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Optimizing Infectious Diseases Outcomes in Antimicrobial Stewardship Programs

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OPTIMIZING INFECTIOUS DISEASES OUTCOMES IN ANTIMICROBIAL

STEWARDSHIP PROGRAMS(ACPE # 0072-9999-10-137-L04-P Knowledge-based)

Craig Martin, Pharm.D

UK HealthCare

University of Kentucky College of Pharmacy

DISCLOSURES

Dr. Martin has disclosed that he has received research grant funding from Pfizer.

OBJECTIVES

Discuss the importance of collaboration among healthcare professionals in the successful implementation of antimicrobial stewardship

List ways to optimize PK/PD relationships to optimize outcomes

Describe the development of evidence-based guidelines to implement clinical pathways


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THE CRITICAL BALANCE

Importance of appropriate empiric therapy

Effect of broad-spectrum therapy on resistance

Infection Prevention and Antimicrobial Stewardship

Silver, L. L.. 2011. Clin. Microbiol. Rev. 24(1):71-109

THE DISCOVERY VOID

GUIDING ANTIMICROBIAL USE TENETS

For severe infections, start broad If you get it wrong, you’re in trouble

Get it in the patient quicklyDe-escalation of therapy is a necessity

The right drug is always the narrowest spectrum agent that produces a successful response and causes the fewest significant adverse effects and the least collateral damage

Treat for the most appropriate length of time, then stop Each of these can be addressed through collaborative

efforts


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ANTIMICROBIAL STEWARDSHIP GUIDELINES: A SUMMARY

Multidisciplinary problem which cannot be solved unilaterally Core Members

ID Physician

ID trained Pharmacist

Additional members

Microbiologist

IT Specialist

IC Professional and/or Epidemiologist

Collaborative Antimicrobial Stewardship

Infection Control

Microbiology

ID Pharmacy and Medicine

Dellit, et al. CID 2007.

ANTIMICROBIAL STEWARDSHIP GUIDELINES

Core Strategies Prospective audit with intervention and feedback

Formulary restriction with preauthorization

Supplemental Strategies Education

Guidelines and clinical pathways

Antimicrobial cycling

Antimicrobial order forms

Combination therapy

Streamlining or de-escalation of therapy

Dose optimization

Parenteral to oral conversion


UK HEALTHCARE ANTIMICROBIAL STEWARDSHIP: COLLABORATIVE EFFORTS

Pharmacist leads an Infection Control rounding team

Microbiology pages pharmacy and IC with MDR pathogen result

Microbiology obtains PNA FISH capability to decrease echinocandin use (and pages pharmacy with result)

Pharmacy reviews Microbiology antibiogram prior to publishing

Microbiology consults pharmacy for “selective” susceptibility reporting and panel purchasing

Pharmacy assists IC in handwashing surveillance

Antimicrobial subcommittee includes all 3 groups, in addition to others


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CURRENT AND RECENT INITIATIVES

SCT/Leukemia Antifungal Guidelines Promote posaconazole for prophylaxis for some patients

Restrict combination therapy

Outline indications for all antifungals

Intraabdominal Infections Guidelines

Candidiasis Guidelines

MOVING FROM “RESTRICTION” TO “FACILITATION”

Martin CA, Armitstead JA, Mynatt RP, and Hoven AD AJHP2011; 68:109-10. Programs with a heavy-handed restriction approach may

inadvertently be doing a disservice to patients

We should be focusing more on getting the right drug to the patient rather than merely restricting drugs

The only dose of a drug proven to save lives is THE FIRST ONE

IMPROVING OUTCOMES THROUGH THOUGHTFUL DOSING AND ADMINISTRATION

Well known that maximizing the benefit of a drug requires maximizing the pharmacodynamic properties of the drug

HOWEVER, with low MIC isolates, it’s not as crucial

Previously, we always had other drugs we could use

With the lack of new drugs for MDR organisms, being strategic with dosing and administration is more important than ever


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EXTENDED-INFUSION DOSING STRATEGIES

Unnecessary to exceed MIC for a 24-hour interval

Target %T > MIC for Beta-Lactam Antibiotics Penicillins – 50% fT > MIC

Cephalosporins – 60-70% fT > MIC

Carbapenems – 40% fT > MIC

Results of PK/PD experiments support extended-infusion dosing regimens for β-lactam antibiotics

MAXIMIZING THE EFFECT OF BETA-LACTAMS

Nicolau. Crit Care 2008.

Marginal additional benefit of doubling the dose (for concentration-independent drugs)

Significant benefit of SAME DOSE given over an extended time frame

PIPERACILLIN/TAZOBACTAMEXTENDED INFUSION

Lodise, et al. CID 2007;44:357-63.


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DORIPENEM EXTENDED INFUSION

Doripenem vs. imipenem for VAP

Patients stratified Duration of mechanical ventilation (<5 vs>5 days)

APACHE (<15 vs>15)

Geography

Randomization Doripenem 500mg every 8h over 4 hours

Imipenem 500mg every 6 hours or 1000mg every 8 hours via 30 or 60min infusion

Chastre, et al. Crit Care Med 2008;36(4)


Chastre, et al. Crit Care Med 2008;36(4)


Merchant, et al. Clinical Ther 2008.


