antimicrobial stewardship

Let’s Shore Up Our Defenses

Presented by:Carmenchu Echiverri Villavicencio, MD, DPCP, DPSMID

Slides byMarion Priscilla A. Kwek, MD, FPCP, DPSMID

July 4, 2015

Outline

• Introduction

– History of Antibiotics

– Magnitude of the Problem

• Antimicrobial Stewardship

– Definition & Rationale

– Interpretation of Antibiogram Data

– Developing Institutional Program

– Stewardship for the primary care physician

Objectives

• Recognize the problem of antimicrobial resistance

• Understand the benefits of an antimicrobial stewardship program

• Apply antimicrobial stewardship in clinical practice

- Alexander Fleming upon accepting the

1945 Nobel Prize in Medicine

The Bad News

• Increasing resistance to available antimicrobials

• Stagnant antibiotic development

– Investment lacking

– Slow to recognize the need and inherent delays in finding and developing new antimicrobials

• The increasing importance of antimicrobials in modern medical practice

– Increasing use of antimicrobials for those patients on immunosuppressants and managed in critical care

Antibiotic Resistance

• A worldwide problem

• Can cross international boundaries and spread with ease

• Pose a catastrophic threat to people in every country in the world

• At least 2M people acquire serious infections with bacteria resistant to one or more of the antibiotics designed to treat those infections

Antibiotic Resistance Threats in the United States, 2013. Centers for Disease Control and Prevention


• At least 23,000 people die each year as a direct result of these antibiotic-resistant infections

• Many more die from other conditions that were complicated by an antibiotic resistant infection

• Infections add considerable and avoidable costs

• Require prolonged and/or costlier treatments, extend hospital stays, necessitate additional doctor visits and healthcare use, and result in greater disability and death



The use of antibiotics is the single most

important factor leading to antibiotic resistance

around the world


http://lumibyte.eu/microbiology-news/antimicrobial-resistance-timeline/http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf

Pucci & Bush Clin Micro Rev 2013;26:792–821

What is “Collateral Damage”?

• Refer to ecological adverse effects of antibiotic therapy; namely, – Selection of drug-resistant organisms and

– Unwanted development of colonization or infection with multidrug resistant organisms (eg, Clostridium difficile Infection)

• Two antibiotic classes commonly linked to collateral damage:– Cephalosporins & Fluoroquinolones

Paterson DL. Clin Infect Dis. 2004;38(suppl 4):S341-S345.

Difficult to Treat Organisms

• MRSA

• Antibiotic-resistant GNBs

• MDR-TB

• C. difficile

Staphylococcus aureus

• MRSA rate 53% (n= 2,317)

• Possible emergence of resistance against vancomycin with 2013 reported rates at 1% (n=1,176).

• No reported VRSA in 2012

2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM

Escherichia coli

• ESBL-suspects at 22%

• Resistance rate:

– AMP 82% (n=4,333)

– SAM 32% (n=4,056)

– CXM 29% (n= 2,210)

– CRO 31% (n= 4,364)

– SXT 66% (n= 3,893)

– AK 4% (n= 4,478)

– CIP 43% (n= 4,332)


Cost of Drug Resistance

Staphylococcus aureus Drugs (PO) Cost per antibiotic day

Methichillin-Susceptible Cloxacillin Php 118

Cefalexin Php 94

Co-Amoxiclav Php 135

CA-Methicillin-Resistant Clindamycin Php 299

HA-Methicillin-Resistant Linezolid Php 6,900

VancomycinIntermediate

Vancomycin Resistant

Drivers of Emergence

• Natural Selection Driven By:– Antimicrobial use in humans– Antimicrobials in food production

• Spread of Resistant Organisms– Population density– Importation– Affected by infection control and

community hygiene practice

• Concern is not just spread of organisms but of transposable genetic elements conferring resistance

Global Antibiotic Consumption by Class 2000-2010

www.thelancet/infection Vol 14 August 2014

Global Antibiotic Consumption by Class 2000-2010

• Consumption of antibiotics increased by 36% Brazil, Russia, India, China, and South Africa accounted for 76% of this increase

• There was increased consumption of carbapenems (45%) and polymixins (13%), two “last-resort” classes of antibiotic drugs.

