Epidemiology and Genetics

To determine the clinical significance of the criteria for the systemic inflammatory response syndrome (SIRS), Alberti and coworker  analyzed risk factors for hospital mortality in 3,608 ICU patients in the European Sepsis Study. Hospital mortality was variable: about 25% in patients with uncomplicated infection or sepsis, 40% in patients with severe sepsis, and 60% in patients with septic shock. Outcome was equivalent for patients who had infection and met SIRS criteria (sepsis) and patients who had infection and did not meet SIRS criteria (infection only). When patients were stratified according to severity of sepsis, the number of fulfilled SIRS criteria had no influence on mortality. On Cox regression, factors associated with outcome included comorbid conditions, severity of acute illness and acute organ dysfunction, shock, nosocomial infection, infection caused by aerobic gram-negative bacilli, enterobacteria, Staphylococcus aureus, and infection from a digestive source or unknown source. The authors conclude that characterization of patients with infection on the basis of SIRS criteria has no prognostic implication, whereas categorization on the basis of organ dysfunction or shock has prognostic significance.

To characterize the epidemiology of septic shock, Annane and coworkers  analyzed data on 100,554 admissions to 22 ICUs in Paris. The overall frequency of septic shock was 8.2 per 100 admissions. Frequency increased from 7% of admissions in 1993 to 9.7% of admissions in 2000. Both the rate of pulmonary infection and septic shock caused by multiresistant bacteria increased over time. Crude mortality was 62.1% in 1993 and 55.9% in 2000. Compared with patients admitted to the ICU without sepsis, the increased risk of death secondary to septic shock was 25.7; the matched odds ratio of death was 3.9. The authors conclude that the frequency of septic shock is increasing and is involving more multiresistant strains, and that mortality is decreasing but remains higher than in nonseptic critically ill patients.

To characterize the epidemiology of sepsis in children, Watson and coworkers  analyzed data on 1,586,253 hospitalizations in children, 19 years of age or younger. These were 42,364 cases of severe sepsis per year nationally in children (0.56 cases per 1,000 population per year). Incidence was highest in infants (5.2 per 1,000), lower in 10- to 14-year-old children (0.2 per 1,000), and 15% higher in boys than in girls. Half the cases had an underlying disease, and 23% were low-birth-weight newborns. The most common infections were respiratory (37%) and primary bacteremia (25%). Hospital mortality was 10.3%, mean length of stay was 31 days, and cost was $40,600. Annual costs were estimated at $1.97 billion nationally. The authors conclude that there are more than 42,000 cases of sepsis with 4,400 associated deaths in the United States each year.

Schaaf and coworkers  asked, "Are patients who are genetically predisposed to increased production of interleukin-10 (as determined by interleukin-10–1082 polymorphism) at increased risk of severe pneumococcal infection leading to septic shock?". Polymorphisms were studied by the polymerase chain reaction in 69 patients with pneumococcal disease (61 with community-acquired pneumonia, 5 with meningitis, and 3 with pneumonia and meningitis) and 50 control subjects. No significant genotype differences were seen between the patients and the control subjects. Of 69 patients with pneumococcal disease, 13 developed septic shock. Interleukin-10 allele G–homozygous patients had the highest risk for septic shock (odds ratio, 6.1). Release of interleukin-10 from whole blood was 46% greater in patients who were homozygous for the interleukin-10 allele G than in nonhomozygotes. No association was found between tumor necrosis factor genotypes and sepsis severity. The authors conclude that patients who are homozygous for interleukin-10–1082 allele G (associated with increased production of interleukin-10) are at increased risk of developing septic shock from pneumococcal infection.

In the proximal coding region of the gene for the lipopolysaccharide binding protein, a T G single nucleotide polymorphism at nucleotide 292 has been reported as a risk for sepsis after trauma. Barber and O'Keefe  used multiple analytical methods to characterize this coding region. The single nucleotide polymorphism at 292 was not found, but an adjacent nucleotide (291) was found to be polymorphic. Among 151 trauma patients, 25% developed severe sepsis and 13% died. Severe sepsis occurred in 13 of 50 C-allele carriers and 24 of 101 TT homozygotes. Genotype was not associated with sepsis or death. The authors conclude that a single nucleotide polymorphism exists at position 291 in the proximal coding region of the gene for lipopolysaccharide binding protein, and that this polymorphism is not associated with complicated sepsis after trauma.

