mycophenolic-acid and Shock--Septic

In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sepsis associated with immunosuppressive medications that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee.. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591.. Immunosuppressed patients, by definition, are susceptible to a wider spectrum of infectious agents than immunologically normal patients and, thus, require a broader spectrum antimicrobial regimen when they present with sepsis or septic shock. Special expertise managing immunosuppressed patient populations is needed to predict and establish the correct diagnosis and to choose appropriate empiric and specific agents and maximize the likelihood that patients will survive these microbial challenges.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibodies, Monoclonal; Antifungal Agents; Antiviral Agents; Aspergillosis; Candidiasis; Consensus Development Conferences as Topic; Evidence-Based Medicine; Hepatitis, Viral, Human; Humans; Immune Tolerance; Immunocompromised Host; Immunophilins; Immunosuppressive Agents; Mycophenolic Acid; Pneumonia; Practice Guidelines as Topic; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

Septic shock is a systemic inflammatory response syndrome, and it is the leading cause of death in intensive care units. Mycophenolate mofetil (MMF) is an immunosuppressant that has been shown to be effective in the treatment of various inflammatory diseases. In this study, the anti-inflammatory effect of MMF in a mouse model of acute lung injury (ALI) induced by lipopolysaccharide (LPS) was evaluated. ALI was induced by intrapleural injection of LPS (250 ng/cavity). The leukocyte migration, exudation, myeloperoxidase and adenosine deaminase activities, nitric oxide products, tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) levels, as well as mRNA expression of TNF-α and IL-1β, were evaluated. This study showed that MMF significantly decreased all parameters studied in a manner comparable to treatment with dexamethasone. In conclusion, MMF has important anti-inflammatory effects that may be useful as an auxiliary treatment for septic shock.

Topics: Acute Lung Injury; Adenosine Deaminase; Animals; Anti-Inflammatory Agents; Cell Movement; Dexamethasone; Disease Models, Animal; Immunosuppressive Agents; Inflammation; Interleukin-1beta; Leukocytes; Lipopolysaccharides; Lung; Mice; Mycophenolic Acid; Nitric Oxide; Peroxidase; RNA, Messenger; Shock, Septic; Tumor Necrosis Factor-alpha