Implementation of Effective Antimicrobial Regimens to ... · and primarily involve the surgical...

Implementation of Effective AntimicrobialRegimens to Combat Multidrug Resistance

Podcast of a Symposium from the 39th ASHP Midyear Clinical Meeting

Implementation of Effective Antimicrobial Regimens to CombatMultidrug Resistance

PROGRAM AGENDA

Welcome and Introductory RemarksBrian L. Erstad, Pharm.D., Program Moderator

Implementation of Effective Antimicrobial Regimens toCombat Multidrug ResistanceDebra A. Goff, Pharm.D.

Questions and Answers

PROGRAM FACULTY

Brian L. Erstad, Pharm.D., Program ModeratorFCCM, FASHP, FCCP, BCPSAssistant Department Head, Pharmacy Practice and ScienceProfessor, Pharmaceutical SciencesThe University of Arizona College of PharmacyTucson, Arizona

Debra A. Goff, Pharm.D.Clinical Associate ProfessorThe Ohio State University College of PharmacyColumbus, Ohio

Implementation of Effective Antimicrobial Regimens to CombatMultidrug Resistance

PROGRAM OBJECTIVES

At the conclusion of this program, the participant should be able to:

• Briefly review the long-term consequences of inappropriate antibioticprescribing in health systems, including the development of multidrugresistance to common pathogens.

• Describe the Ohio State University’s electronic program for detectinginappropriate antibiotic prescribing as an example of an interventiondesigned to help pharmacists manage formulary challenges and multidrugresistance.

• Explain the positive clinical implications to hospitals after implementationof appropriate antibiotic drug-use strategies.

• Compare and contrast the new and existing broad-spectrum antibioticsthat are used for the treatment of multidrug-resistant infections.

• Explain cost-effective methods that health-system pharmacists can use toimprove the quality and management of antibiotic therapies.

CONTINUING EDUCATION ACCREDITATION

The American Society of Health-System Pharmacists is accredited by theAccreditation Council for Pharmacy Education as a provider of continuingpharmacy education. This program provides 1 hour (0.1 CEU) ofcontinuing education credit (program number 204-000-04-423-H01). Upon

completion of the program, attendees may submit and receive their official continuingeducation certificate online.

Implementation of Effective Antimicrobial Regimens to Combat

Multidrug Resistance

Brian L. Erstad, Pharm.D., Program Moderator FCCM, FASHP, FCCP, BCPS Assistant Department Head, Pharmacy Practice and Science Professor, Pharmaceutical Sciences The University of Arizona College of Pharmacy Tucson, Arizona

Brian Erstad, Pharm.D., has been on faculty in the College of Pharmacy at

the University of Arizona for approximately 16 years and has the title of

Professor. Dr. Erstad has authored more than 90 articles and book chapters.

His clinical responsibilities are performed at the Arizona Health Sciences Center

and primarily involve the surgical intensive care area. Dr. Erstad has received

recognition as a Fellow by the following organizations: Society of Critical Care

Medicine, American Society of Health-System Pharmacists, and the American

College of Clinical Pharmacy.

Dr. Erstad obtained his B.S. degree in pharmacy from South Dakota State

University and then worked as a staff pharmacist for approximately eight years in

community hospital practice. He subsequently received his Doctor of Pharmacy

degree from the University of Arizona and completed a residency at the

University of Arizona Medical Center in Tucson, Arizona.



Debra A. Goff, Pharm.D. Associate Professor Infectious Diseases Specialist Antibiotic Utilization Review Coordinator The Ohio State University Medical Center Columbus, Ohio

Debra A. Goff, Pharm.D., is Infectious Diseases Specialist and Antibiotic

Utilization Review Coordinator at The Ohio State University Medical Center

(OSUMC) in Columbus, Ohio. She is also Associate Professor at the College of

Pharmacy. Dr. Goff serves as Preceptor in the Infectious Diseases Residency

Program at the OSUMC. She is Chairperson for the OSUMC Robert J. Fass

Memorial Infectious Diseases Fund. Dr. Goff received her Doctor of Pharmacy

degree and completed a pharmacy residency at the University of Illinois at

Chicago.

