on the Increase in U.S., According to Emory University and CDC Study
incidence of sepsis a severe, whole-body immune response to infection
is increasing by an average of 16% a year in the U.S., according to
research by investigators at Emory University School of Medicine and
the Centers for Disease Control and Prevention (CDC). During the 20-year
period from 1979 to 1999, the incidence of sepsis increased by more
than 329%, from 78 to 259 cases per 100,000 people. Sepsis is a major
public health problem, consuming more than $15 billion in healthcare
costs annually in the U.S.
Emory pulmonologist and intensivist
Greg Martin, M.D., in collaboration with Marc Moss, M.D., of Emory and
David Mannino, M.D., of the CDC presented results of their analysis
of data from the U.S. National Hospital Discharge Survey at the annual
meeting of the American Thoracic Society in Atlanta on Tuesday. The
study is the most comprehensive survey of sepsis epidemiology to date
because it includes statistics from the entire country over a long period
The scientists used selected
groupings of clinical disease classification codes to identify patients
with sepsis. The incidence of sepsis increased in both children and
adults during the 20-year period. Males, African-Americans, and other
non-Caucasians had the highest rates of hospitalization due to sepsis,
although the incidence in females and Caucasians increased more rapidly.
The study also indicated an increase in gram-positive infections, which
by 1999 represented the majority of cases of sepsis (56%), while gram-negative
infections, anaerobic, fungal and viral infections were less common.
Although relatively uncommon, the greatest increase was in sepsis cases
with fungal infections as their source.
Although sepsis begins with
an identifiable infection, when patients become septic their immune
systems are intensely activated, setting off a cascade of events that
may result in uncontrolled inflammation throughout the body. Sepsis
also activates the coagulation system by promoting thrombosis and inhibiting
fibrinolysis, which is how the body breaks up clots. These changes may
contribute to multiple organ failure, which is a major cause of mortality
Following years of research
on sepsis, scientists last year introduced the first effective specific
therapy the drug Xigris, which is activated protein C, a recombinant
form of a natural anticoagulant. Xigris is effective because it is an
anti-coagulant that also reduces inflammation. Before Xigris, the mainstay
of therapy was general, broad-spectrum antibiotics and supportive care.
Physicians must be able to
recognize sepsis quickly in order to treat it. "Studies show that if
you wait even four to eight hours to begin antibiotic therapy, the mortality
from sepsis worsens considerably," notes Dr. Martin. "And antibiotics
must be appropriate. Patients with severe sepsis are in shock, with
organ failure, respiratory failure, and renal failure. Although the
mortality with severe sepsis is approximately 30% to 40%, Xigris reduces
that to approximately 25%.
Although there has been no
scientific study to identify the reasons for the increase in sepsis,
Dr. Martin offers several explanations. "Physicians are identifying
more cases of sepsis because they are aware of how sepsis differs from
other infections," he says. "And sepsis is actually occurring more frequently
due to the overuse of antibiotics and the development of resistant organisms.
This is apparent in the shift towards gram-positive organisms as the
cause of sepsis and the increase in fungal causes. Improvements in care
among individuals with altered immunities also could be leading to an
increase in sepsis. For example, antiretroviral therapy has led to increased
longevity for HIV patients, and we have more patients receiving organ
transplants, bone marrow transplants, and high-dose chemotherapy who
are vulnerable to infection. An increase in medical and surgical procedures
that breach body barriers also predisposes more patients to sepsis."
According to earlier research,
80% of patients with sepsis develop it outside the hospital, while only
20% develop it while in a hospital or nursing home. Although the incidence
of sepsis is increasing, with more than 700,000 cases per year, the
mortality appears to be decreasing, from 29% of cases in 1979 to 17.4%
in 1999. Because of the increased incidence, however, more people continue
to die each year.
Physicians have become much
more adept at diagnosing sepsis, according to Dr. Martin, partly because
of a consensus definition that includes criteria such as changes in
temperature, heart rate, respiratory function, and white blood cell
count. Sepsis is defined as being an initial infection plus at least
two of these four additional criteria.
"This makes it much easier
for physicians to walk to the bedside and identify patients with sepsis,
including those at highest risk," Dr. Martin says. "If a patient has
sepsis with organ failure, physicians need to be very aggressive with
"Not only do we need to treat
sepsis promptly and aggressively, we also need to educate the entire
physician community about how to recognize sepsis early or prevent sepsis
in high-risk patients, We also need to examine how antibiotics, medical
procedures, and an increase in immune-compromised patients and elderly
patients represent increased risk for sepsis. A new understanding of
sepsis could have a major impact on patients and healthcare resources,"
Dr. Martin emphasizes.
The study was funded by Emory
University and the National Institutes of Health.
To contact Dr. Martin, please