Van Boeckel et al Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data Lancet Infect Dis 2014; 14: 742–50

Nicolau ,DP

Perspective of Pharmaceuticals

• All pharmaceutical companies are under pressure by shareholders to maximize returns and sustain strong growth rates – Chronic care medications > acute care medications – Innovation > Me-too’s– Specialized disease products > primary care products

• Pressures to maximize profitability do not necessarily align with appropriate use, promotion, or consumption of antibiotics

• Recognition of antibiotics as a finite strategic resource is rarely compatible with corporate commercial aspirations

Alasdair MacGowan, University of Bristol

Approach to Reducing Antimicrobial Resistance

• Infection Prevention and Control

• Improve diagnostics (i.e. respiratory infections) – Minimize unnecessary antimicrobial use

– Targeted (narrow spectrum) therapy

• Continued discovery of new antimicrobials

• Reduce resistance reservoirs (i.e. animal/environmental use)

• Antimicrobial stewardship programs

Fishman N. Am J Med 2006; 119 (Suppl 1): S53-S61 Dellit TH et al. Clin Infect Dis. 2007;44(2):159-77.

WHAT IS ANTIMICROBIAL STEWARDSHIP?

Antimicrobial Stewardship

• After confirming that the patient has an indication for antimicrobial therapy, antimicrobial stewardship is the:

DrugTimeDoseDurationRoute

Dryden M et al. J Antimicrob Chemother 2011; 66(11): 2441-3http://www.idsociety.org/stewardship_policy/

Why the Need for Antimicrobial Stewardship?

• Up to 50% of antimicrobial use in hospitals is inappropriate

• 77% (51/66) studies of interventions to improve antimicrobial use in hospitals had beneficial results

Davey P. et al. Cochrane Database of Syst Rev 2005.

Understanding Your Local Antibiogram

Most Common Isolates Per Specimen (eg. Urine)

Total Isolates (262) Percent

Escherichia coli 111 42%Klebsiella pneumoniae 34 13%Enterococcus faecalis 26 10%

Understanding Your Local Antibiogram% Susceptibility of E. coli

Ampicillin 32.2

Amoxicillin Clavulanate 73.9

Piperacillin/Tazobactam 100.0

Cefuroxime 78.5Ceftriaxone 91.5Ceftazidime 90.6

Cefepime 93.4Ertapenem 99.4Imipenem 100.0

Meropenem 100.0Levofloxacin 71.4

Amikacin 100.0

Cotrimoxazole 47.0

INAPPROPRIATE ANTIBIOTIC USE

Treating Viral Infections with Antibiotics

• Most common cause of acute upper respiratory tract infections is viral

• Giving quinolones in viral gastroenteritis

Treating Colonizers

• Isolates from respiratory specimens in patients who are clinically well or asymptomatic

• Asymptomatic Bacteriuria

• Pyuria accompanying asymptomatic bacteriuria is not an indication for antimicrobial treatment (A-II).

• Treatment for AB for:– Pregnant (A-I)

– TURP (A-I) or urologic procedures with anticipated bleeding (A-III)

Surgical Prophylaxis

• Prolonged duration of Prophylaxis

• Timing

• Giving of prophylactic antibiotic even when not indicated

• Single dose or continuation for < 24h

• Dose within 1 hr from cutting time (2h for FQ and VA)

• Clean head and neck surgery eg. thyroidectomy

Antimicrobial Stewardship

• Coordinated interventions to monitor and direct antimicrobial use at a health care institution

