining therapeutic efficacy while resolving AEs. We report our experience of dose reduction in individuals who experienced AEs following ETI therapy. We provide mechanistic support for ETI dose reduction by exploring predicted lung exposures and underlying pharmacokinetics-pharmacodynamics (PK-PD) relationships...

OBJECTIVE: To describe the impact of protocol-driven dexmedetomidine (and clonidine) use on opioid exposure in post-surgical neonates. METHODS: A retrospective chart review of surgical patients receiving opioids and alpha-2-agonists (dexmedetomidine and/or clonidine) post-operatively was performed over 2 time periods: one with and one without weaning protocols in place. Comparisons of opioid duration/exposure, NICU outcomes, and protocol process measures were made...

BACKGROUND: Liposomal amphotericin B (LAmB) is used in the treatment of opportunistic fungal and parasitic infections, including leishmaniasis. Given its lack of known teratogenicity in pregnancy LAmB is a preferred agent for treatment for these patients. However, significant gaps remain in determining optimal dosing regimens for LAmB in pregnancy. METHODS: We describe the use of LAmB for a pregnant patient with mucocutaneous leishmaniasis (MCL) using a dosing strategy of 5 mg/kg/day for days 1-7 using ideal body weight followed by 4 mg/kg weekly using adjusted body weight...

Eosinophilic esophagitis (EoE) is an inflammatory condition of the esophagus that is quickly becoming a more recognized cause of esophageal dysfunction and dysphagia. The cause of EoE is thought to be due to an inflammatory response triggered by exposure to dietary or environmental antigens. Symptoms may be progressive and include reflux, nausea, vomiting, dysphagia, and reduction in quality of life. Both children and adults may be affected. Initial treatments for EoE have focused on elimination diets to potentially identify and remove dietary triggers, acid suppression with proton pump inhibitors, and topical delivery of orally administered swallowed corticosteroids...

Antimicrobial susceptibility testing (AST) is a critical function of the clinical microbiology laboratory and is essential for optimizing care of patients with infectious diseases, monitoring antimicrobial resistance (AMR) trends, and informing public health initiatives. Several methods are available for performing AST including broth microdilution, agar dilution, and disk diffusion. Technological advances such as the development of commercial automated susceptibility testing platforms and the advent of rapid diagnostic tests have improved the rapidity, robustness, and clinical application of AST...

Antimicrobial resistance continues to surmount increasing concern globally, and treatment of difficult-to-treat (DTR) Pseudomonas aeruginosa, carbapenem-resistant (CR) Acinetobacter baumannii (CRAB), and CR Enterobacterales (CRE) remains a challenge for clinicians. Although previously rare, the incidence of multi-drug resistant (MDR) and CR infections in pediatric patients has increased drastically in the last decade and is associated with increased morbidity and mortality. To combat this issue, 14 novel antibiotics, including three β-lactam/novel β-lactamase inhibitor combinations (βL-βLIs) and two novel β-lactams (βLs), have received approval from the United States Food and Drug Administration since 2010...

Fosfomycin, originally named phosphonomycin when it was first isolated from fermentation broth of Streptomyces species and synthesized at Merck in 1969. The phosphonic acid containing a structurally strained and reactive epoxide ring confers broad spectrum, bactericidal activity against gram-positive and gram-negative bacteria. Fosfomycin's small size and hydrophilicity permits broad tissues penetration. Although only fosfomycin tromethamine oral is approved for urinary tract infections (UTI) in the United States since 1996, the intravenous form has been utilized worldwide for over four decades...

INTRODUCTION: In the United States, there has been controversy over whether treatment of mild-to-moderate hypertension during pregnancy conveys more benefit than risk. OBJECTIVE: The objective of the study was to compare risks and benefits of treatment of mild-to-moderate hypertension during pregnancy. METHODS: This retrospective cohort study included 11,871 pregnant women with mild-to-moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014...

STUDY OBJECTIVE: Methotrexate (MTX) is a key component of treatment for high-risk pediatric acute lymphoblastic leukemia (ALL) but may cause acute kidney injury and prolonged hospitalization due to delayed clearance. The purpose of this study is to identify clinical and genetic factors that may predict which children are at risk for creatinine increase and prolonged MTX clearance. DESIGN: We conducted a single-center, retrospective cohort study of pediatric patients with ALL who received 4000-5000 mg/m2 of MTX...

STUDY OBJECTIVE: Thromboelastography (TEG) offers a more dynamic assessment of hemostasis over activated partial thromboplastin time (aPTT). However, the clinical utility of TEG in monitoring bivalirudin during extracorporeal membrane oxygenation (ECMO) remains unknown. The purpose of this study was to evaluate the correlation between aPTT and TEG in adult ECMO patients anticoagulated with bivalirudin. DESIGN: Multicenter, retrospective, cohort study conducted over a 2-year period...

BACKGROUND: Aspirin (ASA) has demonstrated inconsistent results in primary prevention of cardiovascular disease (CVD). Guidelines are also inconsistent in the recommendation of routine ASA use for primary prevention of CVD, but advocate dosing as a "one-size-fits-all" approach. MATERIALS AND METHODS: An intention-to-treat, double-blind, randomized, controlled, clinical trial comparing three treatment arms of ASA 81 mg, 325 mg, and 500 mg daily dosed for 14 days were evenly randomized across the dosingcategories to measure the impact of dosing by BMI (20-24...

Bloodstream infections (BSIs) due to Gram-positive organisms have traditionally been treated with prolonged courses of intravenous antimicrobials. However, this dogma is associated with substantial burden to the patient and health care system. Consequently, there is growing interest in the utilization of oral stepdown therapy, defined as the transition of intravenous therapy to an active oral agent, for this indication. This review highlights available literature examining oral stepdown in adult patients with BSI due to commonly encountered Gram-positive pathogens, including Staphylococcus aureus, Streptococcus spp...