Antibiotic Exposure
In healthy adults, the colon contains as many as 10
12
bacteria/g of feces, the majority of which
are anaerobic organisms (21). This flora provides an important host defense by inhibiting
colonization and overgrowth withC. difficileor other potential pathogens. Antibiotics alter this
indigenous microflora, thereby allowingC. difficileto grow to high concentrations. An animal
model (22) showed that agents that disrupt the intestinal flora and lack activity against
C. difficile(such as ceftriaxone) promoted development of CDI during treatment and during the
time that the microflora replenishes after discontinuation of the antibiotics. On the other hand
antimicrobial agents without anaerobic activity (e.g., aztreonam) cause minimal disruption of
the anaerobic microflora and did not promote CDI in hamsters. Evidence from clinical studies
has not consistently supported this theory. Many agents that have minor disruption of the
anaerobic microflora have been associated with CDI (e.g., fluoroquinolones). In general,
however, antibiotics with significant antianaerobic activity, and to whichC. difficilehas either
innate or acquired resistance, pose the highest risk.
Recent observations suggest that antimicrobial resistance inC. difficilestrains may be
playing an important role in the epidemiology of the disease.C. difficilestrains that are
resistant to particular antibiotics may thrive in an environment where other colonic microflora
is being suppressed. There have been large outbreaks with clindamycin-resistant CDI strains in
the early 1990s that led to a decrease in the use of clindamycin in U.S. hospitals (23).
Nearly all antibiotics have been implicated as a risk factor for CDI. Historically, the
antimicrobials most commonly associated with CDI are clindamycin, penicillins, and
cephalosporins. Clindamycin was associated with the greatest risk of CDI, while cephalospor-
ins and broad-spectrum penicillins were associated with the greatest numbers of CDI cases
due to their extensive use (1). Fluoroquinolones (ciprofloxacin) were approved for use in the
United States 1987 and has been frequently used to treat inpatient and outpatient infections.
Recently, outbreaks of fluoroquinolone-resistant CDI have been reported including the B1/
NAP1. All currently available fluoroquinolones have been implicated in the outbreaks, and
switching from one fluoroquinolone to another to avoid CDI is not recommended (21).
The use of combination antibiotic therapy and broad-spectrum antibiotics has been
associated with an increased risk of CDI (24). Longer duration of antimicrobial therapy
increases the risk of CDI by extending the time that the patients are at risk of acquiring CDI
Table 1 Major Risk Factors for Initial Episode of CDIa
- Antibiotic exposure
.Antibiotics associated with
Higher risk of CDI
&Cephalosporins
&Clindamycin
&Fluoroquinolones
&Penicillins
Lower risk of CDI
&Aminoglycosiodes
&Aztreonam
&Piperacillin-tazobactam
&Tetracycline
&Trimethoprim-sulfamethoxazole
.Use of combinations of several antibiotics or broad-spectrum antibiotics
.Prolonged duration of antibiotic use - Hospitalization
.Longer duration of hospitalization
.ICU stay - Advanced age
.Age>65 years - Impaired immunity
.Decreased antibody response to clostridial toxins
aCommunity-acquired CDI cases may have none of these risk factors.
Abbreviation: CDI,Clostridium difficileinfection.
Clostridium difficileInfection in Critical Care 273