Call Girls in Gagan Vihar (delhi) call me [🔝 9953056974 🔝] escort service 24X7
Antimicrobial stewardship clostridium difficile
1. Theme Article
Antimicrobial Stewardship and Clostridium
difficile–Associated Diarrhea
Frank J. Piacenti, PharmD1
, and Kimberly D. Leuthner, PharmD2
Abstract
Antimicrobial stewardship programs are essential to health care institutions to promote the appropriate use of antibiotics not
only to decrease antimicrobial resistance but to prevent the spread and infection of Clostridium difficile. Clostridium difficile–
associated diarrhea is increasing rapidly in the United States and is now considered a major public health problem that poses an
immediate threat to the health of patients prescribed antibiotics, more so than antimicrobial resistance. Clostridium difficile–
associated disease is the result of collateral damage to the normal bacterial flora of the human body, which is an inevitable
consequence of any antibiotic use. Antimicrobial stewardship programs such as audit with feedback and antibiotic restriction are
designed to help limit Clostridium difficile infections and other hospital-associated organisms by optimizing antimicrobial selection,
dosing, de-escalation, and duration of therapy. These programs also incorporate implementation of hospital-wide guidelines, staff
education, enforcement of infection-control policies, and the use of electronic medical records when possible to help control
antibiotic use. This article reviews the literature on how antimicrobial stewardship programs impact Clostridium difficile rates and
discusses experiences in designing, implementing, monitoring, and follow-through of such programs.
Keywords
antimicrobial stewardship, Clostridium difficile, antibiotic usage
Clostridium difficile–associated disease (CDAD) is one of the
leading hospital-acquired infections in the United States and
has increased to historic highs. CDAD infections have been
linked to approximately 14 000 deaths per year with an esti-
mated increase of hospital costs of between US$897 million
and US$1.3 billion.1
Although many conditions have been
associated with the increased risk of CDAD, the most common
is the overuse of antimicrobial agents.
Antibiotic usage accounts for up to 30% to 50% of a hospital
pharmacy’s nonlabor budget; therefore, controlling inappropri-
ate antibiotic usage has become a major focus for many
institutions.2
At least 30% of the hospitalized patients are given
an antibiotic, and these agents are inappropriate between 22%
and 65% of the time.3-5
Hecker et al6
performed a retrospective
evaluation of antimicrobial use in an inpatient setting in 2001.
In a 2-week period, they found 30% (576 of 1941) of antimicro-
bial days of therapy (DOT) were inappropriate. More specifi-
cally, 33.3% (192 of 576) of inappropriate DOT were due to
therapy that was continued longer than necessary, and 32.5%
(187 of 576) of inappropriate use were for noninfectious or
nonbacterial syndromes.
Clostridium difficile and Antimicrobial Use
Clostridium difficile is the causative organism of antibiotic-
associated diarrhea and colitis. Colonization of the intestinal
tract occurs via the fecal–oral route and is facilitated by
disruption of normal intestinal flora due to antimicrobial ther-
apy. The organism is capable of elaborating exotoxins that bind
to receptors on intestinal epithelial cells, leading to inflamma-
tion and diarrhea. C difficile colonization primarily occurs in
hospitals and long-term care facilities. Patients who become
hospitalized and are prescribed broad-spectrum antibiotics are
at an increased risk of this infection. Patients usually become
colonized from unsanitary rooms, medical devices, or hospital
personnel. However, if a patient becomes colonized, he may still
not develop disease. In order for C difficile to flourish and cause
disease, several factors need to be in place. Patients who are
elderly, immunocompromised, and who are prescribed a
broad-spectrum antibiotic have an increase risk of developing
C difficile. However, any patient at any age or immune status
is at risk when prescribed a broad-spectrum antibiotic, especially
when the antibiotic is not necessary.
The reasons why broad-spectrum antibiotics contribute to
C difficile infections are not fully understood. Most organisms
within a host will not overgrow when other organisms are
1
Department of Pharmacy, Lincoln Medical Center, Bronx, NY, USA
2
University Medical Center of Southern Nevada, Las Vegas, NV, USA
Corresponding Author:
Frank J. Piacenti, Lincoln Medical Center, 234 E 149th street, Bronx, NY 10451,
USA.
Email: frank1966@optonline.net
Journal of Pharmacy Practice
26(5) 506-513
ª The Author(s) 2013
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0897190013499528
jpp.sagepub.com
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
2. present (patient not on antibiotics) because of competition for
host resources. For the most part, anaerobes prevent other anae-
robes from overgrowth. It appears that the disruption of indi-
genous flora by antimicrobials, in particular drugs that cause
major disruption of the anaerobic microflora (clindamycin,
cefoxitin, and ceftriaxone [high excretion into intestinal tract]).