Dr. Goff serves as an abstract reviewer for the American College of Clinical

Pharmacy and was honored in 2002 by The Ohio State University Medical Center

Leadership Council for Clinical Value Enhancement for developing “Community-

Acquired Pneumonia in Immunocompetent Adult Patients” clinical practice

guidelines. Her research interests include antimicrobial resistance, clinical

outcomes research, and antifungals. Dr. Goff has received over 100 research

grants and presented over 200 lectures nationally and internationally. She has

published in several journals, including Pharmacotherapy, Current Opinion in

Infectious Diseases, Archives of Internal Medicine, and Clinical Infectious Diseases.

Dr. Goff is a member of the American College of Clinical Pharmacy, the

Infectious Diseases Society of America, the American Society for Microbiology, and

the Society of Infectious Diseases Pharmacists. She is on the Annual Report

Committee of the Society of Infectious Diseases Pharmacists and she currently

serves as an advisory board member of the U.S. Micron and the Academy for

Healthcare Education.



PROGRAM OVERVIEW Overuse of antimicrobials has contributed to the emergence of antimicrobial-

resistant pathogens. Several organizations and experts in infectious diseases

have called for increased efforts to limit overuse of antimicrobials in the hospital

and outpatient settings. Appropriate antimicrobial selection, based on

pharmacokinetic and pharmacodynamic parameters, drug potency, and duration

of therapy, may provide solutions to the problem of resistance. The routine use of

broad spectrum antibiotics needs to be re-evaluated in the hospital setting.

The implementation of computerized physician order entry (CPOE) has the

potential to address the problem of antibiotic misuse. Because CPOE is

expensive and complex, only a few healthcare organizations in the United States

have implemented it. One hospital that used CPOE with an integrated antibiotic

advisor has shown that it could reduce the rates of excessive drug dosages and

antibiotic-susceptibility mismatches. CPOE can improve antibiotic use by

providing physicians guidance when making antibiotic selections.

Implementation of Effective Antimicrobial Regimens to Combat Multidrug Resistance

Debra Goff, Pharm.D.Associate Professor

Infectious Diseases SpecialistThe Ohio State University Medical Center

Outline

Consequences of inappropriate antibiotic prescribing

Compare and contrast broad-spectrum antibiotics

The Ohio State University specific dataImplementation of physician computerized order entry (CPOE)

Resistance trends

Clinical implications after implementation

Annual Antimicrobial Use

McEwen SA, et al. Clin Infect Dis. 2002;34:S93-S106.

Therapeutic

animal food industry

2million lbs in animals

3million lbs in humans

27.5million lbs in Nontherapeutic

FDA Supports Banning Antibiotics in Poultry

Why do farmers use antibiotics for non-therapeutic use?To shift microbial balance in the gut enabling animals to use feed more efficiently.

Why change this habitTo protect public health against further development of antimicrobial resistance

Wegener HC. ASM News 2003;69:9 443

Trends in Gram-Positive Resistance: USThornsberry C. NNIS. 38th ICAAC.1998; San Diego, Calif; Abstract E22;1 Edmond M. CID 1999, MMWR Morb Mortal Wkly Rep. 1997;46:624- 636.2

Perc

ent o

f Pat

hoge

ns R

esis

tant

to A

ntib

iotic

s

0

10

20

30

40

50

60

70

80

90

100

1975 1980 1985 1990 1995 2000

MRSE

MRSA

VRE

DRSP

VISA

1997

Gram Negative Resistance

Pseudomonas aeruginosa

Klebsiella pneumoniaeKlebsiella oxytocaE. coli

Acinetobacter

Gram-Negative ResistanceMulti-Drug resistant Acinetobacter

Battlefield injuries sustained in Operation Iraqi Freedom

Increased from 11-217 during first 12 months

Treat with imipenem + aminoglycoside

Ewell et al ICAAC abstract 2004

The “Superbugs” Aren’t Waiting!

