15
Clostridium difficile Infection in Critical Care
Karin I. Hjalmarson
Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center,
Boston, Massachusetts, U.S.A.Sherwood L. Gorbach
Nutrition/Infection Unit, Department of Public Health and Family Medicine, Tufts University School of Medicine,
and Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center,
Boston, Massachusetts, U.S.A.INTRODUCTION
Clostridium difficilewas first described in 1935 as a component of the normal intestinal flora in
healthy neonates (1). Its role as a pathogen was not clear until 1978 when it was identified as
the cause of antibiotic-associated pseudomembranous colitis (PMC) (2). PMC had been
recognized as early as 1893 but was a rare entity in the preantibiotic era, primarily associated
with colonic, pelvic, or gastric surgery (3). In the 1950s, after antibiotics became available, the
incidence of PMC increased and it was linked to antibiotic use.Staphylococcus aureuswas the
suspected pathogen since it was frequently recovered from patients stool culture samples. In
1974, a study showed high rates of PMC among patients treated with clindamycin, and the
condition was called “clindamycin colitis” (4). In 1978, the association between cytotoxins
released byC. difficileand antibiotic-induced PMC was discovered (2,5). Since then, many cases
of antibiotic-associated diarrhea (AAD) and the vast majority of PMC cases have been
attributed toC. difficile. With increased use of cephalosporins in the 1980 to 2000, it became the
antibiotic class most commonly associated withC. difficileinfection (CDI) (6).
Continued research over the last three decades has identified associated risk factors,
clinical features, diagnosis, and management of CDI. Until the early 2000, CDI was viewed as
an iatrogenic complication, often nosocomial, with low attributable mortality; however, over
recent years, there have been marked increases in incidence and severity of illness. There are
several plausible explanations: the emergence of a new epidemic, hypervirulent strain
(B1/NAP1) that is also resistant to fluoroquinolones, an increasing elderly population, and the
expanding use of broad-spectrum antimicrobials including fluoroquinolones. The epidemiol-
ogy of the disease has also changed with reports of cases of severe community-acquired CDI
(CA-CDI) in populations not previously considered to be at risk for the infection (7).
EPIDEMIOLOGY
Overview
An analysis of the U.S. hospital discharge data from 2006 showed that CDI rates increased
abruptly in 2001, with a doubling of national rates from 2000 to 2003 (8,9).
A review of CDI from Quebec, Canada, of 1771 patients during 1991 to 2003 showed that
the incidence of CDI per 100,000 people increased 4-fold for the entire region and 10-fold for
persons>65 years of age (10). The incidence among hospitalized patients increased from 3 to
12/1000 persons in 1991 to 2001 to 25 to 43/1000 persons in 2003 to 2004. In addition, there
were increased rates of more serious disease that was refractory to therapy.
In a study from 2005 by Pepin et al., patients with CDI were compared with matched
controls and the one year cumulative attributable mortality due to CDI was found to be
16.7% (11).
In 2005, data from the Centers for Disease Control (CDC) suggested increasing frequency
and severity of CDI also in the United States, including eight hospital outbreaks in six states.
This pattern of increased incidence, severity, and more refractory CDI with high rates of
relapse was also observed in Europe. The epidemic was confirmed to be caused by a new
strain ofC. difficilenamed restriction endonuclease analysis group B1/North American pulse