However, many agents that cause minor disruptions of the
anaerobic flora (trimethoprim-sulfamethoxazole and fluoroqui-
nolones) have been associated with C difficile.7
As a class,
fluoroquinolones have poor in vitro activity against C difficile
and anaerobes but seem to be associated with C difficile strains
that are highly resistant to them. Beta-lactam/beta-lactam inhi-
bitors combinations appear to be less strongly associated with
CDAD, because they are highly active against many C difficile
strains.7
Antimicrobial Stewardship
The primary goal of an antimicrobial stewardship program
(ASP) is to optimize clinical outcomes while minimizing unin-
tended consequences of antimicrobial use, including the toxi-
city, the selection of pathogenic organisms, and the
emergence of resistance.8
A prominent pharmacy activity
within the structure of a stewardship program is to closely mon-
itor prescribed agents in order to avoid inappropriate antibio-
tics, duplicate therapy, and unnecessary lengths of therapy.
The concept of an ASP is designed to limit inappropriate
antibiotic use while optimizing antimicrobial selection, dosing,
route of administration, and duration of therapy. Tight control
of antibiotics will optimize clinical cure or prevention of
infection while limiting unintended consequences such as the
emergence of resistant organisms and the development of
C difficile–associated diarrhea. Strategies to limit the misuse
of antibiotics are broadly divided into 2 models, prior authoriza-
tion (formulary restriction or usage criteria) and antibiotic audit
with feedback.8
Antibiotic audit usually involves a pharmacist
with infectious diseases (IDs) certification and/or training who
reviews prescribed antibiotics and performs interventions as
needed.9
This model provides physicians with prescribing auton-
omy. It also eliminates the potential for a delay in therapy if an
ID physician or if an ID pharmacist is not available to approve
the antibiotics. In published surveys, physicians agreed that
knowledge of antibiotics is important and that they would like
more education and feedback on their antibiotic selections. Phy-
sicians also agreed that local guidelines are more helpful than
national guidelines.10-12
The prior authorization model involves
a required approval of given antibiotics from either an ID physi-
cian or an ID pharmacist. In some situations, this model can lead
to a delay in therapy, especially if the prescribing physician is
unable to reach the ID personnel for approval in a timely fashion
and the dispensing pharmacists cannot release the medication
until approval is confirmed.
The Infectious Disease Society of America (IDSA) defines
an ASP as a ‘‘rational, systematic approach to the use of anti-
microbial agents in order to achieve optimal outcomes.’’8
The
exact role of ASPs will vary from institution to institution, but
the overall goals remain similar. There is no perfect ASP nor
does the ‘‘one-size fits all’’ approach apply for any of these
activities. As stated by Aldeyab et al,13
one important aspect
of developing an effective antibiotic-monitoring policy is the
identification of the specific antimicrobial agents associated
with the local issue (ie, CDAD) and then modify practice
toward changing that outcome. The policy included both stew-
ardship approaches, restricted the use of high-risk antibiotics
(cephalosporins and fluoroquinolones clindamycin), and per-
formed audit with feedback on lower risk antibiotics not
included in the policy. As a result of this policy, C difficile rates
were decreased from 1.5 cases/1000 bed days to 0.5 cases/1000
bed days during a 2-year time period.
Successful programs can be as varied as the institutions in
which they are implemented and are limited only by the creativ-
ity of the people involved. Multiple elements will be required to
create a successful program, and continual revision to those
processes may be necessary to mature the program. Some
elements that appear to be similar between productive steward-
ship programs include a prospective audit with feedback, formu-
lary restrictions, antibiotic usage guidelines, staff education,
de-escalation, and the use of electronic medical records
(EMRs).8
Depending upon individual capabilities and back-
ground, some of these activities can be combined to optimize
outcomes.
ASP: Audit With Feedback
Audit with feedback is an essential part of any stewardship
program. Auditing usually begins with an evaluation of the pre-
scribing practices and the antibiotic delivery process by either
the stewardship physician or the pharmacist, with the results of
the audit reported to the institution and physicians. Depending
upon the facility, evaluations can be either prospective or retro-
spective. Retrospective data can provide useful information
regarding activities in the institution; however, these evalua-
tions are more passive toward the physician and may result
in delayed feedback and defensiveness, making modifications
of practices more difficult. Prospective activities can have a
more immediate effect due to the direct interaction between the
physician and the stewardship program. The physician or phar-
macist can provide interactive feedback and education to the
prescriber on a case-by-case basis. This may alter future
prescribing patterns but can be time intensive. This was the
approach taken by Elligsen and colleagues14
at their institution
to control broad-spectrum antimicrobial use. All patients in the
intensive care units who were receiving 3 days of broad-
spectrum antibiotic therapy were evaluated by the stewardship
pharmacist. Opportunities for optimization of care were identi-
fied and entered into a tracking database to determine the
compliance of the responsible physician. As a direct result of
these activities, monthly broad-spectrum use decreased from
644 DOT per 1000 patient-days to 503 DOT per 1000
patient-days (P < .001).
