EVALUATION OF AN ANTIMICROBIAL CULTURE REVIEW AND FOLLOW UP
PROGRAM IN THE EMERGENCY DEPARTMENT
by
Kimberly R. Miller
BS in Biology Pre Health Professions, Shippensburg University, 2008
PharmD, University of Pittsburgh, 2012
Submitted to the Graduate Faculty of
Multidisciplinary Program
Graduate School of Public Health in partial fulfillment
of the requirements for the degree of
Master of Public Health
University of Pittsburgh
2013 1
UNIVERSITY OF PITTSBURGH
GRADUATE SCHOOL OF PUBLIC HEALTH
This essay is submitted
by
Kimberly R. Miller
on
December 2, 2013
and approved by
Essay Advisor:
David Finegold, MD
Multidisciplinary MPH Program Director
University of Pittsburgh
Graduate School of Public Health
Essay Reader:
Nicholas Castle, PhD, MHA
Health Policy and Management
University of Pittsburgh
Graduate School of Public Health
______________________________________
______________________________________
ii
Copyright © by Kimberly R. Miller
2013
iii
David Finegold, MD
EVALUATION OF AN ANTIMICROBIAL CULTURE REVIEW AND FOLLOW UP
PROGRAM IN THE EMERGENCY DEPARTMENT
Kimberly R. Miller, MPH
University of Pittsburgh, 2013
ABSTRACT
Despite rising concern about antimicrobial resistance, there is limited information on the
appropriateness of antimicrobial prescriptions in patients who are discharged from the
emergency department (ED). Lack of antimicrobial stewardship and appropriate follow up is a
public health concern due to inappropriate prescribing of antibiotics resulting in microbial
resistance and inadequately treated patients potentially spreading infectious diseases.
Our
objectives were to describe the prevalence of inappropriate antimicrobial follow up prescriptions,
based on Infectious Diseases Society of America (IDSA) or clinical guidelines, in discharged
adult ED patients.
These patients required follow up due to inadequate antimicrobial
prescription and identify clinical factors associated with such prescription.
iv
TABLE OF CONTENTS
PREFACE ................................................................................................................................... viii
1.0
INTRODUCTION ........................................................................................................ 1
2.0
METHODS.................................................................................................................... 5
3.0
RESULTS ..................................................................................................................... 7
4.0
CONCLUSION........................................................................................................... 10
APPENDIX A: DRUG INTERACTIONS ................................................................................ 12
APPENDIX B: ANTIOBIOTIC RENAL AND LIVER FUNCTION ADJUSTMENT ....... 15
APPENDIX C: STUDY DEFINITIONS ................................................................................. 158
BIBLIOGRAPHY ....................................................................................................................... 19
v
LIST OF TABLES
Table 1: Patient Characteristics Associated with Inappropriate Follow up .................................... 9
Table 2: Renal Adjustment (Micromedex-Version 1.39) ............................................................. 15
Table 3: Liver Adjustment (Micromedex-Version 1.39) .............................................................. 17
vi
LIST OF FIGURES
Figure 1. Appropriate Patient Follow up Based on Levels ............................................................. 8
vii
PREFACE
I would like to acknowledge Alyssa Tomsey, DO, Gajanan G. Hegde, PhD, Jennifer Shang, PhD,
John O’Neill, MD, Arvind Venkat, MD, and Molly McGraw, PharmD, whose assistance and
encouragement made this research possible.
viii
1.0
INTRODUCTION
With an increasing prevalence of multi-drug resistant organisms in both the hospital and
community setting, appropriate antibiotic treatment and follow up is becoming increasingly important.
