Clinical therapeutics
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Clinical therapeutics · Mar 2016
ReviewCeftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-negative Organisms.
Multidrug-resistant gram-negative bacterial infections have emerged as a major threat in hospitalized patients. Treatment options are often inadequate and, as a result, these infections are associated with high mortality. A cephalosporin and a novel synthetic non-β-lactam, β-lactamase inhibitor, ceftazidime-avibactam, is approved for the treatment of serious infections caused by resistant gram-negative bacteria. This article reviews the spectrum of activity, clinical pharmacology, pharmacodynamic and pharmacokinetic properties, clinical efficacy and tolerability, and dosing and administration of ceftazidime-avibactam. ⋯ Currently, ceftazidime-avibactam is approved for the indications of complicated intra-abdominal infections (with metronidazole) and complicated urinary tract infections. Clinical trials published to date on this antimicrobial agent have shown its excellent safety and tolerability. This new combination agent has a role, but its use should be limited to patients without other treatment options in the empiric and documented treatment of multidrug-resistant gram-negative organisms. Further investigation is needed in patients with carbapenemase-producing Enterobacteriaceae and multidrug-resistant P aeruginosa who have bacteremia or nosocomial or ventilator-associated pneumonia. It is imperative that ceftazidime-avibactam be used in a responsible manner so that its effectiveness can be retained.
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Clinical therapeutics · Mar 2016
Impact of an Antimicrobial Stewardship Program on Patient Safety in Veterans Prescribed Vancomycin.
This study aimed to determine the safety impact of an antimicrobial stewardship program (ASP) on vancomycin-associated nephrotoxicity and to examine risk factors contributing to the development of toxicity. ⋯ ASPs represent an important aspect of a patient-safety initiative in order to reduce vancomycin-associated nephrotoxicity. Concurrent piperacillin/tazobactam therapy, surgical service, and elevated maximum trough concentration were risk factors for nephrotoxicity.
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Clinical therapeutics · Feb 2016
Pharmacokinetic Profile and Sustained 24-hour Analgesia of a Once-daily Hydrocodone Bitartrate Extended-release Tablet with Abuse-deterrent Properties.
The purpose of this study was to evaluate the pharmacokinetics (PK) and 24-hour analgesic effectiveness of once-daily, single-entity, extended-release hydrocodone (HYD) with abuse-deterrent properties. ⋯ Once-daily HYD exhibits linear, dose-proportional PK properties and is associated with a lower variability in plasma hydrocodone concentrations when compared with an immediate-release hydrocodone combination product. Notably, analgesia provided by HYD is sustained during the 24-hour dosing interval. ClinicalTrials.gov identifier: NCT01400139 (Study 4).
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Clinical therapeutics · Feb 2016
Randomized Controlled TrialEvaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.
Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. ⋯ The absolute bioavailability of BBUP was 46% to 51% across a 16-fold dose range, with dose-proportional increases in systemic exposure. Apparent steady-state conditions occurred within 3 days of dosing. These pharmacokinetic results suggest that therapeutic buprenorphine plasma concentrations can be obtained with BBUP across a wide dose range in a shorter time than other (eg, transdermal) dosage forms.
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Restless legs syndrome (RLS) is a commonly occurring neurologic disorder that affects up to one third of women during pregnancy. RLS has been associated with increased sympathetic tone in the nonpregnant population. We examined whether a RLS surrogate is associated with a higher prevalence of pregnancy and neonatal outcomes. ⋯ A higher frequency of jumpy or jerky leg symptoms, a proxy for RLS during pregnancy, was associated with a higher likelihood of gestational hypertensive disorders and neonatal outcomes such as gestational age at birth and birth weight. These findings may affect RLS treatment decisions during pregnancy.