Pharmacotherapy
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The United States Food and Drug Administration (FDA) has created approval pathways and designations to accelerate access to medications indicated for serious or life-threatening conditions with limited treatment options. Implemented in 2012, the most recent of these is the breakthrough therapy designation (BTD). The purpose of this article was to review the evidence surrounding approval of medications with nononcology indications approved with the BTD designation from 2012 to 2016. ⋯ The quality of evidence behind these approvals was highly heterogeneous. Much remains unknown about the safety and efficacy of many agents approved through the BTD. Health care professionals should be aware of these limitations to better educate patients and other providers appropriately.
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The emergence and spread of antimicrobial resistance have led to a global public health emergency requiring development of new antimicrobial classes. Lefamulin (formally BC-3781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community-acquired bacterial pneumonia (CABP) as intravenous (IV) and oral (PO) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of bacterial infections in humans. ⋯ Documented resistance and cross-resistance with other gram-positive antibacterials remains low. Additional published in vitro, in vivo, and preclinical trial data suggest further exploration of lefamulin in various infectious disease states (e.g., acute bacterial skin and skin structure infections, and sexually transmitted infections). This review discusses the pertinent bacterial spectrum of activity, preclinical and ongoing clinical data, and potential roles in therapy for lefamulin.
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Randomized Controlled Trial
A Randomized Pharmacokinetic and Pharmacodynamic Evaluation of Every 8-Hour and 12-Hour Dosing Strategies of Vancomycin and Cefepime in Neurocritically ill Patients.
Neurocritically ill patients have clinically significant alterations in pharmacokinetic parameters of renally eliminated medications that may result in subtherapeutic plasma and cerebrospinal fluid antibiotic concentrations. ⋯ This study demonstrated that more frequent dosing of vancomycin and cefepime is required to achieve optimal PD targets in adult neurocritically ill patients. The need for increased total daily doses is potentially secondary to the development of augmented renal clearance.