This rise in multi-drug resistant organisms have been associated with increased mortality, morbidity, and
costs to both the patient and health care systems.1,2 According to the Infectious Disease Society of
America (IDSA) antimicrobial stewardship is defined as the coordinated interventions to measure and
improve appropriate use of antimicrobial medications through the selection of optimal drug regimens,
dose, duration, and route of therapy. This process includes achieving optimal clinical outcomes, while
minimizing costs, adverse events, toxicities, and limiting the development of microbial resistance. While
many health care systems have developed antimicrobial stewardship programs for patients that are
admitted to the hospital, little data and evaluation exist on current practices of antimicrobial stewardship
activities, including culture review and follow up with patients discharged from the emergency
department (ED).
Delays in patient treatment with appropriate antibiotics can lead to an increase in morbidity and
mortality in patients and an increase in possible secondary infections. While this has not been well
documented in patients that have been discharged from the emergency department evidence from the
inpatient setting supports that these delays are associated with negative patient outcomes such as disease
severity and development of a secondary infection.3-5
Appropriate dosing of an antibiotic can be almost as important as selecting the appropriate
antibiotic regimen. Dosing of antibiotic medications can be dependent on many factors including, but not
limited to, the type of infection, the severity of infection, and patient specific factors. Patient specific
1
factors can include renal function, liver function, concomitant medications, or other comorbidities.
Patient’s allergies should also be taken into consideration when prescribing antibiotics and when
overlooked can lead to secondary health issues, treatment failure, or even death.6-8 Preventable adverse
drug events are still common within the health care system and while the estimates range greatly, have
been estimated to be near 1.5 million a year in the United States. 6 It is well known that these medication
errors can lead to increased length of stay in the hospital, unnecessary tests and treatment, and potentially
death.7,8Common preventable adverse drug events consist of incorrect dose and prescribing a medication
to a patient with a known allergy.6
In high volume and fast-pace situations, such as an Emergency Department, follow up with
patients can be difficult. Many times these patients are transferred to other facilities or are discharged
home before culture results are available. Follow up with these patients to ensure that they received
appropriate antimicrobial therapy involves a complex system where patients have to be identified and
then followed until their culture is available for review. Often times this culture review process can be
difficult for Emergency Department physician and nursing staff to perform as it can impede daily
workflow leading to multiple daily interruptions throughout the day. Pharmacists can play a vital role in
a culture review and follow up process as they are equipped with the knowledge and expertise of
appropriate antimicrobial selection and dosing and drug interactions.
Several institutions have
implemented a pharmacist-managed culture review program in the Emergency Department setting but
data is limited with regard to its impact on patient outcomes.
One retrospective study comparing
physician-managed culture follow up program to a pharmacist-managed program showed that the total
number of antibiotic adjustments was similar between groups (12% vs. 15%). However this study did
display a decrease in the rate of unplanned readmissions for the same chief complaint within 96 hours in
the pharmacist-managed culture follow up group compared to the physician-managed program (19% vs.
7%) (p<0.001).9 Possible reasons for unplanned readmission included antibiotic treatment failure,
noncompliance due to cost, noncompliance not related to cost, allergy to prescribed medication, or
adverse drug reaction.9This study supports the evaluation of Emergency Department culture review and
2
follow up programs for possible areas of improvement, including appropriate antibiotic selection and
avoidance of potential adverse drug events.
The current culture review and follow up process implemented in the Emergency Department at
Allegheny General Hospital is primarily managed by registered nurses. The nurses review all patient
charts from the previous day. Using these charts, the nurses note which patients had a microbiology
culture obtained in the emergency department and will require a culture review and possible follow up.
Using the current computer system, lists are created of these patients, noting the type of culture that is
pending results. Once the culture results are available, the nurse compares the culture sensitivities to the
antimicrobial regimen prescribed upon discharge from the emergency department or in cases where no
antibiotic is prescribed, notes the presence or absence of an organism. The nurse then determines if
further follow up is required on each microbial culture depending on the initial antimicrobial given to the
patient, the presence of an organism, and sensitivities of the organism. If it is determined that further
follow up with the patient is not required, the patient is removed from the computer list. If follow up with
the patient is required, the nurse consults with the emergency medicine physician on staff in the
department. The nurse approaches the physician with culture results, sensitivities, and suggestions for
appropriate antimicrobial treatment. The physician then decides the appropriate antimicrobial therapy
and the nurse follows up with the patient. This follow up includes communication with the patient and
calling in a new prescription.
