Efficacy of Macrolide Immunomodulation in Severe Sepsis.

Inclusion Criteria: 1. Subject, or legal representative, has given written informed consent. 2. 18 years of age or older. 3. SIRS is defined as two or more of: * Temperature \> 38o C or \< 36oC * Heart rate \> 90 beats/min * Respiratory rate \> 20 breaths/min or PaCO2\< 32mmHg * White blood cell count \> 12.000/mm3; \< 4000/mm3; or \> 10% immature (band) forms. 4. Presence of a suspected or proven infection. Patients with suspected infection must have evidence of an infection, such as white blood cells in a normally sterile body fluid, perforated viscus, chest x-ray consistent with pneumonia and associated with purulent sputum production, or a clinical syndrome associated with a high probability of infection (for example, purpura fulminans or ascending cholangitis). 5. Presence of one or more sepsis-associated organ failure. The onset of the first sepsis-associated organ failure must occur within the 48-hour period immediately preceding initiation of study drug infusion. A patient must have an organ failure attributable to the sepsis episode. The organ failure must be newly developed and not explained by underlying disease processes or by effects of concomitant therapy. * Cardiovascular: An arterial systolic blood pressure (SBP) of 90 mm Hg or a mean arterial pressure (MAP) 70 mm Hg for at least 1 hour despite adequate fluid resuscitation, adequate intravascular volume status, or the need for vasopressors to maintain SBP 90 mm Hg or MAP 70 mm Hg. * Renal: Average urine output \<0.5 mL/kg/h for 1 hour despite adequate fluid resuscitation * Respiratory: Evidence of acute pulmonary dysfunction PaO2/FiO2 300 and, clinical exam or pulmonary capillary wedge pressure not suggestive of volume overload. If pneumonia is the suspected site of infection, the patient must have a PaO2/FiO2 200. * Hematology: Platelet count \<80,000/mm3 or a 50% decrease in platelet count from the highest value recorded over the last 3 days. * Unexplained metabolic acidosis: Defined by (1) pH 7.30 or base deficit 5.0 mEq/L or (2) plasma lactate level \>1.5 times the upper limit of normal. Adequate fluid resuscitation or adequate intravascular volume is defined as either pulmonary arterial wedge pressure 12 mm Hg or central venous pressure 8 mm Hg. Vasopressors is defined as dopamine 5 g/kg/min or any dose of norepinephrine, epinephrine, or phenylephrine. Dobutamine is not considered a vasopressor. Exclusion Criteria: 1. Macrolide therapy indicated for clinical condition. If after randomization, the treating physician determines that a macrolide is indicated and no other alternative antibiotic is appropriate, the patient will be excluded from the trial. However, if only one dose of azithromycin had been given and the treating physician decided to stop it, azithromycin might be administered. 2. Known allergy to macrolides. 3. Prolonged QT syndrome or on medications with increased risk of QT prolongation. 4. Pregnant or lactating. Immunosuppression as defined by: 1. Chemotherapy within the last 30 days, 2. Leukemia or lymphoma which is not in remission, 3. Solid organ or bone marrow/stem cell transplant, 4. Human Immunodeficiency Virus infection with CD4 count \< 200 cells/mm3, 5. Chronic corticosteroid use equivalent to \> 10 mg prednisone per day, 6. Patient or family decision to limit ICU care.