Journal of Infection and Public Health (2015) 8, 155—160

The evaluation of Clostridium difficile

infection (CDI) in a community hospital
Aju Daniel a, Alwyn Rapose b,c,∗

a Saint Vincent Hospital, Worcester, MA, USA

b University of Massachusetts, Worcester, MA, USA
c Reliant Medical Group, Worcester, MA, USA

Received 27 January 2014 ; received in revised form 10 July 2014; accepted 22 August 2014

KEYWORDS Summary
Clostridium difficile; Introduction: Clostridium difficile is a serious reemerging pathogen in Europe and
Diarrhea; North America. C. difficile infection (CDI) has been of concern over the last decade
Antibiotics in view of its significant morbidity and mortality, as well as the high health care costs
involved with each case. Although multiple risk factors are known to be associated
with CDI, a number of patients develop severe infection even in the absence of known
risk factors. CDI is diagnosed by the detection of the toxin A/B in stools by enzyme
immunoassay (EIA) or by polymerase chain reaction (PCR). There is conflicting liter-
ature regarding whether any particular group of antibiotics is associated with higher
risk for CDI. There is also a tendency to perform repeated stool tests for toxin A/B
if the first test is negative. We evaluated 100 consecutive hospitalized patients who
tested positive for C. difficile over a one-year period.
Methods: We performed a retrospective analysis of 100 consecutive patients with
CDI admitted to our hospital between July 2008 and June 2009. Patient records were
reviewed for risk factors, treatment, and clinical outcomes. We also evaluated the
number of stool tests performed for the detection of C. difficile and fecal leukocyte
testing in each patient.
Results: The majority of the patients were more than 60 years of age (87%). Forty-
four percent of patients presented from a nursing facility. More than 50% were on
Proton Pump Inhibitors (PPIs) at the time of admission. Co-morbidities in our patients
included malignancy in 28%, diabetes mellitus in 25%, and chronic renal disease
in 23%. Most of the patients had multiple co-morbidities. Patients who had taken
antibiotics in the previous six months constituted 74% of the total study population.
A beta-lactam alone or in combination with other antibiotics was prescribed in 48%,
quinolones in 13% and clindamycin in 4% of patients. Stool samples were tested only

∗ Corresponding author at: Reliant Medical Group, Division of Infectious Diseases, 123 Summer Street, Suite # 220, Worcester, MA

01608, USA. Tel.: +1 508 368 3122; fax: +1 508 368 3123.
E-mail addresses: alwyn.rapose@reliantmedicalgroup.org, alwyn.rapose@gmail.com (A. Rapose).

http://dx.doi.org/10.1016/j.jiph.2014.08.002
1876-0341/© 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Limited. All rights reserved.
156 A. Daniel, A. Rapose

once in 53% of patients and twice or more in 43%. Metronidazole was the initial therapy
in 86% of patients. Intensive care unit stay was required in 33% of patients. Seventeen
percent died during their hospitalization.
Conclusions: Elderly patients are especially vulnerable to CDI when exposed to antibi-
otics, and higher mortality and morbidity is observed in this age group. PPI use was
common in our patients. Metronidazole was used as the first line agent in the majority
of patients. We also determined a tendency to test for the C. difficile toxin in more
than one stool sample. All of these practices need to be modified based on the current
guidelines.
© 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier
Limited. All rights reserved.

