DOI: 10.1097/01.CCM.0000048630.38193.72

,  

,  

PMID: 12576978

Issn Print: 0090-3493

Publication Date: 2003/02/01


Print

Granulocyte colony-stimulating factor for severe pneumonia: What do we do when the best laid plans for men (and mice and rats…) fail? *

Michael S. Niederman

    loading  Checking for direct PDF access through Ovid

Excerpt

Pneumonia remains the number one cause of death from infectious diseases in the United States, pointing to the limited benefit of antibiotic therapy as the sole treatment modality for this illness. With intensive care unit-admitted patients, the mortality from com-munity-acquired pneumonia can approach 30% to 35%, whereas the mortality rate for nosocomial pneumonia varies from 20% to 50%. Sepsis is a common complication of pneumonia, with a death rate of 30% to 50% and, as a disease state, sepsis has been the subject of numerous investigations aimed at identifying adjunctive therapies that could add to the benefit of antibiotic therapy.
In approaching the management of pneumonia and sepsis, the inflammatory response to infection has become a key target for interventional therapy. In general, severe sepsis has been viewed as an illness that is characterized by excessive inflammation, and a variety of anti-inflammatory, antimediator therapies have been tested, all with generally no benefit, with the exception of recombinant human activated protein C (1). However, antibacterial strategies, in addition to antibiotics, have also been used, most notably antiendotoxin antibodies, but with limited benefit at best (2, 3). These experiences document the complexity of events in patients with severe sepsis and the conflicting theories of how to enhance our therapeutic interventions. Is the problem primarily one of bodily injury secondary to excessive inflammation, requiring a down-regulation of the host response to promote patient recovery? Or is the problem one of uncontrolled infection, necessitating additional antibacterial strategies to contain infection and its associated deleterious effects on patients? It is very likely that there are subsets of patients who could benefit from either of these approaches, and defining these patients has been difficult and a possible explanation for why few interventions in this population have been successful.
In this issue of Critical Care Medicine, a remarkably well-designed and well-conducted clinical study of adjunctive granulocyte colony stimulating factor (G-CSF) for patients with pneumonia and severe sepsis is reported by Dr. Root and colleagues (4) with disappointingly negative findings. The authors enrolled 701 patients with severe community-acquired pneumonia or nosocomial pneumonia, all of whom also had severe sepsis, into a prospective, randomized, double-blind trial using either G-CSF (348 patients) or placebo (353 patients). All patients had a positive culture of blood or quantitative bronchoscopic samples, and all received antibiotic therapy, with the G-CSF group receiving a 30-min infusion of 300 μg/day for 5 days or until a white cell count >75,000 cells/mm3 was achieved. Of the study population, 80% were individuals with community-acquired pneumonia, and a total of 29% of all patients had a positive blood culture. Overall there were no differences in mortality at 29 days, with 25.5% of patients dying in the placebo group and 29.0% dying in the G-CSF group. Safety of G-CSF was established in this critically ill population, with both groups having similar rates of severe adverse events, including the development of acute respiratory distress syndrome (12% of the placebo group and 16% of the G-CSF group).
Unfortunately, the data from this trial suggest that G-CSF is not likely to be a useful adjunctive therapy for severe pneumonia, although its role as a preventive strategy in patients at risk for severe pneumonia (particularly nosocomial pneumonia) is not yet well defined. There have been a number of animal studies that have suggested that this agent could have been valuable as an adjunctive therapy of for patients with pneumonia and severe sepsis.
    loading  Loading Related Articles