Pharmacotherapy
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Colistin, the most widely used polymyxin antibiotic, was originally introduced in the late 1950s before the establishment of the present-day drug approval process. Originally shelved due to toxicity concerns, colistin, in the form of its inactive prodrug colistin methanesulfonate, has undergone a renaissance in the past 15 years. Unfortunately, this is not because of an improved adverse-effect profile but because colistin is among the only remaining antibiotics with activity against multidrug-resistant gram-negative bacilli. ⋯ Since its reintroduction, published reports regarding colistin have produced discordant results in terms of both efficacy and safety. Because the efficacy and toxicity of colistin are dose dependent, the impact of discordant dosing recommendations cannot be understated. This review highlights the issues leading to differing and often conflicting dosing recommendations, reviews the recent pharmacokinetic advances, and provides recommendations for the optimal use of colistin.
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The polymyxins-colistin and polymyxin B-are an increasingly important part of the antimicrobial arsenal given the rising rate of infections due to multidrug-resistant gram-negative bacteria. Although the drugs have available since the 1950s, only recently have pharmacokinetic and pharmacodynamic data been available to guide appropriate use of these drugs. Far more data and global clinical experience exist for colistin, available as the prodrug colistimethate sodium (CMS), compared with polymyxin B. ⋯ Prospective, comparative data evaluating both drugs in combination with other antimicrobials as well as comparing polymyxin B and CMS directly will inform optimal use of each drug. Some of these investigations are currently under way. In the meantime, based on current data, both drugs appear to be appropriate for use in the clinical setting.
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In March 2014, the largest Ebola outbreak in history exploded across West Africa. As of November 14, 2014, the World Health Organization has reported a total of 21,296 Ebola virus disease (EVD) cases, including 13,427 laboratory-confirmed EVD cases reported from the three most affected countries (Guinea, Liberia, and Sierra Leone). As the outbreak of EVD has spread, clinical disease severity and national EVD case-fatality rates have remained high (21.2-60.8%). ⋯ As knowledge of Ebola virus virology and pathogenesis grows, it is likely that new therapeutic tools will be developed. Deployment of novel Ebola therapies will require unprecedented cooperation as well as investment to ensure that therapeutic tools become available to populations at greatest risk for EVD and its complications. In this article, we review several agents and strategies that are now under active development.
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Idiopathic (viral) pericarditis is the most common form of pericardial disease in the Western world. Despite the combination of colchicine and nonsteroidal antiinflammatory drugs (NSAIDs) plus aspirin (ASA), considered first-line therapy, the incidence of recurrent pericarditis is ~20-30%. In addition, secondary recurrence without optimal first-line therapy is ~50%. ⋯ This review describes contemporary pharmacotherapeutic management of idiopathic (viral) pericarditis, with a particular emphasis on the role of colchicine. Emerging therapies and management strategies, such as high-sensitivity C-reactive protein-guided therapy and novel immunotherapies, are also reviewed. Ultimately, understanding appropriate treatment will assist the clinician in helping decrease the risk of recurrent, incessant, and refractory pericarditis.
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Serotonin syndrome is a syndrome identified by a triad of altered mental status, neuromuscular overactivity, and autonomic instability caused by the overstimulation of serotonin in the central nervous system and periphery. Serotonin syndrome may be provoked with the addition or increase in serotonergic agents such as selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors as well as other agents with serotonergic properties. Some narcotics, including fentanyl and methadone, have these properties and may be associated with the development of serotonin syndrome when used in conjunction with other agents. ⋯ This report provides a brief overview of serotonin syndrome, particularly with cases involving administration of narcotics such as fentanyl and methadone. The case described is the first report associated with fentanyl and methadone without the coadministration of other serotonergic agents, and a possible drug interaction with voriconazole is discussed. This raises awareness of using multiple serotonergic narcotics and the potential precipitation of serotonin syndrome.