• Provides a standard evidence-based approach to judicious antimicrobial use

http://www.idsociety.org/stewardship_policy/

Antimicrobial Stewardship: Goals

• Optimal clinical outcomes

• Minimize toxicity and ADRs

• Limit selection for antimicrobial resistant strains

• Reduce costs of health care


Stewardship: Recommendations

• Multidisciplinary team

– IDS physician

– PharmD

– Clinical Microbiologist

– IT

– Infection Control Practitioner

– Hospital Epidemiologist

• Compensated



• Collaboration b/w the ff:

– Stewardship team

– Infection control

– Pharmacy/Therapeutics Committee

• Administrative/Leadership support


Examples of ASP Strategies/Interventions

• Education • Formulary • Formulary restriction and preauthorization• Selective reporting • Prospective audit with intervention and feedback • Guidelines and clinical pathways • Antimicrobial order forms • Streamlining and de-escalation of therapy • Dose optimization (optimize PK/PD) • Parenteral to oral conversion


Education

• Essential

• Alone, insufficient (II-B)

• No sustained impact

• Education + Intervention (xA-III)


Formulary (A-II)

• Therapeutics Committee

• Evaluating therapeutic efficacy, toxicity and cost

• Limit redundant new agents


Formulary Restrictions (A-II) and Pre-authorization (B-II)

• Restriction of Antibiotics

• ID approval

• ID consult


Selective Reporting A-III

• Clinical Microbiology

• Limiting Antibiotic Susceptibility Reports in Cultures

• Example:

– Urine E. coli isolate susceptible to ampicillin, and all tested antibiotics

– Official culture report: E. coli susceptible to ampicillin, cefuroxime


Prospective Audit with Intervention and Feedback (A-I)

• Very effective

• Resource intensive


Guidelines and Clinical Pathways

• National Guidelines

• Local Guidelines

• Very Effective

Antimicrobial Order Forms (B-II)

• Automatic stop orders

• Clear communication of renewal requirements

Streamlining and de-escalation of therapy (A-II)

• Early de-escalation once with available microbiologic data

• For Severe Infections– Empiric Broad Spectrum Treatment

– Re-evaluate after 3 days and streamline

• De-escalation:– 1 agent: change to narrow spectrum

– 2 agents: change to 1 agent

– Discontinue antibiotics if no evidence of infection

Exceptions to general approach

• Do not discontinue antibiotics in a patient who is decompensating

• Patients may be ill and require therapy, notwithstanding negative culture results

1. Weber DJ. Int J Infect Dis. 2006;10(suppl 2):S17-S24. 2. Höffken G, Niederman MS. Chest. 2002;122:2183-2196. 3. AmericanThoracic Society (ATS)/Infectious Diseases Society of America (IDSA). Am J Respir Crit Care Med. 2005;171:388-416. 4. SinghN et al. Am J Respir Crit Care Med. 2000;162:505-511.

Dose Optimization (A-II)

• Optimize PK/PD

– Septic patients: Increased Vd

• T/MIC for β-lactams

• AUC/MIC and Cmax/MIC for FQ and aminoglycosides

Parenteral to oral conversion (A-III)

• High bioavailability antibiotics– Fluoroquinolones

– TMP/SMX

– Metronidazole

– Clindamycin

– Linezolid

– Minocycline

– Fluconazole

– Voriconazole

– Chloramphenicol


• Health care information technology

• Surveillance


Antibiotics in Development

• As of December 2014, an estimated 37 new antibiotics 1 that have the potential to treat serious bacterial infections are in clinical development for the U.S. market.

• Success rate for drug development is low; at best, only 1 in 5 candidates that enter human testing will be approved for patients.

http://www.pewtrusts.org/en/multimedia/data-visualizations/2014/antibiotics-currently-in-clinical-development

Learning Points

• Antimicrobial resistance is a global concern and needs immediate action

• Antimicrobial stewardship is one way of combating antimicrobial resistance

• Physicians are key players in promoting or curbing antimicrobial resistance

Learning Points

• Treatment of infections should be based on most likely organism following local resistance patterns

• New antibiotics are in the pipeline but preserving available antibiotics is still vital

antimicrobial stewardship

Healthcare