Pharmacotherapy
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Physiologic alterations seen in obesity commonly impact the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics and may result in suboptimal dosing in this expanding but understudied population. Much of the published clinical and PK evidence to date consists of small patient populations and are retrospective with, not infrequently, heterogeneous results that in some cases are contradictory. In the last 10 years, additional antimicrobial PK/PD and clinical data encompassing prolonged infusion strategies and examination of critically ill populations have emerged to inform antimicrobial dosing in obesity. ⋯ Additional studies are needed to better understand and resolve discrepant published results regarding the PK of antibiotics to establish optimal dosing strategies in obese adults. Alternative dosing strategies, such as extended infusions, should be considered for time-dependent antibiotics (e.g., β-lactams) in obese patients to achieve PD targets reliably. Therapeutic drug monitoring across the spectrum of antimicrobials is of increasing importance in this and other populations to ensure optimized dosing.
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Pediatric opioid and benzodiazepine withdrawal are avoidable complications of pain and sedation management that is well described in the literature. To prevent withdrawal from occurring, practitioners regularly use a steady decrease of pain and sedation medications, also known as a weaning or tapering schedule. The weaning schedule is highly variable based on clinician preference and is usually dependent on the clinician. ⋯ The use of a standardized opioid-weaning protocol reduced withdrawal rates compared with nonstandardized weaning plans. Benzodiazepine weaning was inconsistently evaluated and may have affected study outcomes. Identified areas of improvement include the use of newer withdrawal assessment tools validated in the older pediatric population and standardized withdrawal assessment and reporting.
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Review
A Novel Use of Olaparib for the Treatment of Metastatic Castration-Recurrent Prostate Cancer.
Although mortality from prostate cancer has declined over the past 20 years as a result of early detection and treatment, the 5-year survival rate for men with prostate cancer who develop metastatic disease is only 29%. Current treatment options for metastatic castration-recurrent prostate cancer (mCRPC) are associated with toxicity and a limited durable response; therefore, additional lines of efficacious and minimally toxic therapy are needed. Olaparib, a poly(adenosine 5'-diphosphate) ribose polymerase (PARP) inhibitor, received a U. ⋯ In this review, we describe current therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of mCRPC. Olaparib may constitute a promising treatment to prolong survival in patients with mCRPC, with an acceptable adverse effect profile. As the role of PARP inhibition in prostate cancer and other malignancies becomes further elucidated, olaparib may be shown to be beneficial for other patient populations.
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Comparative Study
Intravenous-only or Intravenous Transitioned to Oral Antimicrobials for Enterobacteriaceae-Associated Bacteremic Urinary Tract Infection.
To characterize antibiotic regimens utilized for bacteremic Enterobacteriaceae urinary tract infections and assess treatment failure associated with intravenous-only compared to intravenous transitioned to oral antibiotic treatment. ⋯ Intravenous transitioned to oral treatment (intravenous/oral) was associated with a shorter length of stay and fewer hospital antibiotic days compared with intravenous-only therapy. Transitioning from intravenous to oral antibiotic therapy is a viable treatment option to consider for patients with bacteremic Enterobacteriaceae urinary tract infection.
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Ipilimumab, pembrolizumab, and nivolumab are checkpoint inhibitors (CPIs) that activate T-cell-mediated immune response. CPI can provide durable benefits to some cancer patients with melanoma, renal cell cancer, non-small cell lung cancer, or a growing list of other cancers. However, CPI treatment is also associated with adverse immune-mediated reactions (IMRs) that can be life-threatening. This pharmacovigilance analysis aims to characterize IMR signals in relation to CPI treatment. ⋯ Cancer immunotherapy with CPIs is associated with a multitude of IMRs, especially colitis and pneumonitis. Individual CPIs had variable IMR signals, and pharmacoepidemiologic studies are required to evaluate the identified signals.