To determine whether ARDS complicating bacteremic sepsis has an independent effect on mortality, Eggimann and coworkers  analyzed data on 4,530 admissions to an ICU. There were 196 cases of bacteremic sepsis and 31 (16%) of these patients developed ARDS. On Cox proportional hazards regression, ARDS was associated with increased mortality (unadjusted hazard ratio, 1.8). After adjusting for comorbid factors present before the onset of sepsis, ARDS was still associated with increased mortality (adjusted hazard ratio, 2.2). After adjusting for nonpulmonary organ dysfunction and microbiologic factors, ARDS was not associated with increased mortality (adjusted hazard ratio, 0.6). The authors conclude that ARDS complicating bacteremic sepsis is not independently associated with short-term mortality once the severity of illness and nonpulmonary organ dysfunction have been taken into account.

Citations 1-7 of 7 total displayed.

Differential Gene Expression in Gram-negative and Gram-positive Sepsis

Sung-Liang Yu, Huei-Wen Chen, Pan-Chyr Yang, Konan Peck, Min-Hui Tsai, Jeremy J. W. Chen, and Fang-Yue Lin
Am. J. Respir. Crit. Care Med. 169: 1135 -1143. First published online as doi:10.1164/rccm.200211-1278OC [Abstract] [Full text]  

Pneumococcal Septic Shock Is Associated with the Interleukin-10–1082 Gene Promoter Polymorphism

Bernhard M. Schaaf, Florian Boehmke, Hamed Esnaashari, Ulrike Seitzer, Henning Kothe, Matthias Maass, Peter Zabel, and Klaus Dalhoff
Am. J. Respir. Crit. Care Med. 168: 476 -480. First published online as doi:10.1164/rccm.200210-1164OC [Abstract] [Full text]  

Current Epidemiology of Septic Shock: The CUB-Réa Network

Djillali Annane, Philippe Aegerter, Marie Claude Jars-Guincestre, and Bertrand Guidet
Am. J. Respir. Crit. Care Med. 168: 165-172. [Abstract] [Full text]  

Influence of Systemic Inflammatory Response Syndrome and Sepsis on Outcome of Critically Ill Infected Patients

Corinne Alberti, Christian Brun-Buisson, Sergey V. Goodman, Daniela Guidici, John Granton, Rui Moreno, Mark Smithies, Oliver Thomas, Antonio Artigas, and Jean Roger Le Gall
Am. J. Respir. Crit. Care Med. 168: 77 -84. First published online as doi:10.1164/rccm.200208-785OC [Abstract] [Full text]  

Characterization of a Single Nucleotide Polymorphism in the Lipopolysaccharide Binding Protein and Its Association with Sepsis

Robert C. Barber and Grant E. O'Keefe
Am. J. Respir. Crit. Care Med. 167: 1316 -1320. First published online as doi:10.1164/rccm.200209-1064OC [Abstract] [Full text]  

Acute Respiratory Distress Syndrome after Bacteremic Sepsis Does Not Increase Mortality

Philippe Eggimann, Stephan Harbarth, Bara Ricou, Stephane Hugonnet, Karin Ferriere, Peter Suter, and Didier Pittet
Am. J. Respir. Crit. Care Med. 167: 1210 -1214. First published online as doi:10.1164/rccm.200210-1196OC [Abstract] [Full text]  

The Epidemiology of Severe Sepsis in Children in the United States

R. Scott Watson, Joseph A. Carcillo, Walter T. Linde-Zwirble, Gilles Clermont, Jeffrey Lidicker, and Derek C. Angus
Am. J. Respir. Crit. Care Med. 167: 695 -701. First published online as doi:10.1164/rccm.200207-682OC [Abstract] [Full text]