The rationale of this research project is to determine whether there are opportunities for
improvement on the existing antimicrobial culture review and follow up program in the emergency
department with regard to antibiotic selection, dosing, duration, and potential for adverse drug reactions
related to drug-disease and drug-drug interactions. The possible benefits of this program could include a
more timely culture review and patient follow up process, an increase in appropriate selection and dosing
of antimicrobial therapy, a decrease in antibiotic resistance emergence, a decrease in the length of stay of
patients who are transferred to another health care facility, a decrease in health care system resource
utilization and a decrease in unplanned Emergency Department readmissions within 96 hours for the same
3
chief complaint. This research has the potential to support the implementation of a pharmacist-managed
antimicrobial culture review program.
4
2.0
METHODS
A retrospective, observational cohort analysis of discharged adult ED visits with antimicrobial
cultures at a single, tertiary care center (census: 50,000) (5/1-10/31/12) was performed. Microbial cultures
were identified through the electronic health record (Sunrise) as being negative or positive and requiring
follow up.
Two independent abstractors (An emergency department physician and a pharmacist)
determined the prevalence of visits with inadequate discharge antimicrobial prescription based either on
organism susceptibility result or lack of prescription requiring patient call back for a positive culture.
Paper charts were reviewed to determine whether appropriate follow up was performed on patients who
did not have initial appropriate coverage. Inclusion criteria included patients who presented to the
Allegheny General Hospital (AGH) Emergency Department, had a microbiology culture taken and were
discharged to home.
Patients were included if they were diagnosed with an infection including:
community acquired pneumonia, Streptococcal pharyngitis, bacterial rhinosinusitis, uncomplicated
cystitis and pyelonephritis, urinary tract infection, infectious diarrhea, sexually transmitted disease (STD),
diabetic foot, or skin and soft tissue infection. Patients were excluded if they were admitted to AGH,
were less than 18 years of age, were pregnant, or were a current prisoner.
Information from visits were independently abstracted including patient age, sex and race,
presence of past medical history of end-stage renal disease, chronic renal insufficiency, liver disease,
recent antibiotic use (<30days from presentation), recent hospitalization (<30 days from presentation) or
diabetes, documentation of home medications and allergies, type of culture and whether antimicrobial
prescription was inappropriate (Infectious Disease Society of America (IDSA) Levels: 1. correct selection
of antimicrobial agent based on culture result, 2. appropriate antimicrobial regimen (selection, dose and
5
duration) based on diagnosis and IDSA guidelines, Clinical Levels: 3. antimicrobial regimen prescribed
has a low potential for adverse drug events related to drug-drug interactions with concomitant
medications (See Appendix 1), 4. appropriate antimicrobial medication dosage based on patient’s renal or
liver function (See Appendix 2) and 5. appropriate choice based on patient allergy history). See Appendix
3 for full study and level definitions. The average time to patient follow up attempt was calculated using
the time the patient was admitted in the ED recorded in the Sunrise computer system and the time to first
patient contact attempt as documented by the health care professional in the patient record.
Descriptive Statistics were used for overall appropriate follow up and to describe the type of
inappropriate follow up when applicable. Data was analyzed using multivariable logistic regression to
determine if age, sex, race, presence of any included past medical history or having more than one
positive culture was associated with increased odds of inappropriate antimicrobial prescription at any
level, reported as odds ratios (OR) and 95CI.