Industry is getting out of the anti-infective businessRoche, BMS

No new gram-negative products in the pipeline

Infectious Diseases Society of America (IDSA) Press Release 9/04

Consequences of Inappropriate Antibiotics

MythThere is time to start with 1 antibiotic and then switch to an alternative if the 1st

therapy is found to be inadequate.

FactInadequate initial therapy increase mortality in patients with VAP

Kollef MH et al Chest 1999 115:462-74.Inegui M et al Chest 2002:122;262-8.

Targeted Coverage

Ertapenem

Ampicillin/sulbactam

Piperacillin/tazobactam

Imipenem

Empiric coverage

Anaerobes

Gram-positives

Resistant ESBL’s

Pseudomonas aeruginosaNon-Pseudomonas gram-negatives

OSU specific data

Antibiogram dataUsing micro data to determine formulary antibiotics

Cost-effective measures

Implementing Computerized Physician Order Entry

OSUMC Hospital-wide Antibiogram 1998 - 1999

Pip/tazo

Cefepim

e

Imipenem

Cipro

Tobramycin

K. pneumoniae(954) 91 95 99 88 92E. cloacae(287) 79 95 95 92 91E. coli(1971) 96 99 99 98 98P. aeruginosa(1039) 87 70 81 70 89A. baumannii(121) 91 80 100 70 85

Imipenem

Was restricted (from routine use) in 1996 and reserved for documented MDR gram-negative infections.

All orders were reviewed for appropriate use.

Interventions were made if the guidelines were not followed.

Historical Data for Imipenem

# of Doses

0

5,000

10,000

15,000

20,000

93-94 94-95 95-96 96-97 97-98 98-99

Fiscal Year

intervention

OSU specific data

Hospital wide antibiogramsno resistance problems identified

Unit specific antibiogramsKlebsiella pneumoniaESBL (extended spectrum beta lactamase) resistancePseudomonas aeruginosa multi-drug resistance

Implemented antibiotic cycling x 1 year

OSUMC - MICU AntibiogramJuly 1999 - Dec. 1999 First isolates only

Pip/tazo

Cefepim

e

Imipenem

Cipro

Tobramycin

K. pneumoniae(32) 66 81 100 63 63E. cloacae(13) 77 77 92 77 69E. coli(16) 94 94 94 100 94P. aeruginosa(37) 81 59 70 78 95A. baumannii(21) 86 14 86 52 19

Results II: Number of antibiotic doses in the MICU

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

pre-data post-data

pip/tazo cefepime cipro imipenem tobramycin

MICU First Isolates: Pre and Post Data

5

10

15

20

25

30

35

40

K. pneumoniae* P. aeruginosa S. maltophilia* A. baumannii*E. coli E. cloacae S. marcescens

*p<0.05

# of isolates

Klebsiella pneumoniaeMICU data: first isolates decrease from 32 to 12

30

40

50

60

70

80

90

100

7/99-12/99 1/00-6/00 7/00-12/00

imipenempip/tazocefepimeciprotobramycinpiperacillin

% susceptibility

Hospital - wide use of Imipenem -cilastatin (# of doses)

0

5000

10000

15000

20000

93-94 94-95 95-96 96-97 97-98 98-99 99-00 00-01

Take home message

A hospital-wide antibiogram can mask resistance issues

Individual ICU antibiograms can be useful in guiding the selection of empiric antibiotics

Know if your micro lab is reporting ESBL- producing Klebsiella isolates

The price of antibiotic resistance is much greater than the price of the antibiotic

Microbiology Issues

The results of this study clarified the need to have ESBL producing Klebsiella identified by our micro lab

The new antibiogram identifies ESBL producing Klebsiella

Antibiograms: 2001-2003

Antibiotic resistant pathogens are increasing: MRSA 50% 54% 64%VRE (faecium) 52% 75% 72%K. pneumoniae ESBL 0% 4% 7%

Antibiotic susceptibility for Pseudomonas aeruginosa(most prevalent Gram negative pathogen) is decreasing

Ciprofloxacin 72% 62% 60%Imipenem 85% 71% 52%Pip/tazo 87% 82% 60%Cefepime 84% 72% 63%Gentamicin 87% 65% 60%

99-00 01-02 MICU

Evaluation of clinical outcomes of patients with ESBL K. pneumoniae

Methods:

Patients with ESBL Kp from Oct 00- Dec 02 were identified from the micro database.