Another study that reported prescription audit with feedback
was by Yam et al15
in 2012. A clinical pharmacist, not ID
Piacenti and Leuthner 507
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
3. trained, would review selected broad-spectrum antibiotics for
appropriateness and make recommendations when necessary
to the prescriber. In addition, the pharmacist would present the
cases to the ID physician for review either as electronically or
as weekly case presentations. Over 13 months from May 2010
to June 2011, 311 patient cases were reviewed. Antimicrobial
costs from 2009 to the first 2 quarters of 2011 decreased from
US$13 521 to US$6 583.52 per 1000 antimicrobial costs from
2009 to the first 2 quarters of 2011 decreased from US$13 521
to US$6583.52 per 1000 patient days, respectively. Addition-
ally, hospital-acquired C difficile infection rates decreased
from an average of 5.5 cases per 10 000 patient-days to an aver-
age of 1.6 cases per 10 000 patient-days.
De-Escalation
De-escalation of antibiotics is an important component of an
ASP. De-escalation is defined as switching broad-spectrum
antibiotics to narrower spectrum antibiotics as appropriate.
De-escalation may be necessary once the patient’s diagnosis
is confirmed, when empiric therapy is no longer necessary, or
when final culture and sensitivity results are known. Once
de-escalation criteria are developed, a member of the steward-
ship team should evaluate each patient individually. As neces-
sary, a communication message can be left in the chart, or
preferably, a direct interaction with the prescriber either via
telephone (voice or text) or on medical rounds can be initiated
by a pharmacist in order to discuss the de-escalation criteria. A
problem with leaving notes in the chart is the inherent delay
associated with this process as well as the need for follow-up
by another member of the pharmacy staff. Physicians may hes-
itate to change therapy if the recommendation is different from
their usual practice, or because the patient is improving. With
continued effort and reporting, antibiotic prescribing will be
improved; however, some inappropriate use is to be expected.
The pharmacist who is either accepting antibiotic orders or
monitoring antibiotic usage whose recommendation to de-
escalate was not accepted by the prescribing physician should
address de-escalation opportunities directly to the stewardship
team leader who may then decide on further steps with the
patient’s medical team. This approach may help in increasing
de-escalation criteria compliance.
Antibiotic Restriction
Another antibiotic control strategy many organizations utilize
is formulary restriction with preauthorization. Kallen et al16
used
this approach specifically to combat an outbreak of CDAD
during 2006. Beginning in 2005, an increase in the rate of the
North American pulsed-field gel electrophoresis type 1 strain
causing CDAD was observed at their community hospital. After
extensive evaluation, it was decided to completely restrict
fluoroquinolones, since studies suggested this class of antimicro-
bials may be highly associated with an increased risk of CDAD.
As a result of the restriction, they were able to demonstrate a sig-
nificant change in the slope of hospital-onset CDAD trend (P <
.001) during the time of the restricted medication, along with a
significant decrease in the use of antimicrobial agents. Fluoro-
quinolone usage was decreased from 17.6 DDDs per 100 patient
days to 6.0 DDDs per 100 patient days (P < .001).
The antibiotic restriction strategy was also implemented in a
study by Muto et al.17
As part of a comprehensive C difficile
infection control bundle, they restricted the use of high-risk
C difficile causative agents (clindamycin, Ceftriaxone, and
levofloxacin) by requiring prior approval from an IDs physi-
cian or pharmacist. Before the initiation of the infection control
bundle in 2000, the C difficile rate peaked at 7.2 infections per
1000 hospital discharges. Since then the rate has decreased to
3.0 infections in 2006 along with a 54% decrease in the
CDAD-associated antimicrobials.
Antibiotic restriction as part of stewardship may be a useful
tool. The institution selects specific agents that may be contribut-
ing to an outbreak or a change in resistance patterns and requires
approval by specified individuals before the pharmacy can
dispense the medication. This gives each hospital control over
specific antibiotics; however, this can be a difficult process for
hospitals to implement. To minimize delay in patient care, there
must be someone available at all times for medication use review
and approval. This may be difficult for smaller institutions and
may even increase labor costs. Additionally, physicians may
learn what is required for approval and manipulate the system
to utilize the medication (eg, ‘‘yes, I’m concerned about Pseudo-
monas), bypassing the program and its potential benefits.
Hospital Wide Guidelines
Organizations may develop institutional-specific mediation
guidelines for multiple disease states. Guidelines can be tar-
geted for each individual hospital formulary, site of infection,
patient population, and resistance patterns. With time and use,
guidelines may help modify physicians prescribing patterns.
Implementation of guidelines is similar in many ways to
restricting antibiotics; the major difference is that approval is
not required prior to having the medication dispensed. This
approach was taken by Talpaert et al18
in 2006. The goal of
their plan was to implement narrower spectrum antibiotic
guidelines throughout their institution in an effort to decrease
rates of CDAD. Usage of agents regarded as ‘‘high risk’’ for
causing CDAD was dispensed; however, a member of the ASP
team was notified to ensure that the patient was evaluated. When
prescribed medications fell outside of the criteria of the guide-
lines, the pharmacist would intervene and try to optimize patient
care. As a result of these actions, the institution documented a
statistically significant decrease in CDAD associated with the
interventions as well as usage of targeted antimicrobials.