Introduction elderly forming a significant percentage of in-

Clostridium difficile is a spore-forming anaerobic
bacillus found in the normal colonic flora of 5% of
healthy adults [1], and these carriers may play a sig-
nificant role in the transmission of this infection in
hospitals [2]. C. difficile infection (CDI) is the most
common cause of nosocomial infectious diarrhea in
developed countries and its incidence has been ris-
ing steadily. CDI is widespread in Massachusetts’s
hospitals [3]. CDI is responsible for increased mor-
bidity and a substantial economic burden. The
economic impact of this disease is expected to
increase in the coming years. The widespread use
of antibiotics has contributed to the spread of this
disease to some extent, as antimicrobial therapy
plays a major role in the pathogenesis of CDI,
presumably through the disruption of indigenous
intestinal microflora, thereby allowing C. difficile
to grow and produce toxins. There is conflicting lit-
erature regarding whether any one particular group
of antibiotics is associated with a higher risk for CDI.
While clindamycin has been known for many years
as a risk factor, some studies found fluoroquinolones
as a high risk [4—6] while other authors have impli-
cated cephalosporins as high-risk antibiotics [7,8].
There have been studies published to assess
the need for repeated stool testing in the diag-
nosis of CDI [9,10]. The updated Clinical Practice
Guidelines for CDI in adults by the Society for
Healthcare Epidemiology for America (SHEA) and
the Infectious Diseases Society of America (IDSA)
have advised against repeat testing during the same
episode of diarrhea [11]. Additionally, there has
been conflicting evidence regarding the need for
fecal leukocyte testing (FLT) as a screening test for
CDI. While some authors have concluded that FLT is
a poor predictor of CDI [9,12], others have proposed
that FLT might be useful [1,13].
We present our experience regarding CDI in
patients evaluated over a one-year period in a
280-bed community teaching hospital, with the
hospital admissions. We performed a retrospective
analysis of 100 patients admitted to our hospital
with CDI between July 2008 and June 2009.
Materials and methods
A retrospective analysis of 100 consecutive patients
diagnosed with CDI who were admitted to the
hospital between July 2008 and June 2009 was per-
formed by reviewing electronic medical records.
CDI diagnosis was based on a positive EIA for toxin
A/B in stool. PCR is not available at our hospi-
tal. Approval for the study was obtained from the
hospital’s Institutional Review Board. The inclu-
sion criteria were: patients more than 18 years
of age, with a history of diarrhea as documented
in the chart, and documented CDI by EIA testing
for toxin A/B. The exclusion criteria were patients
with diarrhea but negative EIA testing. The patient
data extracted from the medical records included
age, sex, presentation from home versus nursing
facility (including nursing homes, short-term and
long-term rehabilitation facilities), co-morbidities
— diabetes mellitus, malignancy, kidney disease,
hypertension, coronary artery disease, antibiotic
use in the previous 6 months along with the nature
of the antibiotic (based on a review of previous
hospital records, nursing facility records and out-
patient EMRs if available), the use of PPIs, hospital
course and outcomes. We also evaluated the num-
ber of stool samples tested by EIA for toxin A/B and
testing for fecal leukocytes.
Results
Forty-eight patients were female and 52 were male.
The median age was 80 years (30—96 years), 87%
of patients were above 60 years of age, of which
48% were above the age of 80 years (Table 1).
The evaluation of CDI in a community hospital 157

