Antimicrobial Stewardship at MD Anderson Cancer Center
Primary Author - Frank Tverdek, PharmD, BCPS
secondary author, Dr. Roy Chemaly
Patient Safety
Overview:
Antimicrobial stewardship is a process by which antimicrobials are managed on a systems level
with the intention to decrease unnecessary utilization of antimicrobials, which is thought to lead
to preservation of antimicrobial efficacy and prevention of further development of antimicrobial
resistance. Antimicrobial resistance is a driving determinant in more costly and toxic
antimicrobial use and as such, is a detrimental entity with clinical and financial implications. MD
Anderson Goals 2010-2015 include the delivery of “Safe, Efficient Patient Care” as well as
“Stewardship of Resources.” Antimicrobial stewardship specifically manages antimicrobials as
a critical and finite resource in the effort to manage administration of antimicrobials in an
manner that maximizes efficacy while minimizing harm.
Recommendations and guidelines for antimicrobial stewardship in special populations, such as
patients with cancer are lacking or unclear. Resistance rates to broad spectrum antimicrobials
and the incidence of multi-drug resistant organisms (MDROs) had been on the rise within the
institution. Patients infected with these MDROs have increased morbidity and mortality as well
as require additional resource expenditure. As such, this process is pioneering the extension of
antimicrobial stewardship to the immunocompromised patient population. Infectious Diseases,
Infection Control, Pharmacy, and Clinical Effectiveness were involved in the design and
implementation of the process.
We relate our experience with a passive audit and feedback type approach aimed at reducing
unnecessary utilization of key antimicrobials in a comprehensive cancer center.
Aim Statement (max points 150):
This antimicrobial stewardship program aims to stabilize or decrease the trend of antimicrobial
utilization for the targeted antimicrobials from year to year.
Measures of Success:
The direct impact of the process is described by the trending of antimicrobial utilization over
time of the targeted antimicrobials. Secondarily, changes in antimicrobial cost were tracked
based on the changes in utilization over time.
Use of Quality Tools (max points 250):
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Process flowcharts were utilized to describe the process and uncover areas
hindering compliance
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Histogram analysis of data review of 8 weeks of patient specific data was used
as a snapshot to characterize the utilization of the antimicrobials and identify
focus areas of intervention
Control charts used to track utilization of targeted antimicrobials
Interventions (max points 150 includes points for innovation):
We targeted the following antibiotics in our intervention: meropenem, vancomycin, linezolid,
daptomycin and tigecycline based on an initial assessment of utilization and resistance data. It
was determined that a majority of the targeted antimicrobial use occurred in Leukemia, Stem
Cell Transplant, Lymphoma/Myeloma, and ICU patients. Criteria for use for each drug was
designed by a multi-disciplinary team of Hematology/oncology Critical care and Infectious
Diseases physicians and pharmacists. These criteria consisted of defined indications for which
the antimicrobial’s use was deemed appropriate. This criteria for appropriate usage was
incorporated into the institution’s neutropenic fever guideline as well as the pneumonia and
sepsis institutional algorithms- which are disseminated via the institutions internet site. An
electronic daily list was created of the targeted drugs on the 5th day of therapy for patients being
cared for by the targeted teams mentioned prior. Initially, an email was sent out every morning
to all attending physicians with the list of patients on the 5th day of therapy of a targeted
antimicrobial. The physicians were then instructed to discontinue the drug or fill out an orderset
in the electronic medical record documenting an indication for continued use by choosing from
the predetermined list of approved indications.
An interim analysis schedule of every three months was utilized. Initial analysis showed a low
compliance rate of ~30% (composite endpoint of discontinuation of drug or indication form filled
out.) Therefore, the antimicrobial stewardship team petitioned the end users for feedback
regarding the process. The resultant action was a more descriptive list of antimicrobial use
criteria, as well as a modified process. An individualized email notification was sent to each
inpatient attending physician with details about only their specific patients. In addition, patients
in the ICU were also emailed to the ICU pharmacist. The physician/pharmacist was asked to
again discontinue the antimicrobial or document the rationale for continuation via the electronic
medical record. The details of the process and indications for appropriate use of each drug
were disseminated via education to the affected departments during faculty meetings as well as
via email notifications. Each email notification also contained instructions regarding compliance
with the policy as well as reference to the institutional policy.