Hospital-wide guidelines were also implemented in a study
by Valiquette et al19
in 2006. In order to help control an epi-
demic of nososcomial C difficile infections in a tertiary care
hospital in Quebec, they implemented a nonrestrictive ASP and
local treatment guidelines, which focused on decreasing the use
of antibiotics most commonly associated with CDAD (cepha-
losporins, ciprofloxacin, clindamycin, and macrolides). Their
508 Journal of Pharmacy Practice 26(5)
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
4. results not only showed a marked decrease in total antibiotic
use by 23% but also showed a decrease in targeted antibiotics
by 54%, their incidence of nosocomial CDAD decreased
by 60% over a 3-year period. Although the implementation
of guidelines requires less resources than restrictions (as
described previously), guidelines require continual reevalua-
tion and maintenance by the stewardship team to ensure they
stay current with the resistance patterns of the hospital and
reflect the consensus of experts in the specific disease area.
Staff Education
One element of stewardship programs, which is underappre-
ciated in many institutions, is education. The IDSA guidelines8
consider education essential for influencing prescribing behavior
in conjunction with other elements as described. Stewardship
team members need to understand the use of antimicrobials and
be well versed in the current medical literature. In turn, these
ASP team members must educate the prescribers of their health
system. Practitioners who understand the underlying issues and
concerns appear to be more willing to modify behavior than
those just being forced to change by policies and regulations.
Education to health care workers can be as varied as the steward-
ship programs themselves. Some institutions find teaching ses-
sions useful, whereas others utilize posters and pocket-card
reminders.17,18,20
Face-to-face discussions may prove to be the
best to collaborate with certain practitioners, or communication
through chart documentation is appropriate for others, whereas
those with computer physician order entry systems (CPOEs)
or EMR may utilize electronic resources to update the prescri-
bers.14,18,21
Regardless of the type, the educational component
of an ASP seems to be beneficial for the long-term modifications
of prescribing patterns. It should be emphasized, however, that
education alone is an inadequate modality for sustained
improvement in antibiotic usage. Rather, it must be combined
with other ASP steps enumerated in this article.
Electronic Medical Record
The use and monitoring of compliance within a health care
system is becoming more feasible, as institutions implement
EMR and CPOE. The use of electronic resources as part of the
ASP contributes significantly to decreases in overuse of antibio-
tics as reported by Cook et al.21
This study reported that when
the EMR was implemented, the stewardship pharmacist was able
to increase the number of charts reviewed, increase clinical
recommendations, and increase the number of recommendations
accepted by 36.6%, 98.1%, and 124%, respectively (P < .0001).
The study also demonstrated that decreased antimicrobial use
resulted in decreased rates of CDAD to 18.7% and hospital-
acquired methicillin-resistant Staphylococcus aureus (MRSA)
fell to 45.2% since the implementation of the EMR. The
electronic systems may allow for more patients to be evaluated,
and interventions made in a shorter length of time, resulting in
better overall care for the patient.
An example of a fully integrated EMR is at Lincoln Medical
Center, a 400 bed inner-city hospital that has over 125 000
emergency department (ED) visits per year, 25,000 admissions
per year, and over 350 000 outpatient clinic visits per year.
CPOE has been available since 2000, and fully EMR was
initiated in 2005. Also, automated dispensing machines were
placed throughout the facility in 2003. This type of technology
allows for changes in prescribing practice such as automatic
stop orders for all medications between 3 and 7 days, imple-
ment treatment protocols within the order entry screen, and
insert appropriate typical doses and dose adjustments based
on the renal function. All notes, consults, clinic notes, ED
notes, medications, laboratory values, imaging, and microbiol-
ogy are online, which allow for faster review of patient charts.
In addition, pharmacists can write an electronic pharmacother-
apy note (intervention documentation) for inpatients that
populate within the daily medical notes section of the EMR.
ASP Implementation
In order to implement an ASP, the stewardship team must
address the specific needs of the individual institution, be built
on available resources, adhere to the limitations and advantages
of each institution, and have both the available staff and the
technological infrastructure.22
Following support from senior
leadership and administration, an ASP model can be accom-
plished by identifying patients receiving inappropriate therapy
and effectively communicating with prescribers. The ASP
model should also be able to recognize hospital-wide prescrib-
ing issues in order to modify current and future prescribing
with education and guideline implementation. An advisable
step before formal development of any program is to retrospec-
tively evaluate the institution and determine where problems
exist, for example, by performing a drug-utilization evaluation
on the most commonly prescribed broad-spectrum antibiotics
to determine appropriateness of use. This aspect can be
especially important when determining the cause of a CDAD
outbreak.
