Expert review of anti-infective therapy
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Expert Rev Anti Infect Ther · Oct 2016
ReviewPathogenic, immunologic, and clinical aspects of sepsis - update 2016.
Sepsis is a major cause of death worldwide but its orchestrating components remain incompletely understood. On the one hand, development of sepsis results from an infectious focus that cannot be controlled by the immune system, but on the other, responding immune cells that can eliminate the infection inflict damage to the host by contributing to complications such as endothelial leakage, septic shock, and multiorgan failure. ⋯ In this review we give a comprehensive overview of how sepsis occurs, which exogenous and endogenous factors might affect the immune-pathophysiological course of sepsis and finally how this knowledge translates into up-to-date definitions and therapeutic approaches. Expert commentary: Although new immunological mechanisms altering the course of sepsis have been identified recently, future research needs to address the limitations of experimental approaches, redirect the research focus into translational approaches, and finally evaluate personalized treatment strategies.
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Expert Rev Anti Infect Ther · Oct 2016
ReviewEmerging infection and sepsis biomarkers: will they change current therapies?
Sepsis is a heterogeneous syndrome characterized by both immune hyperactivity and relative immune suppression. Biomarkers have the potential to improve recognition and management of sepsis through three main applications: diagnosis, monitoring response to treatment, and stratifying patients based on prognosis or underlying biological response. ⋯ This review focuses on specific examples of well-studied, evidence-supported biomarkers, and discusses their role in clinical practice with special attention to antibiotic stewardship and cost-effectiveness. Biomarkers were selected based on availability of robust prospective trials and meta-analyses which supported their role as emerging tools to improve the clinical management of sepsis. Expert commentary: Great strides have been made in candidate sepsis biomarker discovery and testing, with the biomarkers in this review showing promise. Yet sepsis remains a dynamic illness with a great degree of biological heterogeneity - heterogeneity which may be further resolved by recently discovered gene expression-based endotypes in septic shock.
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Relapses are important contributors to illness and morbidity in Plasmodium vivax and P. ovale infections. Relapse prevention (radical cure) with primaquine is required for optimal management, control and ultimately elimination of Plasmodium vivax malaria. A review was conducted with publications in English, French, Portuguese and Spanish using the search terms 'P. vivax' and 'relapse'. ⋯ Hypnozoites causing relapses may be activated weeks or months after initial infection. Incidence and temporal patterns of relapse varies geographically. Relapses derive from parasites either genetically similar or different from the primary infection indicating that some derive from previous infections. Malaria illness itself may activate relapse. Primaquine is the only widely available treatment for radical cure. However, it is often not given because of uncertainty over the risks of primaquine induced haemolysis when G6PD deficiency testing is unavailable. Recommended dosing of primaquine for radical cure in East Asia and Oceania is 0.5 mg base/kg/day and elsewhere is 0.25 mg base/kg/day. Alternative treatments are under investigation. Expert commentary: Geographic heterogeneity in relapse patterns and chloroquine susceptibility of P. vivax, and G6PD deficiency epidemiology mean that radical treatment should be given much more than it is today. G6PD testing should be made widely available so primaquine can be given more safely.
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Expert Rev Anti Infect Ther · Aug 2016
ReviewAntifungal agents and liver toxicity: a complex interaction.
The number of antifungal agents has sharply increased in recent decades. Antifungals differ in their spectrum of activity, pharmacokinetic/pharmacodynamic properties, dosing, safety-profiles and costs. Risk of developing antifungal associated hepatotoxicity is multifactorial and is influenced by pre-existing liver disease, chemical properties of the drug, patient demographics, comorbidities, drug-drug interactions, environmental and genetic factors. Antifungal related liver injury typically manifests as elevations in serum aminotransferase levels, although the clinical significance of these biochemical alterations is not always clear. Incidence rates of hepatotoxicity induced by antifungal therapy range widely, occurring most frequently in patients treated with azole antifungals for documented fungal infections. ⋯ This review provides an update regarding the hepatotoxicity profiles of the modern systemic antifungals used in treatment of invasive fungal infections. Expert commentary: Understanding the likelihood and pattern of hepatotoxicity for all suspected drugs can aid the clinician in early detection of liver injury allowing for intervention and potential mitigation of liver damage. Therapeutic drug monitoring is emerging as a potential tool to assess risk for hepatotoxicity.