Invasive candidiasis and candidemia: from current opinions to future perspectives.

Expert Opin Investig Drugs. 2009 Jun;18(6):735-48

Authors: Rueping MJ, Vehreschild JJ, Cornely OA

Candida spp. are the fourth most common cause of nosocomial bloodstream infections in the United States, as well as the single most important cause of opportunistic fungal infections worldwide. A delayed diagnosis of invasive candidiasis and/or inadequate treatment choice is associated with high mortality rates and prolonged hospital stays. Even though the antifungal armamentarium has been broadened significantly over the last years, the best options for diagnosing and treating invasive candidiasis still remain a matter of discussion. In this article we present and analyze current evidence on the epidemiology, diagnostic methods and treatment options of invasive candidiasis, with a focus on results from randomized clinical trials. Finally, the reader is provided with a brief overview on promising clinical trial designs and antifungals that might shape the treatment of invasive candidiasis in the years to come.

PMID: 19426121 [PubMed - indexed for MEDLINE]

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Current drugs and medical treatment algorithms in the management of acute decompensated heart failure.

Expert Opin Investig Drugs. 2009 Jun;18(6):695-707

Authors: Triposkiadis F, Parissis JT, Starling RC, Skoularigis J, Louridas G

BACKGROUND: Acute decompensated heart failure (ADHF) is associated with increased hospitalization rates and high in-hospital mortality, and has emerged as a major public health problem over the past decade. In recent years, several new drugs and therapeutic approaches have failed to reduce short- and long-term morbidity and mortality in ADHF patients. New agents and strategies are under investigation in order to effectively reduce the mortality and morbidity in these patients. OBJECTIVE: To review the recent experimental and clinical evidence on existing therapeutic algorithms and investigational drugs used for the treatment of ADHF. METHODS: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to January 2009. The results of unpublished trials were obtained from presentations at national and international meetings. RESULTS: Renal dysfunction and low systolic blood pressure (SBP) remain the main predictors of adverse clinical outcomes in ADHF patients. Thus, therapy should be tailored according to the level of SBP at admission, renal function and fluid retention. ADHF due to hypertensive disease should be treated with intravenous vasodilators and diuretics at low doses, while patients with low output syndrome need mainly inotropic support. However, few agents currently employed in the treatment of ADHF have been shown in large prospective randomized clinical trials to improve clinical outcomes. The calcium sensitizer levosimendan is superior than traditional inotropes in improving central hemodynamics and neurohormonal response in ADHF patients, without increasing their long-term survival. Vasopressin antagonists also seem to be promising and safe drugs in the treatment of ADHF patients, facilitating diuresis on top of standard-care therapy. Encouraging novel therapies include adenosine receptor antagonists, ularitide, istaroxime, cardiac myosin activators and relaxin. CONCLUSIONS: Clinical scenarios based on SBP are essential determinants of therapeutic approaches used for the management of ADHF. Traditional drugs (diuretics, dobutamine and milrinone) have several limitations in real clinical practice, and increase mortality rates. Investigational drugs targeting to novel pathophysiologic concepts are promising treatment approaches and ongoing trials will define their clinical efficacy and safety.

PMID: 19426120 [PubMed - indexed for MEDLINE]

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New agents for Clostridium difficile-associated disease.

Expert Opin Investig Drugs. 2008 Nov;17(11):1671-83

Authors: Guiles J, Critchley I, Sun X

BACKGROUND: Clostridia-derived diseases, in particular C. difficile-associated disease (CDAD), have been increasing in incidence, severity, and morbidity. The mainstay of treatment options has relied upon metronidazole and vancomycin, but these treatments routinely result in high relapse rates (20%) and, in the case of metronidazole, decreasing efficacy. OBJECTIVE: Evaluate and compare the current clinical and preclinical therapies of CDAD. METHODS: RESULTS/CONCLUSION: The new antibiotics in development and preclinical development reflect next-generation versions of older drugs or two new mechanism-of-action class drugs (OPT-80, REP3123). Based on the current preclinical and clinical data, the next-generation drugs impart only a subtle difference from the intrinsic weaknesses of their genre. In contrast, OPT-80 and REP3123 seem to be differentiated.

PMID: 18922104 [PubMed - indexed for MEDLINE]

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Apixaban, an oral direct Factor Xa inhibitor: awaiting the verdict.

Expert Opin Investig Drugs. 2008 Dec;17(12):1937-45

Authors: Carreiro J, Ansell J

For the last half-century, despite its many limitations warfarin has been the mainstay of treatment for patients with venous and arterial thromboembolic disease. During the past decade, a number of new oral anticoagulant agents have been developed that may offer an alternative to warfarin. Emerging data suggest that Factor Xa may be a target for inhibition. Apixaban is one such agent. It is a potent, selective, reversible, and orally bioavailable FXa inhibitor that demonstrates antithrombotic efficacy, with a favorable pharmacokinetic profile. At present, the safety and efficacy of apixaban for the prophylaxis and treatment of venous thromboembolism is being evaluated in Phase II and Phase III trials involving nearly 25,000 patients. Trials are also underway involving over 20,000 patients for secondary prevention after acute coronary syndromes and the prevention of stroke in patients with non-valvular atrial fibrillation. This review article discusses the discovery, pharmacokinetics, attributes, and current clinical trials of this emerging drug.

PMID: 19012508 [PubMed - indexed for MEDLINE]

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Shared by Robert Mahoney

Full text: http://www.expertopin.com/doi/abs/10.1517/13543784.17.6.925
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