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Let’s Shore Up Our Defenses
Presented by:
Carmenchu Echiverri Villavicencio, MD, DPCP, DPSMID
Slides by
Marion Priscilla A...
Outline
• Introduction
– History of Antibiotics
– Magnitude of the Problem
• Antimicrobial Stewardship
– Definition & Rati...
Objectives
• Recognize the problem of antimicrobial
resistance
• Understand the benefits of an antimicrobial
stewardship p...
- Alexander Fleming upon accepting the
1945 Nobel Prize in Medicine
The Bad News
• Increasing resistance to available antimicrobials
• Stagnant antibiotic development
– Investment lacking
– ...
Antibiotic Resistance
• A worldwide problem
• Can cross international boundaries and spread
with ease
• Pose a catastrophi...
Antibiotic Resistance
• At least 23,000 people die each year as a direct
result of these antibiotic-resistant infections
•...
Antibiotic Resistance
The use of antibiotics is
the single most
important factor leading
to antibiotic resistance
around t...
http://lumibyte.eu/microbiology-news/antimicrobial-resistance-timeline/
http://www.cdc.gov/drugresistance/pdf/ar-threats-2...
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-resi...
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 ...
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)
– ...
2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM
2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM
Cost of Drug Resistance
Staphylococcus aureus Drugs (PO) Cost per
antibiotic day
Methichillin-Susceptible Cloxacillin Php ...
Drivers of Emergence
• Natural Selection Driven By:
– Antimicrobial use in humans
– Antimicrobials in food production
• Sp...
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, Chin...
Nicolau ,DP
Perspective of Pharmaceuticals
• All pharmaceutical companies are under pressure by
shareholders to maximize returns and s...
Approach to Reducing Antimicrobial
Resistance
• Infection Prevention and Control
• Improve diagnostics (i.e. respiratory
i...
WHAT IS ANTIMICROBIAL
STEWARDSHIP?
Antimicrobial Stewardship
• After confirming that the patient has an
indication for antimicrobial therapy,
antimicrobial s...
Why the Need for Antimicrobial
Stewardship?
• Up to 50% of antimicrobial use in hospitals is
inappropriate
• 77% (51/66) s...
Understanding Your Local Antibiogram
Most Common Isolates Per Specimen
(eg. Urine)
Total Isolates (262) Percent
Escherichi...
Understanding Your Local Antibiogram
% Susceptibility of E. coli
Ampicillin 32.2
Amoxicillin Clavulanate 73.9
Piperacillin...
INAPPROPRIATE ANTIBIOTIC USE
Treating Viral Infections with
Antibiotics
• Most common cause of
acute upper respiratory
tract infections is viral
• Givi...
Treating Colonizers
• Isolates from respiratory specimens in
patients who are clinically well or
asymptomatic
• Asymptomat...
• Pyuria accompanying asymptomatic
bacteriuria is not an indication for
antimicrobial treatment (A-II).
• Treatment for AB...
Surgical Prophylaxis
• Prolonged duration of Prophylaxis
• Timing
• Giving of prophylactic antibiotic even when
not indica...
• Single dose or continuation for < 24h
• Dose within 1 hr from cutting time (2h for FQ and
VA)
• Clean head and neck surg...
Antimicrobial Stewardship
• Coordinated interventions to monitor and
direct antimicrobial use at a health care
institution...
Antimicrobial Stewardship: Goals
• Optimal clinical outcomes
• Minimize toxicity and ADRs
• Limit selection for antimicrob...
Stewardship: Recommendations
• Multidisciplinary team
– IDS physician
– PharmD
– Clinical Microbiologist
– IT
– Infection ...
Stewardship: Recommendations
• Collaboration b/w the ff:
– Stewardship team
– Infection control
– Pharmacy/Therapeutics Co...
Examples of ASP
Strategies/Interventions
• Education
• Formulary
• Formulary restriction and preauthorization
• Selective ...
Education
• Essential
• Alone, insufficient (II-B)
• No sustained impact
• Education + Intervention (xA-III)
http://www.id...
Formulary (A-II)
• Therapeutics Committee
• Evaluating therapeutic efficacy, toxicity and
cost
• Limit redundant new agent...
Formulary Restrictions (A-II) and Pre-
authorization (B-II)
• Restriction of Antibiotics
• ID approval
• ID consult
http:/...
Selective Reporting A-III
• Clinical Microbiology
• Limiting Antibiotic Susceptibility Reports in
Cultures
• Example:
– Ur...
Prospective Audit with Intervention
and Feedback (A-I)
• Very effective
• Resource intensive
http://www.idsociety.org/stew...
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...
Exceptions to general approach
• Do not discontinue antibiotics in a patient
who is decompensating
• Patients may be ill a...
Dose Optimization (A-II)
• Optimize PK/PD
– Septic patients: Increased Vd
• T/MIC for β-lactams
• AUC/MIC and Cmax/MIC for...
Parenteral to oral conversion (A-III)
• High bioavailability antibiotics
– Fluoroquinolones
– TMP/SMX
– Metronidazole
– Cl...
Stewardship: Recommendations
• Health care information technology
• Surveillance
http://www.idsociety.org/stewardship_poli...
Antibiotics in Development
• As of December 2014, an estimated 37 new
antibiotics 1 that have the potential to treat
serio...
Learning Points
• Antimicrobial resistance is a global concern
and needs immediate action
• Antimicrobial stewardship is o...
Learning Points
• Treatment of infections should be based on
most likely organism following local resistance
patterns
• Ne...
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
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by Dr. Carmenchu Marie E. Villavisencio

