Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
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Sepsis and septic shock remain a considerable therapeutic challenge. Despite significant advances in supportive care and the availability of potent, broad-spectrum antibiotics, the overall mortality due to sepsis is still approximately 35%, and this increases to 60% if patients develop septic shock. Antibiotics constitute a necessary part of the treatment of sepsis, and there is probably considerable scope to improve the way in which they are used. ⋯ For this reason, considerable efforts have been expended in developing non-antibiotic (or so-called adjunctive) forms of treatment, and here the general approaches to these types of treatment are reviewed. There are three main categories: improvements in supportive care, treatments aimed at bacterial virulence factors, and treatments aimed at host mediators. This is not intended to be a comprehensive review, but rather to provide examples in each category to illustrate the general principles-and the hurdles-that have characterized these approaches to therapy.
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In 2001, the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial demonstrated a 6.1% absolute decrease in mortality in patients with severe sepsis. Recombinant human activated protein C was subsequently licensed for use by both the US Food and Drug Administration and the European Medicines Evaluation Agency. There has been some controversy over aspects of the original study protocol, and subsequent trials have raised concerns about both the efficacy and the side effect profile of recombinant human activated protein C. Significant doubt remains as to the role of recombinant human activated protein C in the management of severe sepsis, and this review aims to summarize the evidence both for and against its use.
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There is increasing discussion of a potential role for statins in the management of sepsis. A search of PubMed, Embase, Scopus and the Cochrane Library databases was performed by combining the terms 'statins', 'infection', 'sepsis', 'bacteraemia', 'pneumonia', and 'ICU infections'. A total of 22 studies were retrieved, which included 177,260 people and compared clinical outcomes between 51,193 statin users and 126,067 non-statin users. ⋯ Five of the nine studies that examined the risk of developing sepsis/infection as a primary outcome (six of nine sepsis studies and all studies in the postoperative setting) found a decreased risk among statin users, whereas the remaining studies found no difference. Irrespective of their design (matched vs. non-matched), the majority of the studies suggested that statins have a beneficial effect on the outcome of infection; however, their observational design does not allow us to draw firm conclusions. The clinical benefit of statin therapy in sepsis remains to be determined by ongoing randomized controlled trials.
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Clin. Microbiol. Infect. · Apr 2009
Monitoring of herpes simplex virus in the lower respiratory tract of critically ill patients using real-time PCR: a prospective study.
Herpes simplex virus (HSV) has increasingly been associated with pulmonary disease in critically ill patients. However, the clinical relevance of HSV is still a topic of debate. Monitoring of HSV in a quantitative way could potentially give relevant information on its role in the pathogenesis of lower respiratory tract infection. ⋯ The fact that no HSV-seronegative patient became positive suggests that all HSV DNA-positive patients had HSV reactivations. Monitoring the HSV viral load in the LRT of critically ill patients showed a typical homogeneous pattern of HSV kinetics. HSV emerged in tracheal and bronchial aspirates after a median of 7 days of intubation (5-11 days), and this was followed by an exponential increase (c. 1 log copies/mL/day) to reach very high HSV peaks (10(6)-10(10) copies/mL) in 78% of the HSV DNA-positive patients.