Treatment of Sepsis

Dual antibiotic therapy has been suggested to improve survival of patients with community-acquired pneumonia (CAP) as compared with single therapy, but this finding was not confirmed in a large international prospective epidemiologic study of bacteremic pneumococcal pneumonia. Baddour and colleagues have reexamined this question in a subgroup of patients with severe pneumonia (n = 94) from that study. Of 47 patients receiving monotherapy, 55.3% had died by 14 days, as compared with 23.4% of 47 (p = 0.0015) patients receiving any combination (mostly a combination of a ß-lactam and macrolide) for at least 2 days. The improved survival appeared independent of country or classes of antibiotics combined or their in vitro activity. In separate analyses of survival accounting for imbalances between the two subgroups, adjusting for HIV infection in one and for mechanical ventilation in the other, the probability of survival markedly—and surprisingly—decreased with the former (odds ratio [OR]: 0.09) and improved with the latter (OR: 8.1), whereas combination therapy remained associated with survival (OR: 3.2 and 2.9, respectively), suggesting an interaction between the two former variables. The authors concluded that combination antibiotic therapy improves survival of critically ill patients with pneumococcal bacteremia. This post hoc analysis should be interpreted cautiously, as the numbers are small, not all patients with severe pneumonia from the whole cohort were included, and adjusted analyses are both limited and yield clinically inconsistent results. A prospective randomized trial appears warranted to confirm the superiority of dual therapy in severe pneumococcal CAP.

In 40 patients with septic shock, Keh and coworkers studied the effects of hydrocortisone on the balance between proinflammation and antiinflammation. Patients were randomized to receive hydrocortisone (100 mg loading dose followed by 10 mg per hour) for the first 3 days followed by placebo for 3 days, or vice versa. Hydrocortisone induced increases in arterial pressure and systemic vascular resistance, and decreases in heart rate, cardiac index, and norepinephrine requirement. Hydrocortisone inhibited the formation of nitric oxide (reflected by a reduction in the ratio of plasma nitrite to nitrate), which was correlated with the reduction in vasopressor support. Hydrocortisone caused attenuation of the inflammatory response (interleukin-6 and interleukin-8), endothelial activation (soluble E-selectin), neutrophil activation (expression of CD11b and CD64), and the antiiflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10). In peripheral blood monocytes, expression of human leukocyte antigen-DR was slightly depressed, and phagocytosis and interleukin-12 (a monocyte-activating cytokine) were increased. The authors conclude that low-dose hydrocortisone rapidly induces hemodynamic stabilization in patients with septic shock, probably secondary to decreased formation of nitric oxide, and increases the antiinfammatory rather than the immunosuppressive response to stress. An editorial commentary by Bornstein and Briegel accompanies this article

Conventional diet (and lipid emulsions) predominates in n-6 fatty acids (including arachidonic acid), whereas fish-based lipids yield n-3 fatty acids (rich in eicosapentaenoic acid and docosahexaenoic acid). To determine the effect of n-3 fatty acids on fat profiles and monocyte cytokine production, Mayer and coworkers entered 21 patients with sepsis into a 5-day randomized trial. Before the trial, plasma-free fatty acid concentrations were greatly increased in the septic patients, and n-6 fatty acids greatly exceeded n-3 fatty acids. The high n-6/n-3 ratio was maintained during conventional lipid infusions. Within 2 days of starting the n-3 fatty acid infusion, free n-3 fatty acids increased, the n-3/n-6 ratio was reversed, and n-3 fatty acids were rapidly incorporated into the membranes of mononuclear leukocytes. Generation of proinflammatory cytokines by mononuclear leukocytes was markedly amplified during n-6 lipid infusion and suppressed during n-3 lipid infusion. After termination of n-3 lipid infusion, the concentration of free n-3 fatty acid and cytokine synthesis by mononuclear leukocytes decreased. The authors conclude that use of n-3 fatty acid infusions may achieve a favorable effect on inflammation and immunologic function in patients with sepsis in addition to nutrition.

Citations 1-4 of 4 total displayed.

Combination Antibiotic Therapy Lowers Mortality among Severely Ill Patients with Pneumococcal Bacteremia

Larry M. Baddour, Victor L. Yu, Keith P. Klugman, Charles Feldman, Ake Ortqvist, Jordi Rello, Arthur J. Morris, Carlos M. Luna, David R. Snydman, Wen Chien Ko, M. Bernadete F. Chedid, David S. Hui, Antoine Andremont, and Christine C. C. Chiou
Am. J. Respir. Crit. Care Med. 170: 440 -444. First published online as doi:10.1164/rccm.200311-1578OC [Abstract] [Full text]

Parenteral Nutrition with Fish Oil Modulates Cytokine Response in Patients with Sepsis

Konstantin Mayer, Stephanie Gokorsch, Christine Fegbeutel, Katja Hattar, Simone Rosseau, Dieter Walmrath, Werner Seeger, and Friedrich Grimminger
Am. J. Respir. Crit. Care Med. 167: 1321 -1328. First published online as doi:10.1164/rccm.200207-674OC [Abstract] [Full text]

A New Role for Glucocorticoids in Septic Shock: Balancing the Immune Response

Stefan R. Bornstein and Josef Briegel
Am. J. Respir. Crit. Care Med. 167: 485-486. [Full text]

Immunologic and Hemodynamic Effects of "Low-Dose" Hydrocortisone in Septic Shock: A Double-Blind, Randomized, Placebo-controlled, Crossover Study

Didier Keh, Thomas Boehnke, Steffen Weber-Cartens, Christina Schulz, Olaf Ahlers, Sven Bercker, Hans-Dieter Volk, Wolf-Dietrich Doecke, Konrad J. Falke, and Herwig Gerlach
Am. J. Respir. Crit. Care Med. 167: 512 -520. First published online as doi:10.1164/rccm.200205-446OC [Abstract] [Full text]

Year in Review Home