International journal of antimicrobial agents
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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.
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Int. J. Antimicrob. Agents · Nov 2008
ReviewImmunomodulatory therapies for sepsis: unexpected effects with macrolides.
Despite intensive efforts to increase our knowledge of the inflammatory pathways involved in the pathogenesis of sepsis, several clinical trials of agents aimed at modulating the immune response of the host, such as anti-endotoxin antibodies, anti-tumour necrosis factor (TNF) antibodies and soluble TNF receptors, have failed to disclose any definite clinical benefit. The same applies to the administration of low-dose hydrocortisone as well as intense glucose control by continuous insulin infusion. Macrolides are a traditional class of antimicrobials proven to act as modulators of the host's response in chronic lung disorders such as diffuse panbronchiolitis and cystic fibrosis. ⋯ Analysis revealed a considerable benefit of clarithromycin in shortening the time to resolution of VAP and to de-intubation from mechanical ventilation. The relative risk of death by septic shock and multiple organ dysfunction was 19.00 among placebo-treated patients; it was reduced to 3.78 among clarithromycin-treated patients. These results render new perspectives for the future application of clarithromycin as an immunomodulatory therapy of sepsis.