Table 1 Demographics.
of patients had definitely received an antibiotic
in the previous 6 months (Fig. 1). Beta-lactams,
Total number 100 more precisely, cephalosporins (first generation
Age distribution cefalexin and cefazolin for skin infections, and
18—40 years 4 third-generation ceftriaxone and cefpodoxime for
41—60 years 6
respiratory infections), were the most commonly
61—80 years 39
>80 years 48
prescribed antibiotics. Forty-eight percent of
Presenting from patients had received beta-lactam alone or in com-
Home 56 bination with vancomycin or macrolide, 13% had
Hospital or nursing facility 44 received a quinolone and 4% had received clin-
Co-morbidities damycin. Seven patients had not received any
Malignancy 28 antibiotic in the 6 months prior to presentation with
Diabetes 25 CDI. Documentation regarding prior antibiotic use
Chronic renal disease 23 could not be defined in 19 patients. In terms of
Medications at admission other gastrointestinal medications at the time of
PPIs 52 admission, 52% were on PPIs.
Laxatives 27
Stool samples were tested for toxin A/B by EIA
just once in 53% of patients and twice or more in
There were 44 patients who presented from a nurs- 43% of patients. Stools were tested for fecal leuko-
ing facility. Eighty-five percent of patients had a cytes in 75 patients. There were no fecal WBC noted
history of admission to a hospital in the previ- in the majority of patients (42.6%) and only 32% had
ous 6 months. Symptoms at presentation included more than 25 WBCs per high power field. Metroni-
fever (>38 ◦ C) 34%, abdominal pain 31%, leukocyto- dazole was the initial therapy in 86% of patients.
sis (>11 cells × 109 /L) 67% and bandemia 30%. The Oral vancomycin was used in 43 patients. In terms
number of episodes of loose stools and the dura- of clinical outcomes, the median length of hospital
tion of disease prior to presentation was not well stay was 6.5 days (2—45 days). Twenty-three per-
documented in the majority of patients. Twenty- cent of patients required hospitalization for more
five percent of patients had diabetes mellitus, than 10 days and 33% of patients required ICU
23% had chronic renal disease and malignancy was admission. There was a high mortality (17%) rate
present in 28% of patients. Seventy-four percent in our study.

No Documentation
19%

No Antibiotics
7%

Linezolid Beta Lactams

1% 48%
Sulfonamides
2%
Macrolides
3%
Vancomycin
3%
Clindamycin
4%
Quinolones
13%

Beta Lactams Quinolones Clindamycin Vancomycin Macrolides

Sulfonamides Linezolid No Antibiotics No Documentation

Figure 1 Antibiotics used in the last 6 months.

