International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Nov 2008
ReviewManagement of invasive Candida infections in non-neutropenic critically ill patients: from prophylaxis to early therapy.
Echinocandins are the treatment of choice for patients with severe forms of candidaemia, including neutropenic patients and those episodes presenting with shock. There is little distinction between the three available echinocandins (caspofungin, anidulafungin and micafungin), but there is more clinical experience with caspofungin. Identifying patients who will benefit from early antifungal therapy using clinical tools such as the 'Candida Score' is an interesting strategy that may reduce the high mortality in critically ill patients with invasive fungal infections.
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Int. J. Antimicrob. Agents · Nov 2008
ReviewProphylaxis, pre-emptive or empirical antifungal therapy: which is best in non-lung transplant recipients?
Renal, liver, heart and lung transplantation are now considered to be the standard therapeutic interventions in patients with end-stage organ failure. Infectious complications following solid organ transplantation (SOT) are relatively common owing to the transplant recipient's overall immunosuppressed status. The incidence of invasive mycoses following SOT ranges from 5% to 42% depending on the organ transplanted. ⋯ To achieve this objective it is essential to have new antifungal drugs with a higher spectrum of activity against the fungal pathogens, both classical and emerging, and showing improvements in pharmacokinetic and pharmacodynamic characteristics, ease of administration and acceptability, and lower rates of adverse effects. This article will review the risk factors for IFIs in NP-SOT recipients and the available antifungal strategies for management. In addition, it will evaluate the role of prophylactic therapy in this group of patients.
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The incidence of candidemia in the overall population ranges from 1.7 to 10 episodes per 100,000 inhabitants and Candida is one of the ten leading causes of bloodstream infections in developed countries. An estimated 33-55% of all episodes of candidemia occur in intensive care units (ICU) and are associated with mortality rates ranging from 5% to 71%. ⋯ In recent years, several studies have shown that ICU patients with mucosal Candida colonization, particularly if multifocal, are at a higher risk for invasive candidiasis, and that colonization selects a population amenable to antifungal prophylaxis or empirical therapy. Candidemia in ICUs is associated with a considerable increase in hospital costs and length of hospital stay.
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Severe sepsis-associated mortality may still be improved by earlier recognition, faster and adequate source control, and targeted resuscitation. Patients who may benefit from the administration of drotrecogin alfa (activated) are currently those at high risk of death, and other indications should be better defined by ongoing trials. ⋯ Trials exploring the role of natural anticoagulants and Toll-like receptor inhibitors are ongoing and should be completed in the coming 3 years. Future trials in severe sepsis should target more homogeneous populations with a well-defined focus of infection and severity, receiving appropriate standard of care, and the tested intervention should be administered in a timely fashion according to the expected host response.
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Int. J. Antimicrob. Agents · Nov 2008
ReviewInvasive fungal infections in lung transplantation: role of aerosolised amphotericin B.
Immunocompromised patients, especially solid organ transplant (SOT) and hematopoietic stem cell transplant recipients, have a high morbidity and mortality rate as a result of invasive fungal infections (IFIs). Therefore, effective and correct prophylaxis of these IFIs continues to be an important issue in these patient populations. Fungal infections in the lung are most often due to Aspergillus spp., but other non-Aspergillus moulds such as Mucor spp. can also cause pulmonary infections. ⋯ Lipid formulations of AmB penetrate the lung better and have a longer half-life than amphotericin B deoxycholate (ABD). Prophylaxis with aerosolised lipid-based AmB products has several advantages over ABD: it can be administered at much longer intervals and is equally effective and better tolerated. Although several studies have been published using aerosolised AmB both as deoxycholate and lipid formulations, available data remain inconclusive owing a lack of standardisation of administration procedures and doses.