6
3.0
RESULTS
Adult ED patients had 3208 cultures during the six month study period from May 1, 2012 to
October 31, 2012. 411 visits had positive cultures in discharged patients. 73 of these visits (17.8% 95CI
(14.1-21.5%)) (patient characteristics: mean age 39.8, 18% male, 41% Black/Other Minority, 1% endstage renal disease, 4% chronic renal insufficiency, 4% recent antibiotic prescription, 3% recent
hospitalization, 14% diabetic, 0% liver disease) had inadequate initial antimicrobial prescription for 100
positive cultures (50% urine, 32% STD, 5% respiratory, 5% throat, 5% wound, 3% blood). 34 of these 73
visits had at least one incidence (14 Level 1, 20 Level 2, 1 Level 3, 4 Level 4) of inappropriate
antimicrobial prescription follow up (46.6% 95CI (35.1-58.0%))(Figure 1).
7
Figure 1. Appropriate Patient Follow up Based on Levels
The average time to first patient follow up attempt was 57 hours and 57 minutes (Range 15:51152:21 (Hours: Minutes)). The presence of any included past medical history characteristic alone was
significantly associated with inappropriate prescription (OR 8.95 95CI (1.56-51.25)). Age, gender, race,
and type of culture had no relationship with inappropriate follow up (Table 1).
8
Table 1: Patient Characteristics Associated with Inappropriate Follow up
Characteristics
Standard
Error
Significance
(p)
95% Confidence Interval
Lower
Upper
Age
0.008
0.655
0.982
1.011
Male
0.818
0.27
0.497
12.167
Race
0.492
0.792
0.335
2.302
Type of Microbial Culture
0.562
0.082
0.125
1.132
Presence of end-stage renal
disease, chronic renal
insufficiency, diabetes, or
liver disease
0.89
0.014
1.564
51.254
9
4.0
CONCLUSION
In this study, a preponderance of discharged adult ED visits requiring follow up for inadequate
antimicrobial prescription fell into IDSA/clinical categories for inappropriate antimicrobial prescription.
Potential reasons for the large amount of inappropriate follow up include lack of knowledge of
appropriate antimicrobial regimens and associated adjustment based on patient characteristics.
Additionally, the nurses who perform follow up have a significant workload that includes follow up on all
tests and procedures that are performed in the ED, along with significant patient care duties. These
patient characteristics have the potential to be overlooked under these conditions.
Past medical history characteristics alone were significantly associated with inappropriate
antimicrobial follow up. Other factors including age, gender, race, and type of microbial culture had no
significant association with inappropriate antimicrobial follow up. Patients who have a significant past
medication history may require additional adjustment to antimicrobial regimens. These patient factors
must be determined through a review of the patient chart and can be overlooked.
Health care
professionals who are not familiar with antimicrobial dosing based on these patient specific factors may
inappropriately prescribe these medications.
Limitations of the study included a retrospective study design and limited written documentation
of follow up action.
While a significant portion of the patient’s medical record can be found
electronically in the Sunrise system, approximately half the emergency department records are in paper
form.
The follow up portion of the patient’s health record is solely paper.
While a standard
documentation sheet is used among all quality assurance nurses to perform follow up, there is no standard
way in filling the information on the form. It is unclear if the documentation in this follow up is a
10
representation of the entire follow up process or if the documentation only includes what medication was
being prescribed and if the patient was reached.
Lack of antimicrobial stewardship and appropriate follow up is a public health concern due to
inappropriate prescribing of antibiotics resulting in microbial resistance and inadequately treated patients
potentially spreading infectious diseases. Patients that are prescribed antibiotics that are not appropriate
based on disease, dose, or duration according to IDSA guidelines, have a higher potential to develop a
resistant organism.3-5 These organisms can cause patients to require stronger antibiotics and additional
treatment, increasing the burden of disease on local health systems.6-8 In addition patients, who believe
that their infection is treated or that they do not require treatment, have the potential to spread the
infection to others. The spread of communicable diseases is a significant public health concern and can
result in an increased prevalence of disease in the community.
The high prevalence of discharged adult ED visits requiring follow up for inadequate
antimicrobial prescription support the rationale that there are opportunities for improvement in the
existing antimicrobial culture review and follow up program.
