Drugs
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Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.
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The ultrashort-acting dihydropyridine calcium channel antagonist clevidipine (Cleviprex(®)) has a rapid onset and offset of effect and reduces blood pressure (BP) by decreasing arteriolar resistance without affecting venous capacitance vessels. This article reviews the clinical efficacy and tolerability of intravenous clevidipine when used to manage BP in perioperative and intensive care settings, as well as summarizing its pharmacological properties. Intravenous clevidipine effectively treated preoperative and postoperative hypertension in patients undergoing cardiac surgery, according to the results of the randomized, multicentre, double-blind, phase III ESCAPE-1 and ESCAPE-2 trials. ⋯ Noncomparative studies demonstrated that clevidipine provided rapid BP control in patients with acute neurological injuries (including intracerebral haemorrhage, subarachnoid haemorrhage and acute ischaemic stroke), and was not associated with 'overshoot' in the vast majority of patients. Intravenous clevidipine was generally well tolerated and was usually associated with no reflex tachycardia or only very modest increases in heart rate. In conclusion, intravenous clevidipine is a valuable agent for the management of BP in perioperative and intensive care settings.
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This article addresses the emergence of echinocandin resistance among Candida species, mechanisms of resistance, factors that promote resistance and confounding issues surrounding standard susceptibility testing. Fungal infections remain a significant cause of global morbidity and mortality, especially among patients with underlying immunosupression. Antifungal therapy is a critical component of patient management for acute and chronic diseases. ⋯ Clinical factors that appear to promote echinocandin resistance include the expanding use of antifungal agents for empiric therapy and prophylaxis. Furthermore, host reservoirs such as biofilms in the gastrointestinal tract or intra-abdominal infections can seed development of resistant organisms during therapy. A fundamental understanding of the primary molecular resistance mechanism, along with cellular and clinical factors that promote resistance emergence, is critical to develop better diagnostic tools and therapeutic strategies to overcome and prevent echinocandin resistance.
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Ceftobiprole, the active metabolite of the prodrug ceftobiprole medocaril (Zevtera(®)), is a new generation broad-spectrum intravenous cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Ceftobiprole exhibits potent in vitro activity against a number of Gram-positive and Gram-negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). It is the first cephalosporin monotherapy approved in the EU for the treatment of both HAP (excluding ventilator associated-pneumonia [VAP]) and CAP. ⋯ In the phase III trials, ceftobiprole medocaril was generally well tolerated, with ≈10 % of patients discontinuing the treatment because of adverse events. The most common treatment-related adverse events occurring in ceftobiprole recipients in the trials in patients with HAP or CAP included nausea, diarrhoea, infusion site reactions, vomiting, hepatic enzyme elevations and hyponatraemia. Therefore, ceftobiprole medocaril monotherapy offers a simplified option for the initial empirical treatment of patients with HAP (excluding VAP) and in those with CAP requiring hospitalization.
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Review Comparative Study
Fluticasone furoate/vilanterol: a review of its use in chronic obstructive pulmonary disease.
Fluticasone furoate/vilanterol (Relvar(®), Breo(®), Revinty(®)) is a fixed combination of a corticosteroid and a long-acting β2-adrenergic agonist (LABA) for once-daily use via a dry powder inhaler (Ellipta(®)). Fluticasone furoate/vilanterol 100/25 µg is approved for the treatment of chronic obstructive pulmonary disease (COPD) in several countries. This article reviews the clinical use of the combination in COPD and summarises pharmacological properties. ⋯ In 12-month trials, fluticasone furoate/vilanterol was generally well tolerated, and in 12- and 24-week trials, the incidence of adverse events was similar overall to that associated with the individual components or fluticasone propionate/salmeterol. However, as with the long-term use of all ICS agents, 12-month data indicate an increase in the risk of pneumonia with fluticasone furoate/vilanterol. In conclusion, fluticasone furoate/vilanterol is an effective and generally well tolerated additional LABA/ICS agent for the treatment of COPD with the added convenience of once-daily administration, which may improve treatment adherence in some patients.