Micro data: antibiotic susceptibility, site of infection (blood, urine, sputum, other)

Patient data: community or nosocomiallyacquired, antibiotic exposure, risk factors for ESBL Kp, mortality

OSUMC Hospital-wide data2000-2002 ESBL-KP n=96

0102030405060708090

100

antibiotic

perc

ent s

usce

ptib

le

imipenemamikacincefepimepip/tazotmp/sulfacipro

Acquisition of Infection

20%

35%

45%

community acquirednosocomialtransfers

Patient location at OSU n=64

18

46

ICUnon-ICU

Patient Outcome Data

62/64 had empiric antibiotics started at OSU

The empiric choice was ineffective (resistant to the ESBL-Kp) in 41/64 (64%)

Overall mortality =19% (12/64)

12 deaths

All died while on antibiotics

10 received ineffective empiric antibiotics

7 died before drug susceptibility results

Conclusions

ESBL-Kp is not just an ICU problem

Mortality is associated with initial antibiotic choice

Carbapenems are the most appropriate choice for patients with nosocomial or community acquired ESBL-Kp

Recent literature indicates ESBL Kp is increasing in frequency (up to 40%)

Can OSU improve antibiotic prescribing?

OSUMC Hospital-wide Antibiogram 2003

Pip/tazo

Cefepim

e

Imipenem

Cipro

Tobramycin

K. pneumoniae(537) 95 98 99 89 98K. pneumoniaeESBL (40) 5 16 100 18 10E. cloacae(211) 76 89 98 77 84E. coli(1026) 93 100 100 82 92P. aeruginosa(741) 82 76 71 52 85A. baumannii(58) 39 42 100 45 62

OSU Formulary Decision

The incidence of multidrug-resistant ESBL K. pneumoniae at OSU increased from 4% to 7% in 2003.

Over 50% of ESBL infections were community acquired.

The only class of antibiotics that had susceptibilities > 70% to the ESBL K. pneumoniae were the carbapenems.

Ertapenem was added to the formulary May 27, 2003.

Ertapenem

New IV Carbapenem

Dosed 1 gm daily

Approved for:complicated intra-abdominal

skin and skin structure

complicated urinary tract and

pelvic infections

community acquired pneumonia

Spectrum of activity is similar to cefoxitin

Ertapenem

Gram positiveMSSA, Strep pyogenes, S. pneumonia, S. agalactiae

Gram Negatives (aerobes)E coli, K. pneumoniaeH. influenzae and oxytoca, M. catarrhalis

AnaerobesBacteroides fragilisB. DOT groupPeptostreptococcusClostridium perfringes, clostridioformeEubacterium lentum

Why Add Ertapenem?

Provide an effective antibiotic for ESBL producing pathogens, without resorting to imipenem

Provide an alternative to ampicillin/sulbactam for the post-operative surgical patients

Not for empiric therapy of nosocomial infections.

Ertapenem does NOT COVER: Pseudomonas aeruginosaEnterococcus species Acinetobacter spp.

Targeted Coverage

Ertapenem

Ampicillin/sulbactam

Piperacillin/tazobactam

Imipenem

Empiric coverage

Anaerobes

Gram-positives

Resistant ESBL’s

Pseudomonas aeruginosaNon-Pseudomonas gram-negatives

Using Computerized Physician Order Entry

(CPOE) to Improve Antibiotic Utilization

Antibiotic Prescribing Committee Winter 2002

Computerized Physician Order Entry (CPOE) was introduced at OSU in May 2000.

