Critical care : the official journal of the Critical Care Forum
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Editorial Comment
Antibiotics for the critically ill: more than just selecting appropriate initial therapy.
Critically ill patients with infection provide a number of challenges to clinicians in terms of optimizing their antimicrobial treatment. Of foremost importance, initial antibiotic treatment should be selected as to provide coverage for the causative pathogens. However, the administration of those antibiotics (dosing, interval of administration, duration of infusion, route of administration) should be prescribed in a manner to ensure optimal drug delivery to the site of infection. ⋯ Intensive care unit practitioners should utilize treatment strategies that strive to deliver antibiotics in an individualized manner aimed at attaining desired pharmacokinetic/pharmacodynamic targets. The goal of such a treatment strategy is to maximize the likelihood of curing the infection and allowing the critically ill patient the best opportunity for recovery. Effective implementation of antimicrobial optimization delivery strategies will likely require a multi-disciplinary approach including intensivists, pharmacists, and infectious disease specialists.
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Epidemiological studies document that males are more prone than females to develop severe sepsis and this is confirmed by Sakr and colleagues in the previous issue of Critical Care. However, the impact of gender on prognosis of severe sepsis is a matter of debate. ⋯ The impact of sexual hormones in older females is less relevant. Treatments aimed at modifying sexual hormone profile are promising but need to be tested in future trials.
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Editorial Comment
The dichotomy of inhibiting nuclear factor kappa-B in pneumonia.
Activation of nuclear factor kappa-B (NF-κB) results in its translocation from the cytoplasm to the nucleus and binding to the promoters of a large number of genes, including those encoding proinflammatory cytokines and other mediators that can contribute to organ system dysfunction in severe infection. While inhibition of NF-κB activation has been proposed as a therapeutic approach in critical illness, several studies have indicated that such an approach may have deleterious effects in persistent infectious states, such as pneumonia. A new report from Devaney and colleagues shows that while inhibition of NF-κB may be useful in severe pneumonia associated with rapid progression to mortality, it leads to worsened pulmonary injury with increased bacterial numbers in the lungs in a model of prolonged pneumonia. Such data raise concerns about therapeutic approaches targeting NF-κB in critically ill patients with persistent infection.