Areas for improvement include
antimicrobial selection, dosing, duration, and potential for adverse drug reactions related to drug-disease
and drug-drug interactions. Since these results, a pharmacy clinical specialist has been reviewing and
following-up on all antimicrobial cultures and prescriptions in the ED. Although the results of the second
phase are pending, possible benefits of including a pharmacist include a more timely culture review and
patient follow up process, an increase in appropriate selection and dosing of antimicrobial therapy, a
decrease in antibiotic resistance emergence, and a decrease in health care system resource utilization. The
second phase of research has the potential to support the implementation of a pharmacist-managed
antimicrobial culture review program.
11
APPENDIX A
DRUG INTERACTIONS
Drug Interactions: Major
Amoxicillin
Methotrexate
Azithromycin
Amiodarone
citalopram
dofetilide
dronedarone
mifepristone
sotalol
thioridazine
ziprasidone
procainamide
quinidine
Ciprofloxacin
citalopram
dronedarone
theophylline
thioridazine
tiZANidine
warfarin
Doxycycline
acitretin
methotrexate
tretinoin
vitamin A
Fluconazole
ALPRAZolam
citalopram
cloZAPine
colchicine
dofetilide
dronedarone
everolimus
fentaNYL
mifepristone
pimozide
ranolazine
sirolimus
tacrolimus
thioridazine
Metronidazole
amprenavir
warfarin
Moxifloxacin
citalopram
dronedarone
ziprasidone
thioridazine
12
toremifene
triazolam
ziprasidone
methadone
warfarin
warfarin
Penicillin
methotrexate
Sulfamethoxazole/trimethoprim
cyclosporine
dofetilide
methotrexate
warfarin
ziprasidone
pimozide
thioridazine
warfarin
Amoxicillin
doxycycline
tetracycline
warfarin
Azithromycin
digoxin
QUEtiapine
cyclosporine
warfarin
Levofloxacin
citalopram
dronedarone
Drug Interactions: Moderate
Ciprofloxacin
methadone
Clindamycin
cyclosporine
Doxycycline
digoxin
warfarin
Fluconazole
carbamazepine
cyclosporine
nitrofurantoin
amitriptyline
phenytoin
quetiapine
rivaroxaban
tipranavir
Metronidazole
amiodarone
carbamazepine
cyclosporine
lithium
phenytoin
tacrolimus
Penicillin
warfarin
Sulfamethoxazole/trimethoprim
phenytoin
13
Cefixime
warfarin
Levofloxacin
QUEtiapine
14
APPENDIX B
ANTIBIOTIC RENAL AND LIVER FUNCTION ADJUSTMENT
Table 2: Renal Adjustment (Micromedex-Version 1.39)
Amoxicillin
Creatine Clearance (CrCl) 10 -30 ml/min
250 mg to 500 mg q 12 hours
CrCl<10 ml/min
250 mg to 500 mg q 24 hours
Hemodialysis
250 mg to 500 mg every 24 hours depending on
severity, additional doses both during and at the end
of dialysis
Amoxicillin/ Clavulanate
CrCl 10 -30 ml/min
Usual dose every 12 hours
CrCl<10 ml/min
Usual dose every 24 hours
Hemodialysis
Usual dose every 24 hours, additional dose both
during and after each hemodialysis session
Cephalexin
CrCl < 50 ml/min
Give usual dose every 12 hours
Ciprofloxacin
CrCl 30-50 ml/min
250 to 500 mg q 12 hours
CrCl 5-29 ml/min
250 to 500 mg q 18 hours
15
Table 2 Continued
Hemodialysis/ peritoneal dialysis
250-500 mg q 24 hours after dialysis
Fluconazole
CrCl<50 ml/min
Administer 50% of usual dose
Hemodialysis
100% of the usual dose after each hemodialysis
session
Metronidazole
CrCl <10 ml/min
Reduce to 50% of normal dose at usual interval
Penicillin
CrCl 10-50 ml/min
75% of usual dose at usual interval
CrCl<10 ml/min
20-50% of usual dose at usual interval
Sulfamethoxazole/Trimethoprim
CrCl 15-30 ml/min
Give one-half of usual dose
CrCl <15
Not recommended
Cefixime
CrCl 21-60 ml/min
75% of usual dose once a day
CrCl <20 ml/min
50% of usual dose once a day
Hemodialysis
75% of usual dose once a day
Peritoneal dialysis
50% of usual dose once a day
Levofloxacin
If normal dose is 750 mg q 24 hours