Once institution-specific problems have been identified, it is
necessary to evaluate potential causes of those problems. An
unbiased process evaluation may demonstrate current practices
and policies that may enable physicians to unwittingly contrib-
ute to inappropriate antibiotic use. For example, at University
Medical Center of Southern Nevada (UMCSN) in Las Vegas,
institutional process evaluation found that many antibiotic
treatment courses extended beyond the recommended standard
length.23
Upon further investigation, it was determined that
automatically generated medication renewal forms being
provided to the physicians were greatly contributing to the
excessive antibiotic duration. The UMCSN policy at the time
was to have the pharmacy computer system automatically gen-
erate the forms, and that they be placed in the chart 48 hours
prior to the expiration of any medication order. As a conveni-
ence, the physician could choose to ‘‘renew’’ or ‘‘DC’’ that med-
ication rather than having to write a new order. When audited, it
was found that in many instances, all medications were being
Piacenti and Leuthner 509
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
5. renewed regardless of continued need. Once discovered, the pol-
icy was modified to exclude antimicrobial agents from these
renewals. Currently, the pharmacy computer system generates
a notification for the physician that the antibiotic order is
approaching 10 DOT and will automatically discontinue unless
a new order is written. This policy change has decreased the
average antibiotic length of time from between 16 and 20 days
to an average of 13.3 days.23
Although not specific to CDAD,
decreased inappropriate use of antibiotics by shortening duration
may minimize development of all hospital-associated pathogens.
Inner City ASP Program
Since 2002, Lincoln Medical Center has recognized the impor-
tance of the rational use of antibiotics. Lincoln employs full-
time in-house physicians for all areas of medicine and surgery.
This helps to promote the rational use of antibiotics whereby
hospital-wide prescribing issues can be addressed and dis-
cussed directly with the in-house staff. The ASP began in the
first half of fiscal year 2004. The implemented ASP at Lincoln
incorporates many of the features of the antimicrobial manage-
ment team concept as described and reported by Carling et al in
2003.24
A clinical pharmacist who specializes in ID was hired
to implement this program who is responsible for evaluating
patients prescribed broad-spectrum antibiotics and making
recommendations with the patients physician or with an ID
physician. This study reported a decrease in the incidence of C
difficile from 2.2 cases per 1000 patient-days to 1.4 cases over
2 years. The study also reported an 18% decrease in overall anti-
biotic expenditures over 4 years, where most of the savings were
related to the use of less costly drugs with little reduction in
overall antibiotic usage.
The implemented ASP at Lincoln Medical Center follows
the model of prescription audit with feedback. All broad-
spectrum antibiotics are identified via a daily antibiotic report
and are concurrently monitored for appropriateness. Monitor-
ing only a selected group of antibiotics may result in an
increase in the use of unmonitored antibiotics.4
The antibiotic
report is reviewed daily for appropriate antibiotic selection
based on the dose, indication, antibiotic length of therapy,
empiric therapy, streamlining therapy, unnecessary antibiotics,
and culture and sensitivity. Once antibiotic issues are recog-
nized, an intervention is performed either immediately via tele-
phone or discussed on IDs rounds or on internal medicine
rounds; the intervention is then documented in the medical
record.
Pharmacist rounding daily with the ID team or internal med-
icine teams not only helps to build strong relationships with the
medical team but also allows for real-time discussion on inter-
ventions as well as education. The ID pharmacist should under-
stand specific IDs states and be able to help choose the best
regimen for the patient. Pharmacy presence on the medical
floors greatly improves efficiency and timeliness of antibiotics
administered to the patient by addressing potential issues
immediately.
Outcomes
Since the implementation of the program in FY04, there has
been many antibiotic interventions and prescribing trends
addressed over the years. The various recommendations made
by the stewardship team more than likely lead to decreases in
rates of hospital onset organisms such as C difficile, MRSA,
and Klebsiella. Although there is no specific intervention data
to show, most of the stewardship interventions were to discon-
tinue antibiotic therapy that decreases cost, antibiotic usage,
C difficile rates, and length of therapy. Increasing lengths of
therapy of mostly any antibiotic probably plays a strong role
in increasing C difficile rates, which was reported in a study
by Pepin et al.25
This study showed that increased duration
of therapy of most classes of antibiotics correlated with an
increased adjusted hazard ratio of developing C difficile. Fluor-
oquinolones at 4 to 6 DOT and at 7 days or greater of therapy
had the highest adjusted hazard ratios for developing C difficile
compared to all other antibiotics studied.
Lincoln Medical Center showed a 60% decrease in overall
antibiotic spending, see Figure 1. The majority of the decreased
spending is related to recommendations based on the
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
1,800,000
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Fiscal Year
Spending
Figure 1. Anti-infective fiscal year spending.
0
2
4
6
8
10
12
14
16
18
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Cost/ptday
Fiscal Year
Figure 2. Total antibiotic cost per patient day. Patient day data
include all patients admitted to medicine, intensive care unit, surgery,
pediatrics, and gynecology.
510 Journal of Pharmacy Practice 26(5)
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
6. discontinuing therapy and the use of narrower, less costly antibio-
tics. Lincoln’s patient admit day per year decreased from 94,427
in FY03 to 81,441 in FY11, a 13.7% decrease, while admissions
tomedicineincreasedfrom10,195inFY03to13,165inFY11and
antibiotic cost/pt day decreased 35% (Figure 2). In addition,
patient’s average length of stay decreased from 4.77 days in
FY03 to 3.55 days in FY11, a 26% decrease.