Can we change antibiotic prescribing via CPOE?

Can we establish indications for ALL antibiotics?

Start with piperacillin-tazobactam(old antibiotic)

Introduce ertapenem (new antibiotic)

Goals: Improve antibiotic utilization and preserve anti-pseudomonal antibiotics for patients with documented or suspected P aeruginosa infections

Ertapenem Specific Goals

Evaluate the effectiveness of using CPOE to identify the utilization of ertapenem.

Monitor the susceptibility of ESBL isolates and other gram negative pathogens to ertapenem

Enter an Indication or Select an Alternative Treatment

Indications screen for piptaz

(Invanz)

If Yes, select at least one, if No then see below

Screen for alternative selection, requires an indication.

Indications screen for Ertapenem (5/03)

If Yes, select at least one, if No then see below (Invanz)

Evaluation of the CPOE System for Antibiotics

Education done prior to implementationsurgeons, heme-onc, internal medicine, pharmacy, nursing

System went live on May 27, 2003

Pharmacy tracked the first 2 weeks of orders manually (n=116)

IS prepared computer reports for the first 9 weeks of orders (n=687)

IS computer summary reports

All patients for 1st 9 weeks

Pip/tazo 687 orders

0

50

100

150

200

250

300

gm - ICU gm - immunoSuspect PA Docum PAother

# of orders

How often did this method change prescribing?

The P/T screen was entered 687 times

25 (4%) patients had amp/sulbactamordered instead of pip/tazo

0 selected ertapenem from the pip/tazoscreen

40 ordered ertapenem as a direct order

ErtapenemIndication for Use (n=120)

86

7 618

0

20

40

60

80

100

use by indication

IA mixed inf ESBLDC to homecare non-pseudomonal mixedother

Ertapenem Use by Service80% prescribed by surgeons

80

15

25

surgery surg onc other

120 orders

Discussion

The CPOE method provided insight into many issues

What has improved because of this?1. Cultures are being ordered2. Underdosing has been identified3. Prescribing was altered for

amp/sulbactam by removing 3 gm option4. Ertapenem was introduced and prescribed

appropriately

Discussion

What needs to improve?Little change takes place after the culture results are back. In order to preserve broad-spectrum antibiotics we MUST streamline if P.aeruginosa is not confirmed.

New antibioticsErtapenem was successfully introduced and used appropriately. All new antimicrobials will be introduced by this method.

Clinical Implications

Pharmacist

Physician

IS supportPatient

This project was successful due the to efforts of the multidisciplinary group. Each of us had something important and unique to contribute.

Patients will benefit by having antibiotics available that are susceptible to the pathogens.

Question and Answer Period

We invite your questions. Please stand and approach the nearest aisle microphone.

Please complete both sides of the evaluation form in your handout booklet. Staff will collect the evaluations as you exit quietly.

Thank you for your attendance and be sure to join us again tomorrow morning.



FACULTY DISCLOSURE STATEMENTS ASHP Advantage requires that faculty members disclose any relationships (e.g., shareholder, recipient of research grant, consultant or member of an advisory committee) that the faculty may have with commercial companies whose products or services may be mentioned in their presentations. The existence of these relationships is provided for the information of attendees and should not be assumed to have an adverse impact on faculty presentations. The faculty reports the following relationships: Brian L. Erstad, Pharm.D., FCCM, FASHP, FCCP, BCPS Dr. Erstad discloses that he is a consultant for Pfizer, Inc. Debra A. Goff, Pharm.D. Dr. Goff discloses that she has received research support from Merck, Pfizer, and Wyeth Pharmaceuticals.