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THE USE OF CLINICAL GUIDELINES TO IMPROVE OUTCOMES

IDSA Guidelines Statements Multidisciplinary development of evidence-based practice guidelines

incorporating local microbiology and resistance patterns can improve antimicrobial utilization (AI).

Guideline implementation can be facilitated through provider education and feedback on antimicrobial use and patient outcomes (AIII).

When possible, use national guidelines

Additional crucial step, however, is to tailor based on microbiology, formulary, etc.

Antimicrobial selection is only one component (diagnostics, etc.)


EVIDENCE FOR GUIDELINE DEVELOPMENT: EXAMPLES

Community-acquired pneumonia1

20 hospitals

Decreased LOS of 1.7 days

Fewer IV therapy days

No increase in complications or readmission

General ICU infections2

77% reduction in antimicrobial use

30% reduction in overall cost of care

Decreased mortality

1. Marrie, et al. JAMA 2000.2. Price, et al. Crit Care Med 1999.

© 1999 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc.2

Evaluation of clinical practice guidelines on outcome of infection in patients in the surgical intensive care unit.

Price, Julie; Ekleberry, Ann; Grover, Amelia; Melendy, Susan; Baddam, Kavitha; McMahon, James; Villalba, Mario; MD, FCCM; Johnson,

Matthew; Zervos, Marcus

Critical Care Medicine. 27(10):2118‐2124, October 1999.

Table 4 . Comparison of antibiotic treatment costs, Phase 1 vs . Phase 2


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TIMING OF FLUCONAZOLE AND EFFECT ON MORTALITY

Garey, et al. Clin Inf Dis 2006:43.

THE CANDIDA SCORE: A RISK STRATIFICATION TOOL

Simple point-based bedside scoring tool

Points Multifocal Candida colonization (1)

Surgery on ICU admission (1)

TPN (1)

Severe sepsis (2)

Scores >2.5 have 7x higher likelihood of invasive Candidiasis

Leon, et al. Crit Care Med 2006

CANDIDA IN UKHC ICU PATIENTSOrganism 1CCU 1CT 1MED 1TIC 2BUR 2NS 2PAC 2SIC 3BMC 4NCU 4NIC 4PIC TOTAL

Candida albicans 24 35 26 26 7 33 7 21 6 9 4 13 211

Candida guilliermondii 0 0 0 1 0 0 0 0 0 0 0 0 1

Candida krusei 0 1 0 1 0 3 0 2 3 0 0 1 11

Candida lipolytica 1 0 0 0 0 0 0 0 0 0 0 0 1

Candida lusitania 0 0 0 0 0 0 0 0 0 1 0 2 3

Candida parapsilosis 2 2 4 3 1 0 1 1 0 1 0 0 15

Candida tropicalis 4 2 12 2 5 9 0 1 1 0 0 3 39

Candida glabrata 19 10 19 13 4 12 3 7 9 1 1 2 100

Grand Total 52 52 63 47 17 60 12 34 19 12 5 23 396Projected flu susceptibility

C. albicans 179 175 98%

C. glabrata 87 60 69% Susceptibility based on surveillance data: Pfaller, et al. JCM 07

C. parapsilosis 14 13 93%

C. tropicalis 35 32 90%

C. krusei 7 0 0.63

Overall 86%


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UK HEALTHCARE: SUSPECTED CANDIDIASIS GUIDELINES

Candida Score >2.5

Yes (Start micafungin)

Cx (-), pt improves (cont.

micafungin)

Cx (-), no improvement

(DC micafungin)

Cx (+), Flu-S species (change

to flu)

Cx (+), Flu-R species (cont. micafungin)

No (No antifungal therapy)

Continue to evaluate

Note: immunocompetent pts.

Decision: echinocandinor fluconazole?

Collaboration: Novel lab methods

INTENDED OUTCOMES FROM THE CANDIDEMIA GUIDELINES

Improved mortality

Shortened LOS

Decreased expenditures Not decreased from baseline; decreased compared with using micafungin for entire

course

Improved working relationship with critical care MDs

ELECTRONIC SEPSIS “BUNDLE”

Electronic order set Can be initiated by any healthcare provider that recognizes sepsis/septic

shock

Automated notification to key personnel Rapid response team

Hospital Operations Administrator (for bed transfer, nursing ratio, etc.)

Materials management

Clinical Pharmacist

Septic Shock Carts Deployed to key areas

Contains all supplies necessary for initial resuscitation

Local, unpublished data.


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IMPACT OF AN ELECTRONIC SEPSIS “BUNDLE” ON ANTIBIOTIC TIMING

0

10

20

30

40

50

60

70

80

90

100

Antibiotics within 1 hour (3 hrs for ED)

Blood Cxs prior to antibiotics

Appropriate Antibiotics for positive cultures

Before (n=46)

After (n=18)

0

1

2

3

4

5

6

7

8

Time to 1st Dose Antibiotics (Hours)

Before (n=46)

After (n=18)

Local, unpublished data.

% o

f pat

ient

s

hour

s

ANTIMICROBIAL STEWARDSHIP: AN HONEST ASSESSMENT

Does a good job of promoting the idea that antimicrobial use matters to society (at least the inpatient society)

Does a poor job of talking about community use

Does a poor job of talking about individual patients (timing, selection, etc.)

We need to be thinking about ways to win wars, not individual battles

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