158
Discussion
Our data are consistent with the previously pub-
lished literature that the elderly population is at
high risk for CDI. Eighty-seven patients in our study
were more than 60 years of age and 10 patients
were older than 90 years. This is in part a reflection
of the population being served by our community
hospital. Many of our elderly patients presented
from a nursing facility. While it was surprising
that 54% of patients in our study presented from
home, the majority of these patients had a his-
tory of hospitalization in the previous 6 months.
Co-morbidities commonly noted were malignancy,
diabetes mellitus and chronic renal disease. This is
again consistent with the fact that when the host
immunity is compromised, patients are at a higher
risk of acquiring CDI. The majority of patients in
our study had received antibiotics in the past six
months. The most commonly implicated class of
antibiotics was cephalosporin either alone or in
combination (48%). Fluoroquinolone was used in
only 13% of patients. It is the opinion of the authors
that this is reflection of the pattern of antibiotic use
rather than a direct etiologic relationship between
cephalosporins to CDI, especially in light of multi-
ple studies that have implicated flouroquinolones
as well as cephalosporins as risk factors for CDI
[4—8]. Stevens and colleagues have proposed that
the cumulative exposure to antibiotics over time
may play a more significant role in the risk for
CDI rather than a single short course of a given
antibiotic [14]. Interestingly, seven patients had
no history of antibiotic use in the preceding six
months. Four of these patients had a history of
hospitalization in the previous 6 months. Regard-
less of the limitations of this study in terms of
the inability to capture all outpatient antibiotic
use, this finding could imply that multiple unde-
fined factors may contribute to the development
of CDI in many patients. Manges and colleagues
concluded that changes in the intestinal flora in
hospitalized patients are not driven exclusively by
antibiotic use and a number of cofactors includ-
ing nonsteroidal anti-inflammatory drug use may
play an important role in the development of CDI
[15]. David Eyre and colleagues performed whole-
genome sequencing on samples from patients with
CDI and found that the majority of infections arise
from genetically diverse sources [16]. In any case,
the increasing incidence of CDI is a call to improve
antimicrobial stewardship programs in health-care
settings [17,18].
Fifty-two patients were noted to be on a PPI at
the time of CDI diagnosis. There has been some
conflicting literature regarding the role of PPIs in
A. Daniel, A. Rapose
relation to CDI. Some studies have documented an
increased incidence of CDI with the use of PPIs
[19—21], while others have not confirmed this [22].
The diagnosis of CDI using a clinical definition of
diarrhea and the detection of toxin A/B in the
stool by EIA has a sensitivity that varies between
63% and 94%, and a specificity ranging from 75% to
100%. These tests have been adopted by more than
90% of laboratories in the United States because of
their ease of use. Processing a single specimen from
a patient at the onset of a symptomatic episode
usually has been considered sufficient. Because of
the low increase in yield and the possibility of
false-positive results, routine testing of multiple
stool specimens is not recommended [11,23]. In
our study, stools were tested for toxin A/B in more
than one sample in 43% of patients. This practice of
repeat testing needs to be discontinued based on
the current guidelines [10]. Newer more sensitive
tests are now available at our facility. Fecal leuko-
cytes were evaluated in 75 patients, and this test
found no WBCs in the majority of patients. There
were many WBCs noted in 24 patients (32%). This
questions the practice of testing for fecal leuko-
cytes in stool specimens in patients with suspected
CDI.
Thirty-three of our patients required admission
to the intensive care unit (ICU). There were 23
patients who required more than 10 days of hospi-
talization. There were no cases of toxic megacolon
or surgical intervention. Unfortunately, there was
high mortality rate (17%) in our study. All these
findings taken together could be a reflection of
the elderly population with multiple co-morbidities
described in our study.
Three factors have been used to define the
severity of illness in patients with CDI — age, leuko-
cytosis and creatinine [11]. Two of these three
factors were observed in the majority of our study
patients (87% of patients were above 60 years of
age and 67% of patients had leukocytosis). Met-
ronidazole was the initial therapy in 86% of the
patients. With 33 patients requiring an ICU stay and
23 patients requiring more than 10 days of hospital-
ization, the authors conclude that oral vancomycin
could have been a better first line therapy in many
of these patients and would be consistent with
the guidelines that recommend oral vancomycin as
the initial choice in patients with severe disease
[11,24].
The main limitations of our study are sec-
ondary to its retrospective observational nature
and lack of a control group. Similarly, details
regarding the frequency of loose stools, chronic
renal disease (creatinine values), glycemic con-
trol (hemoglobin A1C), details of cancer and
The evaluation of CDI in a community hospital
chemotherapeutic agents were not consistently
documented and hence not extracted in detail.
Additionally, this is a study of a patient popula-
tion evaluated at a single facility and based on the
evaluation of available EMRs, and hence the pos-
sible use of antibiotics outside the system could
have been missed. The reason for the prescrip-
tion of antibiotics prior to the CDI and the number
of readmissions after discharge were not evalu-
ated as part of this study. The primary aim of this
study was to describe CDI in a community hospital
setting and also to confirm some of the common
observations in studies performed at larger institu-
tions. The findings of our study also highlight the
need to revisit the practice of performing test-
ing on multiple stool samples, to evaluate the role
of PPIs and encourage the use of oral vancomycin
as a first line agent in patients at risk for poor
outcomes, especially the elderly with multiple co-
morbidities.
Conclusions
Our study is consistent with the published reports
indicating that CDI carries a high mortality and
morbidity in the elderly who often have multiple
underlying co-morbidities. One of the consistent
predisposing factors is the prior use of antibiotics.
However, some patients developed CDI even in the
absence of antibiotic use in the past six months,
implying the role of yet unidentified factors in the
pathogenesis of this disease. It may be prudent
to initiate oral vancomycin as the first-line ther-
apy in patients more than 80 years of age and
patients with multiple co-morbidities. Judicious use
of antibiotics and PPIs in the elderly combined with
the early institution of oral vancomycin treatment
may help reduce the mortality and morbidity of CDI
in our elderly population.
Funding
No funding sources.
Competing interests
None declared.
Ethical approval
Not required.
159
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