ASHP AdvantageInstructions for Receiving Your CE Statements OnlineASHP Advantage’s online CE Request Center allows attendees to obtain their CEstatements conveniently and immediately. To obtain your CE statements for ASHPAdvantage Podcast programs, please follow these steps:

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Continuing Education AccreditationThe American Society of Health-System Pharmacists is accredited by theAccreditation Council for Pharmacy Education as a provider of continuingpharmacy education. This program provides 1 hour (0.1 CEUs) of

continuing education credit (number 204-000-04-423-H01). Attendees must complete aContinuing Pharmacy Education Request online and may immediately print their officialASHP CE statements at the ASHP Advantage CE Processing Center(www.ashpadvantage.com).

Self-Assessment Test Implementation of Effective Antimicrobial Regimens to Combat Multidrug Resistance This program is located at http://symposia.ashp.org/cemornings

1. Effective strategies to reduce the incidence of antibiotic resistance in U.S. hospitals

include all of the following EXCEPT: a. Reliance on a hospital-wide antibiogram to determine physicians’ initial choice of antibiotic therapy. b. Laboratory testing for ESBL-producing Klebsiella isolates. c. Using unit-specific antibiograms within the hospital to determine antibiotic resistance patterns. d. Using formulary management to conserve antibiotics for Pseudomonas aeruginosa infections. 2. Of the following gram-positive pathogens, which is commonly associated with

multidrug resistance in most U.S. hospitals and extended-care facilities? a. VRE b. MRSA c. MRSE d. DRSP 3. The Ohio State University Medical Center’s CPOE program for antibiotic prescribing

was implemented for which of the following reasons? a. Formulary restrictions were needed due to increasing expenditures for antibiotics. b. OSU decided to utilize the IDSA campaign called “Bad Bugs, No Drugs” for educating physicians about bacterial resistance trends. c. Several new antibiotics are being developed for multidrug-resistant Gram negative pathogens. d. Resistance trends identified a need to implement more appropriate antibiotic prescribing habits.


4. Which statement best describes the clinical consequences of inappropriate antibiotic

prescribing in U.S. hospitals? a. Antibiotic formulary expenses increase with inappropriate prescribing. b. Parenteral antibiotics should be restricted to prescribing by infectious diseases specialists. c. High-risk patients being transferred from extended-care facilities should be screened for multidrug resistance. d. Studies indicate that inadequate antibiotic choice during initial therapy increases mortality rates in patients with serious infections. 5. Following implementation of CPOE for antibiotic prescribing at OSU, a greater

percentage of isolates are now being cultured and changed to a non-Pseudomonas agent when indicated by laboratory results.

a. True b. False 6. Klebsiella pneumoniae, when ESBL-producing, is typically susceptible to which of

the following class of antibiotics: a. Quinolones b. Carbapenems c. First-generation cephalosporins d. Aminoglycosides 7. The antimicrobial spectrum of activity for ertapenem includes which of the following? a. K. pneumoniae, including ESBL-producing isolates b. Enterococcus species c. Pseudomonas aeruginosa d. Acinetobacter spp. 8. During implementation of CPOE, which of the following antibiotics on the OSU

formulary were targeted for anti-pseudomonal coverage? a. Ertapenem and ampicillin/sulbactam b. Ertapenem and imipenem c. Piperacillin/tazobactam and imipenem d. Piperacillin/tazobactam and ampicillin/sulbactam


9. Which of the following describes the best choice of initial parenteral antibiotic therapy

for a patient at OSU with complicated intra-abdominal infection? a. Ampicillin/Sulbactam 1.5gm every 8 hours b. Ertapenem 1gm every 24 hours c. Ciprofloxacin 400mg every 12 hours d. Imipenem 500mg every 8 hours

10. Which of the following statements is true? a. New broad-spectrum parenteral antibiotics can be appropriately utilized by hospital physicians with CPOE technology, antibiogram surveillance, and multidisciplinary education. b. New broad-spectrum parenteral antibiotics should be restricted to utilization after documentation of culture results. c. Physicians should be allowed to continue use of anti-pseudomonal antibiotics without culture confirmation of P. aeruginosa. d. Antibiograms are not an effective method to identify and track bacterial resistance trends.

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