Antibiotic cost/Usage data
Figures 3 and 4 show the most common antibiotics prescribed
with the number of completed doses given to patients. The first
drug-specific challenge noted was the unrestricted use of
imipenem in FY04. This antibiotic was heavily monitored at the
onset of the program, and the number of doses used from FY03-
04 decreased by 2000 doses. In FY09-10, the use of imipenem
increased due to the increase in suspected extended-spectrum
beta-lactamase (ESBL) Klebsiella infections, although the actual
rates of ESBL Klebsiella infections decreased from 9.8% in
2006 to 6.1% in 2012. Vancomycin usage remained constant
from FY03-06, but in the following years, its use increased due
to the increasing rates of CA-MRSA skin and soft tissue abscess
while MRSA bacteremias decreased from 13.3% (67 of 501) in
2004 to 3.2% (38 of 1188) in 2010, and hospital-acquired MRSA
rates decreased from 28% (55 of 196) in 2004 to 4.7% (27
of 577) in 2010. No other agents for MRSA are used in signifi-
cant amounts, because Lincoln has established strict MRSA
guidelines.
Another antibiotic-specific challenge encountered was the
use of ticarcillin/clavulanate. Since its use peaked in FY04,
tighter control was implemented, and its use decreased signif-
icantly between FY05 and FY06. In FY06, a new health care-
associated pneumonia (HCAP) guideline was published. From
2006 to 2009, the use of piperacillin/tazobactam increased
substantially due to the new terminology for patients with pneu-
monia. In FY09, the stewardship team recommended cefepime
for its HCAP patients rather than piperacillin/tazobactam. This
switch was incorporated into the hospital’s pneumonia guide-
line, which represented a significant cost savings (US$15 per
day for cefepime compared to US$60 per day for piperacillin/
tazobactam). In addition to cost savings, this switch resulted in
a decrease in empiric anaerobic coverage of patients who for the
most part do not need broad anaerobic coverage. This switch
may have played a role in decreasing C difficile rates. The new
HCAP guideline also resulted in an increased use of ciprofloxa-
cin for double coverage in combination with piperacillin/tazo-
bactam. The stewardship team saw a rapid increase in the
number of doses of ciprofloxacin from 2000 doses in 2006 to
11 000 doses in 2008. The ASP team then recommended against
the use of double coverage in 2009, and the 2010 ciprofloxacin
doses decreased to 3000.
Other cost saving/appropriate usage changes included the
appropriate dosing of ceftriaxone and ampicillin/sulbactam.
In FY04, most prescribers were prescribing a 2-g dose of
ceftriaxone instead of the 1 g dose (Figure 5). In FY05, a recom-
mendation was implemented to use ceftriaxone 1 g for most
indications including pneumonia. Similarly, in FY05, a recom-
mendation was implemented to use ampicillin/sulbactam 1.5 g
for most indications rather than the 3.1 g. Since these recommen-
dations were implemented, there was an increase in the usage of
the lower dose antibiotic and a decrease in the usage of the
higher doses. In both of these cases, the lower dose is about half
the cost of the higher doses. Most infections can be treated with
the lower doses without compromising patient care except for in
patients diagnosed with meningitis or osteomyelitis, which
require the higher doses for penetration purposes. With the
increase in ceftriaxone use since 2005 as the primary agent
for community-acquired pneumonia, there was a substantial
Ceftriaxone 2g
Ceftriaxone 1g
Amp/sulb3.1g
Amp/sulb 1.5g
0
2000
4000
6000
8000
10000
12000
#ofdoses
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Fiscal Year
Figure 5. Ceftriaxone and ampicillin/sulbactam usage.
Ampicillin/sulb
Ceftriaxone
Vancomycin
Gatifloxacin
Moxifloxacin
0
2000
4000
6000
8000
10000
12000
14000
16000
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Fiscal Year
#ofdoses
Figure 4. Antibiotic usage per fiscal year. In FY 2006, Lincoln switched
from gatifloxacin to moxifloxacin as the flouroquinlone of choice.
Imipenem
Piperacillin/tazo
Ticarcillin/clav Ciprofloxacin
Cefepime
0
5000
10000
15000
20000
25000
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Fiscal Year
#ofdoses
Figure 3. Antibiotic usage per fiscal year.
Piacenti and Leuthner 511
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
7. decrease in the respiratory fluoroquinolone use from 9980 doses
in 2005 to 1152 doses in 2012 which may also contribute to
lower C difficile rates.