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Antimicrobial Stewardship

  1. 1. Let’s Shore Up Our Defenses Presented by: Carmenchu Echiverri Villavicencio, MD, DPCP, DPSMID Slides by Marion Priscilla A. Kwek, MD, FPCP, DPSMID July 4, 2015
  2. 2. 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
  3. 3. Objectives • Recognize the problem of antimicrobial resistance • Understand the benefits of an antimicrobial stewardship program • Apply antimicrobial stewardship in clinical practice
  4. 4. - Alexander Fleming upon accepting the 1945 Nobel Prize in Medicine
  5. 5. 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
  6. 6. 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
  7. 7. Antibiotic Resistance • 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 Antibiotic Resistance Threats in the United States, 2013. Centers for Disease Control and Prevention
  8. 8. Antibiotic Resistance The use of antibiotics is the single most important factor leading to antibiotic resistance around the world Antibiotic Resistance Threats in the United States, 2013. Centers for Disease Control and Prevention
  9. 9. http://lumibyte.eu/microbiology-news/antimicrobial-resistance-timeline/ http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
  10. 10. Pucci & Bush Clin Micro Rev 2013;26:792–821
  11. 11. 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.
  12. 12. Difficult to Treat Organisms • MRSA • Antibiotic-resistant GNBs • MDR-TB • C. difficile
  13. 13. 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
  14. 14. 2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM
  15. 15. 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) 2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM
  16. 16. 2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM
  17. 17. 2013 Antimicrobial Resistance Surveillance Program Summary Report, RITM
  18. 18. 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 Vancomycin Intermediate Vancomycin Resistant
  19. 19. 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
  20. 20. Global Antibiotic Consumption by Class 2000-2010 www.thelancet/infection Vol 14 August 2014
  21. 21. 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
  22. 22. Nicolau ,DP
  23. 23. 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
  24. 24. 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.
  25. 25. WHAT IS ANTIMICROBIAL STEWARDSHIP?
  26. 26. Antimicrobial Stewardship • After confirming that the patient has an indication for antimicrobial therapy, antimicrobial stewardship is the: Drug Time Dose Duration Route Dryden M et al. J Antimicrob Chemother 2011; 66(11): 2441-3 http://www.idsociety.org/stewardship_policy/
  27. 27. 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.
  28. 28. 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%
  29. 29. Understanding Your Local Antibiogram % Susceptibility of E. coli Ampicillin 32.2 Amoxicillin Clavulanate 73.9 Piperacillin/Tazobactam 100.0 Cefuroxime 78.5 Ceftriaxone 91.5 Ceftazidime 90.6 Cefepime 93.4 Ertapenem 99.4 Imipenem 100.0 Meropenem 100.0 Levofloxacin 71.4 Amikacin 100.0 Cotrimoxazole 47.0
  30. 30. INAPPROPRIATE ANTIBIOTIC USE
  31. 31. Treating Viral Infections with Antibiotics • Most common cause of acute upper respiratory tract infections is viral • Giving quinolones in viral gastroenteritis
  32. 32. Treating Colonizers • Isolates from respiratory specimens in patients who are clinically well or asymptomatic • Asymptomatic Bacteriuria
  33. 33. • 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)
  34. 34. Surgical Prophylaxis • Prolonged duration of Prophylaxis • Timing • Giving of prophylactic antibiotic even when not indicated
  35. 35. • 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
  36. 36. 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/
  37. 37. Antimicrobial Stewardship: Goals • Optimal clinical outcomes • Minimize toxicity and ADRs • Limit selection for antimicrobial resistant strains • Reduce costs of health care http://www.idsociety.org/stewardship_policy/
  38. 38. Stewardship: Recommendations • Multidisciplinary team – IDS physician – PharmD – Clinical Microbiologist – IT – Infection Control Practitioner – Hospital Epidemiologist • Compensated http://www.idsociety.org/stewardship_policy/
  39. 39. Stewardship: Recommendations • Collaboration b/w the ff: – Stewardship team – Infection control – Pharmacy/Therapeutics Committee • Administrative/Leadership support http://www.idsociety.org/stewardship_policy/
  40. 40. 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 http://www.idsociety.org/stewardship_policy/
  41. 41. Education • Essential • Alone, insufficient (II-B) • No sustained impact • Education + Intervention (xA-III) http://www.idsociety.org/stewardship_policy/
  42. 42. Formulary (A-II) • Therapeutics Committee • Evaluating therapeutic efficacy, toxicity and cost • Limit redundant new agents http://www.idsociety.org/stewardship_policy/
  43. 43. Formulary Restrictions (A-II) and Pre- authorization (B-II) • Restriction of Antibiotics • ID approval • ID consult http://www.idsociety.org/stewardship_policy/
  44. 44. 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 http://www.idsociety.org/stewardship_policy/
  45. 45. Prospective Audit with Intervention and Feedback (A-I) • Very effective • Resource intensive http://www.idsociety.org/stewardship_policy/
  46. 46. Guidelines and Clinical Pathways • National Guidelines • Local Guidelines • Very Effective
  47. 47. Antimicrobial Order Forms (B-II) • Automatic stop orders • Clear communication of renewal requirements
  48. 48. 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
  49. 49. 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. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA). Am J Respir Crit Care Med. 2005;171:388- 416. 4. Singh N et al. Am J Respir Crit Care Med. 2000;162:505-511.
  50. 50. 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
  51. 51. Parenteral to oral conversion (A-III) • High bioavailability antibiotics – Fluoroquinolones – TMP/SMX – Metronidazole – Clindamycin – Linezolid – Minocycline – Fluconazole – Voriconazole – Chloramphenicol
  52. 52. Stewardship: Recommendations • Health care information technology • Surveillance http://www.idsociety.org/stewardship_policy/
  53. 53. 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
  54. 54. 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
  55. 55. 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
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by Dr. Carmenchu Marie E. Villavisencio

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