CrCl 20-49 ml/min
750 mg q 48 hours
CrCl 10-19 ml/min or hemodialysis/ chronic 750 mg initially, then 500 mg every 48 hours
ambulatory peritoneal dialysis (CAPD)
If normal dose is 500 mg every 24 hours
16
Table 2 Continued
CrCl 20-49 ml/min
500 mg initially, then 250 mg every 24 hours
CrCl 10-19 ml/min or hemodialysis or CAPD
500 mg initially then 250 mg every 48 hours
If normal dose is 250 mg every 24 hours
CrCl 10-19 ml/min
250 mg every 48 hours (no dose adjustment
necessary if treating uncomplicated UTI)
Nitrofurantoin
CrCl <60 ml/min or clinically significant elevated
Contraindicated
serum creatinine
Table 3: Liver Adjustment (Micromedex-Version 1.39)
Metronidazole
Severe Hepatic Disease
Reductions
in
dose
are
recommended;
recommendations are not available
17
specific
APPENDIX C
STUDY DEFINITIONS










Appropriate antimicrobial selection (based on infectious etiology/diagnosis) (Level 1): will be
determined utilizing established guidelines from the Infectious Disease Society of America
(IDSA) as well as microbiology culture and sensitivity results individualized for each patient
Appropriate antimicrobial regimen (Level 2) - will be determined utilizing established guidelines
from the Infectious Disease Society of America (IDSA)
Appropriate antimicrobial dosing based on renal and/or liver function (Level 4) – will be
individualized based on antimicrobial medication prescribed and micromedex dosing in this
patient population (see table 2 and 3)
Drug-drug interaction (Level 3) – selected interactions defined in two categories as “moderate”
or “major” within our hospital computer system and have the potential to cause ADEs and may
require increased monitoring or harm to the patient (see Table 1 Drug interaction chart)
“Moderate” Drug Interaction: A drug interaction that has the potential to increase the risk of a
side effect or potentially cause harm to the patient
“Major” Drug Interaction: A drug interaction that has been shown to increase the risk of a side
effect or cause harm to a patient and should be avoided if able
Positive Culture:
Time to action – defined as the time it takes AGH ED to review and act on culture results (action
can include: no patient follow up needed, initiation of antimicrobial therapy for outpatient
treatment, modification to antimicrobial therapy regimen for outpatient treatment, call-back to the
hospital for further treatment (ED or hospital admission))
Renal failure – as documented by physician in patient medical record
Liver failure - as documented by physician in patient medical record
18
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outcomes.Clin Infect Dis. 2003; 36(11): 1433-37.
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sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency
department. Crit Care Med. 2010; 38(4): 1045-53.
4. Joseph NM, Sistla S, DuttaTK, et al. Outcome of ventilator-associated pneumonia: Impact of antibiotic
therapy and other factors. Australas Med J. 2012; 5(2): 135–140.
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S..Appropriateness and delay to initiate therapy in ventilator-associated pneumonia. EurRespir J.
2006;27:158–64.
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events: implications for prevention. JAMA 1995;274:29-34
8. Classen DC, Pestotnik SL, Evans RS, et al. Adverse drug events in hospitalized patients. Excess length
of stay, extra costs, and attributable mortality. JAMA 1997;277(4):301-6.
9. Randolph T, Parker A, Meyer L, et al. Effect of a pharmacist-managed culture review process on
antimicrobial therapy in an emergency department. Am J Health-SystPharm.68: 2011, 916-19.
19