Microbiological Data
Although CDAD is one of the most common hospital-onset
infections nationally, Lincoln Medical Center seems to be con-
sistently below the national average rates. The average rate at
Lincoln over the last 7 years is 2.6 cases/10,000 patient days
(Figure 6) compared to the national rate of 7.4 cases per
10,000 patient days.1
In fiscal years 2007 and 2008, Lincoln saw
a dramatic increase in the use of ciprofloxacin (Figure 3). There
may have been an association between this increase in ciproflox-
acin usage with the increase in CDAD rates, 3.6 cases/10,000
patient days in 2007 and 3.9 in 2008. Once this issue was
addressed and guidelines were implemented, in FY2009, cipro-
floxacin usage began to decline from its peak, and the rates of
CDAD decreased to 2.2. Usage of ceftriaxone has increased at
least 50% from 2005 to 2012, but CDAD rates did not change
in parallel.
Infection Control Departments
Although the described elements of stewardship programs
appear straightforward, there must be a collaborative effort of
multiple disciplines. The department of Infection Control and
Prevention must be an intricate part of the stewardship program
primarily in the role of prevention. An institution can put
together pages of regulations and restrictions to control pre-
scribing patterns and overuse of medications, but without a
strong infection control program, the organisms can and will
continue to spread and colonize the establishment. With an
organism such as C difficile, prevention of spread throughout
the institution must always be a priority for day-to-day opera-
tions and to control outbreak situations. Several institutions
have published experiences in regard to control of CDAD out-
breaks utilizing strict infection control practices.17,26
Each of
these reports have multiple processes in common including iso-
lation of patients, appropriate hand hygiene with soap and
water, and enhanced environmental cleaning with appropriate
compounds (ie, bleach). Both the studies demonstrated a
decrease in the rates of CDAD, but neither could specifically
state the improvements were due to infection control activities
alone. Combined with the enhanced infection control preven-
tion measures, ASPs may have also contributed to the overall
success of decreasing CDAD rates.
Conclusions
Antimicrobial stewardship can be a useful tool for an institution
in its fight against CDAD. Although many individuals think
‘‘stewardship’’ is a fancy way of saying ‘‘controlling’’ antibio-
tics, in reality it is a broad phrase for all activities institutions
perform, develop, and implement with the aim of decreasing
inappropriate antibiotic utilization and preventing or controlling
hospital-associated diseases such as CDAD. There are as many
types of stewardship programs as there are hospitals and health
care organizations. Studies have demonstrated that ASPs work in
a variety of settings. Studies have also demonstrated that no
single activity will optimize poor prescribing habits, improve
susceptibilities, or control for the development of CDAD in a
health care system. Improved prescribing, monitoring, and anal-
ysis of data require a concerted effort by a multidisciplinary team
to investigate, evaluate, and develop a continually evolving
action plan that will make antimicrobial stewardship a successful
instrument toward the elimination of CDAD.
Stewardship programs do not always demonstrate positive
results as they must show and identify unwanted results in
order to make changes in prescribing practices. Antibiotics will
always be required in sick patients within any institution, so
cost savings and decrease in usage will have its limits. With the
continued efforts of an antimicrobial stewardship team, any
changes in prescribing patterns should be monitored and
discussed with pharmacy, leadership, and physicians. Change
takes time but in the long run, documentation, monitoring, edu-
cation, guidelines, and close follow-up of the most appropriate
use of antibiotics will demonstrate the most efficient way to
prescribe antibiotics.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
References
1. McDonald LC, Lessa F, Sievert D, et al. Vital signs: preventing
Clostridium difficile infections. MMWR Morb Mortal Wkly Rep.
2012;61(9):157-162.
2. Colemen RW, Rodondi LC, Kaubisch S, et al. Cost-effectiveness
of prospective and continuous parenteral antibiotic control:
experience at the Palo Alto Veterans Affairs Medical Center from
1987 to 1989. Am J Med. 1991;90(4):439-444.
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Cases/10,000ptdays
2004 2005 2006 2007 2008 2009 2010 2011 2012
Fiscal Year
Figure 6. Hospital-associated Clostridium difficile rates.
512 Journal of Pharmacy Practice 26(5)
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from
8. 3. Fraser GL, Stogsdill P, Dickens JD, et al. Antibiotic optimization.
Arch Intern Med. 1997;157(15):1689-1694.
4. Kaki R, Elligsen M, Walker S, et al. Impact of antimicrobial
stewardship in critical care: a systemic review. J Antimicrob Che-
mother. 2011;66(6):1223-1230.
5. Linares LA, Thornton DJ, Strymish J, et al. Electronic memoran-
dum decreases unnecessary antimicrobial use for asymptomatic
bacteriuria and culture-negative pyuria. Infect Control Hosp
Epidemiol. 2011;32(7):644-648.
6. HeckerMT,AronDC,PatelNP,etal.Unnecessaryuseofantimicro-
bials in hospitalized patients. Arch intern Med. 2003;163(8):
972-978.
7. Owens RC Jr, , Donskey CJ, Gaynes RP, et al. Antimicrobial-
associated risk factors for Clostridium difficile infection. Clin
Infect Dis. 2008;46(suppl 1):S19-S31.