The antimicrobial stewardship team encouraged feedback regarding the process by email as
well as in follow-up discussions during departmental faculty meetings. One issue that was
raised on numerous occasions was in regard to the role of Infectious Diseases consult and their
partial responsibility for antimicrobial choice in consulted patients. As a result of another
scheduled interim analysis, an ad-hoc committee was formed of 7 pharmacists which did a chart
review of patients on targeted antimicrobials over a 6 week period to elucidate the role of
infectious diseases in the management of the targeted antimicrobials. As a result of the
findings, and as infectious diseases is in a position to influence prescribing by being a role
model for antimicrobial use, a pilot email notification system was designed to notify the
infectious diseases consultants of their patients which were on the 5th day of the targeted drugs.
Using a novel email response system, the infectious diseases physicians began to respond to
notifications and their compliance with the process was tracked.
While there exists many successful antimicrobial stewardship programs this particular program
is innovative in that we provided stewardship to a patient population often excluded from these
type of interventions due to the tenuous nature of their immune system. Many programs restrict
antimicrobials up front, however, given the fear of rapid deterioration of these patients should
they not get appropriate antimicrobials we opted for an intervention later in the course of
therapy. Our results confirm that reduction in unnecessary antimicrobials can be performed
without strict restriction practices.
Results (max points 250):
Compliance in the most recent interim analysis:
Infectious Diseases compliance during the pilot phase was 92%.
Monthly data on antibiotic usage and costs were obtained for the pre-intervention (Oct. 2007 –
Oct. 2010) and post-intervention (Nov. 2010 – Jun. 2012) periods. The segmented regression
analysis of interrupted time series was used to assess the significance of changes of antibiotic
use and costs. (Utilizing “QI Analayst” software)
Definition:
DDD: defined daily dose per WHO(World health Organization) definition for each drug
WAC: Wholesale acquisition cost.
Revenue Enhancement /Cost Avoidance / Generalizability (max points
200):
In 2011 the program was associated with a cost savings for 4 out of the 5 drugs targeted; net
cost savings from 2010 to 2011 was $1.25 million. This was validated by evaluating the
wholesale acquisition per year as compared to the actual purchase history of the targeted
antimicrobials. It is important to note that meropenem cost per unit decreased during 2010 and
is partially responsible for decreases in cost. Conversely, daptomycin unit price increased
yielding a net increase in cost despite a slight over all decrease in utilization. The substantial
cost savings associated with the program has prompted an effort to expand it to areas outside
of the departments currently involved; recently the program was extended to include general
internal medicine and gastro-intestinal medical oncology.
Conclusions and Next Steps:
This project was successful in increasing compliance with the process in a step-wise manner.
The success was due in part to the critical feedback given by the end users as well as the
scheduled interim analyses that occurred as a result of such feedback. Objective verification of
said problems through chart review when needed, as well as the ability to adapt the program as
each problem was identified were critical.
Regarding the primary aim, the program was associated with a positive impact on the utilization
of targeted antimicrobials. The program was associated with a decreased mean duration of
therapy for the targeted antimicrobials and the overall usage (DDD/1000 pt days). Additionally,
this decreased utilization contributed to a cost savings.
Moving forward, the plan is to extend the novel email notification/response system beyond
infectious diseases to all targeted physicians. In addition, the program itself will be expanded to
include patient services in the hospital that are not currently receiving notification. Furthermore,
active follow-up on Days 6 and days 14 of therapy will be conducted by the antimicrobial
stewardship team to promote compliance with the process. Consideration is also being given to
the inclusion of other targeted drugs.
While antimicrobial utilization and cost avoidance are key measures of success, ultimately the
impact on antimicrobial resistance is desired. Antimicrobial resistance on a hospital wide scale
may take years to change, however, given that the program is going on 2 years, there will soon
be opportunity to address these endpoints.