8. DellitTH,OwensRC,McGowanJE Jr,etal.Infectiousdiseasesoci-
etyofAmericaandthesocietyforhealthcareepidemiologyofAmer-
ica guidelines for developing an institutional program to enhance
antimicrobial stewardship. Clin Inf Dis. 2007;44(2):159-177.
9. Septimus EJ, Owens RC. Need and potential of antimicrobial
stewardship in community hospitals. Clin Infect Dis. 2011;
53(suppl 1):S8-S14.
10. Abbo L, Sinkowitz-Cochran R, Smith L, et al. Faculty and resi-
dent physicians’ attitudes, perceptions, and knowledge about anti-
microbial use and resistance. Infect Control Hosp Epidemiol.
2011;32(7):714-718.
11. Srinivasan A, Song X, Richards A, et al. A survey of knowledge,
attitudes, and beliefs of house staff physicians from various
specialties concerning antimicrobial use and resistance. Arch
Intern Med. 2004;164(13):1451-1456.
12. Giblin TB, Sinkowitz-Cochran RL, Harris PL, et al. Clinicians’
perceptions of the problem of antimicrobial resistance in health
care facilities. Arch Intern Med. 2004;164(15):1662-1668.
13. Aldeyab MA, Kearney MP, Scott MG, et al. An evaluation of the
impact of antibiotic stewardship on reducing the use of high-risk
antibiotics and its effect on the incidence of Clostridium difficile
infection in hospital settings. J Antimicrob Chemother. 2012;
67(12):2988-2996.
14. Elligsen M, Walker SA, Pinto R, et al. Audit and feedback to
reduce broad-spectrum antibiotic use among intensive care unit
patients: a controlled interrupted time series analysis. Infect
Control Hosp Epidemiol. 2012;33(4):354-361.
15. Yam P, Fales D, Jemison J, et al. Implementation of an antimicro-
bial stewardship program in a rural hospital. Am J Health Syst
Pharm. 2012;69(13):1142-1148.
16. Kallen AJ, Thompson A, Ristaino P, et al. Complete restriction of
fluoroquinolone use to control an outbreak of Clostridium difficile
infection at a community hospital. Infect control Hosp Epidemiol.
2009;30(3):264-272.
17. Muto CA, Blank MK, Marsh JW, et al. Control of an outbreak of
infection with the hypervirulent Clostridium difficile BI strain in a
university hospital using a comprehensive ‘‘bundle’’ approach.
Clin Infect Dis. 2007;45(10):1266-1273.
18. Talpaert MJ, Rao GG, Cooper BS, et al. Impact of guidelines
and enhanced antibiotic stewardship on reducing broad-
spectrum antibiotic usage and its effect on incidence of Clos-
tridium difficile infection. J Antimicrob Chemother. 2011;
66(9):2168-2174.
19. Valiquette L, Cossette B, Garant MP, et al. Impact of a reduc-
tion in the use of high-risk antibiotics on the course of an epi-
demic of Clostridium difficile-associated disease caused by the
hypervirulent NAP1/027 strain. Clin Infect Dis. 2007;45(suppl
2):S112-S121.
20. Fowler A, Webber A, Cooper BS, et al. Successful use of feed-
back to improve antibiotic prescribing and reduce Clostridium dif-
ficile infection: a controlled interrupted time series. J Antimicrob
Chemother. 2007;59(5):990-995.
21. Cook PP, Rizzo S, Gooch M, et al. Sustained reduction in antimi-
crobial use and decrease in methicillin-resistant Staphylococcus
aureus and Clostridium difficile infections following implementa-
tion of an electronic medical record at a tertiary-care teaching
hospital. J Antimicrob Chemother. 2011;66(1):205-209.
22. Ohl CA, Dodds Ashley ES. Antimicrobial stewardship programs
in community hospitals: the evidence base and case studies. Clin
Infect Dis. 2011;52(suppl 1):S23-S28.
23. Leuthner KD, Greenberg A. An antimicrobial stewardship
program without antibiotic restrictions, abstr K-384. In: Abstr 51st
Intersci Conf Antimicrob. Agents Chemother; 2011; Chicago, IL.
24. Carling P, Fung T, Killion A, et al. Favorable impact of a
multidisciplinary antibiotic management program conducted
during 7 years. Infect Control Hosp Epidemiol. 2003;24(9):
699-706.
25. Pepin J, Saheb N, Coulombe MA, et al. Emergence of fluoroqui-
nolones as the predominant risk factor for Clostridium difficile-
associated diarrhea: a cohort study during an epidemic in Quebec.
Clin Infect Dis. 2005;41(9):1254-1260.
26. Weiss K, Boisvert A, Chagnon M, et al. Multipronged interven-
tion strategy to control an outbreak of Clostridium difficile infec-
tion (CDI) and its impact on the rates of CDI from 2002 to 2007.
Infect Control Hosp Epidemiol. 2009;30(2):156-162.
Piacenti and Leuthner 513
at Universidad Nacional Aut Mexic on February 11, 2016jpp.sagepub.comDownloaded from